The Androgenic alopecia and Therapeutic Alternatives. !
La Alopecia Androgenica y Alternativas Terapeuticas. !
EDITORIAL ENGLISH
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Hello friends of the DERMAGIC EXPRESS network today with another
interesting topic, currently much discussed and studied: ANDROGENIC
ALOPECIA, AND THEIR THERAPEUTIC ALTERNATIVES.
Firstly, it is necessary to explain to the NON MEDICAL audience, that androgenic alopecia is the LOSS OF HAIR produced by an increase of
ANDROGENS, (mainly testosterone), in our body, both in man and woman.
Specifically its metabolite or derivative called:
DEHYDROTESTOSTERONE.
This excess of ANDROGENS specifically DYHIDROTESTOSTERONE, are deposited in the hair follicle, and cause the hair to fall. This is the main mechanism that causes ANDROGENIC ALOPECIA.
Characterized by a progressive hair loss, affects both men and women post
pubertal, which can become severe in both sexes. In women diseases such as
the POLYCYSTIC OVARY SYNDROME, it causes an increase in androgens with
subsequent hair loss.
In man, the disease undoubtedly has a genetic component, Because not
everyone is affected, and It is important that you know that, there are
men who will NEVER SUFFER FROM ANDROGENIC ALOPECIA, generally there is
always a history of baldness in those affected.
Also it is necessary to explain that the hair is not "ADHERED WITH GLUE"
to the scalp, it has a cycle of "LIFE: ANAGEN, or growth, lasts from 1 to
7 years, CATAGEN, or transición, that lasts from 2 to 3 months and TELOGEN
or resting which lasts about 3 months, then the hair falls and is replaced
by a new one.
USUALLY 50 TO 100 HAIRS FALL EVERY DAY.
It is interesting that you also know that when the body is submitted to a
great STRESS, and other factors the hair enters prematurely in the TELOGEN
PHASE and the hair begins to fall abundantly producing a remarkable
ALOPECIA.
So factors such as the STRES and others that alter the hair CYCLE will
contribute to the ANDROGENIC ALOPECIA be worse.
Another factor that worsens ANDROGENIC ALOPECIA is the
SEBORRHEIC DERMATITIS
of the scalp, commonly called "INCREASE OF THE GREASE IN THE HAIR, so that
the more you use an anti-dandruff shampoo, there will be less SEBORRHEA
therefore less hair loss.
Treatments for ALOPECIA ANDROGENIC are varied, and I highlight the most
used today:
1.) MINOXIDIL, TOPICAL (ANTIHYPERTENSIVE).
2.)
FINASTERIDE
(5-ALPHA REDUCTASE INHIBITOR).
3.) DUTASTERIDE (5-ALPHA REDUCTASE INHIBITOR).
4.) FLUTAMIDE (5-ALPHA REDUCTASE INHIBITOR).
5.) CYPROTERONE ACETAT. (ORAL ANTICONCEPTIVE)
6.) SPIRONOLACTONE. (ORAL ANTIDIURETIC).
7.)
SERENOA REPENS
OR SAW PALMETTO (NATURIST, ANTI-ANDROGEN).
8.)
CYPERUS ROTUNDUS
(NATURIST).
9.) TOPICAL STEROIDS.
10.) ANTI-DANDRUFF SHAMPOO (KETOCONAZOLE, ZINC PIRYTHIONE,
BIFONAZOLE)
11.) DROSPIRENONE (ORAL ANTICONCEPTIVE).
There is in our body an ezyme called 5 alpha reductase that is responsible for converting TESTOSTERONE IN DIHYDROTESTOSTERONE. By increasing this metabolite, the greater the fall of hair.
Therefore, one of the strategies to avoid ANDROGENIC ALOPECIA is to inhibit the enzyme 5 alpha reductase, and for that already have been invented and discovered pharmacological and natural medicines
There is in our body an ezyme called 5 alpha reductase that is responsible for converting TESTOSTERONE IN DIHYDROTESTOSTERONE. By increasing this metabolite, the greater the fall of hair.
Therefore, one of the strategies to avoid ANDROGENIC ALOPECIA is to inhibit the enzyme 5 alpha reductase, and for that already have been invented and discovered pharmacological and natural medicines
All these medicines have their ADVANTAGES and their ADVERSE EFFECTS, but
if we place ourselves in reality, science has advanced remarkably in this
field, many years ago it was popularly said:
"...TO THE FALL OF THE HAIR ONLY STOPS THE FLOOR OR SOIL .."
Today this old adage is not true, mainly due to the appearance of
drugs like DUTASTERIDE,
FINASTERIDE
and FLUTAMIDE, which inhibit the enzyme 5 alpha reductase, the main cause
of the increase of ANDROGENS in our body.
I leave you 61 bibliographical references on this theme and in the
attached photos of ANDROGENIC ALOPECIA in MEN and WOMEN.
Greetings.
Dr. Jose Lapenta.
EDITORIAL ESPANOL
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Hoy dia este viejo adagio no es cierto, por la aparicion de medicamentos principalmente como DUTASTERIDE, FINASTERIDE Y FLUTAMIDA, los cuales inhiben la enzima 5 alfa reductasa, principal causante del aumento de los ANDRÓGENOS en nuestro cuerpo.
Te dejo 61 referencias bibliográficas sobre el tema y en el adjunto fotos de ALOPECIA ANDROGÉNICA en HOMBRE y MUJER.
Saludos a todos.
Dr. Jose Lapenta.
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REFERENCIAS BIBLIOGRÁFICAS / BIBLIOGRAPHICAL REFERENCES
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1.) Increased scalp skin and serum 5 alpha-reductase reduced androgens in a man relevant to the acquired progressive kinky hair disorder and developing androgenetic alopecia.
2.) Androgen metabolism as it affects hair growth in androgenetic alopecia.
3.) [Finasteride: a new drug for the treatment of male hirsutism and androgenetic alopecia?] [La finasteride: un nuovo farmaco nel trattamento dell'irsutismo e dell' alopecia androgenica maschile?]
4.) Alterations in androgen conjugate levels in women and men with alopecia.
5.) Hormonal basis of male and female androgenic alopecia: clinical relevance.
6.) [Current treatment of androgenetic male and female alopecia(with the exception of hormone treatment)] [Traitements actuels des alopecies androgenetiques masculines et feminines (traitements hormonaux exceptes).]
7.) Androgenetic alopecia: an autosomal dominant disorder.
8.) [Hair growth promoters in androgenetic alopecia. Expectations and reality] [Haarwuchsmittel bei androgenetischer Alopezie. Anspruch und Realitat.]
9.) Effects of ozonized autohaemotherapy on human hair cycle.
10.) Estrogen and progesterone receptors in androgenic alopecia versus alopecia areata.
11.) Androgens and women's health.
12.) Female androgenetic alopecia: an update.
13.) A prospective study of the prevalence of clear-cut endocrine disorders and polycystic ovaries in 350 patients presenting with hirsutism or androgenic alopecia.
14.) Ketoconazole shampoo: effect of long-term use in androgenic alopecia.
15.) Anagen hairs may fail to replace telogen hairs in early androgenic female alopecia.
16.) Different levels of 5alpha-reductase type I and II, aromatase, and androgen receptor in hair follicles of women and men with androgenetic alopecia.
17.) Safety surveillance of esterified estrogens-methyltestosterone
(Estratest and Estratest HS) replacement therapy in the United States.
18.) Balding hair follicle dermal papilla cells contain higher levels ofandrogen receptors than those from non-balding scalp.
19.) A comparison of the culture and growth of dermal papilla cells from hair follicles from non-balding and balding (androgenetic alopecia) scalp.
20.) Messenger RNA expression of steroidogenesis enzyme subtypes in thehuman pilosebaceous unit.
21.) Treatment of androgen excess in females: yesterday, today and tomorrow.
22.) Association of benign prostatic hyperplasia with male pattern baldness.
23.) Hair regrowth. Therapeutic agents.
24.) Androgenic effects of oral contraceptives: implications for patient compliance.
25.) Diffuse hypertrichosis during treatment with 5% topical minoxidil.
26.) Minoxidil upregulates the expression of vascular endothelial growth factor in human hair dermal papilla cells.
27.) Biphasic effects of minoxidil on the proliferation and differentiation of normal human keratinocytes.
28.) Alopecia and mood stabilizer therapy.
29.) Improvement in androgenetic alopecia (stage V) using topical minoxidil in a retinoid vehicle and oral finasteride [see comments]
30.) Clinical significance of testosterone and dihydrotestosteronemetabolism in women]
31.) The 5 alpha-reductase system and its inhibitors. Recent development
and its perspective in treating androgen-dependent skin disorders.
32.) Finasteride: a clinical review.
33.) 19-nor-10-azasteroids: a novel class of inhibitors for human steroid 5alpha-reductases 1 and 2.
34.) Genetic analysis of male pattern baldness and the 5alpha-reductase genes.
35.) Effects of topically applied spironolactone on androgen stimulated sebaceous glands in the hamster pinna.
36.) Androgens affect the activity of human sebocytes in culture in a manner dependent on the localization of the sebaceous glands and their effect is antagonized by spironolactone.
37.) Antiandrogen treatment with spironolactone and linestrenol decreases bone mineral density in eumenorrhoeic women with androgen excess.
38.) [Serum hormones before and during therapy with cyproterone acetate and spironolactone in patients with androgenization]
39.) The insulin resistance in women with hyperandrogenism is partially reversed by antiandrogen treatment: evidence that androgens impair insulin action in women.
40.) Topical spironolactone reduces sebum secretion rates in young adults.
41.) Other antiandrogens.
42.) Mechanism of action and pure antiandrogenic properties of flutamide.
43.) Drospirenone: a novel progestogen with antimineralocorticoid and antiandrogenic activity.
44.) Cutaneous Manifestations of Polycystic Ovary Syndrome: A Cross-Sectional Clinical Study.
45.) A Retrospective Review of Treatment Results for Patients With Central Centrifugal Cicatrical Alopecia.
46.) The effectiveness of treatments for androgenetic alopecia: A systematic review and meta-analysis.
47.) Dutasteride in androgenetic alopecia: An update.
48.) A randomized, active- and placebo-controlled study of the efficacy and safety of different doses of dutasteride versus placebo and finasteride in the treatment of male subjects with androgenetic alopecia.
49.) New Treatments for Hair Loss.
50.) Efficacy and safety of 5% minoxidil topical foam in male pattern hair loss treatment and patient satisfaction.
51.) Post-Finasteride Adverse Effects in Male Androgenic Alopecia: A Case Report of Vitiligo.
52.) Adverse Effects and Safety of 5-alpha Reductase Inhibitors (Finasteride, Dutasteride): A Systematic Review.
53.) Atypical post-finasteride syndrome: A pharmacological riddle.
54.) Emotional Consequences of Finasteride: Fool's Gold.
55.) The importance of dual 5alpha-reductase inhibition in the treatment of male pattern hair loss: results of a randomized placebo-controlled study of dutasteride versus finasteride.
56.) Interventions for female pattern hair loss.
57.) Antiandrogenic Therapy with Ciproterone Acetate in Female Patients Who Suffer from Both Androgenetic Alopecia and Acne Vulgaris.
58.) Treatment of female pattern hair loss.
59.) [Spironolactone in dermatological treatment. On and off label indications].
60.) Treatment of male androgenetic alopecia with topical products containing Serenoa repens extract.
61.) Comparitive effectiveness of finasteride vs Serenoa repens in male androgenetic alopecia: a two-year study.
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1.) Increased scalp skin and serum 5 alpha-reductase reduced androgens in a man relevant to the acquired progressive kinky hair disorder and developing androgenetic alopecia.
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Arch Dermatol 1997 Sep;133(9):1129-33 (ISSN: 0003-987X)
Boudou P; Reygagne P [Find other articles with these Authors]
Department of Hormonal Biology, Saint-Louis University Hospital, Paris,
France.
BACKGROUND: The acquired progressive kinking of scalp hair is a disorder in which affected hairs resemble secondary sexual hairs. Some authors have evoked an androgen-related disorder that heralds the onset of androgenetic alopecia. To verify this hypothesis, we focused our attention on a 23-year-old man who has this unusual disorder, which is progressing toward androgenetic alopecia. Patient's circulating 5 alpha-reductase reduced androgen levels; scalp skin 5 alpha-dihydrotestosterone formation; and trichography, histological, scanning, and polarizing electron microscopy analyses were compared in normal and affected scalp skin areas.
OBSERVATIONS: Results of histological and scalp skin 5 alpha-dihydrotestosterone formation analyses and comparison of growth pattern of kinky hair in the affected areas with that of healthy hair were similar to those found in androgenetic alopecia.
CONCLUSIONS: No data are available to confirm the presence of a sole entity, even if our arguments support our hypothesis. The confirmation of this tendency warrants further investigation.
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2.) Androgen metabolism as it affects hair growth in androgenetic alopecia.
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Dermatol Clin 1996 Oct;14(4):697-711 (ISSN: 0733-8635)
Kaufman KD [Find other articles with this Author]
Merck Research Laboratories, Rahway, New Jersey, USA.
Androgens, in combination with a genetic susceptibility, have been demonstrated to be required for the development of androgenetic alopecia. Disturbances in androgen metabolism or target organ sensitivity are thought to underlie the pathophysiology of the condition.
Observations of patients with disorders of androgen metabolism or function have determined the basic physiology involved in regulation of hair growth by androgens at selective body sites. More recently, in vitro studies of scalp skin and hair follicles have begun to define specific alterations in androgen metabolism at the local level that may play a key role in pathogenesis. The prominent role of 5-reductase in these studies suggests that inhibitors of this enzyme may provide new therapeutic opportunities for patients with androgenetic alopecia.
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3.) [Finasteride: a new drug for the treatment of male hirsutism and androgenetic alopecia?] [La finasteride: un nuovo farmaco nel trattamento dell'irsutismo e dell'alopecia androgenica maschile?]
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Clin Ter 1996 Jun;147(6):305-15 (ISSN: 0009-9074)
Spinucci G; Pasquali R [Find other articles with these Authors]
Dipartimento di Medicina interna e Gastroenterologia, Policlinico S. Orsola-Malpighi, Bologna.
Finasteride is a drug which inhibits the transformation of testosterone into its active metabolite, dihydrotestosterone, in the target organs, i.e. the skin, the scalp, the liver and the prostate. In the pathogenic mechanism of hirsutism and androgenetic alopecia, and important role is presumably played by alterations of the mechanisms which transform testosterone into dihydrotestosterone. In some conditions an increase in dihydrotestosterone has been demonstrated, due to increased activity of the enzyme 5 alpha-reductase.
The effect of finasteride develops above all at the level of type II 5 alpha-reductase. Recent studies have evaluated the effect of finasteride in patients of both sexes with hirsutism and androgenetic alopecia. In women with various forms of hyperandrogenism, the use of the drug at the doses commonly used for the treatment of benign prostatic hyperplasia seems to have induced a significant reduction in the degree of hirsutism. Furthermore, both in animals and men with alopecia, the drug seems to have led to an increase in the number and an improvement in the shape of the follicles in the anagen phase, and a simultaneous decrease of dehydrotestosterone at the level of the scalp. This study represents a review of the main results obtained over the last two years and reports the prospects which the use of finasteride may have in this context.
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4.) Alterations in androgen conjugate levels in women and men with alopecia.
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Fertil Steril 1994 Oct;62(4):744-50 (ISSN: 0015-0282)
Legro RS; Carmina E; Stanczyk FZ; Gentzschein E; Lobo RA [Find other articles with these Authors]
Department of Obstetrics and Gynecology, University of Southern California School of Medicine, Los Angeles.
OBJECTIVE: To assess levels of androgen metabolites thought to reflect, at least in part, peripheral androgen activity in women with androgenic alopecia and men with premature balding in an effort to determine if a common abnormality exists.
DESIGN: Prospective study in various groups of women and men.
SETTING: Reproductive Endocrine Clinic at our university medical center.
PATIENTS: Ten normal ovulatory female controls and 50 hyperandrogenic women divided on the basis of hirsutism and alopecia as follows: [1] 8 hirsute women with androgenic alopecia; [2] 12 nonhirsute women with androgenic alopecia; [3] 18 hirsute women without androgenic alopecia; and [4] 12 nonhirsute women without androgenic alopecia. Ten normal men and 10 young premature balding men matched for age and weight also were compared. I
NTERVENTION: Blood was obtained from all subjects.
MAIN OUTCOME MEASURE: Comparison of blood hormone levels in the various groups.
RESULTS: Serum T, androstenedione, and DHEAS were similarly elevated in hyperandrogenic women with and without alopecia, compared with controls. The female groups were then divided on the basis of hirsutism. Hirsute groups with and without alopecia had similarly elevated levels of unconjugated 3 alpha-androstanediol, 3 alpha-androstanediol glucuronide, 3 alpha-androstanediol sulfate, androsterone glucuronide, and androsterone sulfate compared with controls.
In the nonhirsute groups, androgenic alopecia patients were compared with hyperandrogenic females and cycling controls. The androgenic alopecia patients had elevated levels of 3 alpha androstanediol (0.75 +/- 0.12 versus 0.46 +/- 0.1 and 0.41 +/- 0.1 nmol/L), 3 alpha-androstanediol sulfate (200 +/- 31 versus 79.6 +/- 6 and 67.0 +/- 4.0 nmol/L), elevated ratios of 3 alpha-androstanediol sulfate:3 alpha-androstanediol (267 +/- 49 versus 170 +/- 20 and 164 +/- 49 nmol/L), elevated ratios of 3 alpha-androstanediol sulfate:3 alpha-androstanediol glucuronide (32.2 +/- 6 versus 10.8 +/- 1 and 10.0 +/- 1) and lower ratios of 3 alpha-androstanediol glucuronide:3 alpha-androstanediol glucuronide (8.3 +/- 1.8 versus 17 +/- 1.7 and 15.2 +/- 1.6 nmol/L). I
n men the premature balding group had lower levels of 3 alpha-androstanediol glucuronide compared with the male controls (29.8 +/- 4.4 versus 15.2 +/- 1.6 nmol/L). Also, the ratio of 3 alpha-androstanediol glucuronide:3 alpha-androstanediol was significantly decreased, whereas the ratio of 3 alpha-androstanediol sulfate:3 alpha-androstanediol glucuronide was elevated.
CONCLUSIONS: These data provided evidence confirming that enhanced 5 alpha-reductase activity occurs in androgenic alopecia but also suggests that a disorder of androgen conjugation, favoring sulfurylation over glucuronidation, may be a characteristic feature of scalp hair loss.
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5.) Hormonal basis of male and female androgenic alopecia: clinical relevance.
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Skin Pharmacol 1994;7(1-2):61-6 (ISSN: 1011-0283)
Schmidt JB [Find other articles with this Author]
Department of Dermatology, University of Vienna Medical School, Austria.
A broad range of hormones was determined in males and females with androgenic hair loss (AH). The androgens testosterone, androstenedione, dehydroepiandrosterone sulfate, 17-hydroxyprogesterone and sex hormone binding globulin were evaluated in 65 male and 46 female patients. Besides estradiol (E2), cortisol (F), and the hypophyseal hormones LH, FSH, and prolactin (PRL)
were investigated. Hormone levels were compared with those of 58 age-matched male and 45 female controls. In 38 of the 46 female AH patients, hypophyseal function was moreover evaluated by the 'TRH test', which detects slight, secondary hypothyroidism and/or hyperprolactinemia. Our findings showed a significant elevation of F in both male and female AH patients compared to controls, pointing to the suprarenes as a contributing factor in AH. This is confirmed by the observation of exacerbated AH in periods of increased stress. Concerning specifically male androgens, a significant elevation of androstenedione was noted. The mainly peripheral activity of this hormone and elevated E2 levels in males stress the importance of androgen metabolism especially at the peripheral level.
Additional TRH tests in females demonstrated significant hypophyseal hypothyroidism. Multilayered interaction between thyroid hormones and androgens may contribute to the development of AH in hyperthyroid patients. Another significant finding was elevated PRL after TRH stimulation. Thus, the androgen-stimulating effect of PRL may also play a role in female AH. Our findings show multilayered hormonal influences in AH. Broad-range hormone determination demonstrated a differentiated hormonal situation in this disorder.
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6.) [Current treatment of androgenetic male and female alopecia (with the exception of hormone treatment)] [Traitements actuels des alopecies androgenetiques masculines et feminines (traitements hormonaux exceptes).]
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Schweiz Rundsch Med Prax 1997 Jun 4;86(23):996-9 (ISSN: 1013-2058)
Bouhanna P [Find other articles with this Author]
Centre Sabourdaud du Cuir chevelu, Hopital Saint-Louis, Paris.
Various non-hormonal therapies, either prescribed systemically such as certain hair-specific vitamins, or applied via the topical route, such as 2% Minoxidil, permit a normalisation of androgenic hair loss. The trichogenic action of these products should be verified in each individual with a comparative study using a trichogram and a phototrichogram. Any alopecia, be it large or small, may cause aesthetic discomfort. Currently, no medical or cosmetic product can give hope for a discernible and definitive hair regrowth. Only a micrograft reimplantation, hair by hair, produces tangible, aesthetically-denser hair in the bald region.
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7.) Androgenetic alopecia: an autosomal dominant disorder.
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Am J Med 1995 Jan 16;98(1A):95S-98S (ISSN: 0002-9343)
Bergfeld WF [Find other articles with this Author]
Department of Dermatology, Cleveland Clinic Foundation, Ohio 44195-5032.
A hereditary, androgen-driven disorder, androgenetic alopecia is the most common form of alopecia in humans: its prevalence is 23-87%. Central alopecia is more severe in men; women are more likely to experience diffuse thinning. The acute onset of alopecia in those with inflammatory diseases of the scalp suggests a variety of etiologies, including the impact of inflammatory cells, release of cytokines, presence of growth factors, and increased interaction of stromal cells. Therapeutic modalities, which are most effective when used in combinations, utilize hair growth promoters, antiandrogens, and androgen blockade agents.
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8.) [Hair growth promoters in androgenetic alopecia. Expectations and reality] [Haarwuchsmittel bei androgenetischer Alopezie. Anspruch und Realitat.]
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Hautarzt 1994 Jun;45(6):360-3 (ISSN: 0017-8470)
Schell H; Kiesewetter F; Hornstein OP [Find other articles with these Authors]
Dermatologische Universitats-Klinik, Erlangen.
Androgenetic hair loss is the most frequent reason for the topical application of hair-growth-promoting agents. Such preparations should arrest or even reverse androgen-induced hair follicle regression as well as prolonging the hair cycles, especially of the shortened anagen phase, and thus protect from increased hair loss. True evidence of drug effects on hair growth is problematic, since trichograms, the method chiefly applied by the manufacturers, fail to reveal every factor involved in the follicular activity, especially the duration of anagen stage.
For example, an increase in the anagen rate does not always reflect a lengthening of the anagen stage, but may also be due to shortened hair cycles. Accordingly, drug effects on hair growth should be investigated by methods that analyse the cell cycle kinetics. For this approach DNA-flowcytometry of the outer root sheath in plucked anagen hairs and of complete anagen hair bulbs taken by micropreparative techniques from scalp biopsies offers a reproducible method for quick and reliable evaluation of hair growth.
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9.) Effects of ozonized autohaemotherapy on human hair cycle.
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Panminerva Med 1995 Sep;37(3):129-32 (ISSN: 0031-0808)
Riva Sanseverino E; Castellacci P; Misciali C; Borrello P; Venturo N [Find other articles with these Authors]
Institute of Human Physiology, University of Bologna, Italy.
The present paper deals with the effects of ozonized autohaemotherapy on the human hair cycle in subjects suffering from androgenetic alopecia. The microscopic observation of hairs (trichogram) of 42 subjects (age range = 17-40 years) was carried out before and after cycles of ozonized autohaemotherapy according to the European scientific protocol. The dosage of ozone was 2500-3000 micrograms for each treatment, one cycle consisting of 16 treatments. Results showed a marked improvement of the hair cycle.
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10.) Estrogen and progesterone receptors in androgenic alopecia versus alopecia areata.
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Am J Dermatopathol 1998 Apr;20(2):160-3 (ISSN: 0193-1091)
Wallace ML; Smoller BR [Find other articles with these Authors]
Department of Pathology and Dermatology, Medical College of Virginia/Virginia Commonwealth University, Richmond, USA.
In some situations, hair growth is under hormonal control. Androgenic alopecia is characterized as hormonally driven hair loss in the genetically susceptible individual. During pregnancy, hair growth is increased, as estrogen appears to prolong the anagen phase. However, postpartum hair loss is common, and thus may be related to a decrease in estrogen and or progesterone levels. In contrast, alopecia areata is not considered to be under hormonal control. We compared the immunohistochemical staining characteristics of nine cases of androgenic alopecia with those of 13 cases of alopecia areata using estrogen receptor (ER) and progesterone receptor (PR) markers.
Estrogen receptor positivity in the dermal papilla was found in only two of 13 cases of alopecia areata, and in one case of androgenic alopecia. Six of 13 cases of alopecia areata demonstrated focal reactivity with the progesterone marker in a similar location, while only three cases of androgenic alopecia showed positivity with this antibody. Examination of the perifollicular fibroblasts for the ER marker showed positivity in one of 13 cases of alopecia areata and in one case of androgenic alopecia. Two cases of alopecia areata revealed focal staining in this location for the PR marker, while the androgenic alopecia cases failed to stain.
These results indicate that estrogen and progesterone receptor expression is not significantly increased or decreased in the pilosebaceous units or surrounding mesenchymal cells in androgenic alopecia vs. alopecia areata. Therefore, an indirectly mediated process of estrogen/progesterone control on hair growth and development must be presumed for cases of androgenic alopecia.
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11.) Androgens and women's health.
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Int J Fertil Womens Med 1998 Mar-Apr;43(2):91-7
Redmond GP [Find other articles with this Author]
Center for Health Studies, Inc., Cleveland, Ohio 44122, USA.
Androgenic disorders are those conditions in women characterized by excessive androgen action. They are the most common endocrinopathy of women, affecting from 10% to 20%. Signs are: persistent acne, hirsutism and androgenic alopecia, which is the female equivalent of male pattern baldness.
A subgroup, those traditionally labeled as having polycystic ovary syndrome (PCOS), additionally have anovulation, as well as menstrual abnormalities and, often, obesity. Although women with androgenic disorders usually present themselves for help with the skin or menstrual changes, there are other important implications regarding their health. Women with PCOS have varying degrees of insulin resistance, and an increased incidence of Type II diabetes mellitus, as well as unfavorable lipid patterns.
The presence of these risk factors is suggested by upper segment obesity, darkening of the skin, and the other skin changes that make up acanthosis nigricans. Diagnosis involves measurement of circulating androgens (of which free testosterone is most important), together with prolactin and FSH when menstrual dysfunction is present. Many women with androgenic skin changes have normal serum androgen levels, suggesting increased end organ sensitivity to androgens. Others have hyperandrogenism (of ovarian or adrenal origin).
Treatment is usually successful in controlling acne, reducing hirsutism and stabilizing, or partially reversing, androgenic alopecia. Pharmacological approaches involve suppressing androgen levels, for example, the use of an appropriate oral contraceptive, or antagonizing androgen action with several medications that have this activity. Unfortunately, most women with androgenic disorders are frustrated in their efforts to obtain medical help. Understanding androgenic disorders will enable the physician to significantly help the majority of women with these conditions.
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12.) Female androgenetic alopecia: an update.
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Australas J Dermatol 1995 May;36(2):51-5; quiz 56-7 (ISSN: 0004-8380)
Callan AW; Montalto J [Find other articles with these Authors]
Department of Clinical Biochemistry, Royal Children's Hospital, Parkville,
Victoria, Australia.
Androgenetic alopecia is an androgen dependent disorder occurring in genetically susceptible individuals. The pattern of hair loss in women differs from that of classical male pattern alopecia, being more diffuse and with retention of the frontal hair line in most cases. Characteristic histopathological changes occur but biopsy is rarely helpful in diagnosis. Although research has shown subtle alterations in the androgen status of women with androgenetic alopecia, most patients presenting with this disorder are normal endocrinologically. Anti-androgen therapy will result in some improvement in up to 50% of patients after 6 to 12 months of therapy, but in practice will usually only decrease the rate of hair loss and not result in new hair growth.
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13.) A prospective study of the prevalence of clear-cut endocrine disorders and polycystic ovaries in 350 patients presenting with hirsutism or androgenic alopecia.
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Clin Endocrinol (Oxf) 1994 Aug;41(2):231-6 (ISSN: 0300-0664)
O'Driscoll JB; Mamtora H; Higginson J; Pollock A; Kane J; Anderson DC [Find other articles with these Authors]
Department of Radiology, Skin Hospital, Salford.
OBJECTIVE: To determine the frequency of polycystic ovaries (PCO) on ultrasound and the incidence of clearcut endocrine disorders leading to virilization in patients complaining of hirsutism or androgenic alopecia. The major purpose was to determine a coherent policy for the routine biochemical assessment of such women.
DESIGN: A prospective study of women attending a joint skin/endocrine clinic complaining of these problems.
PATIENTS: Three hundred and fifty consecutive women with hirsutism and/or androgenic alopecia were assessed.
MEASUREMENTS: Baseline endocrine screens were conducted on two occasions and included measurement of serum testosterone, androstenedione, dehydroepiandrosterone sulphate, sex hormone binding globulin, LH, FSH, 17-hydroxyprogesterone and PRL. The ovaries were visualized by high-resolution pelvic ultrasound scanning.
RESULTS: Eight women were identified with relevant endocrine disorders; of these, one was acromegalic and one had a microprolactinoma--in both cases the association may have been fortuitous. Three had clear-cut 21-hydroxylase deficiency, one a rare hepatic enzyme deficiency (11-reductase), one a virilizing adrenal carcinoma and one a Leydig cell tumour. The latter six cases all had persistently elevated levels of serum testosterone ( 5 nmol/l). In all, 13 women had baseline testosterone levels in excess of 5 nmol/l. Polycystic ovaries were present in 81% of the cases who had erratic cycles and 52% of those with regular cycles; PCO were present in two of the women with 21-hydroxylase deficiency and in the woman with 11-oxoreductase deficiency. The Leydig cell tumour (1.2 cm diameter) was not detected on ultrasound or CT scan.
CONCLUSIONS: For the exclusion of enzyme deficiencies and virilizing tumours clinical assessment and a single serum testosterone measurement will suffice.
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14.) Ketoconazole shampoo: effect of long-term use in androgenic alopecia.
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Author
Pi´erard-Franchimont C; De Doncker P; Cauwenbergh G; Pi´erard GE
Address
Department of Dermatopathology, University of Li`ege, Belgium.
Source
Dermatology, 196(4):474-7 1998
Abstract
BACKGROUND: The pathogenesis of androgenic alopecia is not fully understood. A microbial-driven inflammatory reaction abutting on the hair follicles might participate in the hair status anomaly.
OBJECTIVE: The aim of our study was to determine if ketoconazole (KCZ) which is active against the scalp microflora and shows some intrinsic anti-inflammatory activity might improve alopecia.
METHOD: The effect of 2% KCZ shampoo was compared to that of an unmedicated shampoo used in combination with or without 2% minoxidil therapy.
RESULTS: Hair density and size and proportion of anagen follicles were improved almost similarly by both KCZ and minoxidil regimens. The sebum casual level appeared to be decreased by KCZ.
CONCLUSION: Comparative data suggest that there may be a significant action of KCZ upon the course of androgenic alopecia and that Malassezia spp. may play a role in the inflammatory reaction. The clinical significance of the results awaits further controlled study in a larger group of subjects.
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15.) Anagen hairs may fail to replace telogen hairs in early androgenic female alopecia.
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Author
Guarrera M; Rebora A
Address
Department of Dermatology, University of Genoa, Italy.
Source
Dermatology, 192(1):28-31 1996
Abstract
Background: Male baldness develops because of an increased duration of the lag phase. Objective and Methods: To assess if this occurs also in balding women we studied 2 women with Ludwig type I-II patterned baldness for 2 years with monthly phototrichograms. Hairs were identified as thick anagen hairs, thin anagen hairs and telogen hairs.
Results and Conclusions:
Most of the hairs followed the expected development, namely they remained thick anagen hairs or they became thick from thin anagen, telogen from thick anagen or thin anagen from telogen hairs. Other hairs, though, became thin from thick anagen or telogen from thin anagen or thick anagen from telogen hairs. Still others did not regrow immediately after being in the telogen phase, leaving an empty space. Some empty spaces were not refilled for a long time. As in men, in balding women tiny bald spots develop corresponding to telogen hairs not replaced in due time.
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16.) Different levels of 5alpha-reductase type I and II, aromatase, and androgen receptor in hair follicles of women and men with androgenetic alopecia.
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Author
Sawaya ME; Price VH
Address
Department of Medicine, University of Florida, Gainesville 32610, U.S.A.
Source
J Invest Dermatol, 109(3):296-300 1997 Sep
Abstract
In this study, 12 women and 12 men, ages 18-33 y, with androgenetic alopecia were selected for biopsies from frontal and occipital scalp sites. The androgen receptor, type I and II 5alpha-reductase, cytochrome P-450-aromatase enzyme were measured and analyzed in hair follicles from these scalp biopsies. Findings revealed that both women and men have higher levels of receptors and 5alpha-reductase type I and II in frontal hair follices than in occipital follicles, whereas higher levels of aromatase were found in their occipital follicles.
There are marked quantitative differences in levels of androgen receptors and the three enzymes, which we find to be primarily in the outer root sheath of the hair follicles in the two genders. Androgen receptor content in female frontal hair follicles was approximately 40% lower than in male frontal hair follicle.
Cytochrome P-450-aromatase content in women's frontal hair follicles was six times greater than in frontal hair follicles in men. Frontal hair follicles in women had 3 and 3.5 times less 5alpha-reductase type I and II, respectively, than frontal hair follicles in men. These differences in levels of androgen receptor and steroid-converting enzymes may account for the different clinical presentations of androgenetic alopecia in women and men.
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17.) Safety surveillance of esterified estrogens-methyltestosterone (Estratest and Estratest HS) replacement therapy in the United States.
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Author
Phillips E; Bauman C
Address
Drug Safety Unit, Solvay Pharmaceuticals, Inc., Marietta, Georgia, USA.
Source
Clin Ther, 19(5):1070-84 1997 Sep-Oct
Abstract
This paper summarizes all postmarketing safety surveillance data collected by Solvay Pharmaceuticals, Inc. (Marietta, Georgia), between 1989 and 1996 for Estratest and Estratest HS (half-strength). These oral esterified estrogens--methyltestosterone combination products have been marketed in the United States since 1964 for the treatment of moderate-to-severe vasomotor symptoms associated with menopause in patients whose symptoms have not been relieved by estrogens alone.
Between 1989 and 1996, more than 1 million woman-years of exposure occurred. The safety profile contained in this paper is based on a cumulative total of 568 individual cases comprising 863 adverse events (AEs). The proportions of AEs associated with the use of Estratest (575 events; 66.6%) and Estratest HS (288 events; 33.4%) were commensurate with the proportions of individual reports of adverse experiences for the two formulations (369 reports [65.0%] and 199 reports [35.0%], respectively). The rank order and percentage of types of AEs reported were also similar.
The cumulative volume of reports was relatively low given the extent of exposure. Despite the limitations inherent in spontaneous postmarketing surveillance, the safety profile derived from this assessment does not indicate a significant safety concern with Estratest or Estratest HS. No deaths were reported, and no adverse findings indicative of the need for more comprehensive surveillance or concern on the part of the medical community or consumers were observed. Reports of cancer, cardiovascular disease, thromboembolic phenomena, and hepatic dysfunction were few and were assessed as not related to treatment with Estratest or Estratest HS; reports of drug overdose, drug-drug interaction, and birth defects were rare (4 of 863 events; 0.5%).
The most commonly reported AEs were those known to be associated with estrogen therapy (weight gain, headache, nausea, and vasodilatation) and androgen treatment (alopecia, acne, and hirsutism). Twenty-three (4.0%) of the 568 cases reported had at least one event that was regarded as serious, and 53 (6.1%) of the total 863 AEs were regarded as serious. The findings indicate that Estratest and Estratest HS are safe when used as directed and that the marginal increase in risk associated with androgen coadministration can be managed with appropriate patient selection and monitoring, as stated in the package insert for these compounds.
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18.) Balding hair follicle dermal papilla cells contain higher levels of androgen receptors than those from non-balding scalp.
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Author
Hibberts NA; Howell AE; Randall VA
Address
Department of Biomedical Sciences, University of Bradford, UK.
Source
J Endocrinol, 156(1):59-65 1998 Jan
Abstract
Androgens can gradually transform large scalp hair follicles to smaller vellus ones, causing balding. The mechanisms involved are unclear, although androgens are believed to act on the epithelial hair follicle via the mesenchyme-derived dermal papilla. This study investigates whether the levels and type of androgen receptors in primary lines of cultured dermal papilla cells derived from balding scalp hair follicles differ from those of follicles from non-balding scalp. Androgen receptor content was measured by saturation analysis using the non-metabolisable androgen, [3H]mibolerone (0.05-10 nM) in a 9-10 point assay.
Pubic dermal fibroblasts and Shionogi cells were examined as positive controls. Repetitive assays of Shionogi cells showed good precision in the levels of androgen receptor content (coefficient of variation = 3.7%). Specific, high affinity, low capacity androgen receptors were detected in dermal papilla cells from both balding and non-balding follicles. Balding cells contained significantly (P < 0.01) greater levels of androgen receptors (Bmax = 0.06 +/- 0.01 fmol/10(4) cells (mean +/- S.E.M.)) than those from non-balding scalp (0.04 +/- 0.001).
Competition studies with a range of steroids showed no differences in receptor binding specificity in the two cell types. The higher levels of androgen receptors in cells from balding scalp hair follicles with similar properties to those from non-balding scalp concur with the expectations from their in vivo responses to androgens. This supports the hypothesis that androgens act via the dermal papilla and suggests that cultured dermal papilla cells may offer a model system for studying androgen action in androgenetic alopecia.
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19.) A comparison of the culture and growth of dermal papilla cells from hair follicles from non-balding and balding (androgenetic alopecia) scalp.
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Author
Randall VA; Hibberts NA; Hamada K
Address
Department of Biomedical Sciences, University of Bradford, U.K.
Source
Br J Dermatol, 134(3):437-44 1996 Mar
Abstract
Male pattern baldness is a common, androgen-dependent skin problem in adult men which is not well understood, although androgens are believed to act on the hair follicle via the mesenchyme-derived dermal papilla situated in the middle of the hair follicle bulb. Since dermal papilla cells retain specific characteristics in culture, such as hair-growth promoting ability and appropriate features of the mechanism of androgen action, dermal papilla cells from follicles undergoing androgen-stimulated miniaturization may provide a useful in vitro model system. Therefore, dermal papilla cells have been derived from intermediate follicles from balding and nearly clinically normal sites of men with androgenetic alopecia.
Balding dermal papillae were much smaller than non-balding ones and grew much less well under normal growth conditions. Supplementing the medium with human serum, rather than fetal calf serum, increased both the yield of established cultures and the number and health of the dermal papilla cells produced. Non-balding cells also grew faster in human serum. Balding cells retained the normal fibroblastic shape and aggregative behaviour of dermal papilla cells, but always grew less well than non-balding cells.
Nearly clinically normal dermal papillae were similar, or slightly smaller, in size to non-balding ones, but their growth resembled balding cells. Since balding dermal papilla cells can be cultured, though with much greater difficulty than nonbalding ones, and exhibit differing growth characteristics to non-balding cells, they merit further investigation which may increase our understanding of, and ability to control, androgenetic alopecia.
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20.) Messenger RNA expression of steroidogenesis enzyme subtypes in the human pilosebaceous unit.
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Author
Courchay G; Boyera N; Bernard BA; Mahe Y
Address
Hair Biology Research Group, L'Or´eal, Centre de recherche C. Zviak, Clichy, France.
Source
Skin Pharmacol, 9(3):169-76 1996
Abstract
In order to define the respective involvement of steroidogenesis enzymes subtypes in the control of hair follicle homeostasis, we evaluated, by semiquantitative RT/PCR, the expression levels of mRNAs coding for 17 beta-hydroxysteroid dehydrogenase type 1 and type 2, 3 beta-hydroxysteroid dehydrogenase, Cyt.P450-aromatase, steroid 5 alpha-reductase type 1 and type 2 and 11 beta-hydroxysteroid dehydrogenase.
These assays were performed for several components of the pilosebaceous unit (PSU); fresh plucked anagen hairs, sebaceous glands and primary culture of dermal papilla, as well as other tissues involved in an active steroid metabolism (human testis, liver, placenta, prostate, ovary, uterus and adrenals) as controls.
We found that plucked hair (i.e. mainly keratinocytes from the inner and outer root sheaths) expressed: (1) very high levels of 17 beta-hydroxysteroid dehydrogenase type 2 corresponding to levels found in liver and placenta; (2) high levels of steroid 5-alpha-reductase type 1 corresponding to levels found in testis, liver and ovary, and moderate levels of 17 beta-hydroxysteroid dehydrogenase type 1, which corresponded to the expression in testis, prostate and uterus. In contrast, Cyt.P450-aromatase, 3 beta-hydroxysteroid dehydrogenase and steroid 5 alpha-reductase type 2 were poorly expressed in the pilosebaceous unit as compared with other tissues. Interestingly, expression patterns of these enzymes in primary cultures of dermal papilla were distinctive since 5 alpha-reductase type 1 and 11 beta-hydroxysteroid dehydrogenase were the only mRNA detected.
Taken together, these results suggest that not only sebaceous gland but also outer root sheath keratinocytes may contribute, through the activity of the steroid 5 alpha-reductase type 1, to the pathogenesis of androgen-dependent alopecia.
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21.) Treatment of androgen excess in females: yesterday, today and tomorrow.
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Author
Pucci E; Petraglia F
Address
Institute of Endocrinology, University of Pisa, Italy.
Source
Gynecol Endocrinol, 11(6):411-33 1997 Dec
Abstract
Hirsutism, acne and androgenic alopecia represent, in females, some of the manifestations of the clinical spectrum of hyperandrogenism. These pictures represent not only cosmetic damage, but also a source of remarkable psychological distress. Often hirsutism is regarded as presumptive evidence of a lack of femininity. The major diagnostic concern is to exclude an ovarian or adrenal androgen-secreting tumor, a congenital hyperplasia or polycystic ovary disease.
Ethnic background should be taken into account together with the progression of the symptoms. Following the etiology, surgery and exogenous glucocorticoids or inhibition of gonadotropin secretion have to be carefully chosen in the management of different kinds of hyperandrogenism. Several pharmacologic agents have recently shown the ability to block the androgen receptors at target organ sites, thus allowing a specific antiandrogenic treatment. In some cases cosmetic measures could be of great value.
Obesity accompanied by hyperinsulinemia can represent the main cause of ovary androgen hypersecretion; therefore a reduced body weight and muscle activity represent the basis of any treatment. Some other drugs, such as long-acting analogs of somatostatin, could be considered among possible drugs for the future. The aim of this article is to provide an appraisal of what is presently known about the regulation of hair growth, the various causes of excessive androgen secretion and the current methods to solve, safely, this important feminine clinical problem.
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22.) Association of benign prostatic hyperplasia with male pattern baldness.
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Author
Oh BR; Kim SJ; Moon JD; Kim HN; Kwon DD; Won YH; Ryu SB; Park YI
Address
Department of Urology, Chonnam University Medical School, Kwangju, South Korea.
Source
Urology, 51(5):744-8 1998 May
Abstract
OBJECTIVES: Both benign prostatic hyperplasia (BPH) and male pattern baldness (androgenic alopecia) share the pathogenesis of an androgen-dependent disorder and afflict a large population of elderly men with chronobiologic progress. However, it is unclear whether these diseases are related epidemiologically. We evaluated the association of frequency and severity of male pattern baldness between patients with BPH and a control group.
METHODS: A total of 225 patients with BPH (mean age 69.3 +/- 6.5 years) and 1 60 controls (mean age 68.5 +/- 6.4 years), all over 60 years of age, were included in this study. The estimation of baldness severity was based on Norwood's classification (grade I to VII). The International Prostate Symptom Score (IPSS) and genetic tendency for baldness were also evaluated. The difference between IPSS and grade of baldness between the two groups was analyzed by the Mann-Whitney test and the frequency of inherited baldness was compared by the chi-square test. Correlation between severity of baldness and IPSS in each group was estimated by Spearman's rank correlation method.
RESULTS: The patients with BPH had an apparently higher grade of male pattern baldness in comparison with that of controls (median value of grade IV versus III, P <0.001). The proportion of men with male pattern baldness of grade IV or higher in the BPH group was significantly larger than that of controls (53.8% versus 36.9%, P <0.01). There was a greater frequency of inherited baldness in the BPH group than in the controls (31.6% versus 12.5%, P <0.001). No significant correlation was noted between baldness severity and IPSS in either group.
CONCLUSIONS: This study demonstrates a strong association of BPH with male pattern baldness.
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23.) Hair regrowth. Therapeutic agents.
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Author
Shapiro J; Price VH
Address
University of British Columbia Hair Research and Treatment Centre, Division of Dermatology, Vancouver, Canada.
Source
Dermatol Clin, 16(2):341-56 1998 Apr
Abstract
Today there are new classes of hair growth promotors with proven efficacy. This article reviews the current state of the art agents for treatment of two of the most common forms of hair loss encountered in clinical practice, androgenetic alopecia and alopecia areata. Current therapeutic strategies are based on recent advances in the understanding of disordered hair growth. Practical treatment protocols are presented.
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24.) Androgenic effects of oral contraceptives: implications for patient compliance.
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Author
Jones EE
Address
Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, Connecticut.
Source
Am J Med, 98(1A):116S-119S 1995 Jan 16
Abstract
Androgenic disorders have many negative physical effects. These effects may be caused by excess androgen (exogenous or endogenous) or by end-organ sensitivity to normal levels of androgens. Historically, androgenic progestins in oral contraceptives have also been associated with some of these negative effects. The most apparent signs of androgen excess are the external manifestations, including oily skin, acne, hirsutism, android obesity, and androgenic alopecia.
Of equal concern are the potential metabolic disturbances associated with hyperandrogenicity. Unfavorable lipid profiles and increased incidence of diabetes and hypertension are very real threats to long-term health. In oral contraceptive users, external manifestations of androgenicity often lead to poor compliance, decreased efficacy, and discontinuation of oral contraceptive use, especially in the younger patient.
With the introduction of the newer oral contraceptive formulations containing less androgenic progestins (norgestimate, desogestrel, gestodene), androgen-related effects have been reduced and better compliance is anticipated. Language
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25.) Diffuse hypertrichosis during treatment with 5% topical minoxidil.
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Author
Peluso AM; Misciali C; Vincenzi C; Tosti A
Address
Department of Dermatology, University of Borogna, Italy.
Source
Br J Dermatol, 136(1):118-20 1997 Jan
Abstract
Five women affected by androgenetic alopecia developed severe hypertrichosis of the face and limbs after 2-3 months of treatment with 5% topical minoxidil. Minoxidil was discontinued and in all patients the hypertrichosis disappeared from the face and arms after 1-3 months, and from legs after 4-5 months. Systemic absorption of minoxidil, and a high sensitivity to minoxidil of the follicular apparatus in these areas, is hypothesized.
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26.) Minoxidil upregulates the expression of vascular endothelial growth factor in human hair dermal papilla cells.
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Author
Lachgar S; Charveron M; Gall Y; Bonafe JL
Address
Laboratoire de Biologie Cellulaire Cutan´ee, Institut de Recherche Pierre Fabre, Facult´e de M´edecine Rangueil, Toulouse, France.
Source
Br J Dermatol, 138(3):407-11 1998 Mar
Abstract
The hair follicle dermal papilla which controls hair growth, is characterized in the anagen phase by a highly developed vascular network. We have demonstrated in a previous study that the expression of an angiogenic growth factor called vascular endothelial growth factor (VEGF) mRNA varied during the hair cycle. VEGF mRNA is strongly expressed in dermal papilla cells (DPC) in the anagen phase, but during the catagen and telogen phases. VEGF mRNA is less strongly expressed.
This involvement of VEGF during the hair cycle allowed us to determine whether VEGF mRNA expression by DPC was regulated by minoxidil. In addition, the effect of minoxidil on VEGF protein synthesis in both cell extracts and DPC-conditioned medium, was investigated immunoenzymatically. Both VEGF mRNA and protein were significantly elevated in treated DPC compared with controls. DPC incubated with increasing minoxidil concentrations (0.2, 2, 6, 12 and 24 mumol/L) induced a dose-dependent expression of VEGF mRNA.
Quantification of transcripts showed that DPC stimulated with 24 mumol/L minoxidil express six times more VEGF mRNA than controls. Similarly, VEGF protein production increases in cell extracts and conditioned media following minoxidil stimulation.
These studies strongly support the likely involvement of minoxidil in the development of dermal papilla vascularization via a stimulation of VEGF expression, and support the hypothesis that minoxidil has a physiological role in maintaining a good vascularization of hair follicles in androgenetic alopecia.
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27.) Biphasic effects of minoxidil on the proliferation and differentiation of normal human keratinocytes.
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Author
Boyera N; Galey I; Bernard BA
Address
L'Or´eal, Hair Biology Research Group, Clichy, France.
Source
Skin Pharmacol, 10(4):206-20 1997
Abstract
Minoxidil is the most used drug with proved effects in the treatment of androgenetic alopecia (AGA), but little is known about its pharmacological activity and target cells in hair follicles. As AGA is characterized by follicle atrophy, accelerated hair cycles and hair fiber thinning, we postulated that keratinocyte proliferation/differentiation is affected and we tested Minoxidil's effects on those parameters.
Normal human keratinocytes (NHK) of follicular or epidermal origin were cultured in the presence of Minoxidil (0, 0.1, 1, 10, 100, 1,000 microM) during 5-8 days in various media (high-/low-calcium content, with or without serum). Proliferation was assessed by mitochondrial dehydrogenase activity (XTT), BrdU incorporation, lysosome numeration (neutral red incorporation) and total protein dosage. Drug-induced cytotoxicity was measured by lactate dehydrogenase release in culture supernatant, and pro-differentiating effects were evaluated by relative involucrin expression (ELISA dosage).
On this basis, we showed that Minoxidil had biphasic effects on the proliferation and differentiation of NHK: Minoxidil stimulated NHK proliferation at micromolar doses, while antiproliferative, pro-differentiative and partially cytotoxic effects were observed with millimolar concentrations. We can hypothesize that Minoxidil hypertrichotic activity in vivo is possibly mediated by the maintenance of proliferative potential in follicular keratinocytes precociously committed to differentiation.
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28.) Alopecia and mood stabilizer therapy.
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Author
McKinney PA; Finkenbine RD; DeVane CL
Address
Medical University of South Carolina, Charleston 29425, USA.
Source
Ann Clin Psychiatry, 8(3):183-5 1996 Sep
Abstract
Alopecia is a common side effect in patients managed on the mood stabilizers lithium, valproate, and carbamazepine. Clinicians may be reluctant to discontinue medications in patients suffering from hair loss if the mood stabilizer is otherwise efficacious. Therefore it is important to be familiar with the epidemiology, diagnosis, and management of alopecia.
A single representative case is provided to illustrate briefly the common presentation of a patient with mood stabilizer-induced alopecia. A literature search was conducted to provide the basis for discussion of diagnosis, the association of mood stabilizers with alopecia, and some management options of this side effect. The diagnosis of alopecia requires an understanding of normal hair growth and is best made following a careful history, an examination, and the maintenance of a high level of suspicion.
Alopecia occurs in about 10% of persons managed on lithium, up to 12% of persons on valproate, and less than 6% of individuals on carbamazepine. Management of alopecia includes reassurance, hair care techniques, trace mineral supplementation, treatment with minoxidil, and hair replacement pieces. Alopecia due to mood stabilizer drugs can be potentially identified and managed without medication discontinuation.
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29.) Improvement in androgenetic alopecia (stage V) using topical minoxidil in a retinoid vehicle and oral finasteride [see comments]
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Author
Walsh DS; Dunn CL; James WD
Address
Walter Reed Army Medical Center, Washington, DC, USA.
Source
Arch Dermatol, 131(12):1373-5 1995 Dec
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30.) Clinical significance of testosterone and dihydrotestosterone metabolism in women]
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Author
Kor¨si´c M
Address
Zavod za endokrinologiju, dijabetes i bolesti metabolizma Klinike za unutarnje bolesti, KBC Rebro, Zagreb.
Source
Lijec Vjesn, 118 Suppl 1():21-3 1996 Mar
Abstract
Hyperandrogenism in women refers to both excess androgen production and clinical manifestations of androgen excess. Clinical evaluation of women with hyperandrogenism is complex.
The synthesis and release of androgenic steroid in women are normal part of adrenal and ovarian steroidogenesis. One of the classic questions concerning androgenic disorders concerns the source of circulating androgens. Relative roles of adrenal and ovary vary greatly, both can be involved.
The use of gonadal or adrenal steroid administration can sometimes be used to distinguish the source of androgen excess. In many cases of hyperandrogenism no laboratory diagnosis of adrenal and ovarian androgen overproduction can be made. These patients may have increased androgen sensitivity due to increased enzyme 5 alpha-reductase activity in the skin.
To be active in the skin, testosterone (T) must be converted to dihydrotestosterone (DHT) by the 5 alpha-reductase. The increase in DHT production is a localized phenomenon and there is no generalized increase in enzyme activity in women with hyperandrogenism. DHT is rapidly converted to other steroid metabolites including androsteron, androstanediol and their glucuronide and sulfate conjugates. Although once thought to be specific for skin conversion of T to DTH these androgen conjugates reflect adrenal steroid production and metabolism. Antiandrogens (androgen receptor blockers) are the most effective therapeutic modalities of cutaneous hyperandrogenism.
Clinical trials are in progress to determine efficacy of finasteride for the treatment of hirsutism and androgenetic alopecia. Finasteride is the first available medication of a new class of drugs that is an competitive inhibitor of 5 alpha-reductase and therefore should be beneficial for medical treatment of cutaneous hyperandrogenism.
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31.) The 5 alpha-reductase system and its inhibitors. Recent development and its perspective in treating androgen-dependent skin disorders.
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Author
Chen W; Zouboulis CC; Orfanos CE
Address
Department of Dermatology, University Medical Center Benjamin Franklin, Free University of Berlin, Germany.
Source
Dermatology, 193(3):177-84 1996
Abstract
5 alpha-Reductase, the enzyme system that metabolizes testosterone into dihydrotestosterone, occurs in two isoforms. The type 1 isozyme is composed of 259 amino acids, has an optimal pH of 6-9 and represents the 'cutaneous type'; it is located mainly in sebocytes but also in epidermal and follicular keratinocytes, dermal papilla cells and sweat glands as well as in fibroblasts from genital and non-genital skin.
The type 2 isozyme is composed of 254 amino acids, has an optimal pH of about 5.5 and is located mainly in the epididymis, seminal vesicles, prostate and fetal genital skin as well as in the inner root sheath of the hair follicle and in fibroblasts from normal adult genital skin.
The genes encoding type 1 and type 2 isozymes are found in chromosomes 5p and 2p, respectively, and each consists of 5 exons and 4 introns. During the last decade, several steroid analogues and non-steroid agents have been developed to interfere with 5 alpha-reductase activity.
Finasteride, which has a higher affinity for the type 2 isozyme, is the first 5 alpha-reductase antagonist clinically introduced for treatment of benign prostate hyperplasia. The clinical evaluation of finasteride or other 5 alpha-reductase inhibitors in the field of dermatology has been very limited; in particular, those that selectively bind to type 1 isozyme (e.g. MK-386, LY191704) may be regarded as candidates for treatment of androgen-dependent skin disorders such as seborrhoea, acne, hirsutism and/or androgenetic alopecia.
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32.) Finasteride: a clinical review.
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Author
Gormley GJ
Address
Merck Research Laboratories, Rahway, NJ 07065-0914, USA.
Source
Biomed Pharmacother, 49(7-8):319-24 1995
Abstract
Finasteride is the first of a new class of 5 alpha-reductase inhibitors which allows selective androgen deprivation affecting dihydrotestosterone (DHT) levels in target organs such as the prostate and scalp hair without effecting circulating levels of testosterone thus preserving the desired androgen mediated effects on muscle strength, bone density and sexual function.
Finasteride has been demonstrated to produce significant effects in men with an enlarged prostate gland. The long-term data now emerging suggests that progression of benign prostatic hyperplasia (BPH) may be arrested providing additional long term benefits. Experimental uses in prostate cancer prevention and male pattern baldness offer new and exciting possibilities for this class of compounds.
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33.) 19-nor-10-azasteroids: a novel class of inhibitors for human steroid 5alpha-reductases 1 and 2.
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Author
Guarna A; Belle C; Machetti F; Occhiato EG; Payne AH; Cassiani C; Comerci A; Danza G; De Bellis A; Dini S; Marrucci A; Serio M
Address
Dipartimento di Chimica Organica Ugo Schiff, Universit`a di Firenze, Italy. guarna@chimorg.unifi.it
Source
J Med Chem, 40(7):1112-29 1997 Mar 28
Abstract
Steroid 5alpha-reductase is a system of two isozymes (5alphaR-1 and 5alphaR-2) which catalyzes the NADPH-dependent reduction of testosterone to dihydrotestosterone in many androgen sensitive tissues and which is related to several human endocrine diseases such as benign prostatic hyperplasia (BPH), prostatic cancer, acne, alopecia, pattern baldness in men and hirsutism in women. T
he discovery of new potent and selective 5alphaR inhibitors is thus of great interest for pharmaceutical treatment of these diseases. The synthesis of a novel class of inhibitors for human 5alphaR-1 and 5alphaR-2, having the 19-nor-10-azasteroid skeleton, is described.
The inhibitory potency of the 19-nor-10-azasteroids was determined in homogenates of human hypertrophic prostates toward 5alphaR-2 and in DU-145 human prostatic adenocarcinoma cells toward 5alphaR-1, in comparison with finasteride (IC50 = 3 nM for 5alphaR-2 and approximately 42 nM for 5alphaR-1), a drug which is currently used for BPH treatment.
The inhibition potency was dependent on the type of substituent at position 17 and on the presence and position of the unsaturation in the A and C rings. delta9(11)-19-Nor-10-azaandrost-4-ene-3,17-dione (or 10-azaestra-4,9(11)-diene-3,17-dione) (4a) and 19-nor-10-azaandrost-4-ene-3,17-dione (5) were weak inhibitors of 5alphaR-2 (IC50 = 4.6 and 4.4 microM, respectively) but more potent inhibitors of 5alphaR-1 (IC50 = 263 and 299 nM, respectively), whereas 19-nor-10-aza-5alpha-androstane-3,17-dione (7) was inactive for both the isoenzymes.
The best result was achieved with the 9:1 mixture of delta9(11)- and delta8(9)-17beta-(N-tert-butylcarbamoyl)-19-nor-10-aza-4- androsten-3-one (10a,b) which was a good inhibitor of 5alphaR-1 and 5alphaR-2 (IC50 = 127 and 122 nM, respectively), with a potency very close to that of finasteride. The results of ab initio calculations suggest that the inhibition potency of 19-nor-10-azasteroids could be directly related to the nucleophilicity of the carbonyl group in the 3-position.
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34.) Genetic analysis of male pattern baldness and the 5alpha-reductase genes.
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Author
Ellis JA; Stebbing M; Harrap SB
Address
Department of Physiology, The University of Melbourne, Parkville, Victoria, Australia.
Source
J Invest Dermatol, 110(6):849-53 1998 Jun
Abstract
Genetic predisposition and androgen dependence are important characteristics of the common patterned loss of scalp hair known as male pattern baldness. The involvement of the 5alpha-reductase enzyme in male pattern baldness has been postulated due to its role in the metabolism of testosterone to dihydrotestosterone.
There are two known isozymes of 5alpha-reductase. Type I has been predominantly localized to the skin and scalp. Type II, also present on the scalp, is the target of finasteride, a promising treatment for male pattern baldness. We conducted genetic association studies of the 5alpha-reductase enzyme genes (SRD5A1 on chromosome 5 and SRD5A2 on chromosome 2) using dimorphic intragenic restriction fragment length polymorphisms. From a population survey of 828 healthy families comprising 3000 individuals, we identified 58 young bald men (aged 18-30 y) and 114 older nonbald men (aged 50-70 y) for a case control comparison.
No significant differences were found between cases and controls in allele, genotype, or haplotype frequencies for restriction fragment length polymorphisms of either gene. These findings suggest that the genes encoding the two 5alpha-reductase isoenzymes are not associated with male pattern baldness.
Finally, no clear inheritance pattern of male pattern baldness was observed. The relatively strong concordance for baldness between fathers and sons in this study was not consistent with a simple Mendelian autosomal dominant inheritance. A polygenic etiology should be considered.
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35.) Effects of topically applied spironolactone on androgen stimulated sebaceous glands in the hamster pinna.
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Author
Seki T; Toyomoto T; Morohashi M
Address
Department of Dermatology, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Japan.
Source
J Dermatol, 22(4):233-7 1995 Apr
Abstract
The effects of spironolactone (5% SYC-201G, a preparation developed for clinical use in acne vulgaris by Searle Yakuhin K.K.), which is known to have antiandrogenic effects by competitively inhibiting dihydrotestosterone at androgen receptor sites, was topically applied to the androgen stimulated sebaceous glands of adult female golden hamsters. Androgen stimulation, induced by intramuscular injection of testosterone propionate (TP) every other day over a two week period, resulted in a 2.5 to 2.7 time increase in the size of the sebaceous glands of the hamster pinna.
Once-daily treatment with 5% SYC-201G or matching placebo was applied to androgen-stimulated hamsters on one pinna only during the same period as TP injection. Comparison between the treated and untreated sides revealed a significant suppression in the sebaceous gland size (p < 0.05) by 5% SYC-201G; no such effect was observed with placebo. The difference in the suppression rate of the sebaceous gland size between 5% SYC-201G (23%) and matching placebo (-4.7%) was significant (p < 0.01).
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36.) Androgens affect the activity of human sebocytes in culture in a manner dependent on the localization of the sebaceous glands and their effect is antagonized by spironolactone.
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Author
Zouboulis CC; Akamatsu H; Stephanek K; Orfanos CE
Address
Department of Dermatology, University Medical Center Steglitz, Free University of Berlin, FRG.
Source
Skin Pharmacol, 7(1-2):33-40 1994
Abstract
To investigate the varying response of the pilosebaceous unit to androgens functional studies were performed on the effects of testosterone and 5 alpha-dihydrotestosterone on cultured human sebocytes derived from different skin regions. In addition, the effect of spironolactone on the proliferation of androgen-stimulated human sebocytes derived from facial skin was evaluated.
Testosterone (10(-11) to 10(-5) M), 5 alpha-dihydrotestosterone (10(-11) to 10(-5) M) and spironolactone (10(-12) to 10(-7) M) were added for 10 days as single substances or in combinations to human sebocytes in secondary culture maintained in a serum-free medium.
Cell proliferation was assessed using a fluorometric assay. Intracellular lipids were extracted from sebocytes treated with androgens (10(-7) M) for 10 days after confluency. Testosterone inhibited the proliferation of sebocytes derived from the legs with a 50%-inhibitory concentration at 10(-5) M and induced a 50% decrease of intracellular lipids. In contrast, 5 alpha-dihydrotestosterone stimulated the activity of leg sebocytes with a 50% increase of proliferation at 10(-5) M, and a 175% increase of intracellular lipids.
On the other hand, the proliferation of facial sebocytes was significantly stimulated by testosterone with a 50%-stimulatory concentration at 10(-6) to 10(-5) M and mostly by 5 alpha-dihydrotestosterone with a 50% enhancement at 10(-8) to 10(-7) M. Spironolactone inhibited the proliferation of facial sebocytes in a dose-dependent manner with a 25%-inhibitory concentration at 10(-9) M.
Simultaneous treatment of facial sebocytes with spironolactone and testosterone or 5 alpha-dihydrotestosterone resulted in decreased proliferation when compared to the growth obtained under androgens alone.(ABSTRACT TRUNCATED AT 250 WORDS)
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37.) Antiandrogen treatment with spironolactone and linestrenol decreases bone mineral density in eumenorrhoeic women with androgen excess.
======================================================================
Author
Pre¨zelj J; Kocijan¨ci¨c A
Address
Medical Centre Ljubljana, Endocrinology, Ljubljana, Slovenia.
Source
Horm Metab Res, 26(1):46-8 1994 Jan
Abstract
Increased bone mineral density (BMD) has been reported in young women with androgen excess. To determine whether antiandrogen treatment in young women with androgen excess reduces BMD in these patients, the authors measured BMD before and a year after the beginning of antiandrogen therapy with spironolactone and linestrenol in 17 consecutive androgenized patients (median age 22 years). After a year's treatment BMD declined in 15 out of 17 patients, the mean decrease--0.032 g/cm2 (95% CI of the difference 0.016-0.048)--being highly significant (p < 0.001). Androstenedione decrease was the only hormonal variable significantly correlating with BMD decrease (r = 0.5; p = 0.037) according to simple linear regression. A decrease of BMD might become a key factor in deciding about the duration of antiandrogen treatment with spironolactone in functional hyperandrogenemia.
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38.) [Serum hormones before and during therapy with cyproterone acetate and spironolactone in patients with androgenization]
======================================================================
Author
Grunwald K; Rabe T; Schlereth G; Runnebaum B
Address
Abt. f¨ur gyn¨akologische Endokrinologie und Fortpflanzungsmedizin, Universit¨ats-Frauenklinik Heidelberg.
Source
Geburtshilfe Frauenheilkd, 54(11):634-45 1994 Nov
Abstract
The effect of cyproterone acetate (CPA) and spironolactone (SPL) on the serum androgen concentrations of premenopausal women with symptoms of hyperandrogenism were investigated in a total of 39 women. The observation period was 12 months.
CPA was administered according to the Hammerstein regimen: cyproterone acetate (CPA) [Androcur] 100 mg/die 5.-14. day of the cycle; ethinylestradiol (EE) [Progynon C]: 40 mg/die 5.-25. day of the cycle; Spironolactone (SPL) was given in a dosage of 100 mg/die from day 1.-21. of the cycle. During the therapy with CPA a significant decrease of total testosterone (61%), free testosterone (78%), LH (48%) and 17 alpha-Hydroxyprogesterone (72%) was observed; during the medication with spironolacton only a significant decrease of 5 alpha-dihydrotestosterone (81%), which could not be seen during CPA use, was observed. Serum concentrations of total testosterone, free testosterone, LH and 17 alpha-Hydroxyprogesterone remained unchanged. DHA and DHAS did not change during neither medication.
Since peripheral androgens were not suppressed by SPL the positive therapeutical effect of SPL can be explained by the antiandrogenic effect at the level of the receptor. A disadvantage of spironolacton is the lack of contraceptive efficacy. In cases where contraindication for oral contraceptives are present SPL can be considered as a good alternative to CPA. The suppressive effect of CPA/EE on total testosterone, LH addition to the antivulatory effect makes it the preferable medication for hyperandrogenemic patients with polycystic changes of the ovaries (PCOD).
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39.) The insulin resistance in women with hyperandrogenism is partially reversed by antiandrogen treatment: evidence that androgens impair insulin action in women.
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Author
Moghetti P; Tosi F; Castello R; Magnani CM; Negri C; Brun E; Furlani L; Caputo M; Muggeo M
Address
Division of Endocrinology and Metabolic Diseases, University of Verona, Italy.
Source
J Clin Endocrinol Metab, 81(3):952-60 1996 Mar
Abstract
To assess whether androgen excess per se might impair insulin action, insulin sensitivity was measured by a two-step (20 and 80 mU/m2.min) hyperinsulinemic euglycemic clamp combined with indirect calorimetry and tracer glucose infusion in 43 women (13 obese and 30 nonobese) with normal glucose tolerance and clinical evidence of increased androgen action (hirsutism and/or polycystic ovary syndrome) as well as 12 age- and body mass index-matched healthy controls. Hyperandrogenic women were studied basally and after 3-4 months of antiandrogen treatment with 3 different drugs: spironolactone (n = 23), flutamide (n = 10), or the GnRH agonist buserelin (n = 10). Six women given spironolactone were also reexamined after 1 yr of therapy.
At baseline, insulin-mediated glucose uptake was lower in hyperandrogenic women than in controls (by ANOVA, F = 14.3; P < 0.001). Insulin resistance was observed in both ovarian and nonovarian hyperandrogenism, as distinguished by acute GnRH agonist testing. After antiandrogen therapy, insulin action on glucose metabolism significantly increased for both the patients as a whole (F = 7.4; P < 0.01) and each treatment group separately.
However, insulin action remained lower than in controls and showed no further improvement in patients reevaluated after I yr of treatment. Increases in both oxidative and nonoxidative glucose metabolism accounted for the improvement in substrate disposal induced by antiandrogen drugs. The increase in the effectiveness of insulin was greater in the lean subjects, whereas the change was small and not statistically significant in the obese women. Response to treatment was more pronounced in women with nonovarian hyperandrogenism, particularly at the low insulin infusion rate.
Endogenous glucose production in hyperandrogenic patients was similar to that in healthy women and was unaffected by therapy. In conclusion, antiandrogen treatment partially reversed the peripheral insulin resistance associated with hyperandrogenism regardless of which antiandrogen was used. These data strongly suggest that in women, androgen excess per se contributes to impairment of insulin action.
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40.) Topical spironolactone reduces sebum secretion rates in young adults.
======================================================================
Author
Yamamoto A; Ito M
Address
Department of Dermatology, Niigata University School of Medicine, Japan.
Source
J Dermatol, 23(4):243-6 1996 Apr
Abstract
The effects of topically applied spironolactone on the sebum secretion rates (SSR) of young adults were investigated. SSR was expressed as the ratio of wax esters/[cholesterol+cholesterol esters] (WE/[C+CE]) and the amount of sebaceous lipids (squalene, triacylglycerol and wax esters). Topical spironolactone 5% gel applied to the right cheeks of the subjects produced a significant reduction in the SSR at 12 weeks (4 weeks after termination of application), but not at 8 weeks (the end of treatment). Untreated "control" areas (the left cheeks of the subjects) showed no significant change during the study. None of the subjects experienced skin rash or signs of local irritation. This results suggests that topical spironolactone may be effective in the treatment of acne patients with high SSR.
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41.) Other antiandrogens.
======================================================================
Author
Schmidt JB
Address
Department of Dermatology, University of Vienna Medical School, Austria.
Source
Dermatology, 196(1):153-7 1998
Abstract
Various substances of steroidal or nonsteroidal structure may serve as an alternative for the antiandrogenic treatment of acne. Compounds with antiandrogenic properties like cimetidine or ketoconazole are rarely administered for acne due to their weak effects. In contrast, spironolactone is an effective antiandrogen that shows good treatment effects in hirsutism and acne.
Side effects occur frequently and are dose dependent. Isotretinoin--the most effective agent in acne therapy--has been under discussion for additional antiandrogenic properties for years. At present there is additional evidence for the antiandrogenic effects of isotretinoin.
Regarding substances acting on both levels, androgen receptor binding and 5 alpha-reductase inhibition, the question is raised whether the term 'antiandrogen' should be amplified by including the 5 alpha-reductase inhibitors. This would pay tribute to the biological aspect of antiandrogenicity that takes into account not only the mode of action but also the effects of the substance. Under this aspect type 1 5 alpha-reductase inhibitors may gain attention in the future.
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42.) Mechanism of action and pure antiandrogenic properties of flutamide.
======================================================================
Author
Labrie F
Address
Medical Research Council Group, Le Centre Hospitalier de l'Universite Laval Research Center, Laval University, Qu´ebec City, Canada.
Source
Cancer, 72(12 Suppl):3816-27 1993 Dec 15
Abstract
Although treatment of intact adult male rats with the pure antiandrogen flutamide or a luteinizing hormone-releasing hormone (LHRH) agonist alone leads to partial inhibition of ventral prostate weight, maximal inhibition is achieved by combination of the two drugs. Potentializing effects of the two compounds were observed even on prostatic ornithine decarboxylase activity.
Because LHRH agonists are widely used to achieve medical castration in men treated for prostate cancer, it is of interest to observe that in the dog, known for being the best model for studies of the action of LHRH agonists, flutamide does not interfere with the potent desensitizing action of the LHRH agonist on pituitary LH secretion, thus supporting the combined use of flutamide with an LHRH agonist for maximal androgen blockade without loss of efficiency of the LHRH agonist.
Because prostate cancer is known to show a high degree of heterogeneity of its sensitivity to androgens, we analyzed the effect of combined antiandrogen therapy on parameters more sensitive to androgens than ventral prostatic weight itself. In agreement with its pure antiandrogenic characteristics, flutamide alone has no stimulatory effect on the intraprostatic level of mRNA encoding the C1 or C3 component of prostatic binding protein (PBP), whereas cyproterone acetate (CPA), megestrol acetate (MEG), and, especially, medroxyprogesterone acetate (MPA) markedly stimulate PBP-C1 and PBP-C3 mRNA levels, an effect reversed by flutamide, thus further supporting the intrinsic androgenic activity of all these steroidal derivatives.
Similar androgenic effects of the steroidal derivatives were observed on prostatic ornithine decarboxylase activity. Androgen-sensitive Shionogi tumor cells were then used to assess the antiandrogenic/androgenic properties of flutamide and the above-indicated steroidal derivatives. MPA, MEG, CPA as well as spironolactone-stimulated cell proliferation under both in vivo and in vitro conditions, thus illustrating the intrinsic androgenic activity of all these compounds. Flutamide was inactive by itself and reversed the stimulatory effect of all other compounds, thus indicating its pure antiandrogenic activity.
Although castration reduces intraprostatic dihydrotestosterone (DHT) to undetectable levels in the rat and guinea pig, the concentration remains at about 50% of the value found in intact men after castration, thus indicating an important contribution of the adrenals to DHT in the human prostate, a finding that requires the addition of an antiandrogen to block the action of this important amount of DHT remaining after castration.
======================================================================
43.) Drospirenone: a novel progestogen with antimineralocorticoid and antiandrogenic activity.
======================================================================
Author
Muhn P; Fuhrmann U; Fritzemeier KH; Krattenmacher R; Schillinger E
Address
Research Laboratories, Berlin, Germany.
Source
Ann N Y Acad Sci, 761():311-35 1995 Jun 12
Abstract
Drospirenone (ZK 30595; 6 beta, 7 beta, 15 beta, 16 beta-dimethylen-3-oxo-17 alpha-pregn-4-ene-21, 17-carbolactone) is a novel progestogen under clinical development. Drospirenone is characterized by an innovative pharmacodynamic profile which is very closely related to that of progesterone. Potential applications include oral contraception, hormone replacement therapy and treatment of hormonal disorders.
The pharmacological properties of drospirenone were investigated in vitro by receptor binding and transactivation experiments and in vivo in appropriate animal models. In qualitative agreement with progesterone, the compound binds strongly to the progesterone and the mineralocorticoid receptor and with lower affinity to androgen and glucocorticoid receptors.
There is no detectable binding to the estrogen receptor. Steroid hormone agonistic and antagonistic activities of progesterone and drospirenone were compared in transactivation experiments. Individual steroid hormone receptors were artificially expressed together with a reporter gene in appropriate cell lines. Both hormones were unable to induce any androgen receptor-mediated agonistic activity. Rather, both progesterone and drospirenone distinctly antagonized androgen-stimulated transcriptional activation. Likewise, both compounds only very weakly activated the mineralocorticoid receptor but showed potent aldosterone antagonistic activity.
Drospirenone did not induce glucocorticoid receptor-driven transactivation. Progesterone was a weak agonist in this respect. Drospirenone exerts potent progestogenic and antigonadotropic activity which was studied in various animal species. It efficiently promotes the maintenance of pregnancy in ovariectomized rats, inhibits ovulation in rats and mice and stimulates endometrial transformation in the rabbit.
Furthermore, drospirenone shows potent antigonadotropic, i.e., testosterone-lowering activity in male cynomolgus monkeys. The progestogenic potency of drospirenone was found to be in the range of that of norethisterone acetate. The majority of clinically used progestogens are androgenic.
Drospirenone, like progesterone, has no androgenic but rather an antiandrogenic effect. This property was demonstrated in castrated, testosterone propionate substituted male rats by a dose-dependent inhibition of accessory sex organ growth (seminal vesicles, prostate). In this model, the potency of drospirenone was about a third that of cyproterone acetate. Drospirenone, like progesterone, shows antimineralocorticoid activity, which causes moderately increased sodium and water excretion. This is an outstanding characteristic which has not been described for any other synthetic progestogen before.
Drospirenone is eight to ten times more effective in this respect than spironolactone. The natriuretic effect was demonstrable for at least three weeks upon daily treatment of rats with a dose of 10 mg/animal. Drospirenone is devoid of any estrogenic, glucocorticoid or antiglucocorticoid activity. In summary, drospirenone, like progesterone, combines potent progestogenic with antimineralocorticoid and antiandrogenic activity in a similar dose range.
===================
Hola amigos de la red DERMAGIC EXPRESS hoy con otro tema interesante,
actualmente muy discutido y estudiado: ALOPECIA ANDROGÉNICA, Y SUS
ALTERNATIVAS TERAPÉUTICAS.
Primeramente hay que explicar a la audiencia NO MEDICA, que la alopecia androgenica es la perdida del cabello producida por un aumento de los ANDRÓGENOS, (principalmente la testosterona), en nuestro cuerpo, tanto en el hombre como la mujer. específicamente su metabolito o derivado llamado: DIHIDROTESTOSTERONA.
Este exceso de ANDRÓGENOS específicamente la DIHIDROTESTOSTERONA, se depositan en el folículo piloso y provocan la caída del cabello. Este es el mecanismo principal que ocasiona LA ALOPECIA ANDROGÉNICA.
Caracterizada por una caída del cabello progresiva, que afecta tanto hombres como mujeres post puberales, la cual puede llegar a ser severa en ambos sexos. En la mujer enfermedades como el SÍNDROME DE OVARIO POLIQUISTICO, produce aumento de los andrógenos con la subsecuente caída del cabello.
En el hombre, la enfermedad tiene sin duda un componente genético, porque no todo el mundo está afectado, y es importante que usted sepa que, hay hombres que NUNCA SUFRIRÁN DE ALOPECIA ANDROGÉNICA, generalmente siempre hay un historial de calvicie en los afectados.
También hay que explicar que el cabello no esta "ADHERIDO CON PEGAMENTO" al cuero cabelludo, tiene un ciclo de de "VIDA: ANAGENO, o crecimiento, dura de 1 a 7 años, CATAGENO, o de transición, que dura de 2 a 3 meses y TELOGENO o de reposo la cual dura unos 3 meses aproximadamente, luego el cabello se cae y es sustituido por uno nuevo.
NORMALMENTE SE CAEN ENTRE 50 Y 100 CABELLOS DIARIOS.
Es interesante que también sepas que cuando el cuerpo esta sometido a un gran ESTRES, y otros factores el cabello entra prematuramente en FASE TELOGENA y comienza a caerse abundantemente produciendo una notable ALOPECIA.
De modo que factores como el ESTERES y otros que alteren el CICLO del cabello contribuirán a que la ALOPECIA ANDROGÉNICA sea mayor.
Otro factor que que empeora LA ALOPECIA ANDROGÉNICA ES LA DERMATITIS SEBORREICA del cuero cabelludo, comúnmente denominada "AUMENTO DE LA GRASA EN EL CABELLO, de modo que mientras mas uses un champú anti caspa, MENOS SEBORREA habrá, por lo tanto menos caída del cabello.
Tratamientos para LA ALOPECIA ANDROGÉNICA hay variados, y te resalto los mas utilizados hoy dia:
1.) MINOXIDIL, TÓPICO (ANTIHIPERTENSIVO).
2.) FINASTERIDE (INHIBIDOR DE LA 5-ALFA REDUCTASA).
3.) DUTASTERIDE (INHIBIDOR DE LA 5-ALFA REDUCTASA).
4.) FLUTAMIDA (INHIBIDOR DE LA 5-ALFA REDUCTASA).
5.) CYPROTERONA ACETATO (ANTICONCEPTIVO ORAL).
6.) ESPIRONOLACTONA (ANTIDIURETICO ORAL).
7.) SERENOA REPENS O PALMETTO SAW (NATURISTA, ANTI-ANDROGENO).
8.) CYPERUS ROTUNDUS (NATURISTA).
9.) ESTEROIDES TÓPICOS.
10.) CHAMPU ANTI-CASPA. (KETOCONAZOL, PIRITIONATO DE ZINC, BIFONAZOL)
11.) DROSPIRENONA (ANTICONCEPTIVO ORAL).
Existe en nuestro cuerpo una enzima denominada 5 alpha reductasa que es la encargada de convertir la TESTOSTERONA EN DIHIDROTESTOSTERONA. Al aumentar este metabolito, mayor sera la caída del cabello.
Por lo tanto una de las estrategias para evitar la ALOPECIA ANDROGENICA es inhibir la enzima 5 alfa reductasa, y para ello ya se han inventado y descubierto medicinas farmacológicas y naturistas.
Toadas estas medicinas tienen sus VENTAJAS y sus EFECTOS ADVERSOS, pero si nos ubicamos en la realidad, la ciencia ha avanzado notablemente en este campo, hace muchos años se decía popularmente:
" ...A LA CAIDA DEL CABELLO SOLO LA DETIENE EL PISO O SUELO.."
Primeramente hay que explicar a la audiencia NO MEDICA, que la alopecia androgenica es la perdida del cabello producida por un aumento de los ANDRÓGENOS, (principalmente la testosterona), en nuestro cuerpo, tanto en el hombre como la mujer. específicamente su metabolito o derivado llamado: DIHIDROTESTOSTERONA.
Este exceso de ANDRÓGENOS específicamente la DIHIDROTESTOSTERONA, se depositan en el folículo piloso y provocan la caída del cabello. Este es el mecanismo principal que ocasiona LA ALOPECIA ANDROGÉNICA.
Caracterizada por una caída del cabello progresiva, que afecta tanto hombres como mujeres post puberales, la cual puede llegar a ser severa en ambos sexos. En la mujer enfermedades como el SÍNDROME DE OVARIO POLIQUISTICO, produce aumento de los andrógenos con la subsecuente caída del cabello.
En el hombre, la enfermedad tiene sin duda un componente genético, porque no todo el mundo está afectado, y es importante que usted sepa que, hay hombres que NUNCA SUFRIRÁN DE ALOPECIA ANDROGÉNICA, generalmente siempre hay un historial de calvicie en los afectados.
También hay que explicar que el cabello no esta "ADHERIDO CON PEGAMENTO" al cuero cabelludo, tiene un ciclo de de "VIDA: ANAGENO, o crecimiento, dura de 1 a 7 años, CATAGENO, o de transición, que dura de 2 a 3 meses y TELOGENO o de reposo la cual dura unos 3 meses aproximadamente, luego el cabello se cae y es sustituido por uno nuevo.
NORMALMENTE SE CAEN ENTRE 50 Y 100 CABELLOS DIARIOS.
Es interesante que también sepas que cuando el cuerpo esta sometido a un gran ESTRES, y otros factores el cabello entra prematuramente en FASE TELOGENA y comienza a caerse abundantemente produciendo una notable ALOPECIA.
De modo que factores como el ESTERES y otros que alteren el CICLO del cabello contribuirán a que la ALOPECIA ANDROGÉNICA sea mayor.
Otro factor que que empeora LA ALOPECIA ANDROGÉNICA ES LA DERMATITIS SEBORREICA del cuero cabelludo, comúnmente denominada "AUMENTO DE LA GRASA EN EL CABELLO, de modo que mientras mas uses un champú anti caspa, MENOS SEBORREA habrá, por lo tanto menos caída del cabello.
Tratamientos para LA ALOPECIA ANDROGÉNICA hay variados, y te resalto los mas utilizados hoy dia:
1.) MINOXIDIL, TÓPICO (ANTIHIPERTENSIVO).
2.) FINASTERIDE (INHIBIDOR DE LA 5-ALFA REDUCTASA).
3.) DUTASTERIDE (INHIBIDOR DE LA 5-ALFA REDUCTASA).
4.) FLUTAMIDA (INHIBIDOR DE LA 5-ALFA REDUCTASA).
5.) CYPROTERONA ACETATO (ANTICONCEPTIVO ORAL).
6.) ESPIRONOLACTONA (ANTIDIURETICO ORAL).
7.) SERENOA REPENS O PALMETTO SAW (NATURISTA, ANTI-ANDROGENO).
8.) CYPERUS ROTUNDUS (NATURISTA).
9.) ESTEROIDES TÓPICOS.
10.) CHAMPU ANTI-CASPA. (KETOCONAZOL, PIRITIONATO DE ZINC, BIFONAZOL)
11.) DROSPIRENONA (ANTICONCEPTIVO ORAL).
Existe en nuestro cuerpo una enzima denominada 5 alpha reductasa que es la encargada de convertir la TESTOSTERONA EN DIHIDROTESTOSTERONA. Al aumentar este metabolito, mayor sera la caída del cabello.
Por lo tanto una de las estrategias para evitar la ALOPECIA ANDROGENICA es inhibir la enzima 5 alfa reductasa, y para ello ya se han inventado y descubierto medicinas farmacológicas y naturistas.
Toadas estas medicinas tienen sus VENTAJAS y sus EFECTOS ADVERSOS, pero si nos ubicamos en la realidad, la ciencia ha avanzado notablemente en este campo, hace muchos años se decía popularmente:
" ...A LA CAIDA DEL CABELLO SOLO LA DETIENE EL PISO O SUELO.."
Hoy dia este viejo adagio no es cierto, por la aparicion de medicamentos principalmente como DUTASTERIDE, FINASTERIDE Y FLUTAMIDA, los cuales inhiben la enzima 5 alfa reductasa, principal causante del aumento de los ANDRÓGENOS en nuestro cuerpo.
Te dejo 61 referencias bibliográficas sobre el tema y en el adjunto fotos de ALOPECIA ANDROGÉNICA en HOMBRE y MUJER.
Saludos a todos.
Dr. Jose Lapenta.
=============================================================
REFERENCIAS BIBLIOGRÁFICAS / BIBLIOGRAPHICAL REFERENCES
=============================================================
1.) Increased scalp skin and serum 5 alpha-reductase reduced androgens in a man relevant to the acquired progressive kinky hair disorder and developing androgenetic alopecia.
2.) Androgen metabolism as it affects hair growth in androgenetic alopecia.
3.) [Finasteride: a new drug for the treatment of male hirsutism and androgenetic alopecia?] [La finasteride: un nuovo farmaco nel trattamento dell'irsutismo e dell' alopecia androgenica maschile?]
4.) Alterations in androgen conjugate levels in women and men with alopecia.
5.) Hormonal basis of male and female androgenic alopecia: clinical relevance.
6.) [Current treatment of androgenetic male and female alopecia(with the exception of hormone treatment)] [Traitements actuels des alopecies androgenetiques masculines et feminines (traitements hormonaux exceptes).]
7.) Androgenetic alopecia: an autosomal dominant disorder.
8.) [Hair growth promoters in androgenetic alopecia. Expectations and reality] [Haarwuchsmittel bei androgenetischer Alopezie. Anspruch und Realitat.]
9.) Effects of ozonized autohaemotherapy on human hair cycle.
10.) Estrogen and progesterone receptors in androgenic alopecia versus alopecia areata.
11.) Androgens and women's health.
12.) Female androgenetic alopecia: an update.
13.) A prospective study of the prevalence of clear-cut endocrine disorders and polycystic ovaries in 350 patients presenting with hirsutism or androgenic alopecia.
14.) Ketoconazole shampoo: effect of long-term use in androgenic alopecia.
15.) Anagen hairs may fail to replace telogen hairs in early androgenic female alopecia.
16.) Different levels of 5alpha-reductase type I and II, aromatase, and androgen receptor in hair follicles of women and men with androgenetic alopecia.
17.) Safety surveillance of esterified estrogens-methyltestosterone
(Estratest and Estratest HS) replacement therapy in the United States.
18.) Balding hair follicle dermal papilla cells contain higher levels ofandrogen receptors than those from non-balding scalp.
19.) A comparison of the culture and growth of dermal papilla cells from hair follicles from non-balding and balding (androgenetic alopecia) scalp.
20.) Messenger RNA expression of steroidogenesis enzyme subtypes in thehuman pilosebaceous unit.
21.) Treatment of androgen excess in females: yesterday, today and tomorrow.
22.) Association of benign prostatic hyperplasia with male pattern baldness.
23.) Hair regrowth. Therapeutic agents.
24.) Androgenic effects of oral contraceptives: implications for patient compliance.
25.) Diffuse hypertrichosis during treatment with 5% topical minoxidil.
26.) Minoxidil upregulates the expression of vascular endothelial growth factor in human hair dermal papilla cells.
27.) Biphasic effects of minoxidil on the proliferation and differentiation of normal human keratinocytes.
28.) Alopecia and mood stabilizer therapy.
29.) Improvement in androgenetic alopecia (stage V) using topical minoxidil in a retinoid vehicle and oral finasteride [see comments]
30.) Clinical significance of testosterone and dihydrotestosteronemetabolism in women]
31.) The 5 alpha-reductase system and its inhibitors. Recent development
and its perspective in treating androgen-dependent skin disorders.
32.) Finasteride: a clinical review.
33.) 19-nor-10-azasteroids: a novel class of inhibitors for human steroid 5alpha-reductases 1 and 2.
34.) Genetic analysis of male pattern baldness and the 5alpha-reductase genes.
35.) Effects of topically applied spironolactone on androgen stimulated sebaceous glands in the hamster pinna.
36.) Androgens affect the activity of human sebocytes in culture in a manner dependent on the localization of the sebaceous glands and their effect is antagonized by spironolactone.
37.) Antiandrogen treatment with spironolactone and linestrenol decreases bone mineral density in eumenorrhoeic women with androgen excess.
38.) [Serum hormones before and during therapy with cyproterone acetate and spironolactone in patients with androgenization]
39.) The insulin resistance in women with hyperandrogenism is partially reversed by antiandrogen treatment: evidence that androgens impair insulin action in women.
40.) Topical spironolactone reduces sebum secretion rates in young adults.
41.) Other antiandrogens.
42.) Mechanism of action and pure antiandrogenic properties of flutamide.
43.) Drospirenone: a novel progestogen with antimineralocorticoid and antiandrogenic activity.
44.) Cutaneous Manifestations of Polycystic Ovary Syndrome: A Cross-Sectional Clinical Study.
45.) A Retrospective Review of Treatment Results for Patients With Central Centrifugal Cicatrical Alopecia.
46.) The effectiveness of treatments for androgenetic alopecia: A systematic review and meta-analysis.
47.) Dutasteride in androgenetic alopecia: An update.
48.) A randomized, active- and placebo-controlled study of the efficacy and safety of different doses of dutasteride versus placebo and finasteride in the treatment of male subjects with androgenetic alopecia.
49.) New Treatments for Hair Loss.
50.) Efficacy and safety of 5% minoxidil topical foam in male pattern hair loss treatment and patient satisfaction.
51.) Post-Finasteride Adverse Effects in Male Androgenic Alopecia: A Case Report of Vitiligo.
52.) Adverse Effects and Safety of 5-alpha Reductase Inhibitors (Finasteride, Dutasteride): A Systematic Review.
53.) Atypical post-finasteride syndrome: A pharmacological riddle.
54.) Emotional Consequences of Finasteride: Fool's Gold.
55.) The importance of dual 5alpha-reductase inhibition in the treatment of male pattern hair loss: results of a randomized placebo-controlled study of dutasteride versus finasteride.
56.) Interventions for female pattern hair loss.
57.) Antiandrogenic Therapy with Ciproterone Acetate in Female Patients Who Suffer from Both Androgenetic Alopecia and Acne Vulgaris.
58.) Treatment of female pattern hair loss.
59.) [Spironolactone in dermatological treatment. On and off label indications].
60.) Treatment of male androgenetic alopecia with topical products containing Serenoa repens extract.
61.) Comparitive effectiveness of finasteride vs Serenoa repens in male androgenetic alopecia: a two-year study.
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1.) Increased scalp skin and serum 5 alpha-reductase reduced androgens in a man relevant to the acquired progressive kinky hair disorder and developing androgenetic alopecia.
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Arch Dermatol 1997 Sep;133(9):1129-33 (ISSN: 0003-987X)
Boudou P; Reygagne P [Find other articles with these Authors]
Department of Hormonal Biology, Saint-Louis University Hospital, Paris,
France.
BACKGROUND: The acquired progressive kinking of scalp hair is a disorder in which affected hairs resemble secondary sexual hairs. Some authors have evoked an androgen-related disorder that heralds the onset of androgenetic alopecia. To verify this hypothesis, we focused our attention on a 23-year-old man who has this unusual disorder, which is progressing toward androgenetic alopecia. Patient's circulating 5 alpha-reductase reduced androgen levels; scalp skin 5 alpha-dihydrotestosterone formation; and trichography, histological, scanning, and polarizing electron microscopy analyses were compared in normal and affected scalp skin areas.
OBSERVATIONS: Results of histological and scalp skin 5 alpha-dihydrotestosterone formation analyses and comparison of growth pattern of kinky hair in the affected areas with that of healthy hair were similar to those found in androgenetic alopecia.
CONCLUSIONS: No data are available to confirm the presence of a sole entity, even if our arguments support our hypothesis. The confirmation of this tendency warrants further investigation.
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2.) Androgen metabolism as it affects hair growth in androgenetic alopecia.
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Dermatol Clin 1996 Oct;14(4):697-711 (ISSN: 0733-8635)
Kaufman KD [Find other articles with this Author]
Merck Research Laboratories, Rahway, New Jersey, USA.
Androgens, in combination with a genetic susceptibility, have been demonstrated to be required for the development of androgenetic alopecia. Disturbances in androgen metabolism or target organ sensitivity are thought to underlie the pathophysiology of the condition.
Observations of patients with disorders of androgen metabolism or function have determined the basic physiology involved in regulation of hair growth by androgens at selective body sites. More recently, in vitro studies of scalp skin and hair follicles have begun to define specific alterations in androgen metabolism at the local level that may play a key role in pathogenesis. The prominent role of 5-reductase in these studies suggests that inhibitors of this enzyme may provide new therapeutic opportunities for patients with androgenetic alopecia.
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3.) [Finasteride: a new drug for the treatment of male hirsutism and androgenetic alopecia?] [La finasteride: un nuovo farmaco nel trattamento dell'irsutismo e dell'alopecia androgenica maschile?]
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Clin Ter 1996 Jun;147(6):305-15 (ISSN: 0009-9074)
Spinucci G; Pasquali R [Find other articles with these Authors]
Dipartimento di Medicina interna e Gastroenterologia, Policlinico S. Orsola-Malpighi, Bologna.
Finasteride is a drug which inhibits the transformation of testosterone into its active metabolite, dihydrotestosterone, in the target organs, i.e. the skin, the scalp, the liver and the prostate. In the pathogenic mechanism of hirsutism and androgenetic alopecia, and important role is presumably played by alterations of the mechanisms which transform testosterone into dihydrotestosterone. In some conditions an increase in dihydrotestosterone has been demonstrated, due to increased activity of the enzyme 5 alpha-reductase.
The effect of finasteride develops above all at the level of type II 5 alpha-reductase. Recent studies have evaluated the effect of finasteride in patients of both sexes with hirsutism and androgenetic alopecia. In women with various forms of hyperandrogenism, the use of the drug at the doses commonly used for the treatment of benign prostatic hyperplasia seems to have induced a significant reduction in the degree of hirsutism. Furthermore, both in animals and men with alopecia, the drug seems to have led to an increase in the number and an improvement in the shape of the follicles in the anagen phase, and a simultaneous decrease of dehydrotestosterone at the level of the scalp. This study represents a review of the main results obtained over the last two years and reports the prospects which the use of finasteride may have in this context.
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4.) Alterations in androgen conjugate levels in women and men with alopecia.
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Fertil Steril 1994 Oct;62(4):744-50 (ISSN: 0015-0282)
Legro RS; Carmina E; Stanczyk FZ; Gentzschein E; Lobo RA [Find other articles with these Authors]
Department of Obstetrics and Gynecology, University of Southern California School of Medicine, Los Angeles.
OBJECTIVE: To assess levels of androgen metabolites thought to reflect, at least in part, peripheral androgen activity in women with androgenic alopecia and men with premature balding in an effort to determine if a common abnormality exists.
DESIGN: Prospective study in various groups of women and men.
SETTING: Reproductive Endocrine Clinic at our university medical center.
PATIENTS: Ten normal ovulatory female controls and 50 hyperandrogenic women divided on the basis of hirsutism and alopecia as follows: [1] 8 hirsute women with androgenic alopecia; [2] 12 nonhirsute women with androgenic alopecia; [3] 18 hirsute women without androgenic alopecia; and [4] 12 nonhirsute women without androgenic alopecia. Ten normal men and 10 young premature balding men matched for age and weight also were compared. I
NTERVENTION: Blood was obtained from all subjects.
MAIN OUTCOME MEASURE: Comparison of blood hormone levels in the various groups.
RESULTS: Serum T, androstenedione, and DHEAS were similarly elevated in hyperandrogenic women with and without alopecia, compared with controls. The female groups were then divided on the basis of hirsutism. Hirsute groups with and without alopecia had similarly elevated levels of unconjugated 3 alpha-androstanediol, 3 alpha-androstanediol glucuronide, 3 alpha-androstanediol sulfate, androsterone glucuronide, and androsterone sulfate compared with controls.
In the nonhirsute groups, androgenic alopecia patients were compared with hyperandrogenic females and cycling controls. The androgenic alopecia patients had elevated levels of 3 alpha androstanediol (0.75 +/- 0.12 versus 0.46 +/- 0.1 and 0.41 +/- 0.1 nmol/L), 3 alpha-androstanediol sulfate (200 +/- 31 versus 79.6 +/- 6 and 67.0 +/- 4.0 nmol/L), elevated ratios of 3 alpha-androstanediol sulfate:3 alpha-androstanediol (267 +/- 49 versus 170 +/- 20 and 164 +/- 49 nmol/L), elevated ratios of 3 alpha-androstanediol sulfate:3 alpha-androstanediol glucuronide (32.2 +/- 6 versus 10.8 +/- 1 and 10.0 +/- 1) and lower ratios of 3 alpha-androstanediol glucuronide:3 alpha-androstanediol glucuronide (8.3 +/- 1.8 versus 17 +/- 1.7 and 15.2 +/- 1.6 nmol/L). I
n men the premature balding group had lower levels of 3 alpha-androstanediol glucuronide compared with the male controls (29.8 +/- 4.4 versus 15.2 +/- 1.6 nmol/L). Also, the ratio of 3 alpha-androstanediol glucuronide:3 alpha-androstanediol was significantly decreased, whereas the ratio of 3 alpha-androstanediol sulfate:3 alpha-androstanediol glucuronide was elevated.
CONCLUSIONS: These data provided evidence confirming that enhanced 5 alpha-reductase activity occurs in androgenic alopecia but also suggests that a disorder of androgen conjugation, favoring sulfurylation over glucuronidation, may be a characteristic feature of scalp hair loss.
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5.) Hormonal basis of male and female androgenic alopecia: clinical relevance.
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Skin Pharmacol 1994;7(1-2):61-6 (ISSN: 1011-0283)
Schmidt JB [Find other articles with this Author]
Department of Dermatology, University of Vienna Medical School, Austria.
A broad range of hormones was determined in males and females with androgenic hair loss (AH). The androgens testosterone, androstenedione, dehydroepiandrosterone sulfate, 17-hydroxyprogesterone and sex hormone binding globulin were evaluated in 65 male and 46 female patients. Besides estradiol (E2), cortisol (F), and the hypophyseal hormones LH, FSH, and prolactin (PRL)
were investigated. Hormone levels were compared with those of 58 age-matched male and 45 female controls. In 38 of the 46 female AH patients, hypophyseal function was moreover evaluated by the 'TRH test', which detects slight, secondary hypothyroidism and/or hyperprolactinemia. Our findings showed a significant elevation of F in both male and female AH patients compared to controls, pointing to the suprarenes as a contributing factor in AH. This is confirmed by the observation of exacerbated AH in periods of increased stress. Concerning specifically male androgens, a significant elevation of androstenedione was noted. The mainly peripheral activity of this hormone and elevated E2 levels in males stress the importance of androgen metabolism especially at the peripheral level.
Additional TRH tests in females demonstrated significant hypophyseal hypothyroidism. Multilayered interaction between thyroid hormones and androgens may contribute to the development of AH in hyperthyroid patients. Another significant finding was elevated PRL after TRH stimulation. Thus, the androgen-stimulating effect of PRL may also play a role in female AH. Our findings show multilayered hormonal influences in AH. Broad-range hormone determination demonstrated a differentiated hormonal situation in this disorder.
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6.) [Current treatment of androgenetic male and female alopecia (with the exception of hormone treatment)] [Traitements actuels des alopecies androgenetiques masculines et feminines (traitements hormonaux exceptes).]
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Schweiz Rundsch Med Prax 1997 Jun 4;86(23):996-9 (ISSN: 1013-2058)
Bouhanna P [Find other articles with this Author]
Centre Sabourdaud du Cuir chevelu, Hopital Saint-Louis, Paris.
Various non-hormonal therapies, either prescribed systemically such as certain hair-specific vitamins, or applied via the topical route, such as 2% Minoxidil, permit a normalisation of androgenic hair loss. The trichogenic action of these products should be verified in each individual with a comparative study using a trichogram and a phototrichogram. Any alopecia, be it large or small, may cause aesthetic discomfort. Currently, no medical or cosmetic product can give hope for a discernible and definitive hair regrowth. Only a micrograft reimplantation, hair by hair, produces tangible, aesthetically-denser hair in the bald region.
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7.) Androgenetic alopecia: an autosomal dominant disorder.
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Am J Med 1995 Jan 16;98(1A):95S-98S (ISSN: 0002-9343)
Bergfeld WF [Find other articles with this Author]
Department of Dermatology, Cleveland Clinic Foundation, Ohio 44195-5032.
A hereditary, androgen-driven disorder, androgenetic alopecia is the most common form of alopecia in humans: its prevalence is 23-87%. Central alopecia is more severe in men; women are more likely to experience diffuse thinning. The acute onset of alopecia in those with inflammatory diseases of the scalp suggests a variety of etiologies, including the impact of inflammatory cells, release of cytokines, presence of growth factors, and increased interaction of stromal cells. Therapeutic modalities, which are most effective when used in combinations, utilize hair growth promoters, antiandrogens, and androgen blockade agents.
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8.) [Hair growth promoters in androgenetic alopecia. Expectations and reality] [Haarwuchsmittel bei androgenetischer Alopezie. Anspruch und Realitat.]
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Hautarzt 1994 Jun;45(6):360-3 (ISSN: 0017-8470)
Schell H; Kiesewetter F; Hornstein OP [Find other articles with these Authors]
Dermatologische Universitats-Klinik, Erlangen.
Androgenetic hair loss is the most frequent reason for the topical application of hair-growth-promoting agents. Such preparations should arrest or even reverse androgen-induced hair follicle regression as well as prolonging the hair cycles, especially of the shortened anagen phase, and thus protect from increased hair loss. True evidence of drug effects on hair growth is problematic, since trichograms, the method chiefly applied by the manufacturers, fail to reveal every factor involved in the follicular activity, especially the duration of anagen stage.
For example, an increase in the anagen rate does not always reflect a lengthening of the anagen stage, but may also be due to shortened hair cycles. Accordingly, drug effects on hair growth should be investigated by methods that analyse the cell cycle kinetics. For this approach DNA-flowcytometry of the outer root sheath in plucked anagen hairs and of complete anagen hair bulbs taken by micropreparative techniques from scalp biopsies offers a reproducible method for quick and reliable evaluation of hair growth.
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9.) Effects of ozonized autohaemotherapy on human hair cycle.
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Panminerva Med 1995 Sep;37(3):129-32 (ISSN: 0031-0808)
Riva Sanseverino E; Castellacci P; Misciali C; Borrello P; Venturo N [Find other articles with these Authors]
Institute of Human Physiology, University of Bologna, Italy.
The present paper deals with the effects of ozonized autohaemotherapy on the human hair cycle in subjects suffering from androgenetic alopecia. The microscopic observation of hairs (trichogram) of 42 subjects (age range = 17-40 years) was carried out before and after cycles of ozonized autohaemotherapy according to the European scientific protocol. The dosage of ozone was 2500-3000 micrograms for each treatment, one cycle consisting of 16 treatments. Results showed a marked improvement of the hair cycle.
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10.) Estrogen and progesterone receptors in androgenic alopecia versus alopecia areata.
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Am J Dermatopathol 1998 Apr;20(2):160-3 (ISSN: 0193-1091)
Wallace ML; Smoller BR [Find other articles with these Authors]
Department of Pathology and Dermatology, Medical College of Virginia/Virginia Commonwealth University, Richmond, USA.
In some situations, hair growth is under hormonal control. Androgenic alopecia is characterized as hormonally driven hair loss in the genetically susceptible individual. During pregnancy, hair growth is increased, as estrogen appears to prolong the anagen phase. However, postpartum hair loss is common, and thus may be related to a decrease in estrogen and or progesterone levels. In contrast, alopecia areata is not considered to be under hormonal control. We compared the immunohistochemical staining characteristics of nine cases of androgenic alopecia with those of 13 cases of alopecia areata using estrogen receptor (ER) and progesterone receptor (PR) markers.
Estrogen receptor positivity in the dermal papilla was found in only two of 13 cases of alopecia areata, and in one case of androgenic alopecia. Six of 13 cases of alopecia areata demonstrated focal reactivity with the progesterone marker in a similar location, while only three cases of androgenic alopecia showed positivity with this antibody. Examination of the perifollicular fibroblasts for the ER marker showed positivity in one of 13 cases of alopecia areata and in one case of androgenic alopecia. Two cases of alopecia areata revealed focal staining in this location for the PR marker, while the androgenic alopecia cases failed to stain.
These results indicate that estrogen and progesterone receptor expression is not significantly increased or decreased in the pilosebaceous units or surrounding mesenchymal cells in androgenic alopecia vs. alopecia areata. Therefore, an indirectly mediated process of estrogen/progesterone control on hair growth and development must be presumed for cases of androgenic alopecia.
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11.) Androgens and women's health.
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Int J Fertil Womens Med 1998 Mar-Apr;43(2):91-7
Redmond GP [Find other articles with this Author]
Center for Health Studies, Inc., Cleveland, Ohio 44122, USA.
Androgenic disorders are those conditions in women characterized by excessive androgen action. They are the most common endocrinopathy of women, affecting from 10% to 20%. Signs are: persistent acne, hirsutism and androgenic alopecia, which is the female equivalent of male pattern baldness.
A subgroup, those traditionally labeled as having polycystic ovary syndrome (PCOS), additionally have anovulation, as well as menstrual abnormalities and, often, obesity. Although women with androgenic disorders usually present themselves for help with the skin or menstrual changes, there are other important implications regarding their health. Women with PCOS have varying degrees of insulin resistance, and an increased incidence of Type II diabetes mellitus, as well as unfavorable lipid patterns.
The presence of these risk factors is suggested by upper segment obesity, darkening of the skin, and the other skin changes that make up acanthosis nigricans. Diagnosis involves measurement of circulating androgens (of which free testosterone is most important), together with prolactin and FSH when menstrual dysfunction is present. Many women with androgenic skin changes have normal serum androgen levels, suggesting increased end organ sensitivity to androgens. Others have hyperandrogenism (of ovarian or adrenal origin).
Treatment is usually successful in controlling acne, reducing hirsutism and stabilizing, or partially reversing, androgenic alopecia. Pharmacological approaches involve suppressing androgen levels, for example, the use of an appropriate oral contraceptive, or antagonizing androgen action with several medications that have this activity. Unfortunately, most women with androgenic disorders are frustrated in their efforts to obtain medical help. Understanding androgenic disorders will enable the physician to significantly help the majority of women with these conditions.
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12.) Female androgenetic alopecia: an update.
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Australas J Dermatol 1995 May;36(2):51-5; quiz 56-7 (ISSN: 0004-8380)
Callan AW; Montalto J [Find other articles with these Authors]
Department of Clinical Biochemistry, Royal Children's Hospital, Parkville,
Victoria, Australia.
Androgenetic alopecia is an androgen dependent disorder occurring in genetically susceptible individuals. The pattern of hair loss in women differs from that of classical male pattern alopecia, being more diffuse and with retention of the frontal hair line in most cases. Characteristic histopathological changes occur but biopsy is rarely helpful in diagnosis. Although research has shown subtle alterations in the androgen status of women with androgenetic alopecia, most patients presenting with this disorder are normal endocrinologically. Anti-androgen therapy will result in some improvement in up to 50% of patients after 6 to 12 months of therapy, but in practice will usually only decrease the rate of hair loss and not result in new hair growth.
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13.) A prospective study of the prevalence of clear-cut endocrine disorders and polycystic ovaries in 350 patients presenting with hirsutism or androgenic alopecia.
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Clin Endocrinol (Oxf) 1994 Aug;41(2):231-6 (ISSN: 0300-0664)
O'Driscoll JB; Mamtora H; Higginson J; Pollock A; Kane J; Anderson DC [Find other articles with these Authors]
Department of Radiology, Skin Hospital, Salford.
OBJECTIVE: To determine the frequency of polycystic ovaries (PCO) on ultrasound and the incidence of clearcut endocrine disorders leading to virilization in patients complaining of hirsutism or androgenic alopecia. The major purpose was to determine a coherent policy for the routine biochemical assessment of such women.
DESIGN: A prospective study of women attending a joint skin/endocrine clinic complaining of these problems.
PATIENTS: Three hundred and fifty consecutive women with hirsutism and/or androgenic alopecia were assessed.
MEASUREMENTS: Baseline endocrine screens were conducted on two occasions and included measurement of serum testosterone, androstenedione, dehydroepiandrosterone sulphate, sex hormone binding globulin, LH, FSH, 17-hydroxyprogesterone and PRL. The ovaries were visualized by high-resolution pelvic ultrasound scanning.
RESULTS: Eight women were identified with relevant endocrine disorders; of these, one was acromegalic and one had a microprolactinoma--in both cases the association may have been fortuitous. Three had clear-cut 21-hydroxylase deficiency, one a rare hepatic enzyme deficiency (11-reductase), one a virilizing adrenal carcinoma and one a Leydig cell tumour. The latter six cases all had persistently elevated levels of serum testosterone ( 5 nmol/l). In all, 13 women had baseline testosterone levels in excess of 5 nmol/l. Polycystic ovaries were present in 81% of the cases who had erratic cycles and 52% of those with regular cycles; PCO were present in two of the women with 21-hydroxylase deficiency and in the woman with 11-oxoreductase deficiency. The Leydig cell tumour (1.2 cm diameter) was not detected on ultrasound or CT scan.
CONCLUSIONS: For the exclusion of enzyme deficiencies and virilizing tumours clinical assessment and a single serum testosterone measurement will suffice.
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14.) Ketoconazole shampoo: effect of long-term use in androgenic alopecia.
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Author
Pi´erard-Franchimont C; De Doncker P; Cauwenbergh G; Pi´erard GE
Address
Department of Dermatopathology, University of Li`ege, Belgium.
Source
Dermatology, 196(4):474-7 1998
Abstract
BACKGROUND: The pathogenesis of androgenic alopecia is not fully understood. A microbial-driven inflammatory reaction abutting on the hair follicles might participate in the hair status anomaly.
OBJECTIVE: The aim of our study was to determine if ketoconazole (KCZ) which is active against the scalp microflora and shows some intrinsic anti-inflammatory activity might improve alopecia.
METHOD: The effect of 2% KCZ shampoo was compared to that of an unmedicated shampoo used in combination with or without 2% minoxidil therapy.
RESULTS: Hair density and size and proportion of anagen follicles were improved almost similarly by both KCZ and minoxidil regimens. The sebum casual level appeared to be decreased by KCZ.
CONCLUSION: Comparative data suggest that there may be a significant action of KCZ upon the course of androgenic alopecia and that Malassezia spp. may play a role in the inflammatory reaction. The clinical significance of the results awaits further controlled study in a larger group of subjects.
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15.) Anagen hairs may fail to replace telogen hairs in early androgenic female alopecia.
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Author
Guarrera M; Rebora A
Address
Department of Dermatology, University of Genoa, Italy.
Source
Dermatology, 192(1):28-31 1996
Abstract
Background: Male baldness develops because of an increased duration of the lag phase. Objective and Methods: To assess if this occurs also in balding women we studied 2 women with Ludwig type I-II patterned baldness for 2 years with monthly phototrichograms. Hairs were identified as thick anagen hairs, thin anagen hairs and telogen hairs.
Results and Conclusions:
Most of the hairs followed the expected development, namely they remained thick anagen hairs or they became thick from thin anagen, telogen from thick anagen or thin anagen from telogen hairs. Other hairs, though, became thin from thick anagen or telogen from thin anagen or thick anagen from telogen hairs. Still others did not regrow immediately after being in the telogen phase, leaving an empty space. Some empty spaces were not refilled for a long time. As in men, in balding women tiny bald spots develop corresponding to telogen hairs not replaced in due time.
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16.) Different levels of 5alpha-reductase type I and II, aromatase, and androgen receptor in hair follicles of women and men with androgenetic alopecia.
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Author
Sawaya ME; Price VH
Address
Department of Medicine, University of Florida, Gainesville 32610, U.S.A.
Source
J Invest Dermatol, 109(3):296-300 1997 Sep
Abstract
In this study, 12 women and 12 men, ages 18-33 y, with androgenetic alopecia were selected for biopsies from frontal and occipital scalp sites. The androgen receptor, type I and II 5alpha-reductase, cytochrome P-450-aromatase enzyme were measured and analyzed in hair follicles from these scalp biopsies. Findings revealed that both women and men have higher levels of receptors and 5alpha-reductase type I and II in frontal hair follices than in occipital follicles, whereas higher levels of aromatase were found in their occipital follicles.
There are marked quantitative differences in levels of androgen receptors and the three enzymes, which we find to be primarily in the outer root sheath of the hair follicles in the two genders. Androgen receptor content in female frontal hair follicles was approximately 40% lower than in male frontal hair follicle.
Cytochrome P-450-aromatase content in women's frontal hair follicles was six times greater than in frontal hair follicles in men. Frontal hair follicles in women had 3 and 3.5 times less 5alpha-reductase type I and II, respectively, than frontal hair follicles in men. These differences in levels of androgen receptor and steroid-converting enzymes may account for the different clinical presentations of androgenetic alopecia in women and men.
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17.) Safety surveillance of esterified estrogens-methyltestosterone (Estratest and Estratest HS) replacement therapy in the United States.
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Author
Phillips E; Bauman C
Address
Drug Safety Unit, Solvay Pharmaceuticals, Inc., Marietta, Georgia, USA.
Source
Clin Ther, 19(5):1070-84 1997 Sep-Oct
Abstract
This paper summarizes all postmarketing safety surveillance data collected by Solvay Pharmaceuticals, Inc. (Marietta, Georgia), between 1989 and 1996 for Estratest and Estratest HS (half-strength). These oral esterified estrogens--methyltestosterone combination products have been marketed in the United States since 1964 for the treatment of moderate-to-severe vasomotor symptoms associated with menopause in patients whose symptoms have not been relieved by estrogens alone.
Between 1989 and 1996, more than 1 million woman-years of exposure occurred. The safety profile contained in this paper is based on a cumulative total of 568 individual cases comprising 863 adverse events (AEs). The proportions of AEs associated with the use of Estratest (575 events; 66.6%) and Estratest HS (288 events; 33.4%) were commensurate with the proportions of individual reports of adverse experiences for the two formulations (369 reports [65.0%] and 199 reports [35.0%], respectively). The rank order and percentage of types of AEs reported were also similar.
The cumulative volume of reports was relatively low given the extent of exposure. Despite the limitations inherent in spontaneous postmarketing surveillance, the safety profile derived from this assessment does not indicate a significant safety concern with Estratest or Estratest HS. No deaths were reported, and no adverse findings indicative of the need for more comprehensive surveillance or concern on the part of the medical community or consumers were observed. Reports of cancer, cardiovascular disease, thromboembolic phenomena, and hepatic dysfunction were few and were assessed as not related to treatment with Estratest or Estratest HS; reports of drug overdose, drug-drug interaction, and birth defects were rare (4 of 863 events; 0.5%).
The most commonly reported AEs were those known to be associated with estrogen therapy (weight gain, headache, nausea, and vasodilatation) and androgen treatment (alopecia, acne, and hirsutism). Twenty-three (4.0%) of the 568 cases reported had at least one event that was regarded as serious, and 53 (6.1%) of the total 863 AEs were regarded as serious. The findings indicate that Estratest and Estratest HS are safe when used as directed and that the marginal increase in risk associated with androgen coadministration can be managed with appropriate patient selection and monitoring, as stated in the package insert for these compounds.
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18.) Balding hair follicle dermal papilla cells contain higher levels of androgen receptors than those from non-balding scalp.
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Author
Hibberts NA; Howell AE; Randall VA
Address
Department of Biomedical Sciences, University of Bradford, UK.
Source
J Endocrinol, 156(1):59-65 1998 Jan
Abstract
Androgens can gradually transform large scalp hair follicles to smaller vellus ones, causing balding. The mechanisms involved are unclear, although androgens are believed to act on the epithelial hair follicle via the mesenchyme-derived dermal papilla. This study investigates whether the levels and type of androgen receptors in primary lines of cultured dermal papilla cells derived from balding scalp hair follicles differ from those of follicles from non-balding scalp. Androgen receptor content was measured by saturation analysis using the non-metabolisable androgen, [3H]mibolerone (0.05-10 nM) in a 9-10 point assay.
Pubic dermal fibroblasts and Shionogi cells were examined as positive controls. Repetitive assays of Shionogi cells showed good precision in the levels of androgen receptor content (coefficient of variation = 3.7%). Specific, high affinity, low capacity androgen receptors were detected in dermal papilla cells from both balding and non-balding follicles. Balding cells contained significantly (P < 0.01) greater levels of androgen receptors (Bmax = 0.06 +/- 0.01 fmol/10(4) cells (mean +/- S.E.M.)) than those from non-balding scalp (0.04 +/- 0.001).
Competition studies with a range of steroids showed no differences in receptor binding specificity in the two cell types. The higher levels of androgen receptors in cells from balding scalp hair follicles with similar properties to those from non-balding scalp concur with the expectations from their in vivo responses to androgens. This supports the hypothesis that androgens act via the dermal papilla and suggests that cultured dermal papilla cells may offer a model system for studying androgen action in androgenetic alopecia.
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19.) A comparison of the culture and growth of dermal papilla cells from hair follicles from non-balding and balding (androgenetic alopecia) scalp.
======================================================================
Author
Randall VA; Hibberts NA; Hamada K
Address
Department of Biomedical Sciences, University of Bradford, U.K.
Source
Br J Dermatol, 134(3):437-44 1996 Mar
Abstract
Male pattern baldness is a common, androgen-dependent skin problem in adult men which is not well understood, although androgens are believed to act on the hair follicle via the mesenchyme-derived dermal papilla situated in the middle of the hair follicle bulb. Since dermal papilla cells retain specific characteristics in culture, such as hair-growth promoting ability and appropriate features of the mechanism of androgen action, dermal papilla cells from follicles undergoing androgen-stimulated miniaturization may provide a useful in vitro model system. Therefore, dermal papilla cells have been derived from intermediate follicles from balding and nearly clinically normal sites of men with androgenetic alopecia.
Balding dermal papillae were much smaller than non-balding ones and grew much less well under normal growth conditions. Supplementing the medium with human serum, rather than fetal calf serum, increased both the yield of established cultures and the number and health of the dermal papilla cells produced. Non-balding cells also grew faster in human serum. Balding cells retained the normal fibroblastic shape and aggregative behaviour of dermal papilla cells, but always grew less well than non-balding cells.
Nearly clinically normal dermal papillae were similar, or slightly smaller, in size to non-balding ones, but their growth resembled balding cells. Since balding dermal papilla cells can be cultured, though with much greater difficulty than nonbalding ones, and exhibit differing growth characteristics to non-balding cells, they merit further investigation which may increase our understanding of, and ability to control, androgenetic alopecia.
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20.) Messenger RNA expression of steroidogenesis enzyme subtypes in the human pilosebaceous unit.
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Author
Courchay G; Boyera N; Bernard BA; Mahe Y
Address
Hair Biology Research Group, L'Or´eal, Centre de recherche C. Zviak, Clichy, France.
Source
Skin Pharmacol, 9(3):169-76 1996
Abstract
In order to define the respective involvement of steroidogenesis enzymes subtypes in the control of hair follicle homeostasis, we evaluated, by semiquantitative RT/PCR, the expression levels of mRNAs coding for 17 beta-hydroxysteroid dehydrogenase type 1 and type 2, 3 beta-hydroxysteroid dehydrogenase, Cyt.P450-aromatase, steroid 5 alpha-reductase type 1 and type 2 and 11 beta-hydroxysteroid dehydrogenase.
These assays were performed for several components of the pilosebaceous unit (PSU); fresh plucked anagen hairs, sebaceous glands and primary culture of dermal papilla, as well as other tissues involved in an active steroid metabolism (human testis, liver, placenta, prostate, ovary, uterus and adrenals) as controls.
We found that plucked hair (i.e. mainly keratinocytes from the inner and outer root sheaths) expressed: (1) very high levels of 17 beta-hydroxysteroid dehydrogenase type 2 corresponding to levels found in liver and placenta; (2) high levels of steroid 5-alpha-reductase type 1 corresponding to levels found in testis, liver and ovary, and moderate levels of 17 beta-hydroxysteroid dehydrogenase type 1, which corresponded to the expression in testis, prostate and uterus. In contrast, Cyt.P450-aromatase, 3 beta-hydroxysteroid dehydrogenase and steroid 5 alpha-reductase type 2 were poorly expressed in the pilosebaceous unit as compared with other tissues. Interestingly, expression patterns of these enzymes in primary cultures of dermal papilla were distinctive since 5 alpha-reductase type 1 and 11 beta-hydroxysteroid dehydrogenase were the only mRNA detected.
Taken together, these results suggest that not only sebaceous gland but also outer root sheath keratinocytes may contribute, through the activity of the steroid 5 alpha-reductase type 1, to the pathogenesis of androgen-dependent alopecia.
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21.) Treatment of androgen excess in females: yesterday, today and tomorrow.
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Author
Pucci E; Petraglia F
Address
Institute of Endocrinology, University of Pisa, Italy.
Source
Gynecol Endocrinol, 11(6):411-33 1997 Dec
Abstract
Hirsutism, acne and androgenic alopecia represent, in females, some of the manifestations of the clinical spectrum of hyperandrogenism. These pictures represent not only cosmetic damage, but also a source of remarkable psychological distress. Often hirsutism is regarded as presumptive evidence of a lack of femininity. The major diagnostic concern is to exclude an ovarian or adrenal androgen-secreting tumor, a congenital hyperplasia or polycystic ovary disease.
Ethnic background should be taken into account together with the progression of the symptoms. Following the etiology, surgery and exogenous glucocorticoids or inhibition of gonadotropin secretion have to be carefully chosen in the management of different kinds of hyperandrogenism. Several pharmacologic agents have recently shown the ability to block the androgen receptors at target organ sites, thus allowing a specific antiandrogenic treatment. In some cases cosmetic measures could be of great value.
Obesity accompanied by hyperinsulinemia can represent the main cause of ovary androgen hypersecretion; therefore a reduced body weight and muscle activity represent the basis of any treatment. Some other drugs, such as long-acting analogs of somatostatin, could be considered among possible drugs for the future. The aim of this article is to provide an appraisal of what is presently known about the regulation of hair growth, the various causes of excessive androgen secretion and the current methods to solve, safely, this important feminine clinical problem.
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22.) Association of benign prostatic hyperplasia with male pattern baldness.
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Author
Oh BR; Kim SJ; Moon JD; Kim HN; Kwon DD; Won YH; Ryu SB; Park YI
Address
Department of Urology, Chonnam University Medical School, Kwangju, South Korea.
Source
Urology, 51(5):744-8 1998 May
Abstract
OBJECTIVES: Both benign prostatic hyperplasia (BPH) and male pattern baldness (androgenic alopecia) share the pathogenesis of an androgen-dependent disorder and afflict a large population of elderly men with chronobiologic progress. However, it is unclear whether these diseases are related epidemiologically. We evaluated the association of frequency and severity of male pattern baldness between patients with BPH and a control group.
METHODS: A total of 225 patients with BPH (mean age 69.3 +/- 6.5 years) and 1 60 controls (mean age 68.5 +/- 6.4 years), all over 60 years of age, were included in this study. The estimation of baldness severity was based on Norwood's classification (grade I to VII). The International Prostate Symptom Score (IPSS) and genetic tendency for baldness were also evaluated. The difference between IPSS and grade of baldness between the two groups was analyzed by the Mann-Whitney test and the frequency of inherited baldness was compared by the chi-square test. Correlation between severity of baldness and IPSS in each group was estimated by Spearman's rank correlation method.
RESULTS: The patients with BPH had an apparently higher grade of male pattern baldness in comparison with that of controls (median value of grade IV versus III, P <0.001). The proportion of men with male pattern baldness of grade IV or higher in the BPH group was significantly larger than that of controls (53.8% versus 36.9%, P <0.01). There was a greater frequency of inherited baldness in the BPH group than in the controls (31.6% versus 12.5%, P <0.001). No significant correlation was noted between baldness severity and IPSS in either group.
CONCLUSIONS: This study demonstrates a strong association of BPH with male pattern baldness.
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23.) Hair regrowth. Therapeutic agents.
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Author
Shapiro J; Price VH
Address
University of British Columbia Hair Research and Treatment Centre, Division of Dermatology, Vancouver, Canada.
Source
Dermatol Clin, 16(2):341-56 1998 Apr
Abstract
Today there are new classes of hair growth promotors with proven efficacy. This article reviews the current state of the art agents for treatment of two of the most common forms of hair loss encountered in clinical practice, androgenetic alopecia and alopecia areata. Current therapeutic strategies are based on recent advances in the understanding of disordered hair growth. Practical treatment protocols are presented.
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24.) Androgenic effects of oral contraceptives: implications for patient compliance.
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Author
Jones EE
Address
Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, Connecticut.
Source
Am J Med, 98(1A):116S-119S 1995 Jan 16
Abstract
Androgenic disorders have many negative physical effects. These effects may be caused by excess androgen (exogenous or endogenous) or by end-organ sensitivity to normal levels of androgens. Historically, androgenic progestins in oral contraceptives have also been associated with some of these negative effects. The most apparent signs of androgen excess are the external manifestations, including oily skin, acne, hirsutism, android obesity, and androgenic alopecia.
Of equal concern are the potential metabolic disturbances associated with hyperandrogenicity. Unfavorable lipid profiles and increased incidence of diabetes and hypertension are very real threats to long-term health. In oral contraceptive users, external manifestations of androgenicity often lead to poor compliance, decreased efficacy, and discontinuation of oral contraceptive use, especially in the younger patient.
With the introduction of the newer oral contraceptive formulations containing less androgenic progestins (norgestimate, desogestrel, gestodene), androgen-related effects have been reduced and better compliance is anticipated. Language
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25.) Diffuse hypertrichosis during treatment with 5% topical minoxidil.
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Author
Peluso AM; Misciali C; Vincenzi C; Tosti A
Address
Department of Dermatology, University of Borogna, Italy.
Source
Br J Dermatol, 136(1):118-20 1997 Jan
Abstract
Five women affected by androgenetic alopecia developed severe hypertrichosis of the face and limbs after 2-3 months of treatment with 5% topical minoxidil. Minoxidil was discontinued and in all patients the hypertrichosis disappeared from the face and arms after 1-3 months, and from legs after 4-5 months. Systemic absorption of minoxidil, and a high sensitivity to minoxidil of the follicular apparatus in these areas, is hypothesized.
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26.) Minoxidil upregulates the expression of vascular endothelial growth factor in human hair dermal papilla cells.
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Author
Lachgar S; Charveron M; Gall Y; Bonafe JL
Address
Laboratoire de Biologie Cellulaire Cutan´ee, Institut de Recherche Pierre Fabre, Facult´e de M´edecine Rangueil, Toulouse, France.
Source
Br J Dermatol, 138(3):407-11 1998 Mar
Abstract
The hair follicle dermal papilla which controls hair growth, is characterized in the anagen phase by a highly developed vascular network. We have demonstrated in a previous study that the expression of an angiogenic growth factor called vascular endothelial growth factor (VEGF) mRNA varied during the hair cycle. VEGF mRNA is strongly expressed in dermal papilla cells (DPC) in the anagen phase, but during the catagen and telogen phases. VEGF mRNA is less strongly expressed.
This involvement of VEGF during the hair cycle allowed us to determine whether VEGF mRNA expression by DPC was regulated by minoxidil. In addition, the effect of minoxidil on VEGF protein synthesis in both cell extracts and DPC-conditioned medium, was investigated immunoenzymatically. Both VEGF mRNA and protein were significantly elevated in treated DPC compared with controls. DPC incubated with increasing minoxidil concentrations (0.2, 2, 6, 12 and 24 mumol/L) induced a dose-dependent expression of VEGF mRNA.
Quantification of transcripts showed that DPC stimulated with 24 mumol/L minoxidil express six times more VEGF mRNA than controls. Similarly, VEGF protein production increases in cell extracts and conditioned media following minoxidil stimulation.
These studies strongly support the likely involvement of minoxidil in the development of dermal papilla vascularization via a stimulation of VEGF expression, and support the hypothesis that minoxidil has a physiological role in maintaining a good vascularization of hair follicles in androgenetic alopecia.
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27.) Biphasic effects of minoxidil on the proliferation and differentiation of normal human keratinocytes.
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Author
Boyera N; Galey I; Bernard BA
Address
L'Or´eal, Hair Biology Research Group, Clichy, France.
Source
Skin Pharmacol, 10(4):206-20 1997
Abstract
Minoxidil is the most used drug with proved effects in the treatment of androgenetic alopecia (AGA), but little is known about its pharmacological activity and target cells in hair follicles. As AGA is characterized by follicle atrophy, accelerated hair cycles and hair fiber thinning, we postulated that keratinocyte proliferation/differentiation is affected and we tested Minoxidil's effects on those parameters.
Normal human keratinocytes (NHK) of follicular or epidermal origin were cultured in the presence of Minoxidil (0, 0.1, 1, 10, 100, 1,000 microM) during 5-8 days in various media (high-/low-calcium content, with or without serum). Proliferation was assessed by mitochondrial dehydrogenase activity (XTT), BrdU incorporation, lysosome numeration (neutral red incorporation) and total protein dosage. Drug-induced cytotoxicity was measured by lactate dehydrogenase release in culture supernatant, and pro-differentiating effects were evaluated by relative involucrin expression (ELISA dosage).
On this basis, we showed that Minoxidil had biphasic effects on the proliferation and differentiation of NHK: Minoxidil stimulated NHK proliferation at micromolar doses, while antiproliferative, pro-differentiative and partially cytotoxic effects were observed with millimolar concentrations. We can hypothesize that Minoxidil hypertrichotic activity in vivo is possibly mediated by the maintenance of proliferative potential in follicular keratinocytes precociously committed to differentiation.
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28.) Alopecia and mood stabilizer therapy.
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Author
McKinney PA; Finkenbine RD; DeVane CL
Address
Medical University of South Carolina, Charleston 29425, USA.
Source
Ann Clin Psychiatry, 8(3):183-5 1996 Sep
Abstract
Alopecia is a common side effect in patients managed on the mood stabilizers lithium, valproate, and carbamazepine. Clinicians may be reluctant to discontinue medications in patients suffering from hair loss if the mood stabilizer is otherwise efficacious. Therefore it is important to be familiar with the epidemiology, diagnosis, and management of alopecia.
A single representative case is provided to illustrate briefly the common presentation of a patient with mood stabilizer-induced alopecia. A literature search was conducted to provide the basis for discussion of diagnosis, the association of mood stabilizers with alopecia, and some management options of this side effect. The diagnosis of alopecia requires an understanding of normal hair growth and is best made following a careful history, an examination, and the maintenance of a high level of suspicion.
Alopecia occurs in about 10% of persons managed on lithium, up to 12% of persons on valproate, and less than 6% of individuals on carbamazepine. Management of alopecia includes reassurance, hair care techniques, trace mineral supplementation, treatment with minoxidil, and hair replacement pieces. Alopecia due to mood stabilizer drugs can be potentially identified and managed without medication discontinuation.
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29.) Improvement in androgenetic alopecia (stage V) using topical minoxidil in a retinoid vehicle and oral finasteride [see comments]
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Author
Walsh DS; Dunn CL; James WD
Address
Walter Reed Army Medical Center, Washington, DC, USA.
Source
Arch Dermatol, 131(12):1373-5 1995 Dec
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30.) Clinical significance of testosterone and dihydrotestosterone metabolism in women]
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Author
Kor¨si´c M
Address
Zavod za endokrinologiju, dijabetes i bolesti metabolizma Klinike za unutarnje bolesti, KBC Rebro, Zagreb.
Source
Lijec Vjesn, 118 Suppl 1():21-3 1996 Mar
Abstract
Hyperandrogenism in women refers to both excess androgen production and clinical manifestations of androgen excess. Clinical evaluation of women with hyperandrogenism is complex.
The synthesis and release of androgenic steroid in women are normal part of adrenal and ovarian steroidogenesis. One of the classic questions concerning androgenic disorders concerns the source of circulating androgens. Relative roles of adrenal and ovary vary greatly, both can be involved.
The use of gonadal or adrenal steroid administration can sometimes be used to distinguish the source of androgen excess. In many cases of hyperandrogenism no laboratory diagnosis of adrenal and ovarian androgen overproduction can be made. These patients may have increased androgen sensitivity due to increased enzyme 5 alpha-reductase activity in the skin.
To be active in the skin, testosterone (T) must be converted to dihydrotestosterone (DHT) by the 5 alpha-reductase. The increase in DHT production is a localized phenomenon and there is no generalized increase in enzyme activity in women with hyperandrogenism. DHT is rapidly converted to other steroid metabolites including androsteron, androstanediol and their glucuronide and sulfate conjugates. Although once thought to be specific for skin conversion of T to DTH these androgen conjugates reflect adrenal steroid production and metabolism. Antiandrogens (androgen receptor blockers) are the most effective therapeutic modalities of cutaneous hyperandrogenism.
Clinical trials are in progress to determine efficacy of finasteride for the treatment of hirsutism and androgenetic alopecia. Finasteride is the first available medication of a new class of drugs that is an competitive inhibitor of 5 alpha-reductase and therefore should be beneficial for medical treatment of cutaneous hyperandrogenism.
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31.) The 5 alpha-reductase system and its inhibitors. Recent development and its perspective in treating androgen-dependent skin disorders.
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Author
Chen W; Zouboulis CC; Orfanos CE
Address
Department of Dermatology, University Medical Center Benjamin Franklin, Free University of Berlin, Germany.
Source
Dermatology, 193(3):177-84 1996
Abstract
5 alpha-Reductase, the enzyme system that metabolizes testosterone into dihydrotestosterone, occurs in two isoforms. The type 1 isozyme is composed of 259 amino acids, has an optimal pH of 6-9 and represents the 'cutaneous type'; it is located mainly in sebocytes but also in epidermal and follicular keratinocytes, dermal papilla cells and sweat glands as well as in fibroblasts from genital and non-genital skin.
The type 2 isozyme is composed of 254 amino acids, has an optimal pH of about 5.5 and is located mainly in the epididymis, seminal vesicles, prostate and fetal genital skin as well as in the inner root sheath of the hair follicle and in fibroblasts from normal adult genital skin.
The genes encoding type 1 and type 2 isozymes are found in chromosomes 5p and 2p, respectively, and each consists of 5 exons and 4 introns. During the last decade, several steroid analogues and non-steroid agents have been developed to interfere with 5 alpha-reductase activity.
Finasteride, which has a higher affinity for the type 2 isozyme, is the first 5 alpha-reductase antagonist clinically introduced for treatment of benign prostate hyperplasia. The clinical evaluation of finasteride or other 5 alpha-reductase inhibitors in the field of dermatology has been very limited; in particular, those that selectively bind to type 1 isozyme (e.g. MK-386, LY191704) may be regarded as candidates for treatment of androgen-dependent skin disorders such as seborrhoea, acne, hirsutism and/or androgenetic alopecia.
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32.) Finasteride: a clinical review.
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Author
Gormley GJ
Address
Merck Research Laboratories, Rahway, NJ 07065-0914, USA.
Source
Biomed Pharmacother, 49(7-8):319-24 1995
Abstract
Finasteride is the first of a new class of 5 alpha-reductase inhibitors which allows selective androgen deprivation affecting dihydrotestosterone (DHT) levels in target organs such as the prostate and scalp hair without effecting circulating levels of testosterone thus preserving the desired androgen mediated effects on muscle strength, bone density and sexual function.
Finasteride has been demonstrated to produce significant effects in men with an enlarged prostate gland. The long-term data now emerging suggests that progression of benign prostatic hyperplasia (BPH) may be arrested providing additional long term benefits. Experimental uses in prostate cancer prevention and male pattern baldness offer new and exciting possibilities for this class of compounds.
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33.) 19-nor-10-azasteroids: a novel class of inhibitors for human steroid 5alpha-reductases 1 and 2.
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Author
Guarna A; Belle C; Machetti F; Occhiato EG; Payne AH; Cassiani C; Comerci A; Danza G; De Bellis A; Dini S; Marrucci A; Serio M
Address
Dipartimento di Chimica Organica Ugo Schiff, Universit`a di Firenze, Italy. guarna@chimorg.unifi.it
Source
J Med Chem, 40(7):1112-29 1997 Mar 28
Abstract
Steroid 5alpha-reductase is a system of two isozymes (5alphaR-1 and 5alphaR-2) which catalyzes the NADPH-dependent reduction of testosterone to dihydrotestosterone in many androgen sensitive tissues and which is related to several human endocrine diseases such as benign prostatic hyperplasia (BPH), prostatic cancer, acne, alopecia, pattern baldness in men and hirsutism in women. T
he discovery of new potent and selective 5alphaR inhibitors is thus of great interest for pharmaceutical treatment of these diseases. The synthesis of a novel class of inhibitors for human 5alphaR-1 and 5alphaR-2, having the 19-nor-10-azasteroid skeleton, is described.
The inhibitory potency of the 19-nor-10-azasteroids was determined in homogenates of human hypertrophic prostates toward 5alphaR-2 and in DU-145 human prostatic adenocarcinoma cells toward 5alphaR-1, in comparison with finasteride (IC50 = 3 nM for 5alphaR-2 and approximately 42 nM for 5alphaR-1), a drug which is currently used for BPH treatment.
The inhibition potency was dependent on the type of substituent at position 17 and on the presence and position of the unsaturation in the A and C rings. delta9(11)-19-Nor-10-azaandrost-4-ene-3,17-dione (or 10-azaestra-4,9(11)-diene-3,17-dione) (4a) and 19-nor-10-azaandrost-4-ene-3,17-dione (5) were weak inhibitors of 5alphaR-2 (IC50 = 4.6 and 4.4 microM, respectively) but more potent inhibitors of 5alphaR-1 (IC50 = 263 and 299 nM, respectively), whereas 19-nor-10-aza-5alpha-androstane-3,17-dione (7) was inactive for both the isoenzymes.
The best result was achieved with the 9:1 mixture of delta9(11)- and delta8(9)-17beta-(N-tert-butylcarbamoyl)-19-nor-10-aza-4- androsten-3-one (10a,b) which was a good inhibitor of 5alphaR-1 and 5alphaR-2 (IC50 = 127 and 122 nM, respectively), with a potency very close to that of finasteride. The results of ab initio calculations suggest that the inhibition potency of 19-nor-10-azasteroids could be directly related to the nucleophilicity of the carbonyl group in the 3-position.
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34.) Genetic analysis of male pattern baldness and the 5alpha-reductase genes.
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Author
Ellis JA; Stebbing M; Harrap SB
Address
Department of Physiology, The University of Melbourne, Parkville, Victoria, Australia.
Source
J Invest Dermatol, 110(6):849-53 1998 Jun
Abstract
Genetic predisposition and androgen dependence are important characteristics of the common patterned loss of scalp hair known as male pattern baldness. The involvement of the 5alpha-reductase enzyme in male pattern baldness has been postulated due to its role in the metabolism of testosterone to dihydrotestosterone.
There are two known isozymes of 5alpha-reductase. Type I has been predominantly localized to the skin and scalp. Type II, also present on the scalp, is the target of finasteride, a promising treatment for male pattern baldness. We conducted genetic association studies of the 5alpha-reductase enzyme genes (SRD5A1 on chromosome 5 and SRD5A2 on chromosome 2) using dimorphic intragenic restriction fragment length polymorphisms. From a population survey of 828 healthy families comprising 3000 individuals, we identified 58 young bald men (aged 18-30 y) and 114 older nonbald men (aged 50-70 y) for a case control comparison.
No significant differences were found between cases and controls in allele, genotype, or haplotype frequencies for restriction fragment length polymorphisms of either gene. These findings suggest that the genes encoding the two 5alpha-reductase isoenzymes are not associated with male pattern baldness.
Finally, no clear inheritance pattern of male pattern baldness was observed. The relatively strong concordance for baldness between fathers and sons in this study was not consistent with a simple Mendelian autosomal dominant inheritance. A polygenic etiology should be considered.
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35.) Effects of topically applied spironolactone on androgen stimulated sebaceous glands in the hamster pinna.
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Author
Seki T; Toyomoto T; Morohashi M
Address
Department of Dermatology, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Japan.
Source
J Dermatol, 22(4):233-7 1995 Apr
Abstract
The effects of spironolactone (5% SYC-201G, a preparation developed for clinical use in acne vulgaris by Searle Yakuhin K.K.), which is known to have antiandrogenic effects by competitively inhibiting dihydrotestosterone at androgen receptor sites, was topically applied to the androgen stimulated sebaceous glands of adult female golden hamsters. Androgen stimulation, induced by intramuscular injection of testosterone propionate (TP) every other day over a two week period, resulted in a 2.5 to 2.7 time increase in the size of the sebaceous glands of the hamster pinna.
Once-daily treatment with 5% SYC-201G or matching placebo was applied to androgen-stimulated hamsters on one pinna only during the same period as TP injection. Comparison between the treated and untreated sides revealed a significant suppression in the sebaceous gland size (p < 0.05) by 5% SYC-201G; no such effect was observed with placebo. The difference in the suppression rate of the sebaceous gland size between 5% SYC-201G (23%) and matching placebo (-4.7%) was significant (p < 0.01).
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36.) Androgens affect the activity of human sebocytes in culture in a manner dependent on the localization of the sebaceous glands and their effect is antagonized by spironolactone.
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Author
Zouboulis CC; Akamatsu H; Stephanek K; Orfanos CE
Address
Department of Dermatology, University Medical Center Steglitz, Free University of Berlin, FRG.
Source
Skin Pharmacol, 7(1-2):33-40 1994
Abstract
To investigate the varying response of the pilosebaceous unit to androgens functional studies were performed on the effects of testosterone and 5 alpha-dihydrotestosterone on cultured human sebocytes derived from different skin regions. In addition, the effect of spironolactone on the proliferation of androgen-stimulated human sebocytes derived from facial skin was evaluated.
Testosterone (10(-11) to 10(-5) M), 5 alpha-dihydrotestosterone (10(-11) to 10(-5) M) and spironolactone (10(-12) to 10(-7) M) were added for 10 days as single substances or in combinations to human sebocytes in secondary culture maintained in a serum-free medium.
Cell proliferation was assessed using a fluorometric assay. Intracellular lipids were extracted from sebocytes treated with androgens (10(-7) M) for 10 days after confluency. Testosterone inhibited the proliferation of sebocytes derived from the legs with a 50%-inhibitory concentration at 10(-5) M and induced a 50% decrease of intracellular lipids. In contrast, 5 alpha-dihydrotestosterone stimulated the activity of leg sebocytes with a 50% increase of proliferation at 10(-5) M, and a 175% increase of intracellular lipids.
On the other hand, the proliferation of facial sebocytes was significantly stimulated by testosterone with a 50%-stimulatory concentration at 10(-6) to 10(-5) M and mostly by 5 alpha-dihydrotestosterone with a 50% enhancement at 10(-8) to 10(-7) M. Spironolactone inhibited the proliferation of facial sebocytes in a dose-dependent manner with a 25%-inhibitory concentration at 10(-9) M.
Simultaneous treatment of facial sebocytes with spironolactone and testosterone or 5 alpha-dihydrotestosterone resulted in decreased proliferation when compared to the growth obtained under androgens alone.(ABSTRACT TRUNCATED AT 250 WORDS)
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37.) Antiandrogen treatment with spironolactone and linestrenol decreases bone mineral density in eumenorrhoeic women with androgen excess.
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Author
Pre¨zelj J; Kocijan¨ci¨c A
Address
Medical Centre Ljubljana, Endocrinology, Ljubljana, Slovenia.
Source
Horm Metab Res, 26(1):46-8 1994 Jan
Abstract
Increased bone mineral density (BMD) has been reported in young women with androgen excess. To determine whether antiandrogen treatment in young women with androgen excess reduces BMD in these patients, the authors measured BMD before and a year after the beginning of antiandrogen therapy with spironolactone and linestrenol in 17 consecutive androgenized patients (median age 22 years). After a year's treatment BMD declined in 15 out of 17 patients, the mean decrease--0.032 g/cm2 (95% CI of the difference 0.016-0.048)--being highly significant (p < 0.001). Androstenedione decrease was the only hormonal variable significantly correlating with BMD decrease (r = 0.5; p = 0.037) according to simple linear regression. A decrease of BMD might become a key factor in deciding about the duration of antiandrogen treatment with spironolactone in functional hyperandrogenemia.
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38.) [Serum hormones before and during therapy with cyproterone acetate and spironolactone in patients with androgenization]
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Author
Grunwald K; Rabe T; Schlereth G; Runnebaum B
Address
Abt. f¨ur gyn¨akologische Endokrinologie und Fortpflanzungsmedizin, Universit¨ats-Frauenklinik Heidelberg.
Source
Geburtshilfe Frauenheilkd, 54(11):634-45 1994 Nov
Abstract
The effect of cyproterone acetate (CPA) and spironolactone (SPL) on the serum androgen concentrations of premenopausal women with symptoms of hyperandrogenism were investigated in a total of 39 women. The observation period was 12 months.
CPA was administered according to the Hammerstein regimen: cyproterone acetate (CPA) [Androcur] 100 mg/die 5.-14. day of the cycle; ethinylestradiol (EE) [Progynon C]: 40 mg/die 5.-25. day of the cycle; Spironolactone (SPL) was given in a dosage of 100 mg/die from day 1.-21. of the cycle. During the therapy with CPA a significant decrease of total testosterone (61%), free testosterone (78%), LH (48%) and 17 alpha-Hydroxyprogesterone (72%) was observed; during the medication with spironolacton only a significant decrease of 5 alpha-dihydrotestosterone (81%), which could not be seen during CPA use, was observed. Serum concentrations of total testosterone, free testosterone, LH and 17 alpha-Hydroxyprogesterone remained unchanged. DHA and DHAS did not change during neither medication.
Since peripheral androgens were not suppressed by SPL the positive therapeutical effect of SPL can be explained by the antiandrogenic effect at the level of the receptor. A disadvantage of spironolacton is the lack of contraceptive efficacy. In cases where contraindication for oral contraceptives are present SPL can be considered as a good alternative to CPA. The suppressive effect of CPA/EE on total testosterone, LH addition to the antivulatory effect makes it the preferable medication for hyperandrogenemic patients with polycystic changes of the ovaries (PCOD).
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39.) The insulin resistance in women with hyperandrogenism is partially reversed by antiandrogen treatment: evidence that androgens impair insulin action in women.
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Author
Moghetti P; Tosi F; Castello R; Magnani CM; Negri C; Brun E; Furlani L; Caputo M; Muggeo M
Address
Division of Endocrinology and Metabolic Diseases, University of Verona, Italy.
Source
J Clin Endocrinol Metab, 81(3):952-60 1996 Mar
Abstract
To assess whether androgen excess per se might impair insulin action, insulin sensitivity was measured by a two-step (20 and 80 mU/m2.min) hyperinsulinemic euglycemic clamp combined with indirect calorimetry and tracer glucose infusion in 43 women (13 obese and 30 nonobese) with normal glucose tolerance and clinical evidence of increased androgen action (hirsutism and/or polycystic ovary syndrome) as well as 12 age- and body mass index-matched healthy controls. Hyperandrogenic women were studied basally and after 3-4 months of antiandrogen treatment with 3 different drugs: spironolactone (n = 23), flutamide (n = 10), or the GnRH agonist buserelin (n = 10). Six women given spironolactone were also reexamined after 1 yr of therapy.
At baseline, insulin-mediated glucose uptake was lower in hyperandrogenic women than in controls (by ANOVA, F = 14.3; P < 0.001). Insulin resistance was observed in both ovarian and nonovarian hyperandrogenism, as distinguished by acute GnRH agonist testing. After antiandrogen therapy, insulin action on glucose metabolism significantly increased for both the patients as a whole (F = 7.4; P < 0.01) and each treatment group separately.
However, insulin action remained lower than in controls and showed no further improvement in patients reevaluated after I yr of treatment. Increases in both oxidative and nonoxidative glucose metabolism accounted for the improvement in substrate disposal induced by antiandrogen drugs. The increase in the effectiveness of insulin was greater in the lean subjects, whereas the change was small and not statistically significant in the obese women. Response to treatment was more pronounced in women with nonovarian hyperandrogenism, particularly at the low insulin infusion rate.
Endogenous glucose production in hyperandrogenic patients was similar to that in healthy women and was unaffected by therapy. In conclusion, antiandrogen treatment partially reversed the peripheral insulin resistance associated with hyperandrogenism regardless of which antiandrogen was used. These data strongly suggest that in women, androgen excess per se contributes to impairment of insulin action.
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40.) Topical spironolactone reduces sebum secretion rates in young adults.
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Author
Yamamoto A; Ito M
Address
Department of Dermatology, Niigata University School of Medicine, Japan.
Source
J Dermatol, 23(4):243-6 1996 Apr
Abstract
The effects of topically applied spironolactone on the sebum secretion rates (SSR) of young adults were investigated. SSR was expressed as the ratio of wax esters/[cholesterol+cholesterol esters] (WE/[C+CE]) and the amount of sebaceous lipids (squalene, triacylglycerol and wax esters). Topical spironolactone 5% gel applied to the right cheeks of the subjects produced a significant reduction in the SSR at 12 weeks (4 weeks after termination of application), but not at 8 weeks (the end of treatment). Untreated "control" areas (the left cheeks of the subjects) showed no significant change during the study. None of the subjects experienced skin rash or signs of local irritation. This results suggests that topical spironolactone may be effective in the treatment of acne patients with high SSR.
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41.) Other antiandrogens.
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Author
Schmidt JB
Address
Department of Dermatology, University of Vienna Medical School, Austria.
Source
Dermatology, 196(1):153-7 1998
Abstract
Various substances of steroidal or nonsteroidal structure may serve as an alternative for the antiandrogenic treatment of acne. Compounds with antiandrogenic properties like cimetidine or ketoconazole are rarely administered for acne due to their weak effects. In contrast, spironolactone is an effective antiandrogen that shows good treatment effects in hirsutism and acne.
Side effects occur frequently and are dose dependent. Isotretinoin--the most effective agent in acne therapy--has been under discussion for additional antiandrogenic properties for years. At present there is additional evidence for the antiandrogenic effects of isotretinoin.
Regarding substances acting on both levels, androgen receptor binding and 5 alpha-reductase inhibition, the question is raised whether the term 'antiandrogen' should be amplified by including the 5 alpha-reductase inhibitors. This would pay tribute to the biological aspect of antiandrogenicity that takes into account not only the mode of action but also the effects of the substance. Under this aspect type 1 5 alpha-reductase inhibitors may gain attention in the future.
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42.) Mechanism of action and pure antiandrogenic properties of flutamide.
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Author
Labrie F
Address
Medical Research Council Group, Le Centre Hospitalier de l'Universite Laval Research Center, Laval University, Qu´ebec City, Canada.
Source
Cancer, 72(12 Suppl):3816-27 1993 Dec 15
Abstract
Although treatment of intact adult male rats with the pure antiandrogen flutamide or a luteinizing hormone-releasing hormone (LHRH) agonist alone leads to partial inhibition of ventral prostate weight, maximal inhibition is achieved by combination of the two drugs. Potentializing effects of the two compounds were observed even on prostatic ornithine decarboxylase activity.
Because LHRH agonists are widely used to achieve medical castration in men treated for prostate cancer, it is of interest to observe that in the dog, known for being the best model for studies of the action of LHRH agonists, flutamide does not interfere with the potent desensitizing action of the LHRH agonist on pituitary LH secretion, thus supporting the combined use of flutamide with an LHRH agonist for maximal androgen blockade without loss of efficiency of the LHRH agonist.
Because prostate cancer is known to show a high degree of heterogeneity of its sensitivity to androgens, we analyzed the effect of combined antiandrogen therapy on parameters more sensitive to androgens than ventral prostatic weight itself. In agreement with its pure antiandrogenic characteristics, flutamide alone has no stimulatory effect on the intraprostatic level of mRNA encoding the C1 or C3 component of prostatic binding protein (PBP), whereas cyproterone acetate (CPA), megestrol acetate (MEG), and, especially, medroxyprogesterone acetate (MPA) markedly stimulate PBP-C1 and PBP-C3 mRNA levels, an effect reversed by flutamide, thus further supporting the intrinsic androgenic activity of all these steroidal derivatives.
Similar androgenic effects of the steroidal derivatives were observed on prostatic ornithine decarboxylase activity. Androgen-sensitive Shionogi tumor cells were then used to assess the antiandrogenic/androgenic properties of flutamide and the above-indicated steroidal derivatives. MPA, MEG, CPA as well as spironolactone-stimulated cell proliferation under both in vivo and in vitro conditions, thus illustrating the intrinsic androgenic activity of all these compounds. Flutamide was inactive by itself and reversed the stimulatory effect of all other compounds, thus indicating its pure antiandrogenic activity.
Although castration reduces intraprostatic dihydrotestosterone (DHT) to undetectable levels in the rat and guinea pig, the concentration remains at about 50% of the value found in intact men after castration, thus indicating an important contribution of the adrenals to DHT in the human prostate, a finding that requires the addition of an antiandrogen to block the action of this important amount of DHT remaining after castration.
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43.) Drospirenone: a novel progestogen with antimineralocorticoid and antiandrogenic activity.
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Author
Muhn P; Fuhrmann U; Fritzemeier KH; Krattenmacher R; Schillinger E
Address
Research Laboratories, Berlin, Germany.
Source
Ann N Y Acad Sci, 761():311-35 1995 Jun 12
Abstract
Drospirenone (ZK 30595; 6 beta, 7 beta, 15 beta, 16 beta-dimethylen-3-oxo-17 alpha-pregn-4-ene-21, 17-carbolactone) is a novel progestogen under clinical development. Drospirenone is characterized by an innovative pharmacodynamic profile which is very closely related to that of progesterone. Potential applications include oral contraception, hormone replacement therapy and treatment of hormonal disorders.
The pharmacological properties of drospirenone were investigated in vitro by receptor binding and transactivation experiments and in vivo in appropriate animal models. In qualitative agreement with progesterone, the compound binds strongly to the progesterone and the mineralocorticoid receptor and with lower affinity to androgen and glucocorticoid receptors.
There is no detectable binding to the estrogen receptor. Steroid hormone agonistic and antagonistic activities of progesterone and drospirenone were compared in transactivation experiments. Individual steroid hormone receptors were artificially expressed together with a reporter gene in appropriate cell lines. Both hormones were unable to induce any androgen receptor-mediated agonistic activity. Rather, both progesterone and drospirenone distinctly antagonized androgen-stimulated transcriptional activation. Likewise, both compounds only very weakly activated the mineralocorticoid receptor but showed potent aldosterone antagonistic activity.
Drospirenone did not induce glucocorticoid receptor-driven transactivation. Progesterone was a weak agonist in this respect. Drospirenone exerts potent progestogenic and antigonadotropic activity which was studied in various animal species. It efficiently promotes the maintenance of pregnancy in ovariectomized rats, inhibits ovulation in rats and mice and stimulates endometrial transformation in the rabbit.
Furthermore, drospirenone shows potent antigonadotropic, i.e., testosterone-lowering activity in male cynomolgus monkeys. The progestogenic potency of drospirenone was found to be in the range of that of norethisterone acetate. The majority of clinically used progestogens are androgenic.
Drospirenone, like progesterone, has no androgenic but rather an antiandrogenic effect. This property was demonstrated in castrated, testosterone propionate substituted male rats by a dose-dependent inhibition of accessory sex organ growth (seminal vesicles, prostate). In this model, the potency of drospirenone was about a third that of cyproterone acetate. Drospirenone, like progesterone, shows antimineralocorticoid activity, which causes moderately increased sodium and water excretion. This is an outstanding characteristic which has not been described for any other synthetic progestogen before.
Drospirenone is eight to ten times more effective in this respect than spironolactone. The natriuretic effect was demonstrable for at least three weeks upon daily treatment of rats with a dose of 10 mg/animal. Drospirenone is devoid of any estrogenic, glucocorticoid or antiglucocorticoid activity. In summary, drospirenone, like progesterone, combines potent progestogenic with antimineralocorticoid and antiandrogenic activity in a similar dose range.
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44.) Cutaneous Manifestations of Polycystic Ovary Syndrome: A Cross-Sectional Clinical Study.
=================================================
Indian Dermatol Online J. 2017 Mar-Apr;8(2):104-110. doi: 10.4103/2229-5178.202275.
Keen MA1, Shah IH1, Sheikh G1.
Author information
1
Department of Dermatology, STD and Leprosy, GMC Srinagar and associated SMHS Hospital, Srinagar, Jammu and Kashmir, India.
Abstract
BACKGROUND:
Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women, affecting 5-10% of reproductive-aged women. The dermatologic manifestations of hyperandrogenism, chiefly hirsutism, acne vulgaris, androgenic alopecia, and acanthosis nigricans, are among the cardinal manifestations of PCOS.
AIM:
To study the incidence and prevalence of various cutaneous manifestations in patients with PCOS and to correlate these skin manifestations with hormonal changes.
SETTINGS AND DESIGN:
This study was conducted at a dermatology centre over a period of 1 year from November 2012 to 2013.
MATERIALS AND METHODS:
The present study included 100 women diagnosed to have PCOS. Hormonal analysis as well as radiological assessment was done in all the cases. Cutaneous manifestations were ascertained and inferences were drawn.
STATISTICAL ANALYSIS:
Statistical analysis was carried out by the Chi-square test and independent samples t-test. Statistical significance was determined at a level of P < 0.05.
RESULTS:
In our study, the prevalence of hirsutism, acne, female pattern hair loss, acanthosis nigricans, seborrhea, striae and acrochordons was 78%, 48%, 31%, 30%, 29%, 13%, and 9%, respectively.
CONCLUSION:
Dermatologic manifestations of PCOS play a significant role in making the diagnosis and constitute a substantial portion of the symptoms experienced by women with this syndrome.
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45.) A Retrospective Review of Treatment Results for Patients With Central Centrifugal Cicatrical Alopecia.
==================================================
J Drugs Dermatol. 2017 Apr 1;16(4):317-320.
Eginli A, Dothard E, Bagayoko CW, Huang K, Daniel A, McMichael AJ.
Abstract
INTRODUCTION: Central centrifugal cicatricial alopecia (CCCA) is a form of scarring alopecia primarily affecting women of African descent on the crown of the scalp. Limited data exists regarding evidence-based treatment for CCCA.</p> <p>OBJECTIVE: To examine photos of subjects with CCCA before and after treatment in order to evaluate results of treatment and compare results of different treatment regimens.</p> <p>METHODS: Photographs of 15 subjects with CCCA before and after treatment were evaluated by two blinded investigators who assigned disease severity scores to photographs based on a published scale: Central Scalp Alopecia Photographic Scale in African American Women.</p> <p>RESUTLS: Median change in severity score (post-treatment severity score - pre-treatment severity score) was 0.5 (P = 0.58) for all 15 subjects receiving a series of 7 to 8 intralesional steroid injections along with topical steroids (Class I/II) +/- minoxidil and +/- anti-dandruff shampoo, indicating worsening of disease after treatment. Subjects receiving minoxidil versus those who did not (0.25 vs 0.5; P = 0.38) and subjects receiving anti-dandruff shampoo versus those who did not (0.0 vs 0.5; P = 0.42) demonstrated no statistically significant difference in pre- and post-treatment severity scores. Of 15 subjects, 5/15 (33.3%) had decreased severity scores, 8/15 (53.3%) had increased severity scores, and 2/15 (13.3%) had no change in severity scores.</p> <p>CONCLUSIONS: Although no statistically significant difference was found in pre- versus post-treatment disease severity, this may indicate intralesional steroid injections and topical steroids +/- minoxidil and +/- anti-dandruff shampoo halt disease progression.
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46.) The effectiveness of treatments for androgenetic alopecia: A systematic review and meta-analysis.
=======================================
J Am Acad Dermatol. 2017 Apr 7. pii: S0190-9622(17)30306-7. doi: 10.1016/j.jaad.2017.02.054. [Epub ahead of print]
Adil A1, Godwin M2.
Author information
1
Memorial University of Newfoundland, St. John's, Newfoundland.
2
Memorial University of Newfoundland, St. John's, Newfoundland. Electronic address: godwinm@mun.ca.
Abstract
BACKGROUND:
Androgenetic alopecia, or male pattern hair loss, is a hair loss disorder mediated by dihydrotestosterone, the potent form of testosterone. Currently, minoxidil and finasteride are Food and Drug Administration (FDA)-approved, and HairMax LaserComb, which is FDA-cleared, are the only treatments recognized by the FDA as treatments of androgenetic alopecia.
OBJECTIVE:
This systematic review and meta-analysis assesses the efficacy of nonsurgical treatments of androgenetic alopecia in comparison to placebo for improving hair density, thickness, growth (defined by an increased anagen:telogen ratio), or subjective global assessments done by patients and investigators.
METHODS:
A systematic review of randomized controlled trials was conducted. PubMed, Embase, and Cochrane were searched up to December 2016, with no lower limit on the year. We included only randomized controlled trials of good or fair quality based on the US Preventive Services Task Force quality assessment process.
RESULTS:
A meta-analysis was conducted separately for 5 groups of studies that tested the following hair loss treatments: low-level laser light therapy in men, 5% minoxidil in men, 2% minoxidil in men, 1 mg finasteride in men, and 2% minoxidil in women. All treatments were superior to placebo (P < .00001) in the 5 meta-analyses. Other treatments were not included because the appropriate data were lacking.
LIMITATIONS:
High heterogeneity in most studies.
CONCLUSIONS:
This meta-analysis strongly suggests that minoxidil, finasteride, and low-level laser light therapy are effective for promoting hair growth in men with androgenetic alopecia and that minoxidil is effective in women with androgenetic alopecia.
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47.) Dutasteride in androgenetic alopecia: An update.
========================================
Curr Clin Pharmacol. 2017 Mar 10. doi: 10.2174/1574884712666170310111125. [Epub ahead of print]
Arif T1, Dorjay K1, Adil M1, Sami M1.
Author information
1
Department of Dermatology, STDs and Leprosy, Jawaharlal Nehru Medical College (JNMC), Aligarh Muslim University (AMU), Aligarh, India.
Abstract
BACKGROUND:
Androgenetic alopecia is a common condition characterized by thinning of scalp hair. Conversion of testosterone to dihydrotestosterone, a more potent androgen, by the enzyme 5-a-reductase is responsible for underlying pathogenesis. Dutasteride, a synthetic 4-azasteroid, is a selective and competitive inhibitor of both type-1 and type-2 isoenzymes of 5-alpha-reductase. Finasteride and minoxidil are the only approved drugs for androgenetic alopecia. Dutasteride has been demonstrated to be effective in several randomized, double-blind, placebo controlled trials in androgenetic alopecia. In this review, after the pharmacology of dutasteride, the authors have discussed the status of dutasteride in androgenetic alopecia and has compared its efficacy with that of finasteride.
OBJECTIVE:
This article aims to review the current status of dutasteride in androgenetic alopecia. The structure, mechanism of action, pharmacokinetic and side effects are discussed along with its comparission with finasteride in androgenetic alopecia.
METHODS:
The main source of our information was Medline Pubmed, Google scholar and Scopus including original articles and review articles. The keywords dutasteride, dutasteride in androgenetic alopecia were used for search.
CONCLUSION:
Like finasteride, dutasteride is now becoming popular treatment option in AGA, due to its good response shown by various randomized control studies and meta-analysis. Also, in most of these studies dutasteride found to be better than finasteride with comparable adverse effect. Therefore, dutasteride could become a treatment of choice for AGA in near future.
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48.) A randomized, active- and placebo-controlled study of the efficacy and safety of different doses of dutasteride versus placebo and finasteride in the treatment of male subjects with androgenetic alopecia.
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J Am Acad Dermatol. 2014 Mar;70(3):489-498.e3. doi: 10.1016/j.jaad.2013.10.049. Epub 2014 Jan 9.
Gubelin Harcha W1, Barboza Martínez J2, Tsai TF3, Katsuoka K4, Kawashima M5, Tsuboi R6, Barnes A7, Ferron-Brady G8, Chetty D9.
Author information
1
Centro Médico Skinmed and Universidad de los Andes, Santiago, Chile. Electronic address: wgubelin@skinmed.cl.
2
Unidad de Investigación, Clínica Internacional, Lima, Peru.
3
Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
4
Department of Dermatology, Kitasato University, Tokyo, Japan.
5
Department of Dermatology, Tokyo Women's Medical University, Tokyo, Japan.
6
Department of Dermatology, Tokyo Medical University, Tokyo, Japan.
7
GlaxoSmithKline Research & Development, Research Triangle Park, North Carolina.
8
GlaxoSmithKline Research & Development, King of Prussia, Pennsylvania.
9
GlaxoSmithKline Research & Development, Singapore.
Abstract
BACKGROUND:
Dihydrotestosterone is the main androgen causative of androgenetic alopecia, a psychologically and physically harmful condition warranting medical treatment.
OBJECTIVE:
We sought to compare the efficacy and safety of dutasteride (type 1 and 2 5-alpha reductase inhibitor) with finasteride (type 2 5-alpha reductase inhibitor) and placebo in men with androgenetic alopecia.
METHODS:
Men aged 20 to 50 years with androgenetic alopecia were randomized to receive dutasteride (0.02, 0.1, or 0.5 mg/d), finasteride (1 mg/d), or placebo for 24 weeks. The primary end point was hair count (2.54-cm diameter) at week 24. Other assessments included hair count (1.13-cm diameter) and width, photographic assessments (investigators and panel), change in stage, and health outcomes.
RESULTS:
In total, 917 men were randomized. Hair count and width increased dose dependently with dutasteride. Dutasteride 0.5 mg significantly increased hair count and width in a 2.54-cm diameter and improved hair growth (frontal view; panel photographic assessment) at week 24 compared with finasteride (P = .003, P = .004, and P = .002, respectively) and placebo (all P < .001). The number and severity of adverse events were similar among treatment groups.
LIMITATIONS:
The study was limited to 24 weeks.
CONCLUSIONS:
Dutasteride increased hair growth and restoration in men with androgenetic alopecia and was relatively well tolerated.
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49.) New Treatments for Hair Loss.
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Actas Dermosifiliogr. 2017 Apr;108(3):221-228. doi: 10.1016/j.ad.2016.11.010. Epub 2017 Jan 3.
[Article in English, Spanish]
Vañó-Galván S1, Camacho F2.
Author information
1
Servicio de Dermatología, Unidad de Tricología, Hospital Universitario Ramón y Cajal, IRYCIS, Universidad de Alcalá, Madrid, España. Electronic address: drsergiovano@gmail.com.
2
Hospital Virgen Macarena, Sevilla, España.
Abstract
The treatment of hair loss is an important part of clinical dermatology given the prevalence of the problem and great impact on patients' quality of life. Many new treatments have been introduced in recent years. This review summarizes the main ones in 4 groups: a) For androgenetic alopecia, we discuss new excipients for oral minoxidil, dutasteride, and finasteride as well as new forms of topical application; prostaglandin agonists and antagonists; low-level laser therapy; and regenerative medicine with Wnt signaling activators and stem cell therapy. b) For alopecia areata, Janus kinase inhibitors are reviewed. c) For frontal fibrosing alopecia, we discuss the use of antiandrogens and, for some patients, pioglitazone. d) Finally, we mention new robotic devices for hair transplant procedures and techniques for optimal follicular unit extraction.
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50.) Efficacy and safety of 5% minoxidil topical foam in male pattern hair loss treatment and patient satisfaction.
========================================
Acta Dermatovenerol Alp Pannonica Adriat. 2016 Sep;25(3):41-44.
Hasanzadeh H1, Nasrollahi SA1, Halavati N2, Saberi M3, Firooz A1,2.
Author information
1
Pharmaceutical, Cosmeceutical, and Hygienic Skin Products Clinical Evaluation Lab (DermaLab), Center for Research & Training in Skin Diseases & Leprosy (CRTSDL), Tehran University of Medical Sciences (TUMS), Tehran, Iran.
2
Clinical Trial Center (CTC), Tehran University of Medical Sciences (TUMS), Tehran, Iran.
3
Community-Based Participatory Research Center, Iranian Institute for Reduction of High-Risk Behaviors, Tehran University of Medical Sciences (TUMS), Tehran, Iran.
Abstract
INTRODUCTION:
Male pattern hair loss is widespread around the world. Its prevalence indicates the importance of finding the best treatment modalities. This study evaluates the efficacy and safety of minoxidil 5% topical foam in male pattern hair loss treatment and patient satisfaction.
METHODS:
This study was a before-and-after trial on 17 male patients with male pattern hair loss. Subjects were instructed to apply one capful (1 ml) of minoxidil 5% topical foam on the scalp daily for 6 months. Efficacy was assessed through hair counts, subject assessment, and global photographic review.
RESULTS:
Seventeen male volunteers were recruited, and three volunteers were withdrawn; 14 participated in the trial for 16 weeks, and 12 continued up to 24 weeks. The average hair count with a camera at week 16 (181.87 ± 52.42) and week 24 (194.58 ± 62.82) and with an eye count at week 16 (62.57 ± 15.28) and week 24 (69.91 ± 15.61) increased significantly compared to the baseline after intervention.
CONCLUSIONS:
This study confirmed that minoxidil 5% topical foam is a safe and effective treatment for MPHL. The effect of it is evident after 24 weeks of use.
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51.) Post-Finasteride Adverse Effects in Male Androgenic Alopecia: A Case Report of Vitiligo.
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Skin Pharmacol Physiol. 2017;30(1):42-45. doi: 10.1159/000455972. Epub 2017 Feb 22.
Motofei IG1, Rowland DL, Georgescu SR, Tampa M, Paunica S, Constantin VD, Balalau C, Manea M, Baleanu BC, Sinescu I.
Author information
1
Department of Surgery/Dermatology, Carol Davila University, Bucharest, Romania.
Abstract
Finasteride has proved to be relatively safe and effective in the therapeutic management of male androgenic alopecia. However, literature data report several endocrine imbalances inducing various adverse effects, which often persist after treatment cessation in the form of post-finasteride syndrome. Here we present the case of a 52-year-old man receiving finasteride (1 mg/day) who developed an uncommon adverse effect represented by generalized vitiligo 2 months after finasteride discontinuation. Associated adverse effects encountered were represented by mild sexual dysfunction (as determined by the International Index of Erectile Function, IIEF) and moderate depressive symptoms (according to DSM-V criteria), all of these manifestations aggregating within/as a possible post-finasteride syndrome. Further studies should develop and compare several therapeutic approaches, taking into account not only compounds that decrease the circulating dihydrotestosterone level but also those that could block the dihydrotestosterone receptors (if possible, compounds with selective tropism towards the skin). In addition, the possibility of predicting adverse effects of finasteride (according to hand preference and sexual orientation) should be taken into account.
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52.) Adverse Effects and Safety of 5-alpha Reductase Inhibitors (Finasteride, Dutasteride): A Systematic Review.
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J Clin Aesthet Dermatol. 2016 Jul;9(7):56-62. Epub 2016 Jul 1.
Hirshburg JM1, Kelsey PA2, Therrien CA2, Gavino AC1, Reichenberg JS1.
Author information
1
Dell Medical School, University of Texas at Austin, Austin, Texas;
2
University of Texas Medical Branch, Galveston, Texa.
Abstract
Finasteride and dutasteride, both 5-alpha reductase inhibitors, are considered first-line treatment for androgenetic hair loss in men and used increasingly in women. In each case, patients are expected to take the medications indefinitely despite the lack of research regarding long-term adverse effects. Concerns regarding the adverse effects of these medications has led the United States National Institutes of Health to add a link for post-finasteride syndrome to its Genetic and Rare Disease Information Center. Herein, the authors report the results of a literature search reviewing adverse events of 5-alpha reductase inhibitors as they relate to prostate cancer, psychological effects, sexual health, and use in women. Several large studies found no increase in incidence of prostate cancer, a possible increase of high-grade cancer when detected, and no change in survival rate with 5-alpha reductase inhibitor use. Currently, there is no direct link between 5-alpha reductase inhibitor use and depression; however, several small studies have led to depression being listed as a side effect on the medication packaging. Sexual effects including erectile dysfunction and decreased libido and ejaculate were reported in as many as 3.4 to 15.8 percent of men. To date, there are very few studies evaluating 5-alpha reductase inhibitor use in women. Risks include birth defects in male fetuses if used in pregnancy, decreased libido, headache, gastrointestinal discomfort, and isolated reports of changes in menstruation, acne, and dizziness. Overall, 5-alpha reductase inhibitors were well-tolerated in both men and women, but not without risk, highlighting the importance of patient education prior to treatment.
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53.) Atypical post-finasteride syndrome: A pharmacological riddle.
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Indian J Pharmacol. 2016 May-Jun;48(3):316-7. doi: 10.4103/0253-7613.182898.
Gupta AK1, Sharma N1, Shukla P1.
Author information
1
Department of Pharmacology, Government Medical College, Patiala, Punjab, India.
Abstract
Finasteride and dutasteride are commonly used 5-alpha reductase inhibitors. While finasteride is a selective inhibitor of 5-alpha reductase Type II, dutasteride inhibits 5- alpha reductase Type I and II. The United States Food and Drug Administration approved the use of finasteride for benign prostatic hypertrophy (BPH) as well as androgenic alopecia (AGA) while dutasteride is approved only for BPH. Off-label use of dutasteride is not uncommon in AGA as well. Although the postfinasteride syndrome (PFS) is a well-established entity, its symptomatology is quite variable. Here, we describe a case of an atypical PFS in a patient treated with dutasteride and finasteride for AGA. The multisystem involvement and irreversible nature of this case warrant its reporting.
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54.) Emotional Consequences of Finasteride: Fool's Gold.
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Am J Mens Health. 2016 Feb 11. pii: 1557988316631624. [Epub ahead of print]
Ganzer CA1, Jacobs AR2.
Información del autor
1
Hunter-Bellevue School of Nursing, New York, NY, USA cganzer@hunter.cuny.edu.
2
Hunter-Bellevue School of Nursing, New York, NY, USA.
Abstract
Androgenetic alopecia, the gradual, progressive loss of hair frequently results in psychological despair, in part related to changes in self-image. Current androgenetic alopecia treatments are limited to hair transplantation and medications that inhibit dihydrotestosterone, a potent androgen associated with follicular micronization. Users of finasteride, which prevents dihydrotestosterone production, report serious physical and emotional adverse effects, collectively known as post-finasteride syndrome. Psychiatric illnesses and personality traits, specifically neuroticism influence emotional well-being. Limited research exists exploring the psychological corollaries of post-finasteride syndrome and preexisting Axis I and Axis II mental health conditions. The aim of this study was to explore how having a preexisting personal and/or familial history of a psychiatric diagnosis and certain personality traits may influence anxiety and depression among finasteride users. Participants in this online survey completed the Beck Depression Inventory, the Beck Anxiety Inventory, and Ten-Item Personality Inventory. An important finding in this study was that almost 57% (n = 97) of men reported a psychiatric diagnosis and 28% (n = 27) had a first-degree relative with a mental health disorder, of this group 17 only had a family history. Nearly 50% of the men surveyed reported clinically significant depression as evidenced by Beck Depression Inventory score and 34% experienced anxiety on the Beck Anxiety Inventory. There were no statistically significant trends in personality traits reported. Results provide evidence on the need to screen for psychiatric history and counseling patients about the potential psychological consequences of finasteride. Prescribing clinicians should carefully weigh the risk/benefit ratio with these patients.
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55.) The importance of dual 5alpha-reductase inhibition in the treatment of male pattern hair loss: results of a randomized placebo-controlled study of dutasteride versus finasteride.
========================================
J Am Acad Dermatol. 2006 Dec;55(6):1014-23.
Olsen EA1, Hordinsky M, Whiting D, Stough D, Hobbs S, Ellis ML, Wilson T, Rittmaster RS; Dutasteride Alopecia Research Team.
Author information
1
Duke University Medical Center, Durham, North Carolina, USA. olsen001@mc.duke.edu
Abstract
BACKGROUND:
Male pattern hair loss (MPHL) is a potentially reversible condition in which dihydrotestosterone is an important etiologic factor.
OBJECTIVE:
Our aim was to evaluate the efficacy of the type 1 and 2 5alpha-reductase inhibitor dutasteride in men with MPHL.
METHODS:
Four hundred sixteen men, 21 to 45 years old, were randomized to receive dutasteride 0.05, 0.1, 0.5 or 2.5 mg, finasteride 5 mg, or placebo daily for 24 weeks.
RESULTS:
Dutasteride increased target area hair count versus placebo in a dose-dependent fashion and dutasteride 2.5 mg was superior to finasteride at 12 and 24 weeks. Expert panel photographic review and investigator assessment of hair growth confirmed these results. Scalp and serum dihydrotestosterone levels decreased, and testosterone levels increased, in a dose-dependent fashion with dutasteride.
LIMITATIONS:
The study was limited to 24 weeks.
CONCLUSION:
Dutasteride increases scalp hair growth in men with MPHL. Type 1 and type 2 5alpha-reductase may be important in the pathogenesis and treatment of MPHL.
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56.) Interventions for female pattern hair loss.
=======================================
Cochrane Database Syst Rev. 2016 May 26;(5):CD007628. doi: 10.1002/14651858.CD007628.pub4.
van Zuuren EJ1, Fedorowicz Z, Schoones J.
Author information
1
Department of Dermatology, Leiden University Medical Center, PO Box 9600, B1-Q, Leiden, Netherlands, 2300 RC.
Abstract
BACKGROUND:
Female pattern hair loss (FPHL), or androgenic alopecia, is the most common type of hair loss affecting women. It is characterised by progressive shortening of the duration of the growth phase of the hair with successive hair cycles, and progressive follicular miniaturisation with conversion of terminal to vellus hair follicles (terminal hairs are thicker and longer, while vellus hairs are soft, fine, and short). The frontal hair line may or may not be preserved. Hair loss can have a serious psychological impact on women.
OBJECTIVES:
To determine the efficacy and safety of the available options for the treatment of female pattern hair loss in women.
SEARCH METHODS:
We updated our searches of the following databases to July 2015: the Cochrane Skin Group Specialised Register, CENTRAL in the Cochrane Library (2015, Issue 6), MEDLINE (from 1946), EMBASE (from 1974), PsycINFO (from 1872), AMED (from 1985), LILACS (from 1982), PubMed (from 1947), and Web of Science (from 1945). We also searched five trial registries and checked the reference lists of included and excluded studies.
SELECTION CRITERIA:
We included randomised controlled trials that assessed the efficacy of interventions for FPHL in women.
DATA COLLECTION AND ANALYSIS:
Two review authors independently assessed trial quality, extracted data and carried out analyses.
MAIN RESULTS:
We included 47 trials, with 5290 participants, of which 25 trials were new to this update. Only five trials were at 'low risk of bias', 26 were at 'unclear risk', and 16 were at 'high risk of bias'.The included trials evaluated a wide range of interventions, and 17 studies evaluated minoxidil. Pooled data from six studies indicated that a greater proportion of participants (157/593) treated with minoxidil (2% and one study with 1%) reported a moderate to marked increase in their hair regrowth when compared with placebo (77/555) (risk ratio (RR) = 1.93, 95% confidence interval (CI) 1.51 to 2.47; moderate quality evidence). These results were confirmed by the investigator-rated assessments in seven studies with 1181 participants (RR 2.35, 95% CI 1.68 to 3.28; moderate quality evidence). Only one study reported on quality of life (QoL) (260 participants), albeit inadequately (low quality evidence). There was an important increase of 13.18 in total hair count per cm² in the minoxidil group compared to the placebo group (95% CI 10.92 to 15.44; low quality evidence) in eight studies (1242 participants). There were 40/407 adverse events in the twice daily minoxidil 2% group versus 28/320 in the placebo group (RR 1.24, 95% CI 0.82 to 1.87; low quality evidence). There was also no statistically significant difference in adverse events between any of the individual concentrations against placebo.Four studies (1006 participants) evaluated minoxidil 2% versus 5%. In one study, 25/57 participants in the minoxidil 2% group experienced moderate to greatly increased hair regrowth versus 22/56 in the 5% group (RR 1.12, 95% CI 0.72 to 1.73). In another study, 209 participants experienced no difference based on a visual analogue scale (P = 0.062; low quality evidence). The assessments of the investigators based on three studies (586 participants) were in agreement with these findings (moderate quality evidence). One study assessed QoL (209 participants) and reported limited data (low quality evidence). Four trials (1006 participants) did not show a difference in number of adverse events between the two concentrations (RR 1.02, 95% CI 0.91 to 1.20; low quality evidence). Both concentrations did not show a difference in increase in total hair count at end of study in three trials with 631 participants (mean difference (MD) -2.12, 95% CI -5.47 to 1.23; low quality evidence).Three studies investigated finasteride 1 mg compared to placebo. In the finasteride group 30/67 participants experienced improvement compared to 33/70 in the placebo group (RR 0.95, 95% CI 0.66 to 1.37; low quality evidence). This was consistent with the investigators' assessments (RR 0.77, 95% CI 0.31 to 1.90; low quality evidence). QoL was not assessed. Only one study addressed adverse events (137 participants) (RR 1.03, 95% CI 0.45 to 2.34; low quality evidence). In two studies (219 participants) there was no clinically meaningful difference in change of hair count, whilst one study (12 participants) favoured finasteride (low quality evidence).Two studies (141 participants) evaluated low-level laser comb therapy compared to a sham device. According to the participants, the low-level laser comb was not more effective than the sham device (RR 1.54, 95% CI 0.96 to 2.49; and RR 1.18, 95% CI 0.74 to 1.89; moderate quality evidence). However, there was a difference in favour of low-level laser comb for change from baseline in hair count (MD 17.40, 95% CI 9.74 to 25.06; and MD 17.60, 95% CI 11.97 to 23.23; low quality evidence). These studies did not assess QoL and did not report adverse events per treatment arm and only in a generic way (low quality evidence). Low-level laser therapy against sham comparisons in two separate studies also showed an increase in total hair count but with limited further data.Single studies addressed the other comparisons and provided limited evidence of either the efficacy or safety of these interventions, or were unlikely to be examined in future trials.
AUTHORS' CONCLUSIONS:
Although there was a predominance of included studies at unclear to high risk of bias, there was evidence to support the efficacy and safety of topical minoxidil in the treatment of FPHL (mainly moderate to low quality evidence). Furthermore, there was no difference in effect between the minoxidil 2% and 5% with the quality of evidence rated moderate to low for most outcomes. Finasteride was no more effective than placebo (low quality evidence). There were inconsistent results in the studies that evaluated laser devices (moderate to low quality evidence), but there was an improvement in total hair count measured from baseline.Further randomised controlled trials of other widely-used treatments, such as spironolactone, finasteride (different dosages), dutasteride, cyproterone acetate, and laser-based therapy are needed.
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57.) Antiandrogenic Therapy with Ciproterone Acetate in Female Patients Who Suffer from Both Androgenetic Alopecia and Acne Vulgaris.
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Clujul Med. 2014;87(4):226-34. doi: 10.15386/cjmed-386. Epub 2014 Nov 12.
Coneac A1, Muresan A2, Orasan MS3.
Author information
1
Department of Histology, Morphological Sciences Division, Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
2
Department of Physiology, Physiological Sciences Division, Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
3
Department of Pathophysiology, Physiological Sciences Division, Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
Abstract
BACKGROUND:
Androgenetic Alopecia in Women (AGA) occurs due to an underlying susceptibility of hair follicles to androgenic miniaturization, caused by androgens. Clinically, AGA is characterized by progressive hair loss, with a marked hair thinning in the fronto-parietal area so that the scalp can be easily seen. Acne vulgaris is androgen-dependent and often affects the skin that has an increased number of oil glands: face, back and chest. Although the sebaceous glands are present on the scalp too, it is very rare to get acne at this site, as the hair acts as a wig and allows the sebum to drain and does not block the pores. Both AGA and Acne Vulgaris are signs of hyperandrogenism. Cyproterone acetate/ethinyl estradiol (2mg/0.035mg) products are authorized for the treatment of androgenetic symptoms in women, such as acne, seborrhea, mild forms of hirsutism and androgenetic alopecia. Our study had a double purpose: - To evaluate the result of the study regimen Melleva 35 (one pill per day, for 3 consecutive months) in patients with moderate to severe acne, suffering also from Androgenetic Alopecia;- To establish the efficacy of the drug on acne and alopecia improvement, both from the doctor's and patient's point of view.
PATIENTS AND METHODS:
After being informed of the aims and procedures of the study, participants provided a written informed consent. A number of 35 female subjects with moderate to severe acne vulgaris remained in the study. The subjects had also been diagnosed as suffering from AGA, on the basis of clinical criteria, including the pattern of hair loss and trichoscopy assessment.
RESULTS:
83% of study subjects reported that their hair did not continue to fall after 3 months of antiandrogen therapy. The females were evaluated using trichoscopy and the doctor noticed hair regrowth in 77% of the cases. Regarding the improvement of acne lesions after the treatment, 40% of study subjects recorded good improvement and 26% recorded excellent results with Melleva 35. The acceptance of the treatment was very high, 86% patients were compliant with the study therapy. The rate of adverse events (5 cases) was within the limits of the treatment tested by the study. Almost a third of the total number of subjects (28.5%) reached a good satisfaction level after the treatment, while 37.1% claimed moderate satisfaction.
CONCLUSION:
There was no correlation between the age of the subjects and the treatment for acne therefore our first hypothesis was rejected. As a conclusion, antiandrogenic therapy with Melleva 35, 1 pill per day, for 3 consecutive months, shows good results for patients who suffer from both Androgenetic Alopecia and Acne Vulgaris.
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58.) Treatment of female pattern hair loss.
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Skinmed. 2012 Jul-Aug;10(4):218-27.
Hassani M1, Gorouhi F, Babakoohi S, Moghadam-Kia S, Firooz A.
Author information
1
Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Abstract
Female pattern hair loss (FPHL) as a distinctive entity was first described about 30 years ago. The objective of this study was to perform a systematic review of all randomized controlled trials for treatment of FPHL. A preliminary search was carried out in several databases up to August 2008 to identify all randomized controlled trials on nonsurgical interventions for treatment of FPHL. Studies reporting fewer than 10 patients and non-English articles were excluded. Additionally, references of relevant articles and reviews were checked manually in search for additional sources. Among 238 citations found in the preliminary search, 12 fulfilled all criteria to be included in the systematic review. Topical minoxidil 1% to 5% for 24 to 48 weeks was shown to be effective in FPHL and its effect was not related to age or androgen level of patients. In addition, it may be effective in women with FPHL, both with and without hyperandrogenism, and in young and old premenopausal or postmenopausal. In patients with increased serum androgens, oral flutamide but not finasteride or cyproterone acetate was more effective than no treatment. Topical minoxidil is effective in patients with FPHL, with or without hyperandrogenism, but there is limited evidence for the efficacy of antiandrogens.
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59.) [Spironolactone in dermatological treatment. On and off label indications].
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[Article in German]
Salavastru CM1, Fritz K, Tiplica GS.
Author information
1
2nd Clinic of Dermatology, "Colentina" Clinical Hospital, Bucharest, Romania, galati1968@yahoo.com.
Abstract
There are no currently FDA/EMEA-approved dermatologic indications for spironolactone and its off-label uses are, among others, female acne, female pattern hair loss, hidradenitis suppurativa or hirsutism. The rationale behind these relays on the mechanism of action of spironolactone which interferes with the hormone-controlled sebum and sweat gland secretion and with androgen stimulated hair growth. The average dose used by the dermatologits is 50-100 mg daily. It should not be used in pregnant and lactating women and it is not used in men due to the risk of feminization. Although further studies to assess its efficacy and safety are necessary, currently spironolactone is regarded as a useful tool in the dermatologic treatment armamentarium.
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60.) Treatment of male androgenetic alopecia with topical products containing Serenoa repens extract.
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Wessagowit V1, Tangjaturonrusamee C2, Kootiratrakarn T1, Bunnag T1, Pimonrat T3, Muangdang N3, Pichai P3.
Author information
1
Molecular Genetics Unit, Institute of Dermatology, Bangkok, Thailand.
2
Hair & Nail Unit, Institute of Dermatology, Bangkok, Thailand.
3
Research Unit, Institute of Dermatology, Bangkok, Thailand.
Abstract
BACKGROUND/OBJECTIVES:
Male androgenetic alopecia (AGA) is a common hair problem. Serenoa repens extract has been shown to inhibit both types of 5-α reductase and, when taken orally, has been shown to increase hair growth in AGA patients. The aim of this study was to assess the efficacy of topical products containing S. repens extract for the treatment of male AGA.
METHODS:
This was a pilot, prospective, open, within-subject comparison limited to 24 weeks using no placebo controls. In all, 50 male volunteers aged between 20 and 50 years received topical S. repens products for 24 weeks. The primary end-point was a hair count in an area of 2.54 cm(2) at week 24. Secondary end-points included hair restoration, investigators' photographic assessment, patients' evaluation and discovering adverse events.
RESULTS:
The average hair count and terminal hair count increased at weeks 12 and 24 compared to baseline. Some of these positive results levelled off at week 24, presumably because the concentrated topical product containing S. repens extract was stopped after 4 weeks. The patients were satisfied with the products and the side-effects were limited.
CONCLUSIONS:
The topical application of S. repens extract could be an alternative treatment in male pattern baldness in male patients who do not want or cannot tolerate the side-effects of standard medications, but the use of a concentrated S. repens product beyond 4 weeks may be necessary for sustained efficacy.
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61.) Comparitive effectiveness of finasteride vs Serenoa repens in male androgenetic alopecia: a two-year study.
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Int J Immunopathol Pharmacol. 2012 Oct-Dec;25(4):1167-73.
Rossi A, Mari E, Scarno M, Garelli V, Maxia C, Scali E, Iorio A, Carlesimo M.
Abstract
The objective of this open label study is to determine the effectiveness of Serenoa repens in treating male androgenetic alopecia (AGA), by comparing its results with finasteride. For this purpose, we enrolled 100 male patients with clinically diagnosed mild to moderate AGA. One group received Serenoa repens 320 mg every day for 24 months, while the other received finasteride 1 mg every day for the same period. In order to assess the efficacy of the treatments, a score index based on the comparison of the global photos taken at the beginning (T0) and at the end (T24) of the treatment, was used. The results showed that only 38% of patients treated with Serenoa repens had an increase in hair growth, while 68% of those treated with finasteride noted an improvement. Moreover finasteride was more effective for more than half of the patients (33 of 50, i.e. 66%), with level II and III alopecia. We can summarize our results by observing that Serenoa repens could lead to an improvement of androgenetic alopecia, while finasteride confirmed its efficacy. We also clinically observed, that finasteride acts in both the front area and the vertex, while Serenoa repens prevalently in the vertex. Obviously other studies will be necessary to clarify the mechanisms that cause the different responses of these two treatments.
44.) Cutaneous Manifestations of Polycystic Ovary Syndrome: A Cross-Sectional Clinical Study.
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Indian Dermatol Online J. 2017 Mar-Apr;8(2):104-110. doi: 10.4103/2229-5178.202275.
Keen MA1, Shah IH1, Sheikh G1.
Author information
1
Department of Dermatology, STD and Leprosy, GMC Srinagar and associated SMHS Hospital, Srinagar, Jammu and Kashmir, India.
Abstract
BACKGROUND:
Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women, affecting 5-10% of reproductive-aged women. The dermatologic manifestations of hyperandrogenism, chiefly hirsutism, acne vulgaris, androgenic alopecia, and acanthosis nigricans, are among the cardinal manifestations of PCOS.
AIM:
To study the incidence and prevalence of various cutaneous manifestations in patients with PCOS and to correlate these skin manifestations with hormonal changes.
SETTINGS AND DESIGN:
This study was conducted at a dermatology centre over a period of 1 year from November 2012 to 2013.
MATERIALS AND METHODS:
The present study included 100 women diagnosed to have PCOS. Hormonal analysis as well as radiological assessment was done in all the cases. Cutaneous manifestations were ascertained and inferences were drawn.
STATISTICAL ANALYSIS:
Statistical analysis was carried out by the Chi-square test and independent samples t-test. Statistical significance was determined at a level of P < 0.05.
RESULTS:
In our study, the prevalence of hirsutism, acne, female pattern hair loss, acanthosis nigricans, seborrhea, striae and acrochordons was 78%, 48%, 31%, 30%, 29%, 13%, and 9%, respectively.
CONCLUSION:
Dermatologic manifestations of PCOS play a significant role in making the diagnosis and constitute a substantial portion of the symptoms experienced by women with this syndrome.
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45.) A Retrospective Review of Treatment Results for Patients With Central Centrifugal Cicatrical Alopecia.
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J Drugs Dermatol. 2017 Apr 1;16(4):317-320.
Eginli A, Dothard E, Bagayoko CW, Huang K, Daniel A, McMichael AJ.
Abstract
INTRODUCTION: Central centrifugal cicatricial alopecia (CCCA) is a form of scarring alopecia primarily affecting women of African descent on the crown of the scalp. Limited data exists regarding evidence-based treatment for CCCA.</p> <p>OBJECTIVE: To examine photos of subjects with CCCA before and after treatment in order to evaluate results of treatment and compare results of different treatment regimens.</p> <p>METHODS: Photographs of 15 subjects with CCCA before and after treatment were evaluated by two blinded investigators who assigned disease severity scores to photographs based on a published scale: Central Scalp Alopecia Photographic Scale in African American Women.</p> <p>RESUTLS: Median change in severity score (post-treatment severity score - pre-treatment severity score) was 0.5 (P = 0.58) for all 15 subjects receiving a series of 7 to 8 intralesional steroid injections along with topical steroids (Class I/II) +/- minoxidil and +/- anti-dandruff shampoo, indicating worsening of disease after treatment. Subjects receiving minoxidil versus those who did not (0.25 vs 0.5; P = 0.38) and subjects receiving anti-dandruff shampoo versus those who did not (0.0 vs 0.5; P = 0.42) demonstrated no statistically significant difference in pre- and post-treatment severity scores. Of 15 subjects, 5/15 (33.3%) had decreased severity scores, 8/15 (53.3%) had increased severity scores, and 2/15 (13.3%) had no change in severity scores.</p> <p>CONCLUSIONS: Although no statistically significant difference was found in pre- versus post-treatment disease severity, this may indicate intralesional steroid injections and topical steroids +/- minoxidil and +/- anti-dandruff shampoo halt disease progression.
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46.) The effectiveness of treatments for androgenetic alopecia: A systematic review and meta-analysis.
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J Am Acad Dermatol. 2017 Apr 7. pii: S0190-9622(17)30306-7. doi: 10.1016/j.jaad.2017.02.054. [Epub ahead of print]
Adil A1, Godwin M2.
Author information
1
Memorial University of Newfoundland, St. John's, Newfoundland.
2
Memorial University of Newfoundland, St. John's, Newfoundland. Electronic address: godwinm@mun.ca.
Abstract
BACKGROUND:
Androgenetic alopecia, or male pattern hair loss, is a hair loss disorder mediated by dihydrotestosterone, the potent form of testosterone. Currently, minoxidil and finasteride are Food and Drug Administration (FDA)-approved, and HairMax LaserComb, which is FDA-cleared, are the only treatments recognized by the FDA as treatments of androgenetic alopecia.
OBJECTIVE:
This systematic review and meta-analysis assesses the efficacy of nonsurgical treatments of androgenetic alopecia in comparison to placebo for improving hair density, thickness, growth (defined by an increased anagen:telogen ratio), or subjective global assessments done by patients and investigators.
METHODS:
A systematic review of randomized controlled trials was conducted. PubMed, Embase, and Cochrane were searched up to December 2016, with no lower limit on the year. We included only randomized controlled trials of good or fair quality based on the US Preventive Services Task Force quality assessment process.
RESULTS:
A meta-analysis was conducted separately for 5 groups of studies that tested the following hair loss treatments: low-level laser light therapy in men, 5% minoxidil in men, 2% minoxidil in men, 1 mg finasteride in men, and 2% minoxidil in women. All treatments were superior to placebo (P < .00001) in the 5 meta-analyses. Other treatments were not included because the appropriate data were lacking.
LIMITATIONS:
High heterogeneity in most studies.
CONCLUSIONS:
This meta-analysis strongly suggests that minoxidil, finasteride, and low-level laser light therapy are effective for promoting hair growth in men with androgenetic alopecia and that minoxidil is effective in women with androgenetic alopecia.
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47.) Dutasteride in androgenetic alopecia: An update.
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Curr Clin Pharmacol. 2017 Mar 10. doi: 10.2174/1574884712666170310111125. [Epub ahead of print]
Arif T1, Dorjay K1, Adil M1, Sami M1.
Author information
1
Department of Dermatology, STDs and Leprosy, Jawaharlal Nehru Medical College (JNMC), Aligarh Muslim University (AMU), Aligarh, India.
Abstract
BACKGROUND:
Androgenetic alopecia is a common condition characterized by thinning of scalp hair. Conversion of testosterone to dihydrotestosterone, a more potent androgen, by the enzyme 5-a-reductase is responsible for underlying pathogenesis. Dutasteride, a synthetic 4-azasteroid, is a selective and competitive inhibitor of both type-1 and type-2 isoenzymes of 5-alpha-reductase. Finasteride and minoxidil are the only approved drugs for androgenetic alopecia. Dutasteride has been demonstrated to be effective in several randomized, double-blind, placebo controlled trials in androgenetic alopecia. In this review, after the pharmacology of dutasteride, the authors have discussed the status of dutasteride in androgenetic alopecia and has compared its efficacy with that of finasteride.
OBJECTIVE:
This article aims to review the current status of dutasteride in androgenetic alopecia. The structure, mechanism of action, pharmacokinetic and side effects are discussed along with its comparission with finasteride in androgenetic alopecia.
METHODS:
The main source of our information was Medline Pubmed, Google scholar and Scopus including original articles and review articles. The keywords dutasteride, dutasteride in androgenetic alopecia were used for search.
CONCLUSION:
Like finasteride, dutasteride is now becoming popular treatment option in AGA, due to its good response shown by various randomized control studies and meta-analysis. Also, in most of these studies dutasteride found to be better than finasteride with comparable adverse effect. Therefore, dutasteride could become a treatment of choice for AGA in near future.
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48.) A randomized, active- and placebo-controlled study of the efficacy and safety of different doses of dutasteride versus placebo and finasteride in the treatment of male subjects with androgenetic alopecia.
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J Am Acad Dermatol. 2014 Mar;70(3):489-498.e3. doi: 10.1016/j.jaad.2013.10.049. Epub 2014 Jan 9.
Gubelin Harcha W1, Barboza Martínez J2, Tsai TF3, Katsuoka K4, Kawashima M5, Tsuboi R6, Barnes A7, Ferron-Brady G8, Chetty D9.
Author information
1
Centro Médico Skinmed and Universidad de los Andes, Santiago, Chile. Electronic address: wgubelin@skinmed.cl.
2
Unidad de Investigación, Clínica Internacional, Lima, Peru.
3
Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
4
Department of Dermatology, Kitasato University, Tokyo, Japan.
5
Department of Dermatology, Tokyo Women's Medical University, Tokyo, Japan.
6
Department of Dermatology, Tokyo Medical University, Tokyo, Japan.
7
GlaxoSmithKline Research & Development, Research Triangle Park, North Carolina.
8
GlaxoSmithKline Research & Development, King of Prussia, Pennsylvania.
9
GlaxoSmithKline Research & Development, Singapore.
Abstract
BACKGROUND:
Dihydrotestosterone is the main androgen causative of androgenetic alopecia, a psychologically and physically harmful condition warranting medical treatment.
OBJECTIVE:
We sought to compare the efficacy and safety of dutasteride (type 1 and 2 5-alpha reductase inhibitor) with finasteride (type 2 5-alpha reductase inhibitor) and placebo in men with androgenetic alopecia.
METHODS:
Men aged 20 to 50 years with androgenetic alopecia were randomized to receive dutasteride (0.02, 0.1, or 0.5 mg/d), finasteride (1 mg/d), or placebo for 24 weeks. The primary end point was hair count (2.54-cm diameter) at week 24. Other assessments included hair count (1.13-cm diameter) and width, photographic assessments (investigators and panel), change in stage, and health outcomes.
RESULTS:
In total, 917 men were randomized. Hair count and width increased dose dependently with dutasteride. Dutasteride 0.5 mg significantly increased hair count and width in a 2.54-cm diameter and improved hair growth (frontal view; panel photographic assessment) at week 24 compared with finasteride (P = .003, P = .004, and P = .002, respectively) and placebo (all P < .001). The number and severity of adverse events were similar among treatment groups.
LIMITATIONS:
The study was limited to 24 weeks.
CONCLUSIONS:
Dutasteride increased hair growth and restoration in men with androgenetic alopecia and was relatively well tolerated.
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49.) New Treatments for Hair Loss.
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Actas Dermosifiliogr. 2017 Apr;108(3):221-228. doi: 10.1016/j.ad.2016.11.010. Epub 2017 Jan 3.
[Article in English, Spanish]
Vañó-Galván S1, Camacho F2.
Author information
1
Servicio de Dermatología, Unidad de Tricología, Hospital Universitario Ramón y Cajal, IRYCIS, Universidad de Alcalá, Madrid, España. Electronic address: drsergiovano@gmail.com.
2
Hospital Virgen Macarena, Sevilla, España.
Abstract
The treatment of hair loss is an important part of clinical dermatology given the prevalence of the problem and great impact on patients' quality of life. Many new treatments have been introduced in recent years. This review summarizes the main ones in 4 groups: a) For androgenetic alopecia, we discuss new excipients for oral minoxidil, dutasteride, and finasteride as well as new forms of topical application; prostaglandin agonists and antagonists; low-level laser therapy; and regenerative medicine with Wnt signaling activators and stem cell therapy. b) For alopecia areata, Janus kinase inhibitors are reviewed. c) For frontal fibrosing alopecia, we discuss the use of antiandrogens and, for some patients, pioglitazone. d) Finally, we mention new robotic devices for hair transplant procedures and techniques for optimal follicular unit extraction.
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50.) Efficacy and safety of 5% minoxidil topical foam in male pattern hair loss treatment and patient satisfaction.
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Acta Dermatovenerol Alp Pannonica Adriat. 2016 Sep;25(3):41-44.
Hasanzadeh H1, Nasrollahi SA1, Halavati N2, Saberi M3, Firooz A1,2.
Author information
1
Pharmaceutical, Cosmeceutical, and Hygienic Skin Products Clinical Evaluation Lab (DermaLab), Center for Research & Training in Skin Diseases & Leprosy (CRTSDL), Tehran University of Medical Sciences (TUMS), Tehran, Iran.
2
Clinical Trial Center (CTC), Tehran University of Medical Sciences (TUMS), Tehran, Iran.
3
Community-Based Participatory Research Center, Iranian Institute for Reduction of High-Risk Behaviors, Tehran University of Medical Sciences (TUMS), Tehran, Iran.
Abstract
INTRODUCTION:
Male pattern hair loss is widespread around the world. Its prevalence indicates the importance of finding the best treatment modalities. This study evaluates the efficacy and safety of minoxidil 5% topical foam in male pattern hair loss treatment and patient satisfaction.
METHODS:
This study was a before-and-after trial on 17 male patients with male pattern hair loss. Subjects were instructed to apply one capful (1 ml) of minoxidil 5% topical foam on the scalp daily for 6 months. Efficacy was assessed through hair counts, subject assessment, and global photographic review.
RESULTS:
Seventeen male volunteers were recruited, and three volunteers were withdrawn; 14 participated in the trial for 16 weeks, and 12 continued up to 24 weeks. The average hair count with a camera at week 16 (181.87 ± 52.42) and week 24 (194.58 ± 62.82) and with an eye count at week 16 (62.57 ± 15.28) and week 24 (69.91 ± 15.61) increased significantly compared to the baseline after intervention.
CONCLUSIONS:
This study confirmed that minoxidil 5% topical foam is a safe and effective treatment for MPHL. The effect of it is evident after 24 weeks of use.
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51.) Post-Finasteride Adverse Effects in Male Androgenic Alopecia: A Case Report of Vitiligo.
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Skin Pharmacol Physiol. 2017;30(1):42-45. doi: 10.1159/000455972. Epub 2017 Feb 22.
Motofei IG1, Rowland DL, Georgescu SR, Tampa M, Paunica S, Constantin VD, Balalau C, Manea M, Baleanu BC, Sinescu I.
Author information
1
Department of Surgery/Dermatology, Carol Davila University, Bucharest, Romania.
Abstract
Finasteride has proved to be relatively safe and effective in the therapeutic management of male androgenic alopecia. However, literature data report several endocrine imbalances inducing various adverse effects, which often persist after treatment cessation in the form of post-finasteride syndrome. Here we present the case of a 52-year-old man receiving finasteride (1 mg/day) who developed an uncommon adverse effect represented by generalized vitiligo 2 months after finasteride discontinuation. Associated adverse effects encountered were represented by mild sexual dysfunction (as determined by the International Index of Erectile Function, IIEF) and moderate depressive symptoms (according to DSM-V criteria), all of these manifestations aggregating within/as a possible post-finasteride syndrome. Further studies should develop and compare several therapeutic approaches, taking into account not only compounds that decrease the circulating dihydrotestosterone level but also those that could block the dihydrotestosterone receptors (if possible, compounds with selective tropism towards the skin). In addition, the possibility of predicting adverse effects of finasteride (according to hand preference and sexual orientation) should be taken into account.
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52.) Adverse Effects and Safety of 5-alpha Reductase Inhibitors (Finasteride, Dutasteride): A Systematic Review.
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J Clin Aesthet Dermatol. 2016 Jul;9(7):56-62. Epub 2016 Jul 1.
Hirshburg JM1, Kelsey PA2, Therrien CA2, Gavino AC1, Reichenberg JS1.
Author information
1
Dell Medical School, University of Texas at Austin, Austin, Texas;
2
University of Texas Medical Branch, Galveston, Texa.
Abstract
Finasteride and dutasteride, both 5-alpha reductase inhibitors, are considered first-line treatment for androgenetic hair loss in men and used increasingly in women. In each case, patients are expected to take the medications indefinitely despite the lack of research regarding long-term adverse effects. Concerns regarding the adverse effects of these medications has led the United States National Institutes of Health to add a link for post-finasteride syndrome to its Genetic and Rare Disease Information Center. Herein, the authors report the results of a literature search reviewing adverse events of 5-alpha reductase inhibitors as they relate to prostate cancer, psychological effects, sexual health, and use in women. Several large studies found no increase in incidence of prostate cancer, a possible increase of high-grade cancer when detected, and no change in survival rate with 5-alpha reductase inhibitor use. Currently, there is no direct link between 5-alpha reductase inhibitor use and depression; however, several small studies have led to depression being listed as a side effect on the medication packaging. Sexual effects including erectile dysfunction and decreased libido and ejaculate were reported in as many as 3.4 to 15.8 percent of men. To date, there are very few studies evaluating 5-alpha reductase inhibitor use in women. Risks include birth defects in male fetuses if used in pregnancy, decreased libido, headache, gastrointestinal discomfort, and isolated reports of changes in menstruation, acne, and dizziness. Overall, 5-alpha reductase inhibitors were well-tolerated in both men and women, but not without risk, highlighting the importance of patient education prior to treatment.
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53.) Atypical post-finasteride syndrome: A pharmacological riddle.
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Indian J Pharmacol. 2016 May-Jun;48(3):316-7. doi: 10.4103/0253-7613.182898.
Gupta AK1, Sharma N1, Shukla P1.
Author information
1
Department of Pharmacology, Government Medical College, Patiala, Punjab, India.
Abstract
Finasteride and dutasteride are commonly used 5-alpha reductase inhibitors. While finasteride is a selective inhibitor of 5-alpha reductase Type II, dutasteride inhibits 5- alpha reductase Type I and II. The United States Food and Drug Administration approved the use of finasteride for benign prostatic hypertrophy (BPH) as well as androgenic alopecia (AGA) while dutasteride is approved only for BPH. Off-label use of dutasteride is not uncommon in AGA as well. Although the postfinasteride syndrome (PFS) is a well-established entity, its symptomatology is quite variable. Here, we describe a case of an atypical PFS in a patient treated with dutasteride and finasteride for AGA. The multisystem involvement and irreversible nature of this case warrant its reporting.
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54.) Emotional Consequences of Finasteride: Fool's Gold.
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Am J Mens Health. 2016 Feb 11. pii: 1557988316631624. [Epub ahead of print]
Ganzer CA1, Jacobs AR2.
Información del autor
1
Hunter-Bellevue School of Nursing, New York, NY, USA cganzer@hunter.cuny.edu.
2
Hunter-Bellevue School of Nursing, New York, NY, USA.
Abstract
Androgenetic alopecia, the gradual, progressive loss of hair frequently results in psychological despair, in part related to changes in self-image. Current androgenetic alopecia treatments are limited to hair transplantation and medications that inhibit dihydrotestosterone, a potent androgen associated with follicular micronization. Users of finasteride, which prevents dihydrotestosterone production, report serious physical and emotional adverse effects, collectively known as post-finasteride syndrome. Psychiatric illnesses and personality traits, specifically neuroticism influence emotional well-being. Limited research exists exploring the psychological corollaries of post-finasteride syndrome and preexisting Axis I and Axis II mental health conditions. The aim of this study was to explore how having a preexisting personal and/or familial history of a psychiatric diagnosis and certain personality traits may influence anxiety and depression among finasteride users. Participants in this online survey completed the Beck Depression Inventory, the Beck Anxiety Inventory, and Ten-Item Personality Inventory. An important finding in this study was that almost 57% (n = 97) of men reported a psychiatric diagnosis and 28% (n = 27) had a first-degree relative with a mental health disorder, of this group 17 only had a family history. Nearly 50% of the men surveyed reported clinically significant depression as evidenced by Beck Depression Inventory score and 34% experienced anxiety on the Beck Anxiety Inventory. There were no statistically significant trends in personality traits reported. Results provide evidence on the need to screen for psychiatric history and counseling patients about the potential psychological consequences of finasteride. Prescribing clinicians should carefully weigh the risk/benefit ratio with these patients.
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55.) The importance of dual 5alpha-reductase inhibition in the treatment of male pattern hair loss: results of a randomized placebo-controlled study of dutasteride versus finasteride.
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J Am Acad Dermatol. 2006 Dec;55(6):1014-23.
Olsen EA1, Hordinsky M, Whiting D, Stough D, Hobbs S, Ellis ML, Wilson T, Rittmaster RS; Dutasteride Alopecia Research Team.
Author information
1
Duke University Medical Center, Durham, North Carolina, USA. olsen001@mc.duke.edu
Abstract
BACKGROUND:
Male pattern hair loss (MPHL) is a potentially reversible condition in which dihydrotestosterone is an important etiologic factor.
OBJECTIVE:
Our aim was to evaluate the efficacy of the type 1 and 2 5alpha-reductase inhibitor dutasteride in men with MPHL.
METHODS:
Four hundred sixteen men, 21 to 45 years old, were randomized to receive dutasteride 0.05, 0.1, 0.5 or 2.5 mg, finasteride 5 mg, or placebo daily for 24 weeks.
RESULTS:
Dutasteride increased target area hair count versus placebo in a dose-dependent fashion and dutasteride 2.5 mg was superior to finasteride at 12 and 24 weeks. Expert panel photographic review and investigator assessment of hair growth confirmed these results. Scalp and serum dihydrotestosterone levels decreased, and testosterone levels increased, in a dose-dependent fashion with dutasteride.
LIMITATIONS:
The study was limited to 24 weeks.
CONCLUSION:
Dutasteride increases scalp hair growth in men with MPHL. Type 1 and type 2 5alpha-reductase may be important in the pathogenesis and treatment of MPHL.
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56.) Interventions for female pattern hair loss.
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Cochrane Database Syst Rev. 2016 May 26;(5):CD007628. doi: 10.1002/14651858.CD007628.pub4.
van Zuuren EJ1, Fedorowicz Z, Schoones J.
Author information
1
Department of Dermatology, Leiden University Medical Center, PO Box 9600, B1-Q, Leiden, Netherlands, 2300 RC.
Abstract
BACKGROUND:
Female pattern hair loss (FPHL), or androgenic alopecia, is the most common type of hair loss affecting women. It is characterised by progressive shortening of the duration of the growth phase of the hair with successive hair cycles, and progressive follicular miniaturisation with conversion of terminal to vellus hair follicles (terminal hairs are thicker and longer, while vellus hairs are soft, fine, and short). The frontal hair line may or may not be preserved. Hair loss can have a serious psychological impact on women.
OBJECTIVES:
To determine the efficacy and safety of the available options for the treatment of female pattern hair loss in women.
SEARCH METHODS:
We updated our searches of the following databases to July 2015: the Cochrane Skin Group Specialised Register, CENTRAL in the Cochrane Library (2015, Issue 6), MEDLINE (from 1946), EMBASE (from 1974), PsycINFO (from 1872), AMED (from 1985), LILACS (from 1982), PubMed (from 1947), and Web of Science (from 1945). We also searched five trial registries and checked the reference lists of included and excluded studies.
SELECTION CRITERIA:
We included randomised controlled trials that assessed the efficacy of interventions for FPHL in women.
DATA COLLECTION AND ANALYSIS:
Two review authors independently assessed trial quality, extracted data and carried out analyses.
MAIN RESULTS:
We included 47 trials, with 5290 participants, of which 25 trials were new to this update. Only five trials were at 'low risk of bias', 26 were at 'unclear risk', and 16 were at 'high risk of bias'.The included trials evaluated a wide range of interventions, and 17 studies evaluated minoxidil. Pooled data from six studies indicated that a greater proportion of participants (157/593) treated with minoxidil (2% and one study with 1%) reported a moderate to marked increase in their hair regrowth when compared with placebo (77/555) (risk ratio (RR) = 1.93, 95% confidence interval (CI) 1.51 to 2.47; moderate quality evidence). These results were confirmed by the investigator-rated assessments in seven studies with 1181 participants (RR 2.35, 95% CI 1.68 to 3.28; moderate quality evidence). Only one study reported on quality of life (QoL) (260 participants), albeit inadequately (low quality evidence). There was an important increase of 13.18 in total hair count per cm² in the minoxidil group compared to the placebo group (95% CI 10.92 to 15.44; low quality evidence) in eight studies (1242 participants). There were 40/407 adverse events in the twice daily minoxidil 2% group versus 28/320 in the placebo group (RR 1.24, 95% CI 0.82 to 1.87; low quality evidence). There was also no statistically significant difference in adverse events between any of the individual concentrations against placebo.Four studies (1006 participants) evaluated minoxidil 2% versus 5%. In one study, 25/57 participants in the minoxidil 2% group experienced moderate to greatly increased hair regrowth versus 22/56 in the 5% group (RR 1.12, 95% CI 0.72 to 1.73). In another study, 209 participants experienced no difference based on a visual analogue scale (P = 0.062; low quality evidence). The assessments of the investigators based on three studies (586 participants) were in agreement with these findings (moderate quality evidence). One study assessed QoL (209 participants) and reported limited data (low quality evidence). Four trials (1006 participants) did not show a difference in number of adverse events between the two concentrations (RR 1.02, 95% CI 0.91 to 1.20; low quality evidence). Both concentrations did not show a difference in increase in total hair count at end of study in three trials with 631 participants (mean difference (MD) -2.12, 95% CI -5.47 to 1.23; low quality evidence).Three studies investigated finasteride 1 mg compared to placebo. In the finasteride group 30/67 participants experienced improvement compared to 33/70 in the placebo group (RR 0.95, 95% CI 0.66 to 1.37; low quality evidence). This was consistent with the investigators' assessments (RR 0.77, 95% CI 0.31 to 1.90; low quality evidence). QoL was not assessed. Only one study addressed adverse events (137 participants) (RR 1.03, 95% CI 0.45 to 2.34; low quality evidence). In two studies (219 participants) there was no clinically meaningful difference in change of hair count, whilst one study (12 participants) favoured finasteride (low quality evidence).Two studies (141 participants) evaluated low-level laser comb therapy compared to a sham device. According to the participants, the low-level laser comb was not more effective than the sham device (RR 1.54, 95% CI 0.96 to 2.49; and RR 1.18, 95% CI 0.74 to 1.89; moderate quality evidence). However, there was a difference in favour of low-level laser comb for change from baseline in hair count (MD 17.40, 95% CI 9.74 to 25.06; and MD 17.60, 95% CI 11.97 to 23.23; low quality evidence). These studies did not assess QoL and did not report adverse events per treatment arm and only in a generic way (low quality evidence). Low-level laser therapy against sham comparisons in two separate studies also showed an increase in total hair count but with limited further data.Single studies addressed the other comparisons and provided limited evidence of either the efficacy or safety of these interventions, or were unlikely to be examined in future trials.
AUTHORS' CONCLUSIONS:
Although there was a predominance of included studies at unclear to high risk of bias, there was evidence to support the efficacy and safety of topical minoxidil in the treatment of FPHL (mainly moderate to low quality evidence). Furthermore, there was no difference in effect between the minoxidil 2% and 5% with the quality of evidence rated moderate to low for most outcomes. Finasteride was no more effective than placebo (low quality evidence). There were inconsistent results in the studies that evaluated laser devices (moderate to low quality evidence), but there was an improvement in total hair count measured from baseline.Further randomised controlled trials of other widely-used treatments, such as spironolactone, finasteride (different dosages), dutasteride, cyproterone acetate, and laser-based therapy are needed.
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57.) Antiandrogenic Therapy with Ciproterone Acetate in Female Patients Who Suffer from Both Androgenetic Alopecia and Acne Vulgaris.
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Clujul Med. 2014;87(4):226-34. doi: 10.15386/cjmed-386. Epub 2014 Nov 12.
Coneac A1, Muresan A2, Orasan MS3.
Author information
1
Department of Histology, Morphological Sciences Division, Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
2
Department of Physiology, Physiological Sciences Division, Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
3
Department of Pathophysiology, Physiological Sciences Division, Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
Abstract
BACKGROUND:
Androgenetic Alopecia in Women (AGA) occurs due to an underlying susceptibility of hair follicles to androgenic miniaturization, caused by androgens. Clinically, AGA is characterized by progressive hair loss, with a marked hair thinning in the fronto-parietal area so that the scalp can be easily seen. Acne vulgaris is androgen-dependent and often affects the skin that has an increased number of oil glands: face, back and chest. Although the sebaceous glands are present on the scalp too, it is very rare to get acne at this site, as the hair acts as a wig and allows the sebum to drain and does not block the pores. Both AGA and Acne Vulgaris are signs of hyperandrogenism. Cyproterone acetate/ethinyl estradiol (2mg/0.035mg) products are authorized for the treatment of androgenetic symptoms in women, such as acne, seborrhea, mild forms of hirsutism and androgenetic alopecia. Our study had a double purpose: - To evaluate the result of the study regimen Melleva 35 (one pill per day, for 3 consecutive months) in patients with moderate to severe acne, suffering also from Androgenetic Alopecia;- To establish the efficacy of the drug on acne and alopecia improvement, both from the doctor's and patient's point of view.
PATIENTS AND METHODS:
After being informed of the aims and procedures of the study, participants provided a written informed consent. A number of 35 female subjects with moderate to severe acne vulgaris remained in the study. The subjects had also been diagnosed as suffering from AGA, on the basis of clinical criteria, including the pattern of hair loss and trichoscopy assessment.
RESULTS:
83% of study subjects reported that their hair did not continue to fall after 3 months of antiandrogen therapy. The females were evaluated using trichoscopy and the doctor noticed hair regrowth in 77% of the cases. Regarding the improvement of acne lesions after the treatment, 40% of study subjects recorded good improvement and 26% recorded excellent results with Melleva 35. The acceptance of the treatment was very high, 86% patients were compliant with the study therapy. The rate of adverse events (5 cases) was within the limits of the treatment tested by the study. Almost a third of the total number of subjects (28.5%) reached a good satisfaction level after the treatment, while 37.1% claimed moderate satisfaction.
CONCLUSION:
There was no correlation between the age of the subjects and the treatment for acne therefore our first hypothesis was rejected. As a conclusion, antiandrogenic therapy with Melleva 35, 1 pill per day, for 3 consecutive months, shows good results for patients who suffer from both Androgenetic Alopecia and Acne Vulgaris.
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58.) Treatment of female pattern hair loss.
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Skinmed. 2012 Jul-Aug;10(4):218-27.
Hassani M1, Gorouhi F, Babakoohi S, Moghadam-Kia S, Firooz A.
Author information
1
Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Abstract
Female pattern hair loss (FPHL) as a distinctive entity was first described about 30 years ago. The objective of this study was to perform a systematic review of all randomized controlled trials for treatment of FPHL. A preliminary search was carried out in several databases up to August 2008 to identify all randomized controlled trials on nonsurgical interventions for treatment of FPHL. Studies reporting fewer than 10 patients and non-English articles were excluded. Additionally, references of relevant articles and reviews were checked manually in search for additional sources. Among 238 citations found in the preliminary search, 12 fulfilled all criteria to be included in the systematic review. Topical minoxidil 1% to 5% for 24 to 48 weeks was shown to be effective in FPHL and its effect was not related to age or androgen level of patients. In addition, it may be effective in women with FPHL, both with and without hyperandrogenism, and in young and old premenopausal or postmenopausal. In patients with increased serum androgens, oral flutamide but not finasteride or cyproterone acetate was more effective than no treatment. Topical minoxidil is effective in patients with FPHL, with or without hyperandrogenism, but there is limited evidence for the efficacy of antiandrogens.
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59.) [Spironolactone in dermatological treatment. On and off label indications].
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[Article in German]
Salavastru CM1, Fritz K, Tiplica GS.
Author information
1
2nd Clinic of Dermatology, "Colentina" Clinical Hospital, Bucharest, Romania, galati1968@yahoo.com.
Abstract
There are no currently FDA/EMEA-approved dermatologic indications for spironolactone and its off-label uses are, among others, female acne, female pattern hair loss, hidradenitis suppurativa or hirsutism. The rationale behind these relays on the mechanism of action of spironolactone which interferes with the hormone-controlled sebum and sweat gland secretion and with androgen stimulated hair growth. The average dose used by the dermatologits is 50-100 mg daily. It should not be used in pregnant and lactating women and it is not used in men due to the risk of feminization. Although further studies to assess its efficacy and safety are necessary, currently spironolactone is regarded as a useful tool in the dermatologic treatment armamentarium.
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60.) Treatment of male androgenetic alopecia with topical products containing Serenoa repens extract.
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Wessagowit V1, Tangjaturonrusamee C2, Kootiratrakarn T1, Bunnag T1, Pimonrat T3, Muangdang N3, Pichai P3.
Author information
1
Molecular Genetics Unit, Institute of Dermatology, Bangkok, Thailand.
2
Hair & Nail Unit, Institute of Dermatology, Bangkok, Thailand.
3
Research Unit, Institute of Dermatology, Bangkok, Thailand.
Abstract
BACKGROUND/OBJECTIVES:
Male androgenetic alopecia (AGA) is a common hair problem. Serenoa repens extract has been shown to inhibit both types of 5-α reductase and, when taken orally, has been shown to increase hair growth in AGA patients. The aim of this study was to assess the efficacy of topical products containing S. repens extract for the treatment of male AGA.
METHODS:
This was a pilot, prospective, open, within-subject comparison limited to 24 weeks using no placebo controls. In all, 50 male volunteers aged between 20 and 50 years received topical S. repens products for 24 weeks. The primary end-point was a hair count in an area of 2.54 cm(2) at week 24. Secondary end-points included hair restoration, investigators' photographic assessment, patients' evaluation and discovering adverse events.
RESULTS:
The average hair count and terminal hair count increased at weeks 12 and 24 compared to baseline. Some of these positive results levelled off at week 24, presumably because the concentrated topical product containing S. repens extract was stopped after 4 weeks. The patients were satisfied with the products and the side-effects were limited.
CONCLUSIONS:
The topical application of S. repens extract could be an alternative treatment in male pattern baldness in male patients who do not want or cannot tolerate the side-effects of standard medications, but the use of a concentrated S. repens product beyond 4 weeks may be necessary for sustained efficacy.
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61.) Comparitive effectiveness of finasteride vs Serenoa repens in male androgenetic alopecia: a two-year study.
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Int J Immunopathol Pharmacol. 2012 Oct-Dec;25(4):1167-73.
Rossi A, Mari E, Scarno M, Garelli V, Maxia C, Scali E, Iorio A, Carlesimo M.
Abstract
The objective of this open label study is to determine the effectiveness of Serenoa repens in treating male androgenetic alopecia (AGA), by comparing its results with finasteride. For this purpose, we enrolled 100 male patients with clinically diagnosed mild to moderate AGA. One group received Serenoa repens 320 mg every day for 24 months, while the other received finasteride 1 mg every day for the same period. In order to assess the efficacy of the treatments, a score index based on the comparison of the global photos taken at the beginning (T0) and at the end (T24) of the treatment, was used. The results showed that only 38% of patients treated with Serenoa repens had an increase in hair growth, while 68% of those treated with finasteride noted an improvement. Moreover finasteride was more effective for more than half of the patients (33 of 50, i.e. 66%), with level II and III alopecia. We can summarize our results by observing that Serenoa repens could lead to an improvement of androgenetic alopecia, while finasteride confirmed its efficacy. We also clinically observed, that finasteride acts in both the front area and the vertex, while Serenoa repens prevalently in the vertex. Obviously other studies will be necessary to clarify the mechanisms that cause the different responses of these two treatments.
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