EDITORIAL ESPANOL:

====================

Hola Amigos del DERMA Cyber, DERMAGIC con su primera entrega del año les

trae este interesante tema sobre LA ALOPECIA ANDROGENICA, revisión pedida por el Dr. Rondón Lugo. 

Encontré 43 referencias que nos ilustran muy bien este tena que nunca

dejara de ser de interés para todos. 

Hace unos años se decía en el argot: "solo el piso detiene la caída del

cabello", en son de juerga. Hoy podemos decir que con una pastillita

(finasteride) y una loción (minoxidil), la cosa ha cambiado radicalmente. 

Feliz nuevo año para todos !!!!! 

Dr José Lapenta R.

 EDITORIAL ENGLISH:

===================

Hello Friends of the DERMA Cyber, DERMAGIC with the first delivery of the

year brings this interesting topic on THE ANDROGENIC ALOPECIA. I found 43

references that illustrate us very well this topic that never left of

being of interest for all. 

Some years ago it was said in the jargon: "alone the floor stops the fall

of the hair". Today we can say that with a pill (finasteride) and a lotion

(minoxidil), the thing change radically. 

Happy New year for all !!!! 

Dr. José Lapenta R. 

================================================================

DERMAGIC/EXPRESS(27)

================================================================

ALOPECIA ANDROGENICA// ANDROGENIC ALOPECIA 

================================================================

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 of

androgen 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 the

human 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 dihydrotestosterone

metabolism 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. 

======================================================================

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.

======================================================================

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. 

======================================================================

2.) Androgen metabolism as it affects hair growth in 

androgenetic alopecia.

======================================================================

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. 

======================================================================

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?]

======================================================================

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. 

======================================================================

4.) Alterations in androgen conjugate levels in women and men with alopecia.

======================================================================

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.

INTERVENTION:

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). In 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. 

======================================================================

5.) Hormonal basis of male and female androgenic alopecia: clinical relevance.

======================================================================

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. 

======================================================================

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).]

======================================================================

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. 

======================================================================

7.) Androgenetic alopecia: an autosomal dominant disorder.

======================================================================

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. 

======================================================================

8.) [Hair growth promoters in androgenetic alopecia. Expectations and reality]

[Haarwuchsmittel bei androgenetischer Alopezie. Anspruch und Realitat.]

======================================================================

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. 

======================================================================

9.) Effects of ozonized autohaemotherapy on human hair cycle.

======================================================================

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. 

======================================================================

10.) Estrogen and progesterone receptors in androgenic alopecia

versus alopecia areata.

======================================================================

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. 

======================================================================

11.) Androgens and women's health.

======================================================================

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. 

======================================================================

12.) Female androgenetic alopecia: an update.

======================================================================

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. 

======================================================================

13.) A prospective study of the prevalence of clear-cut endocrine

disorders and polycystic ovaries in 350 patients presenting

with hirsutism or androgenic alopecia.

======================================================================

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. 

======================================================================

14.) Ketoconazole shampoo: effect of long-term use in androgenic alopecia. 

======================================================================

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. 

======================================================================

15.) Anagen hairs may fail to replace telogen hairs in early androgenic

female alopecia. 

======================================================================

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. 

======================================================================

16.) Different levels of 5alpha-reductase type I and II, aromatase, and

androgen receptor in hair follicles of women and men with androgenetic

alopecia. 

======================================================================

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. 

======================================================================

17.) Safety surveillance of esterified estrogens-methyltestosterone

(Estratest and Estratest HS) replacement therapy in the United States. 

======================================================================

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. 

======================================================================

18.) Balding hair follicle dermal papilla cells contain higher levels of

androgen receptors than those from non-balding scalp. 

======================================================================

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. 

======================================================================

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. 

======================================================================

20.) Messenger RNA expression of steroidogenesis enzyme subtypes in the

human pilosebaceous unit. 

======================================================================

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. 

======================================================================

21.) Treatment of androgen excess in females: yesterday, today and tomorrow. 

======================================================================

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. 

======================================================================

22.) Association of benign prostatic hyperplasia with male pattern baldness. 

======================================================================

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. 

======================================================================

23.) Hair regrowth. Therapeutic agents. 

======================================================================

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. 

======================================================================

24.) Androgenic effects of oral contraceptives: implications for patient

compliance. 

======================================================================

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 

======================================================================

25.) Diffuse hypertrichosis during treatment with 5% topical minoxidil.

======================================================================

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. 

======================================================================

26.) Minoxidil upregulates the expression of vascular endothelial growth

factor in human hair dermal papilla cells. 

======================================================================

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. 

======================================================================

27.) Biphasic effects of minoxidil on the proliferation and differentiation

of normal human keratinocytes. 

======================================================================

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. 

======================================================================

28.) Alopecia and mood stabilizer therapy. 

======================================================================

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. 

======================================================================

29.) Improvement in androgenetic alopecia (stage V) using topical minoxidil

in a retinoid vehicle and oral finasteride [see comments] 

======================================================================

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 

======================================================================

30.) Clinical significance of testosterone and dihydrotestosterone

metabolism in women] 

======================================================================

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. 

======================================================================

31.) The 5 alpha-reductase system and its inhibitors. Recent development

and its perspective in treating androgen-dependent skin disorders. 

======================================================================

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. 

======================================================================

32.) Finasteride: a clinical review. 

======================================================================

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. 

======================================================================

33.) 19-nor-10-azasteroids: a novel class of inhibitors for human steroid

5alpha-reductases 1 and 2. 

======================================================================

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. The 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. 

======================================================================

34.) Genetic analysis of male pattern baldness and the 5alpha-reductase

genes. 

======================================================================

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. 

======================================================================

35.) Effects of topically applied spironolactone on androgen stimulated

sebaceous glands in the hamster pinna. 

======================================================================

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). 

======================================================================

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. 

======================================================================

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) 

======================================================================

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. 

======================================================================

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). 

======================================================================

39.) The insulin resistance in women with hyperandrogenism is partially

reversed by antiandrogen treatment: evidence that androgens impair insulin

action in women. 

======================================================================

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. 

======================================================================

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.

======================================================================

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. 

======================================================================

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.

======================================================================

DATA-MÉDICOS/DERMAGIC-EXPRESS No (27) 06/01/99 DR. JOSE LAPENTA R. 

=====================================================================

Produced by Dr. José Lapenta R. Dermatologist

Venezuela 1.998-2.024

Producido por Dr. José Lapenta R. Dermatólogo
Venezuela 1.998-2.024

Tlf: 0414-2976087 - 04127766810