Androgen Production and Skin Metabolism in Hirsutism

Abstract

The concentrations of testosterone, androstenedione and dihydrotestosterone (DHT) in the plasma and 5\g=a\-androstane-3\g=a\,17\g=b\-diol(androstanediol) in the urine were measured in 40 women with hirsutism of ovarian, adrenal and idiopathic origin. Conversion of [3H]testosterone to DHT, 3\g=a\-and 3\g=b\-androstanediols was also studied in homogenates of pubic skin obtained from 15 of the patients. Results were compared with values obtained from normal men and women.Values for the levels of testosterone, DHT and androstenedione in the plasma and androstanediol in the urine of hirsute women were all above control levels, especially for plasma androstenedione and urinary androstanediol (P < 0\m=.\001). This finding was particularly marked in patients with hirsutism of ovarian origin. Conversion of [3H]testosterone to 5\g=a\-reducedmetabolites by homogenates of skin obtained from hirsute women was significantly greater than by homogenates of skin from normal women (P < 0\m=.\001) but was the same as the value for normal men. The highest values for conversion were obtained from the patients with idiopathic hirsutism.These results indicate that androstenedione is the principal androgen secreted in hirsutism. In sexual skin this steroid may be converted to DHT and 3\g=a\-, and 3\g=b\-androstanediols and the increased activity of testosterone 5\g=a\-reductase may result in an exaggerated 'utilization' of androstenedione in this tissue. The high rate of excretion of androstanediol in the urine of patients with idiopathic hirsutism may be explained by the fact that this steroid is an end-product of testosterone metabolism. * Present address and address for reprint requests: Hôpital Necker, 149 rue de Sèvres, 75730 Paris Cedex 15, France.

The 5alpha-reductase type 1, but not type 2, gene is expressed in anagen hairs plucked from the vertex area of the scalp of hirsute women and normal individuals

“…Previous studies have also described a similar 5α-reductase activity in hair follicles from men and women (12,34). In contrast, a higher 5α-reductase activity in pubic skin samples was detected in normal men than in normal women (1). Taken together, these results suggest that in normal individuals 5α-reductase regulation seems to differ between follicular keratinocytes of scalp and pubic skin fibroblasts.…”

3 alpha, 17 beta-androstanediol glucuronide in plasma. A marker of androgen action in idiopathic hirsutism.

“…The degree of elevation was very impressive and was as much as 15-fold over normal, yielding values within the male range. In vitro the formation of 5a-reduced steroid from skin in IH has been noted to approach male values (25).…”

5α-reductases=physiology and pathology

“…P a r contre la 5 a -r 6 d u c t a s e est 61ev6e, atteig n a n t chez ces femmes les valeurs observ6es chez l ' h o m m e n o r m a l [10]. La 5a-r 6 d u c t a s e joue donc d a n s ce cas u n r61e d'amplificateur de l'action des androg~nes, p e r m e t t a n t , ~ p a r t i r d'une production de testost6rone pratiquement normale, la production de suffisamment de DHT pour provoquer l'hirsutisme.…”