Clinical relevance of testosterone and dihydrotestosterone metabolism in women

Androgens are part of normal female physiology. When they are secreted in excess or when they cause unwanted symptoms such as hirsutism and male-pattern baldness, the term hyperandrogenism is used. In many hyperandrogenic women, there is no well-defined hormonal abnormality, but the women are simply on one end of a normal spectrum of androgen secretion and cutaneous androgen sensitivity. To be active in the skin, testosterone must be converted to dihydrotestosterone by the enzyme 5α-reductase. Androgen sensitivity is determined, in part, by 5α-reductase activity in the skin. This is a localized phenomenon, and there is no generalized increase in 5α-reductase activity in these women. Dihydrotestosterone can be converted to glucuronide and sulfate conjugates, including androstanediol glucuronide. These androgen conjugates have been proposed to be serum markers of cutaneous androgen metabolism, but recent evidence indicates that they arise from adrenal precursors and are more likely to be markers of adrenal steroid production and metabolism. Antiandrogens (androgen receptor blockers) are the best medical treatment of cutaneous hyperandrogenism. 5α-Reductase inhibitors have recently been approved for the treatment of benign prostatic hyperplasia, and research is currently underway to determine their effectiveness in treating hirsutism and male-pattern baldness.