Cyproterone acetate for hirsutism

Hyperandrogenism (elevation of masculinizing hormones) is probably the commonest endocrine disturbance in women. The clinical manifestations of hyperandrogenism vary from mild skin changes (increased oiliness), acne, excess facial and body hair through to voice changes, enlargement of the clitoris and change in body habitus.

Hirsutism is the growth of terminal hair in sites at which it is usually considered a male secondary sexual characteristic e.g. chest and beard area. About one third of women in the reproductive years have some hair on their face, abdomen or chest (McKnight 1984).

Among older women, up to 75% may have slightly increased facial hair, because the main product of the postmenopausal ovaries is androstenedione which is converted to testosterone in the peripheral tissue.

The three main naturally occurring steroids responsible for androgen action are testosterone, dehydroepiandrosterone (DHEA) and androstenedione. Testosterone is the most important androgen and conversion by five alpha-reductase to the more potent dihydrotestosterone is necessary for its biological action (Franks 1989). Androstenedione and DHEA may be regarded as pre hormones which are converted in peripheral tissue to testosterone before they exert any androgenic influence. Production, peripheral conversion and protein binding are important determinants of androgenic effect. Total testosterone measurements, which reflect bound and free hormone do not accurately reflect tissue exposure to androgens. The derived free androgen index (testosterone x 100 divided by sex hormone binding globulin levels) may be used to give an indirect estimation of the free testosterone levels.

The distribution and quality of the hair and the concentration of androgen receptors in the skin are genetically determined, and hence the clinical effects of hyperandrogenaemia are influenced by genetic predisposition (Flamigni 1971; Mowszowicz 1981). Once five alpha-reductase activity has been induced in a hair follicle, it remains sensitive to androgen stimulation for the rest of its life cycle. The hair cycle varies in different parts of the body - from three-six months on the face to five+ years on the scalp (Saitoh 1970; Seago 1985). As a result, therapeutic interventions result in gradual changes in the clinical presentation and the development of hirsutism itself reflects prolonged androgen stimulation.

Androgens also increase the rate of mitosis and epithelial proliferation of sebaceous gland acini and cause enhanced sebum production - both these factors contribute to the development of acne (Ashton 1987; Nurnberger 1987).

Hyperandrogenism may result from ovarian and/or adrenal overproduction of androgens and/or altered peripheral metabolism and/or altered end organ sensitivity. The diagnosis in the majority of women who present with hirsutism will be the polycystic ovary syndrome which is characterised by a typical ultrasound appearance of the ovaries and a variable endocrine and clinical picture (Conway 1989; Adams 1986; Bunker 1989).