The Evaluation of the Role of Androgens in Hirsutism and the Use of a New Anti-androgen “Cyproterone Acetate” for Therapy

Abstract

When the mean plasma testosterone levels in normal (14) and hirsute women (26) based on 4 plasma readings were compared, a highly significant difference was noted (p < 0.001). The individual reading of each patient was outside the 95% confidence limits of normality. However, when the mean values were based on two readings from each patient or a single determination, an overlap with the normal range was noted in a number of patients. It was therefore concluded that in all patients studied hirsutism was associated with elevated testosterone readings. Attempts to locate the source of androgen excess were performed by 1) short-term (2 days) adrenal stimulation and suppression tests and 2) by longterm (one menstrual cycle) adrenal and ovarian suppression, using dexamethazone, and an estrogen-progestogen mixture in the form of an oral contraceptive pill respectively. While inconsistent changes in plasma and urinary testosterone reading were noted following short-term pharmacodynamic tests; long-term suppression gave a more informative result. The data obtained from 5 patients on long-term pharmacodynamic tests clearly demonstrated a dual contribution of both glands to the androgen pool, although the bulk was largely derived from one source. Despite long-term suppression (12 months or more) of testosterone concentrations in these patients, either by dexamethazone or an oral contraceptive pill, no significant improvement in hirsutism was noted. A new anti-androgen, cyproterone acetate (CA) was given to a group of 5 patients; the endocrine function of two was regularly monitored by serial estimations of plasma testosterone, urinary testosterone, LH, FSH, total oestrogens and pregnanediol. The drug was administered in combination with ethinyl oestradiol (EE) to avoid the risk of pregnancy and to ensure cycle regularity. The results showed that after 12 months of therapy, a marked reduction in hirsutism was noted, the frequency of shaving was reduced from an average of 3 times/week to 3 times/month. There was a significant increase in the rate of hair growth following cessation of CA alone, but not EE; with the frequency of shaving returning back to a rate similar to that reported prior to therapy. Both plasma and urinary testosterone levels were reduced during therapy, in the 2 patients studied, although in one the level remained significantly higher than those noted in normal individuals.