In hyperinsulinemic hyperandrogenemic nonobese PCOS adolescents on a combination of metformin (850 mg per day) and ﬂutamide (62.5 mg per day), the low-dose OC containing drospirenone resulted in a more effective and more efficient reduction in total and abdominal fat excess than was demonstrated by those utilizing an OC with gestodene as the progestin (124). The combination of ethinyl-drospirenone, metformin, and ﬂutamide is effective in reducing excess total and abdominal fat and attenuating dysadipocytokinemia in young women with hyperinsulinemic PCOS. The use of the antiandrogen ﬂutamide appeared to emphasize effects (125). Many patients taking ﬂutamide (50% to 75%) report dry skin, blue-green discoloration of urine, and liver enzyme elevation. Liver toxicity or failure and death are rare but severe side effects of ﬂutamide appear to be dose related (126). The 2008 Endocrine Society clinical practice guidelines do not recommend using ﬂutamide as first-line therapy for treating hirsutism. If it is used, the lowest effective dose should be given, and the patient’s liver function should be monitored closely (4). Flutamide should not be used in women desiring pregnancy.
Finasteride Finasteride is a specific inhibitor of type 2 5α-reductase enzyme activity, approved in the United States at a 5-mg dose for the treatment of benign prostatic hyperplasia, and at a 1-mg dose to treat male-pattern baldness. In a study in which finasteride (5 mg daily) was compared with spironolactone (100 mg daily), both drugs resulted in similar significant improvement in hirsutism, despite differing effects on androgen levels (127). Most of the improvement in hirsutism with finasteride occurred after 6 months of therapy with 7.5 mg of finasteride daily (128). The improvement in hirsutism in the presence of rising testosterone levels is convincing evidence that it is the binding of DHT, and not testosterone, to the androgen receptor that is responsible for hair growth. Finasteride does not prevent ovulation or cause menstrual irregularity. The increase in SHBG caused by OCs further decreases free testosterone levels; OCs in combination with finasteride are more effective in reducing hirsutism than finasteride alone. As with spironolactone and ﬂutamide, finasteride could theoretically feminize a male fetus; therefore, both of these agents are used only with additional contraception.
Ovarian Wedge Resection Bilateral ovarian wedge resection is associated with only a transient reduction in androstenedione levels and a prolonged minimal decrease in plasma testosterone (129,130). In patients with hirsutism and PCOS who had wedge resection, hair growth was reduced by approximately 16% (17,131). Although Stein and Leventhal’s original report cited a pregnancy rate of 85% following wedge resection and maintenance of ovulatory cycles, subsequent reports show lower pregnancy rates and a concerning incidence of periovarian adhesions (17,132). Instances of premature ovarian failure and infertility were reported (133).