This group of medications can be used only when not attempting a pregnancy and with some form of adequate birth control. There is at least a theoretical, risk of feminizing the genitals of a male fetus. The value of the agents for PCOS patients is to improve the skin problems that occur with PCOS.
Spironolactone (Aldactone) is a diuretic used to treat hypertension. It has an idiosyncratic action as an anti-androgen and can reduce excessive hair growth by blocking the effects of androgen. It is the most widely prescribed anti-androgen in the United States. At high doses spironolactone blocks the metabolic pathway called the cytochrome P-450 system that affects the capacity of ovary and adrenal gland to make androgens. It also alters the conversion of testosterone to dihydrotestosterone (DHT) by 5a-reductase enzyme. Some patients have a surprisingly good response to therapy while others seem completely resistant. In some cases, especially when OC’s can not be used, it may represent first line therapy. The effects of OC therapy may be additive, as well as reducing a tendency of irregular bleeding seen in some patients using spironolactone. The usual starting dose is 50 mg. Once, or twice daily and may be increased to 100 mg. twice daily. It is prudent to have blood testing and reassessed after several weeks of therapy. Although an adverse effect of spironolactone use may be hyperkalemia (high levels of potassium in the blood), it is rarely seen in young healthy women. Because spironolactone is metabolized in the liver, baseline liver function testing should be performed. The most common side-effects are nausea and indigestion, with some patients reporting increased fatigue.
Cyproterone acetate (CA) is a potent anti-androgen and weak progestin. CA is available only outside the United States. Its effectiveness in treatment of hirsutism is well substantiated. Most patients will report decreased hair growth and some patients become amenorrheic. While CA is usually well tolerated, its glucocorticoid activity may cause weight gain. The usual dose is 50 mg. daily in conjunction with an oral contraceptive. CA has also been compounded with ethinyl estradiol and marketed as an oral contraceptive, Diane. The usefulness of Diane in the treatment of hirsutism has been questioned; but it may help to control hair growth. Drug induced hepatitis has been reported and it is prudent to monitor liver function.
Flutamide (Eulexin) is a non-steroidal anti-androgen indicated for treatment of prostatic cancer. Its action is similar to spironolactone and cyproterone acetate in that androgen action is reversibly blocked at the androgen receptor. Flutamide is theoretically superior to cyproterone due to its absence of prednisone (steroid) like activity and to spironolactone because of its lack of alteration in kidney function. A majority of patients report the side effect of dry skin. Less common side-effects are hot flushes, increased appetite, headache, fatigue, and nausea. It is metabolized by the liver and fatal liver toxicity has been reported. The usual dose is 125-250 mg. once, or twice daily for treatment of hirsutism. While some have reported the drug as safe and superior to spironolactone, others report a similar efficacy and avoid its use due to its high cost and potential of serious liver damage.
Finasteride (Proscar, Propecia) is not a true anti-androgen, but since it is an alternative to anti-androgen therapy, it is described here. Finasteride is an inhibitor of 5a-reductase activity and was initially indicated for use in the management of benign prostatic hypertrophy. Now it has been approved and received the most publicity for its capacity to thwart male pattern baldness in some men. Since its action is directed at the point of production of the active skin androgen dihydrotestosterone, the drug shows promise in the treatment of hirsutism. The dose of 5 mg. daily is usually prescribed. Finasteride is questionably as effective as spironolactone. The safety profile and tolerance appears to be very good. Despite the pregnancy warning and high cost, the theoretical advantages and excellent tolerance may make this a drug to consider.
Vaniqa (eflornithine) does not inhibit the production or action of androgens but interferes with an enzyme found in the hair follicle needed for hair growth (ornithine decarboxylase). It is a cream used twice daily and only on the face. About one in three patients have reported marked improvement Some improvement is seen in about another one-third, but this is also about the improvement when women used a cream containing no active ingredient (placebo). Improvement is gradual and may not be evident for two months, and may take as long as six months. If there is no improvement in six months, use is discontinued. Less than one percent of the active ingredient is absorbed into the body. Side effects are rare and usually limited to skin sensitivity. While the risks are unknown, use in those attempting a pregnancy should be discouraged.