Oral Contraceptives Oral contraceptives may be effective for hirsutism by decreasing ovarian androgen production and increasing circulating levels of sex hormone–binding globulin, leading to decreased free androgen in the circulation.
Antiandrogens Spironolactone decreases androgen production and competes with androgens at the androgen receptor. Side effects include diuresis and dysfunctional uterine bleeding. The use of spironolactone is typically combined with oral contraceptives to avoid irregular bleeding and to prevent pregnancy from occurring while on spironolactone. Flutamide is approved by the U.S. Food and Drug Administration (FDA) for adjuvant therapy in prostatic cancer and for treatment of hirsutism. Its effects are similar to those of spironolactone (132). Liver function should be monitored because of the rare complication of hepatotoxicity. Cyproterone acetate, a strong progestin and antiandrogen, is used abroad but is not available in the United States. It is usually administered in combination with ethinyl estradiol in an oral contraceptive. By decreasing circulating androgen and LH levels, and by inducing antagonism of androgen effects at the peripheral level, cyproterone acetate is effective in treating hirsutism (133). Finasteride, a 5α-reductase inhibitor, is approved by the FDA for the treatment of benign prostatic hypertrophy (Proscar) and male pattern baldness (Propecia). It is effective in treating hirsutism, although perhaps is no more effective than other available agents (134,135). Its major advantage is that it is exceptionally well tolerated and may be used when side effects preclude the use of other therapeutic options for hirsutism.
All antiandrogens are teratogenic as they may lead to feminization of the external genitalia of a male fetus (ambiguous genitalia) if the patient should conceive while taking the medication. Therefore, antiandrogens are typically used in combination with oral contraceptives.
GnRH Agonist Administration of GnRH agonist agents virtually eliminates ovarian steroid production, and estrogen-progestogen add-back therapy allows long-term administration and protection against osteoporosis.
Eﬂornithine Hydrochloride Eﬂornithine hydrochloride is a topical cream that is approved by the FDA for use on the face and chin. Improvements in facial hirsutism may be seen in 4 to 8 weeks of twice-daily applications.
Ovulation Induction A large subset of patients with amenorrhea or oligomenorrhea and chronic anovulation seek care because they are unable to conceive (see Chapter 32). Ovulation induction therapy is generally the treatment of choice for such patients, but pretreatment counseling should be provided in sufficient detail to ensure realistic expectations. The patient should be provided with information regarding the chances of a successful pregnancy (considering age of the patient and treatment modality), potential complications (hyperstimulation and multiple gestation), expense, time, and psychological impact involved in completing the course of therapy. Treatment should be individualized (136).
Earlier studies raised the possibility of a relationship between ovulation induction and the risk of ovarian cancer (137,138). Ongoing studies are attempting to address this issue conclusively, but data support an increase of approximately 2.5-fold in ovarian cancer in patients with infertility, which appears unrelated to the use of ovulation-inducing drugs (139140). There is no conclusive evidence to link fertility drug use and ovarian cancer; thus, no change in current ovulation induction practices seems warranted at present (141). Pregnancy and use of oral contraceptives before or after childbearing may protect against ovarian cancer.