Oral Contraceptives Combination oral contraceptives (OCs) decrease adrenal and ovarian androgen production and reduce hair growth in nearly two-thirds of hirsute patients (91–94). Treatment with OCs offers the following benefits: 1.
The progestin component suppresses LH, resulting in diminished ovarian androgen production.
2.
The estrogen component increases hepatic production of SHBG, resulting in decreased free testosterone concentration (95,96).
3.
Circulating androgen levels are reduced, including those of DHEAS, which to some extent is independent of the effects of both LH and SHBG (30,97).
4.
Estrogens decrease conversion of testosterone to DHT in the skin by inhibition of 5α-reductase.
When an OC is used to treat hirsutism, a balance must be maintained between the decrease in free testosterone levels and the intrinsic androgenicity of the progestin. Three progestin compounds that are present in OCs (norgestrel, norethindrone, and norethindrone acetate) are believed to be androgen dominant. The androgenic bioactivity of these steroids may be a factor of their shared structural similarity with 19-nortestosterone steroids (98). Oral contraceptives containing the so-called new progestins (desogestrel, gestodene, norgestimate, and drospirenone) have minimized androgenic activity. However, there is limited evidence of clinically measurable differences in outcome resulting from the disparity of in vitro estimates of androgenic potency.
The use of OCs alone may be relatively ineffective (<10% success rate) in the treatment of hirsutism in women with PCOS, and the OCs may exacerbate insulin resistance in these patients (99,100). Effective protocols for pharmacologic management of significant hirsutism with OCs usually include coadministration of agents that impede androgen action.
Oral or intramuscular administration of medroxyprogesterone acetate (MPA) successfully treats hirsutism (101). It directly affects the hypothalamic–pituitary axis by decreasing GnRH production and the release of gonadotropins, thereby reducing testosterone and estrogen production by the ovary. Despite a decrease in SHBG, total and free androgen levels are decreased significantly (102). The recommended oral dose for GnRH suppression is 20 to 40 mg daily in divided dosages or 150 mg given intramuscularly every 6 weeks to 3 months in the depot form. Hair growth is reduced in up to 95% of patients (103). Side effects of the treatment include amenorrhea, bone mineral density loss, depression, ﬂuid retention, headaches, hepatic dysfunction, and weight gain. MPA is not commonly used for hirsutism.
Administration of GnRH agonists may allow the differentiation of androgen produced by adrenal sources from that of ovarian sources (47). It was shown to suppress ovarian steroids to castrate levels in patients with PCOS (104). Treatment with leuprolide acetate given intramuscularly every 28 days decreases hirsutism and hair diameter in both idiopathic hirsutism and hirsutism secondary to PCOS (105). Ovarian androgen levels are significantly and selectively suppressed. The addition of OC or estrogen replacement therapy to GnRH agonist treatment (addback therapy) prevents bone loss and other side effects of menopause, such as hot ﬂushes and genital atrophy. The hirsutism-reducing effect is retained (102,106). Suppression of hirsutism is not potentiated by the addition of estrogen replacement therapy to GnRH agonist treatment (107).