Treatment of Hyperandrogenism in Female Adolescents

PCOS

The treatment of hyperandrogenism in women with PCOS aims at interrupting androgen production and/or action. Suppression of ovarian function with oral contraceptives is usually the first line of therapy. It will arrest progression of hirsutism but does not lead to substantial improvement. This treatment lowers free T levels by reducing serum gonadotropin levels, increasing SHBG levels, and modestly lowering DHEAS levels. One of the new generations of pills containing a non-androgenic progestin such as desogestrel, gestodene or norgestimate is advisable. Cyproterone acetate is the major antiandrogen available outside the USA. It is a potent progestin taken up by fat and released slowly.

When given for 21 days every 4 weeks at a 50-mg daily dose, it inhibits pituitary gonadotropin secretion and acts as a potent antiandrogen upon the pilosebaceous unit. An excellent response of hirsutism is seen in up to 90% of cases. It must be administered with an estrogen to avoid irregular bleeding or amenorrhea due to endometrial atrophy.

Natural estradiol (either percutaneously or orally, 2mg/day for 1 - 21 days) is preferable to ethinyl estradiol, which has more metabolic effects. Spironolactone, 50 - 100 mg bid, has been shown to be effective and is the most potent and safest antiandrogen available in the USA. It is potentially teratogenic to fetal male genital development and may cause menstrual disturbance. Therefore, it should be prescribed with an oral contraceptive. Corticosteroid therapy is seldom useful.

In obese subjects, weight loss is very important, having beneficial effects on most aspects of the syndrome, such as subjective symptoms, infertility, hyperinsulinemia and related metabolic aberrations, and long-term health risks. Whether a long-term treatment with insulin-sensitizing drugs should be undertaken as soon as adolescence starts is an unsolved issue, until long-term studies demonstrate that the benefit/risk or cost ratio is favorable.

NCAH

As in classic forms, the conventional treatment of NCAH is glucocorticoid therapy. This aims mainly to reduce adrenal hyperandrogenism, while the necessity for cortisol replacement is less evident. Our opinion is that DXM should be used rather than less potent ACTH-inhibiting compounds such as hydrocortisone or prednisone. Very low doses of DXM are needed (0.25 - 0.5 mg at night). Physicians should not aim to normalize the morning 17-HP plasma level, since it has been shown that adrenal androgens are more sensitive to the glucocorticoid-suppressive effect than are the C-21 steroids. Therefore, the T or A plasma levels, rather than 17-HP, should be monitored.

The fact that much of the intra-adrenal abnormalities in NCAH may be ACTH-independent may explain why 17-HP serum levels are frequently not completely normalized by glucocorticoid treatment despite adequate ACTH suppression.