Any drugs causing hirsutism (see above) should be stopped. Any underlying medical causes of hirsutism (eg, Cushing syndrome, acromegaly) should be treated.
Androgenizing tumors of the adrenal or ovary are resected laparoscopically. Postmenopausal women with severe hyperandrogenism should undergo laparoscopic bilateral oophorectomy (if CT scan of the adrenals and ovaries is normal), since small hilar cell tumors of the ovary may not be visible on scans. Women with classic salt-wasting congenital adrenal hyperplasia and infertility or treatment-resistant hyperandrogenism may be treated with laparoscopic bilateral adrenalectomy.
B. Laser and Topical Treatments
Laser therapy (photoepilation) can be a very effective treatment for facial hirsutism, particularly for women with dark hair and light skin. For women of color, a longer-wavelength laser such as Nd:YAG or diode laser given with skin cooling is used. In such women, laser removal of facial hair significantly improves their appearance and quality of life. Repeated laser treatments are usually required. However, laser does not remove nonpigmented hairs. Potential side effects include local pain, erythema, and hyperpigmentation (20%) that usually resolves; skin hypopigmentation occurs rarely. Accidental eye injuries have been reported; eye shields should be used during treatments. Laser therapy is not recommended for Middle Eastern and Mediterranean women with facial hirsutism, since they have a particularly increased risk of paradoxical hypertrichosis with laser therapy.
Local treatment of facial hirsutism is by shaving or depilatories, waxing, electrolysis, or bleaching. Eflornithine (Vaniqa) 13.9% topical cream retards hair growth when applied twice daily to unwanted facial hair; improvement is noted within 4–8 weeks. Eflornithine may be used during laser therapy for a more dramatic response. However, local skin irritation may occur. Hirsutism returns with discontinuation, unless it is given with laser therapy.
Topical minoxidil may be used to treat androgenic alopecia and is mildly effective when applied to the scalp twice daily. Only the 2% formulation is FDA approved for women.
Oral contraceptives are warranted as an initial therapy for women with hirsutism who are not actively pursuing pregnancy. To reduce the risk of deep venous thrombosis, an oral contraceptive is recommended with a low-dose of estradiol (20 mcg) and a progestin having a relatively low risk of venous thrombosis (norethindrone, norgestimate, levonorgestrel). A favored formulation for daily use contains norethindrone 1 mg with ethinyl estradiol 20 mcg. Nevertheless, such oral contraceptives confer over twofold increased risk of deep venous thrombosis. Also, levonorgestrel causes insulin resistance, so its use is problematic in women with polycystic ovary syndrome. Oral contraceptives that contain particularly antiandrogenic progestins such as desogestrel (Azurette, Kariva), drospirenone (Yaz, Gianvi), norgestimate (Ortho Tri-Cyclen Lo), or cyproterone acetate (Diane 35, not available in United States) more effectively reduce hirsutism and acne; however, such antiandrogenic oral contraceptives confer a fourfold risk of deep venous thrombosis, and their use is discouraged in high-risk patients.
Cyproterone acetate is a unique progestin that is used to treat women with hirsutism worldwide, except in the United States, where it is not FDA-approved. Cyproterone acetate blocks androgen receptors as well as 5-alpha-reductase activity while also suppressing testosterone levels. It is typically prescribed as an oral contraceptive in a dose of 2 mg with ethinyl estradiol 35 mcg.
Combined oral contraceptives are relatively contraindicated for women who are predisposed to thromboembolism, such as women who are smokers or who have migraines, women who are over age 39 years or who are obese, those with hypertension or a personal history of thromboembolism. Metabolic syndrome and hypertriglyceridemia are seen, particularly with antiandrogenic progestins.
Spironolactone is effective for reducing hirsutism, acne, and androgenic alopecia in women and is a first-line medical strategy for these women. It may be taken in doses of 100–200 mg orally daily (taken as a single dose or in two divided doses) on days 5–25 of the menstrual cycle or daily if used concomitantly with an oral contraceptive. Spironolactone is contraindicated in pregnancy, so reproductive-age women must use reliable contraception during this therapy. Hyperkalemia is an uncommon side effect, but serum potassium should be checked 1 month after beginning therapy or after dosage increases. Spironolactone should be avoided or used cautiously in women with kidney disease or who are taking an ACE inhibitor or ARB. Spironolactone should not be given with an oral contraceptive containing drospirenone because the progestin has an anti-mineralocorticoid effect that predisposes to hyperkalemia. Trimethoprim-sulfamethoxazole should not be taken along with high-dose spironolactone. Trimethoprim has potassium-sparing diuretic effects and combining it with spironolactone increases the risk of severe hyperkalemia and sudden death. Side effects of spironolactone include breast tenderness, menstrual irregularity, headaches, nausea, and fatigue, which may improve with continued treatment or dose reduction; paradoxical scalp hair loss has been reported at higher doses.
Flutamide and bicalutamide inhibit testosterone binding to androgen receptors and also suppress serum testosterone. These drugs can rarely cause severe hepatotoxicity. Also, exposure during pregnancy causes fetal malformations and disorders of sexual development in male infants. Therefore, the use of these drugs for hirsutism is discouraged. They should only be used as a last resort for women with severe hirsutism/virilization and only with strict contraceptive precautions and very close monitoring for hepatic toxicity. Flutamide is given orally in a dosage of 250 mg twice daily for the first year and then 125–250 mg/day for maintenance. Flutamide decreases cortisol renal clearance and corticosteroid replacement doses (eg, in congenital adrenal hyperplasia) should be reduced when flutamide is added. Bicalutamide is given in a dosage of 50 mg once daily.
Finasteride inhibits 5-alpha-reductase, the enzyme that converts testosterone to active dihydrotestosterone in the skin. It provides inconsistent reduction in hirsutism and androgenic alopecia over 6 months. Also, this drug causes pseudohermaphroditism in male infants if mistakenly taken during pregnancy. Therefore, the use of finasteride for hirsutism is strongly discouraged.
Metformin alone is ineffective in improving hirsutism, but can enhance the anti-hirsutism effect of spironolactone. Start metformin at a dose of 500 mg/day with breakfast for 1 week, then increased to 500 mg with breakfast and dinner. If this dose is clinically insufficient but tolerated, the dose may be increased to 850–1000 mg twice daily with meals. The most common side effects are dose-related gastrointestinal upset and diarrhea or constipation. Metformin appears to be nonteratogenic. Although metformin reduces insulin resistance, it does not cause hypoglycemia in nondiabetic patients. Metformin is contraindicated in severe kidney or liver disease. GLP-1 agonist therapy reduced weight and serum testosterone levels in women with PCOS in one short-term study. However, an effect on hirsutism has not been demonstrated clinically.
Simvastatin can reduce hirsutism in women with PCOS. In one study, simvastatin 20 mg orally daily was given to women receiving an oral contraceptive for PCOS. Besides improving their serum lipid profiles, women receiving simvastatin had greater decreases in hirsutism and serum free testosterone levels than the women receiving an oral contraceptive alone. Atorvastatin also reduced serum testosterone by an average of 25% in women with PCOS.
Glucocorticoid replacement is necessary for women with classical congenital adrenal hyperplasia (21-hydroxylase deficiency) with hirsutism and adrenal insufficiency that requires glucocorticoid and mineralocorticoid replacement. However, women with partial “late-onset” 21-hydroxylase deficiency are not cortisol deficient and do not require glucocorticoid replacement. Also, glucocorticoids are ineffective in reducing hirsutism in these women. However, such women may require replacement doses of glucocorticoids (prednisone, methylprednisolone) to normalize menses and for ovulation induction. Dexamethasone is not recommended due to its potency and risk of causing iatrogenic Cushing syndrome.
GnRH agonist therapy has been successful in treating postmenopausal women with severe ovarian hyperandrogenism when laparoscopic oophorectomy is contraindicated or declined by the patient.
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