Systemic therapies directed at hirsutism can be divided into those that decrease ovarian or adrenal androgen production and those that inhibit androgen action in the skin. The systemic therapies include glucocorticoids, oral contraceptives (OCs), spironolactone, flutamide, finasteride, cyproterone acetate (not available in the United States), and insulin sensitizers (metformin and rosiglitazone).
Glucocorticoids: Glucocorticoids (dexamethasone or prednisone), which suppress adrenocorticotropin hormone (ACTH)βdependent adrenal androgen synthesis, have been used with variable success in women with adrenal hirsutism, as in congenital adrenal hyperplasia (CAH) or idiopathic adrenal hyperandrogenism. Usually, 0.5-1 mg of dexamethasone at bedtime is sufficient to suppress ACTH and adrenal androgen production. Unfortunately, some patients gain weight and develop cushingoid features, even with this small of a dose. Further investigations may establish that lower doses (perhaps 0.25 mg) can be effective without adverse effects.
OCs: The drugs most widely used to suppress ovarian androgen production are OCs. They are probably the first choice for young women with hirsutism who do not want to become pregnant.
OCs are inexpensive and promote regular uterine bleeding. In addition, OCs can be used in combination with one of the antiandrogens or other forms of therapy. On the other hand, do not use OCs in women with a history of migraines, known or possible thrombotic disease, or breast or uterine cancer.
Moreover, for several reasons, OCs have a significant failure rate in patients with hirsutism. Low-dose OCs and progestin-only minipills fail to suppress ovulation in as many as 50% of women. Ovarian function continues at a variable rate, and ovarian androgens continue to be produced. Second, the progestins in OCs are attenuated derivatives of testosterone and have variable degrees of androgenic activity in women. The degree depends on the type of progestin and, more importantly, on individual susceptibility.
Spironolactone: Spironolactone, in daily doses of 50-200 mg, blocks androgen receptors. Spironolactone also decreases testosterone production, making it additionally effective for hirsutism. Spironolactone is especially useful in a patient with hypertension or edema because the drug is a mild diuretic.
Sexually active women taking spironolactone should ensure that contraceptive measures are adequate. In some cases, spironolactone can be combined with an OC for added effect on the hirsutism.
With current systemic therapies for hirsutism, 6 months to a year of therapy is usually required before results are noticeable. Even then, only approximately one half to three quarters of patients show improvement. The problem may lie partially in the nature of the hair follicle, which persists for 6 months to a year even after androgen levels have been normalized. Ineffectiveness may also be due to the inability of treatment to completely normalize elevated tissue dihydrotestosterone levels. Newer therapies directed at inhibition of 5-alpha-reductase or blockade of the androgen receptor may improve the ability to treat patients.
Flutamide: Flutamide, an example of the newer therapies, is a potent nonsteroidal selective antiandrogen without progestational, estrogenic, corticoid, or antigonadotropin activity. Preliminary data indicate that it is effective as therapy for hirsutism (and also acne); however, flutamide is expensive and has caused fatal hepatitis.
Finasteride: Finasteride is a 5-alpha-reductase inhibitor approved for the treatment of benign prostatic hyperplasia. No adverse effects have been reported in women, and the efficacy is similar to that of spironolactone. In at least one study, finasteride was added to spironolactone, demonstrating an additive reduction in hirsutism scores. The main concern with finasteride, however, is the risk of ambiguous genitalia in male fetuses exposed to the enzyme inhibitor during the first trimester. Therefore, use this drug only in women who are postmenopausal with no chance of becoming pregnant.
Cyproterone acetate has been effective in the treatment of hirsutism. When added to ethinyl estradiol, it is as effective as flutamide in the treatment of hirsutism. Cyproterone is not available in the United States.
Insulin sensitizers: Both metformin and rosiglitazone improve insulin resistance and have been shown to be effective in lowering androgen levels and in treating hirsutism.
Sibutramine: Weight loss with this anorectic agent improves hirsutism scores, androgen levels, and cardiovascular risk factors in women with polycystic ovary syndrome (PCOS).
Cosmetic measures for hirsutism and their disadvantages are as follows:
Hydrogen peroxide bleaching is not suitable for severe hirsutism.
Plucking can cause skin irritation, folliculitis, and scarring.
Waxing can cause skin irritation, folliculitis, and scarring. The wax used has a low melting point.
Shaving may be psychologically unacceptable.
Chemical depilatories can cause skin irritation.
Electrolysis can be painful, and short-wave diathermy can cause scarring.
Laser therapy has been shown not only to reduce unwanted hair but also to improve depression and anxiety in women with hirsutism.
DRUG(S) OF CHOICE
After tumor has been ruled out:
. Oral contraceptives:
. Any brand is effective
. Estrogen and progesterone can be given separately
. Medroxyprogesterone (Depo-Provera) IM every 3 months; less effective
. Metformin: decreases insulin secretion which decreases androgen production in polycystic ovaries
. Eflornithine (Vaniqa) HCL cream - apply bid; reduces facial hair in 40% of women (with long term use)
Contraindications: Avoid giving medications in pregnancy
ALTERNATIVE DRUGS
. Antiandrogenic drugs (often used when workup is negative and oral contraceptives are not helping. They
have low efficacy and many side effects):
. Spironolactone: up to 200 mg/day - onset of action is slow; side effects include menorrhagia; contraindicated in pregnancy
. Cyproterone: orphan drug not routinely available
- usually combined with estrogen - contraindicated in pregnancy. Monitor LFTs.
. Flutamide: 250 mg tid - nonsteroidal antiandrogen. Monitor LFTs. Need concurrent oral contraceptives.
. Ketoconazole: 400 mg day - avoid with astemizole, triazolam, cisapride
. Leuprolide (Lupron): lowers LH. Side effects of menopause.
. Danazol: lowers LH. Side effects of menopause
. Serenoa repens (saw palmetto) - in small studies decreases hair growth via blocking 5-alpha-reductase
activity in the skin