Polycystic ovary syndrome: Cosmetic and dietary approaches

Although polycystic ovary syndrome (PCOS) is the most common endocrine abnormality in women of reproductive age, affecting at least 1 in 15 women in this population, its precise cause is unknown. As a result, management of PCOS requires a focus on its individual effects, among them anovulation, infertility, hyperandrogenism, and insulin resistance.

So far in this four-part series, we have covered diagnosis and treatment, the role of obesity and insulin resistance, and long-term metabolic risks. In this concluding article, we focus on cosmetic and dietary issues, and describe emerging diagnostic approaches to this common disorder.

My patient has excessive hair growth and acne and only cares about cosmetic results. Other than the traditional therapy of oral contraceptives (OCs), what medical treatment options does she have?

Management of hirsutism and acne should focus on combination therapy that includes androgen suppression and peripheral androgen blockade, with or without mechanical or cosmetic reduction or destruction of unwanted hair. The choice of treatment depends on the side-effect profile. To maximize benefits, treatments should be continued for at least 2 years. All of the therapies described in this article have teratogenic potential (inhibiting normal development of male external genitalia) and should be prescribed only with adequate contraception that is used consistently.

Medical treatment of hirsutism and acne

Oral contraceptives are the most popular treatment for hirsutism. They suppress pituitary production of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which in turn suppress ovarian androgen production. OCs also may reduce adrenal androgen production, although the mechanism of action is unclear.

The estrogen component in OCs increases hepatic production of sex hormone-binding globulin (SHBG), thereby decreasing free testosterone levels. The progestin component antagonizes 5α-reductase and the androgen receptor; it also may increase hepatic metabolism of testosterone and can increase SHBG when the OC has low androgenic activity.

Spironolactone is an aldosterone antagonist and mild diuretic that competes primarily with androgens for the androgen receptor. It also:

• inhibits the 5α-reductase enzyme, preventing the conversion of testosterone to the more potent dihydrotestosterone (DHT)
• increases hepatic production of SHBG, thereby decreasing free testosterone levels
• suppresses enzymes in the biosynthesis of androgens.

A dose of 100 mg twice daily is effective, although higher doses of 200 mg to 300 mg may be required. Start with a dose of 25 mg daily, with a progressive increase over 3 weeks to minimize side effects (TABLE).

Medical treatment of hirsutism in women with PCOS

Drug	Brand name	Cost	Side effects
Spironolactone	Aldactone, Novo-Spiroton, Aldactazide, Spiractin, Spirotone, Verospiron, Berlactone	$30 for thirty 50-mg tabs	Dyspepsia, nausea, polyuria, nocturia, fatigue, headache, breast tenderness, reduced libido, photosensitivity, hyperkalemia (rare)
Flutamide	Eulexin	$170 for one hundred 250-mg tabs	Greenish urine, excessive dryness of skin and scalp, liver enzyme abnormalities, hepatic toxicity
Bicalutamide	Casodex, Cosudex, Calutide, Kalumid	$30–$490 for thirty 50-mg tabs	Breast tenderness, gynecomastia, hot flushes, gastrointestinal disorders, diarrhea, nausea, hepatic changes, asthenia, pruritus
Cyproterone acetate	Androcur, Cyprostat, Cyproteron, Procur, Cyprone, Cyprohexal, Ciproterona, Cyproteronum, Neoproxil, Siterone	$35–$50 for twenty 50-mg tabs (generic) $90 for sixty 50-mg tabs (Androcur)	Liver toxicity, adrenal insufficiency, loss of libido, and depressive mood changes
Finasteride	Proscar, Propecia	$8.75–$17.50 for thirty to sixty 5-mg tabs	Teratogenicity is a major concern

Flutamide (Eulexin) is approved by the US Food and Drug Administration as an adjuvant treatment for prostate cancer. It is not a steroid but a substituted anilide that competes with testosterone and its powerful metabolite, DHT, for binding to androgen receptors. Flutamide may also be used to treat excess androgen levels and hirsutism in women. It is given at a dose of 500 mg daily. Side effects include greenish urine, excessive dryness of skin and scalp, liver enzyme abnormalities, and hepatic toxicity.

Flutamide is now being replaced by a newer member of this class of drugs, bicalutamide (launched in 1995 and marketed as Casodex, Cosudex, Calutide, Kalumid), due to a better side-effect profile. Bicalutamide acts as a pure antiandrogen by binding to the androgen receptor and preventing its activation and subsequent upregulation of androgen-responsive genes by androgenic hormones. In addition, bicalutamide accelerates the degradation of the androgen receptor. Preliminary studies suggest that a dose of 25 mg daily produces significant improvement in Ferriman-Gallwey scores. Side effects include breast tenderness, gynecomastia, hot flushes, gastrointestinal disorders, diarrhea, nausea, hepatic changes (elevated levels of transaminases; jaundice), asthenia, and pruritus.

Cyproterone acetate is a synthetic derivative of 17-hydroxyprogesterone. It inhibits the steroidogenic enzyme 21-hydroxylase and, to a lesser extent, 3-beta-hydroxysteroid dehydrogenase, both of which are needed to synthesize cortisol and aldosterone.