The ultimate goals of treatment include decreasing androgen levels to improve hirsutism, protecting the endometrium, optimizing reproductive function in those desiring fertility, and reducing the long-term sequelae of insulin resistance. The initial therapeutic strategy in the management of PCOS should be directed at management of the patient's presenting symptoms. Pharmacologic agents commonly used in the treatment of PCOS are listed in Table 5 .
If the patient is overweight or obese (BMI ≥ 26 kg/m2), specifically with abdominal obesity (i.e., waist circumference > 35 inches), lifestyle modification in the form of moderate calorie restriction and exercise is essential no matter what other intervention is chosen. One study showed that moderate calorie restriction that resulted in a 2% to 5% weight loss resulted in a 21% decline in free testosterone; 9 of 18 women with irregular cycles resumed regular ovulation; and 2 of the 18 women became pregnant. It has been shown that metformin (Glucophage), a biguanide antihyperglycemic, together with a low-calorie diet, is associated with more weight loss than a low-calorie diet alone.
Treatment options for patients with hirsutism include local measures, such as shaving, bleaching, depilatories, electrolysis, and laser therapy as well as pharmacologic therapy. Weight loss should be encouraged in women presenting with hirsutism because weight loss will result in increased levels of sex hormone-binding globulin, thereby decreasing free testosterone levels. Pharmacologic treatment is aimed at blocking androgen action at hair follicles or suppression of androgen production. It is important to note that response to pharmacologic agents is slow, occurring over many months, and that medical therapies limit new hair growth but do not affect existing hair.[12,19]
Eflornithine (Vaniqa) topical cream is approved for use in the treatment of facial hirsutism. It should be applied twice daily at least 8 hours apart. The treated area should not be washed for at least 4 hours after application of the medication. Its primary action is that of hair growth inhibition; it is not a depilatory. Vaniqa can be used in conjunction with other methods of hair removal (e.g., plucking, waxing, electrolysis, or laser). Once Eflornithine (Vaniqa) is discontinued, hair growth usually returns to pretreatment levels in about 8 weeks.
Oral contraceptives (OCs), although not approved by the US Food and Drug Administration for treatment of hirsutism, have been shown to also increase sex hormone-binding globulin production in the liver, thereby reducing the free, or unbound, level of circulating testosterone. Although no specific OC has proved to be a better treatment for hirsutism, Yasmin, a monophasic pill containing 30 mcg ethinyl estradiol and 3 mg drospirenone (an analogue of spironolactone) has been shown to suppress both ovarian and adrenal androgen production. Antiandrogens may be combined with OCs, although data have not shown that combined therapy is significantly better for the treatment of hirsutism than single agents alone. Patients who use antiandrogens alone tend to experience irregular uterine bleeding and may benefit from the use of OCs for this reason.
The most commonly used antiandrogens are spironolactone (Aldactone) and flutamide (Eulexin). As with OCs, these medications have not been approved for the treatment of hirsutism. Spironolactone is most frequently used because it is safe, available, and less expensive than other antiandrogens. Flutamide has been shown to be as effective as spironolactone; however, this drug may be hepatotoxic, and hepatic function must be regularly monitored. It is recommended that Spironolactone be discontinued 3 months prior to conception because of its association with menstrual irregularity and possible teratogenic effects.
For women with PCOS whose hirsutism does not decrease significantly with antiandrogen therapy, treatment with insulin-sensitizing agents, such as metformin (Glucophage) or thiazolidinedione (Actos) may be used.
Pharmacologic therapies that are not indicated in the treatment of hirsutism include long-acting gonadotropin-releasing hormone agonist therapy (Lupron) because it induces a hypoestrogenic state, and glucocorticoids, such as dexamethasone, because PCOS hyperandrogenism is a result of ovarian and not adrenal androgen production. In addition, glucocorticoids tend to increase insulin resistance, which would be an unwanted side effect in this patient population.
Oral contraceptives have clear benefits in the treatment of menstrual dysfunction associated with PCOS. These include 1) induction of regular withdrawal bleeding, 2) protection of the endometrium from unopposed estrogen, 3) reduction in LH secretion and consequent reduction in ovarian androgen secretion, 4) increased levels of sex hormone-binding globulin and a consequent reduction in free testosterone, and 5) improvement in hirsutism and acne. A randomized clinical trial comparing OCs and metformin (Glucophage) in obese women with PCOS found that regular menstruation occurred more frequently with the use of OCs than with metformin (Glucophage). An alternative to OCs for the protection of the endometrium is cyclic administration of a progestin, such as medroxyprogesterone acetate (Provera) 5 to 10 mg PO every day for 5 to 10 days or micronized progesterone (Prometrium) 400 mg PO daily for 10 days to promote withdrawal bleeding.
A common reason that women with PCOS seek care is infertility. Once anovulation has been diagnosed and other problems such as tubal occlusion have been excluded, the treatment is ovulation induction. An initial therapeutic approach to infertility in women with PCOS is weight loss through diet and exercise. Huber-Buchholz et al. observed that lifestyle modification is the best initial management for obese women seeking to improve their reproductive function. If the patient continues to be anovulatory, the next step is pharmacotherapy. Clomiphene citrate (Clomid) is the drug of choice to stimulate ovulation induction for women with PCOS. The strategy is to use the lowest dose possible to initiate ovulation. The starting dose is 50 mg/day, for 5 days (usually days 5-9). If there is no follicle development with this dose, the dose and/or duration of treatment can be increased. Overall, approximately 80% of women treated with clomiphene citrate will ovulate. If the patient continues to be anovulatory, metformin (Glucophage) may be added to the treatment regimen.[5,11,18] In a small group of women with PCOS who failed to ovulate in response to 150 mg/day of clomiphene citrate, 8 of 11 women ovulated on a regimen of clomiphene citrate plus metformin (Glucophage) given 500 mg TID, compared to only 3 of 14 women who ovulated on a regimen of placebo plus clomiphene citrate.
Long-term Health Risks
Some women with PCOS may seek health care because of concerns regarding long-term health risks. As noted above, if the patient is overweight, counseling regarding nutrition and exercise should be emphasized, and screening for diabetes, dyslipidemia, and hypertension should be performed. Depending on the results of these tests, specific pharmacologic treatment for these conditions should be initiated in conjunction with their primary care practitioner. Because of its favorable impact on insulin levels and lipids, metformin may be useful in the overall management of these women, although long-term data regarding the use of metformin in PCOS are not available.[23,24]
Insulin sensitivity has also been shown to improve with dietary modifications such as a low glycemic diet. The glycemic index of a carbohydrate is a measure of a particular food item's postprandial effect on blood glucose levels. The lower the glycemic index, the less influence the carbohydrate has on postprandial glucose and insulin levels. Dietary fiber, fish oil, D-chiro-inositol, and chromium have all been shown to improve insulin sensitivity, although the data are limited.
Physical exercise is an important adjunct in the improvement of insulin sensitivity and overall glucose homeostasis. Exercise can markedly increase the sensitivity of insulin-stimulated glucose uptake in skeletal muscle, although few studies have evaluated this link in patients with PCOS.
J Midwifery Womens Health. 2006;51(6):415-422. © 2006 Elsevier Science, Inc.
Cite this: Polycystic Ovary Syndrome - Medscape - Nov 01, 2006.