Polycystic ovary syndrome: Cosmetic and dietary approaches
What we know about treatment of hirsutism and acne, the effects of weight loss, and emerging diagnostic tests
IN THIS ARTICLE
Gonadotropin production is reduced by the progestational and glucocorticoid effects of cyproterone acetate and may result in lower testosterone levels. However, the blockade of adrenal 21-hydroxylase may lead to the accumulation of androgen precursors, which may be converted to testosterone, reducing the efficacy of antiandrogen treatment. For this reason, cyproterone acetate is sometimes combined with other agents. Studies of hirsutism have demonstrated increased efficacy with combination therapy, compared with cyproterone acetate alone. This drug is approved for use only in the United Kingdom and Canada.
A dose of 50 mg to 100 mg is recommended. The most serious potential side effect is liver toxicity. Patients should be monitored for changes in liver enzymes, especially if they are taking a high dose (200–300 mg/day). Other side effects include adrenal insufficiency, loss of libido, and depressive mood changes.
Finasteride (approved in 1992 and marketed as Proscar, Propecia) is a synthetic antiandrogen that inhibits 5a-reductase, the enzyme that converts testosterone to DHT. It is used as a treatment for benign prostatic hyperplasia in low doses, and for prostate cancer in higher doses. A dose of 2.5 mg to 5 mg daily is typical for women with hirsutism.
In randomized clinical trials, finasteride has produced significant improvements in hirsutism, compared with placebo, but no significant differences compared with other therapies. Although the side-effect profile is less severe than that of other therapies, teratogenicity is a major concern.
Numerous dietary interventions have been explored in women with PCOS.1 A few studies have involved manipulation of the dietary macronutrient profile, but only two have used a controlled study design to compare different macronutrient compositions. Two different groups tested a high-protein (30%) diet, compared with lower protein (15%), while keeping fat intake (30%) the same.2,3
In a study by Moran and colleagues, women were prescribed a reduced-calorie diet for 12 weeks, followed by a maintenance diet for 4 weeks.2 There were no differences between the high-protein and low-protein groups in terms of weight or fat loss (as assessed by dual-energy x-ray absorptiometry). However, the 38% dropout rate was higher than anticipated, and the authors acknowledge that the inability to detect a difference between groups could be due to insufficient power.2
In the study by Stamets and colleagues, the same macronutrient profile was used, but for only 4 weeks—too short a time to detect much difference in weight loss.3 Not surprisingly, no difference in weight loss was found between groups.
In both studies, dietary compliance and the rate of study retention were confounding and limiting factors.2,3 To date, there is insufficient evidence that a particular dietary approach, such as modified macronutrient composition, will enhance weight loss in women with PCOS. However, general dietary and lifestyle modifications still remain the first line of therapy to address the metabolic consequences of PCOS for overweight and obese women.1 In appropriate clinical situations, consideration should also be given to alternative weight-loss approaches, such as weight-loss medication or bariatric surgery.
Although the fundamental pathophysiologic mechanism is unclear, both lean and obese women with PCOS have greater LH pulse frequency and amplitude, leading to increased 24-hour mean concentrations of LH. Because androgen production by theca cells is LH-dependent, it would seem to follow that the elevated LH levels seen in women with PCOS are responsible for excess androgen production. The most likely cause of anovulation is an FSH level too low to fully mature the follicles. FSH levels may be suppressed by negative feedback inhibition from midfollicular estradiol levels.
While the defect in PCOS is unknown, it is clear that there are altered gonadotropin dynamics. Nonetheless, current consensus is that elevated LH is not essential for the definition of PCOS, despite this frequent finding and the understanding that high LH levels have adverse effects on oocyte quality, maturity, pregnancy outcomes, and miscarriages.4,5
In recent years there has been increasing interest in anti-Müllerian hormone (AMH) (also known as Müllerian-inhibiting substance), which is exclusively of ovarian origin in women, as a marker of ovarian reserve and female reproductive function. Several studies on the role of AMH in ovarian physiology indicate that the hormone has two main functions with respect to folliculogenesis, at least according to mice models:
