Persistent Anovulation (Polycystic Ovary Syndrome)

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Introduction

Essentials of Diagnosis

• Chronic anovulation.
  
• Infertility.
  
• Elevated plasma testosterone.
  
• Insulin resistance.
  
• Evidence of hyperandrogenism including hirsutism, acne, and alopecia.

General Considerations

Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting 4-6% of women of reproductive age. The primary lesion is unknown. These patients have a steady state of relatively high estrogen, androgen, and LH levels rather than the fluctuating condition seen in ovulating women. Increased levels of estrone come from obesity (conversion of ovarian and adrenal androgens to estrone in body fat) or from excessive levels of androgens seen in some women of normal weight. The high estrone levels are believed to cause suppression of pituitary FSH and a relative increase in LH. Constant LH stimulation of the ovary results in anovulation, multiple cysts, and theca cell hyperplasia with excess androgen output.

Women with Cushing’s syndrome, congenital adrenal hyperplasia, and androgen-secreting adrenal tumors also tend to have high circulating androgen levels and anovulation with polycystic ovaries.

Clinical Findings

PCOS is manifested by hirsutism (50% of cases), obesity (40%), and virilization (20%). Fifty percent of patients have amenorrhea, 30% have abnormal uterine bleeding, and 20% have normal menstruation. Additionally, they show insulin resistance and hyperinsulinemia when infused with glucose, and these women are at increased risk of early-onset type 2 diabetes mellitus. The patients are generally infertile, although they may ovulate occasionally. They have an increased long-term risk of cancer of the breast and endometrium because of unopposed estrogen secretion.

Differential Diagnosis

Anovulation in the reproductive years may also be due to (1) premature menopause (high FSH and LH levels); (2) rapid weight loss, extreme physical exertion (normal FSH and LH levels for age), or obesity; (3) discontinuation of hormonal contraceptives (anovulation for 6 months or more occasionally occurs); (4) pituitary adenoma with elevated prolactin (galactorrhea may or may not be present); and (5) hyperthyroidism or hypothyroidism. When amenorrhea has persisted for 6 months or more without a diagnosis, FSH, LH, prolactin, TSH, testosterone, and 17-hydroxyprogesterone should be checked. A 10-day course of progestin (eg, medroxyprogesterone acetate, 10 mg/d) will cause withdrawal bleeding if estrogen levels are high. This will aid in the diagnosis and prevent endometrial hyperplasia. Because of the high risk of insulin resistance and dyslipidemia, all women with PCOS should have a 2-hour glucose determination after a 75-g glucose load and a lipoprotein profile.

Treatment

In obese patients with PCOS, weight reduction is often effective; a decrease in body fat will lower the conversion of androgens to estrone and thereby help to restore ovulation.

If the patient wishes to become pregnant, clomiphene or other drugs can be employed for ovulatory stimulation.

The addition of dexamethasone, 0.5 mg at bedtime, to a clomiphene regimen may increase the likelihood of ovulation by suppression of ACTH and circulating adrenal androgens. For women who are unresponsive to clomiphene, 3- to 6-month courses of the oral hypoglycemic agent metformin, 500 mg three times daily, may bring resumption of regular cycles and ovulation. This agent reduces the hyperinsulinemia and hyperandrogenemia seen with polycystic ovary syndrome.

If the patient does not desire pregnancy, medroxyprogesterone acetate, 10 mg/d for the first 10 days of each month, should be given. This will ensure regular shedding of the endometrium so that hyperplasia will not occur. If contraception is desired, a low-dose combination oral contraceptive can be used; this is also useful in controlling hirsutism, for which treatment must be continued for 6-12 months before results are seen.

Hirsutism may be managed with epilation and electrolysis. Dexamethasone, 0.5 mg each night, is helpful in women with excess adrenal androgen secretion. If hirsutism is severe, some patients will elect to have a hysterectomy and bilateral oophorectomy followed by estrogen replacement therapy. Spironolactone, an aldosterone antagonist, is also useful for hirsutism in doses of 25 mg three or four times daily. Flutamide, 250 mg daily, and finasteride, 5 mg daily, are also effective for treating hirsutism. Because these three agents are potentially teratogenic, they should be used only in conjunction with secure contraception.

Preferences:
ACOG Practice Bulletin. Clinical Management Guidelines for Obstetricians-Gynecologists: number 41, December 2002. Obstet Gynecol 2002;100:1389.

Guzick DS (editor): Polycystic ovarian syndrome. Obstet Gynecol Clin North Am 2001;28:1

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