Polycystic ovary syndrome, with a prevalence of approximately 7% of women, is a common, important, and often underrecognized condition.
Although definitions vary, PCOS is characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovaries. Obesity often results in hyperinsulinemia, which may contribute to decreased levels of sex hormone–binding globulin (SHBG), increased circulating androgen, and increased androgen production. Obesity may exacerbate the clinical manifestations of PCOS, but not all women with PCOS are obese.
Diagnostic Criteria
The three following diagnostic criteria are commonly referenced for PCOS:
• NIH criteria. Hyperandrogenism and menstrual abnormalities (amenorrhea or oligomenorrhea) must be present.
• Rotterdam criteria. Ultrasonography of polycystic ovaries is an important component of the diagnosis of PCOS (12 or more follicles, 2- to 9-mm diameter, or increased ovarian volume greater than 10 cm3). This testing has been criticized for increasing the number of PCOS diagnoses and subjecting women without PCOS to unwarranted management.
• Androgen Excess Society criteria. Hyperandrogenism (whether present clinically or in serum) must be present.
Dr. Neil Skolnik and Dr. Charissa Myers
Appropriate history and physical should include medications, onset of androgen excess, menstrual history, family history, blood pressure, body mass index, waist circumference, signs of hyperandrogenism (acne, clitoromegaly, body hair distribution, balding), and signs of insulin resistance (acanthosis nigricans, obesity). Lab assessments should include fasting lipids, fasting glucose, 2-hour oral glucose tolerance test, total testosterone (free testosterone and SHBG), as well as thyroid-stimulating hormone, prolactin, and 17-hydroxyprogesterone. If Cushing’s disease is suspected, 24-hour urinary free-cortisol excretion test or low-dose dexamethasone suppression test should be obtained. A pelvic ultrasonography can be used to evaluate for polycystic ovaries and endometrial abnormalities.
Clinical Manifestations
Clinical manifestations include menstrual dysfunction, infertility, hirsutism, acne, androgenic alopecia, insulin resistance, and metabolic syndrome. Long-term sequelae include an increased risk of type 2 diabetes, cardiovascular disease, and endometrial cancer.
Differential Diagnosis
Diseases to consider in patients with the clinical manifestations listed above are thyroid disease, exogenous androgens, primary ovarian failure, and prolactin disorders. In addition, be aware of rare disorders that can cause symptoms similar to PCOS, including Cushing’s syndrome, androgen-secreting tumors of the ovaries or adrenals, and nonclassical congenital adrenal hyperplasia.
Weight Loss With PCOS
Weight loss in obese women with PCOS produces increases in SHBG, decreased circulating-androgen levels, resumption of menses, and improved pregnancy rates. Weight loss also decreases hirsutism, insulin resistance, and lipid levels. Weight loss that occurs by lifestyle modifications, pharmacologic agents (such as orlistat), and gastric bypass have shown similar effects.
PCOS and Diabetes Risk
There is a two- to fivefold increased risk of diabetes in women with PCOS. Women with PCOS should be screened with a fasting-glucose level and a 2-hour glucose level after a 75-g glucose load. Metabolic syndrome (defined as blood pressure greater than 130/85, waist circumference greater than 35 inches, fasting glucose greater than 100 mg/dL, HDL cholesterol less than 50 mg/dL, and triglycerides greater than 150 mg/dL) affects nearly 33% of women with PCOS. Although there are insufficient data to recommend insulin-sensitizing pharmacological agents prophylactically, the National Institute of Diabetes and Digestive and Kidney Diseases’ Diabetic Prevention Program trials showed a decreased risk of developing type 2 diabetes in women with PCOS when lifestyle modifications or metformin (1,500-2,000 mg/day) were used by those with impaired glucose tolerance.
Cardiovascular Disease Risk
There is no well-documented evidence of increased risk of cardiovascular events in women with PCOS. However, given the increase in cardiovascular risk factors, their cardiovascular risk should be periodically assessed. These risks can be reduced through exercise, caloric restriction, weight control, and possibly by introducing statins and insulin-sensitizing agents.
Menstrual Dysfunction
Combination low-dose hormonal contraceptives are the primary treatment for menstrual dysfunction. They work by suppressing luteinizing hormone and androgen secretion by the ovaries and increasing circulating SHBG. Progestin-only contraceptives or intrauterine devices prevent endometrial cancer in women with PCOS and can be used as an alternative. There is an increased risk (50%-89%) of abnormal bleeding.
Although not FDA approved for treating menstrual abnormalities, insulin-sensitizing agents are associated with improved ovulation and glucose tolerance, and decreased circulating androgen levels by increasing SHBG.
Ovulation Induction in PCOS
Clomiphene citrate is the first-line agent that is recommended to induce ovulation, followed by either laparoscopic ovarian surgery or exogenous gonadotropins. Ovulation induction carries the risk of ovarian hyperstimulation, multiple births, and hypertensive disorder. Gonadotropins carry a lesser risk of ovarian hyperstimulation but an increased risk of multiple births. Aromatase inhibitors have been proposed to be similar to clomiphene, with higher implantation rates, less risk of multiple pregnancies, and a shorter half-life. Although metformin has been suggested, success rates are not as high as with clomiphene – although some studies show increased success rates when metformin is combined with clomiphene.