Teaching topics from the New England Journal of Medicine - Vol. 358, No. 1, January 3, 2008
Polycystic Ovary Syndrome
The polycystic ovary syndrome is a clinical diagnosis characterized by the presence of two or more of the following features: chronic oligo-ovulation or anovulation, androgen excess, and polycystic ovaries. It affects 5 to 10% of women of childbearing age, and is the most common cause of anovulatory infertility in developed countries. Common clinical manifestations include menstrual irregularities and signs of androgen excess such as hirsutism, acne, and alopecia. The presence of type 2 diabetes in the United States is 10 times as high among young women with the polycystic ovary syndrome as among normal women, and impaired glucose tolerance or overt type 2 diabetes develops by the age of 30 years in 30 to 50% of obese women with PCOS.
Metformin: Mechanism of Action
Metformin, a biguanide, is the most widely used drug for the treatment of type 2 diabetes worldwide. Its primary action is to inhibit hepatic glucose production, but it also increases the sensitivity of peripheral tissues to insulin. Metformin can also lower fasting serum insulin and androgen levels in women with the polycystic ovary syndrome — and may improve ovulation and menstrual cycling. (Hyperinsulinemia inhibits the hepatic production of sex hormone-binding globulin — increasing the circulating free testosterone levels.) Although metformin is not approved by the F.D.A. for the treatment of polycystic ovary syndrome, it is often used for this purpose.
Morning Report Questions
Q: What are the absolute contraindications for the use of metformin?
A: Metformin should not be used in patients with renal impairment (a serum creatinine level greater than 1.4 mg per deciliter [124 µmol per liter]), hepatic dysfunction, severe congestive heart failure, or a history of alcohol abuse. Repeat testing during metformin treatment is not indicated unless the patient develops another illness or condition (e.g., dehydration) that might affect renal or hepatic function.
Q: What are risk factors for type 2 diabetes?
A: Obesity, family history of diabetes, and polycystic ovary syndrome are all risk factors for type 2 diabetes. In fact all women with the polycystic ovary syndrome, regardless of weight, should be screened for glucose intolerance with the use of a glucose-tolerance test at the initial presentation and every 2 years thereafter. (J Clin Endocrinol Metab, 2007.)