Opinion: Metabolic syndrome: What the ob/gyn should know

While there are various definitions of the disorder, I think the most useful is that of the National Cholesterol Education Program – Adult Treatment Panel III.¹ (See TABLE 1, "Current metabolic syndrome definitions," in our September 2009 article, "Cardiometabolic disorders and weight: A special report on metabolic syndrome.") Using that definition and National Health and Nutrition Examination Survey (NHANES) data for 1999–2002, the age-adjusted prevalence of MS among US women is 34.5%, with more than 50% of women over age 50 being affected.² Even more sobering, the prevalence of MS among US women has climbed 150% since the 1988-1994 NHANES data collection!³ The rise in prevalence of the MS has almost perfectly paralleled the obesity epidemic, underscoring the profound contribution of excess weight to the syndrome's pathological metabolic milieu. In women, beyond obesity, additional contributing factors for metabolic syndrome include postmenopausal status, a high carbohydrate intake, smoking, low income, physical inactivity, and abstinence from alcohol.⁴ A racial and ethnic predilection is appreciated, with the highest prevalence of MS found among Native Americans and Mexican-Americans; among the latter, more than 70% of women over age 50 are affected.²

Early detection of this disorder is crucial and ob/gyns are in an ideal position to identify patients at risk and make an early diagnosis. Firstly, we are often the only physician caring for most premenopausal women. Secondly, we are uniquely privy to its pregnancy-related prodromal conditions (i.e., gestational diabetes, preeclampsia, and fetal macrosomia). Thirdly, the initial presentation of the syndrome in the nonpregnant state often has obvious gynecologic sequelae. For example, PCOS affects 7% to 10% of reproductive-aged women and is associated with insulin resistance in up to 70% of cases.⁵ Realizing that the adverse health outcomes ascribable to MS include reproductive as well as nonreproductive concerns, we ob/gyns have the perfect bully pulpit to convince patients to lose weight, and exercise before they develop the full blown syndrome.

Controversy exists over whether to add metformin in insulin-resistant patients without overt diabetes since there is some evidence that it may slow the progression to type 2 diabetes.⁷ The Diabetes Prevention Program Research Group randomized 3,234 nondiabetic patients who had elevated fasting and post-load plasma glucose levels to either placebo, metformin, or a lifestyle-modification program and noted an incidence of diabetes after 3 years of follow-up of 11.0, 7.8, and 4.8 cases per 100 person-years, respectively. When compared to placebo, lifestyle modification elicited the greatest reduction in the incidence of overt diabetes (58%, 95% CI; 48%–66%), but metformin alone reduced the incidence of diabetes by 31% (95% CI; 17%–43%). To prevent one case of diabetes during the 3-year observation period, 14 insulin-resistant patients would have to be treated with metformin. Among insulin-resistant PCOS patients, metformin lowers fasting insulin levels, reduces LDL cholesterol, and lowers blood pressure.⁵ Moreover, although it is less effective than clomiphene citrate in achieving live born pregnancies among PCOS patients,⁸ the likelihood of having a singleton gestation is increased when metformin is used with clomiphene and it may be of value in oligo-ovulatory infertile women who are resistant to clomiphene.⁵ Thus, metformin may be a particularly useful adjunct to the ob/gyn's management armamentarium against metabolic syndrome.

In my opinion, ob/gyns are ideally positioned to not just prevent the complications of metabolic syndrome, but ultimately to reduce its prevalence. An aggressive pursuit of disease detection, complemented with forceful implementation of "patient tailored" lifestyle modifications (including diet and exercise strategies), are recipes for success. As primary caregivers, we must also be prepared to treat hypertension, and add lipid-lowering and insulin-sensitizing agents when diet and exercise are insufficient to correct the associated hemodynamic or metabolic derangements. Finally, we need to practice what we preach-and be sure that we stay fit, eat smart, and avoid the syndrome ourselves.

DR. LOCKWOOD, Editor in Chief, is Anita O'Keefe Young Professor and Chair, Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT.