Polycystic ovary syndrome: How are obesity and insulin resistance involved?
Which of my patients with PCOS do I screen for insulin sensitivity? What screening tests are available, and which are most appropriate? Two experts continue to tackle a long list of questions that your clinician–colleagues have been posing.
IN THIS ARTICLE
Part 1. Where we stand with diagnosis and treatment—and
where we're going
Polycystic ovary syndrome, or PCOS, is an enigmatic condition. It presents with varying levels of severity of those symptoms and conditions associated with it—clinical hyperandrogenism (hirsutism, acne, alopecia), obesity, and menstrual disturbance. Although its exact cause is unknown, at least half of all women with PCOS are overweight or obese. What does obesity and, more specifically, insulin resistance, contribute to the pathogenesis of PCOS, and why is it important to screen your patient with PCOS for insulin resistance?
In part 2 of this 4-part series, which will continue to be posted here on the OBG Management Web site, we address these questions. [Editor’s note: As they are published, future installments of this series will continue to be collected on a single Web page for ease of access.]
The roles of obesity and insulin resistance
Overweight: BMI ≥ 25 kg/m2
Obesity: BMI ≥ 30 kg/m2
Morbid obesity: BMI ≥ 40 kg/m2
PCOS is associated with truncal fat distribution, manifesting as an increased waist-to-hip ratio. According to the Centers for Disease Control and Prevention (CDC), more than one-third of the population was obese in 2009 and 2010.1 Approximately 50% to 65% of women with PCOS are overweight or obese, and most of them have the truncal fat distribution phenotype. 2
Obesity is associated with an increase in insulin resistance (IR) and hyperinsulinemia. IR can be characterized as impaired action of insulin in the uptake and metabolism of glucose. Impaired insulin action leads to elevated insulin levels. Insulin synergizes with abnormally high secretion of luteinizing hormone (perhaps induced by hyperinsulinemia) to promote excess androgen production by intraovarian theca cells and an arrest of follicular development resulting in chronic anovulation.
In addition, hyperinsulinemia causes a decrease in hepatic sex hormone binding globulin, resulting in free circulating androgens and, thus, hirsutism and acne issues. While this picture tends to be more pronounced in women who have PCOS and are obese, it is important to realize that a nonobese patient with PCOS also may have IR, which suggests that insulin plays a major role in the pathogenesis of this disease.3,4
Most of the evidence suggests that hyperinsulinemia causes hyperandrogenism and not the reverse. Weight loss and insulin sensitizers are associated with a reduction in androgens, particularly testosterone and androstenedione. Gonadotropin-releasing hormone–analogs, which reduce androgen secretion from the ovaries, do not result in a reduction in insulin.3,4
Screening for insulin resistance: The rationale
The documented prevalence of IR and type 2 diabetes mellitus (DM) in women with PCOS suggests that impaired glucose tolerance (IGT) is present in 31% to 35% of women with PCOS5,6—and DM, classified according to World Health Organization (WHO) criteria, is present in 7.5% to 10% of women with PCOS.
The prevalence of IR and DM are considerably lower in women without PCOS. According to the Third National Health and Nutrition Examination Survey, in US women of similar age, the prevalence of IR is 1.6%, and the prevalence of DM is 2.2%.7
2003 consensus: Screen for IGT in obese PCOS patients. In view of the high prevalence of IR and IGT, a 2003 PCOS consensus8 established that obese women with PCOS should be screened for insulin sensitivity and undergo screening for the metabolic syndrome, including glucose intolerance. For nonobese women, the consensus recommended screening only if additional risk factors are present.
Unfortunately, IGT also occurs independent of obesity. In lean women with PCOS, 5% may have IGT, while 2% are frankly diabetic. Moreover, the conversion from normal glucose tolerance to IGT in patients with PCOS can be as high as 16% per year,9 while the conversion rate from IGT to DM among women with PCOS has been reported to be as high as 2% per year.
2007 position statement: Screen for IGT in all PCOS patients. A position statement by the Androgen Excess–PCOS Society on glucose intolerance and PCOS recommends screening for IGT in all PCOS women, regardless of BMI, at least once every 2 years.10
Screening for insulin resistance: The methods
There are two ways to determine insulin sensitivity:
