Oral Contraceptives in Polycystic Ovary Syndrome: Risk-Benefit Assessment

Bulent O. Yildiz, M.D.

Disclosures

Semin Reprod Med. 2008;26(1):111-120. 

In This Article

OCP Use and Diabetes Risk in PCOS

Insulin resistance with compensatory hyperinsulinemia is a prominent feature of PCOS, diagnosed in both lean and obese patients. The exact mechanisms for abnormalities of insulin action in the syndrome have yet to be fully elucidated.[56] Depending on the definition of insulin resistance, the method for the measurement of this abnormality, and the population studied, up to 70% of women with PCOS will show insulin resistance and compensatory hyperinsulinemia.[57] Nevertheless, not all women with PCOS have documented insulin resistance, and no measure of insulin sensitivity is included in the current diagnostic criteria of PCOS.[58]

Women with PCOS are at substantially higher risk for impaired glucose tolerance (IGT); and type 2 diabetes, with combined prevalence rates between 18% and 40% for glucose intolerance.[59,60,61,62] The rate of undiagnosed diabetes is ∼10% in PCOS.[60] Additionally, the rate of conversion from normal glucose tolerance (NGT); to IGT or diabetes or from IGT to diabetes is substantial in women with PCOS, particularly those with high BMI.[63] Indeed, PCOS has now been recognized as an independent risk factor for the development of type 2 diabetes. Current American Diabetes Association (ADA); guidelines suggest diabetes screening in women with PCOS.[64] Detection of glucose homeostasis abnormalities in PCOS is best performed by means of oral glucose tolerance test (OGTT); rather than fasting plasma glucose measurements.[60]

The strong association between PCOS and insulin resistance and increased risk of diabetes in this disorder has boosted the number of insulin sensitizer studies in PCOS within the past decade. On the other hand, there have been only a few studies evaluating the metabolic effects of OCPs in PCOS. Surprisingly, no randomized double-blind studies are available in the literature comparing the metabolic effects of an OCP either with another OCP or with an insulin sensitizer or with an OCP/insulin sensitizer combination.

There are a few prospective studies on a limited number of subjects using different combinations of OCPs with a duration ranging from 3 to 12 months ( Table 2 );. The results regarding the effects of OCPs on insulin sensitivity, measured by various methods ranging from fasting insulin to clamp studies, are inconsistent and contradictory in that decreased,[65,66,67,68,69] unchanged,[43,68,70,71,72,73,74,75,76] and increased[69,77] insulin sensitivity measurements have been reported. More importantly, in all but two studies, glucose tolerance status did not change ( Table 2 );. One of the earlier single-arm observational trials investigated 16 PCOS women with acanthosis nigricans (9 NGT/7 IGT); and reported that 5 NGT women developed IGT, 2 IGT women developed diabetes, and a woman with IGT converted to NGT after 6 months of therapy with ethinyl estradiol/desogestrel combination.[66] Another study comparing ethinyl estradiol/cyproterone acetate combination with metformin in a randomized open-label fashion found that, out of 10 individuals in the OCP arm, 1 with impaired fasting glucose (IFG); developed diabetes and 3 NGT patients developed IGT after 6 months of therapy.[70] Of note, both of these studies included morbidly obese PCOS patients with average BMI of 36.8 and 37.2 kg/m2, respectively. Additionally, insulin sensitivity, measured by area under the curve of insulin during OGTT[66] and by euglycemic clamp,[70] did not change after OCP treatment in these studies. Finally, potential confounding factors that might have influenced the results such as ethnicity, family history of diabetes, and level of physical activity were not reported.[66,70]

Overall, these limited available data suggest that low-dose OCP use for up to a year does not have an adverse impact on insulin sensitivity in most of the PCOS patients although decreased or increased insulin sensitivity might be observed in a small group of individuals. Low-dose OCP use within a year does not appear to increase the incidence of type 2 diabetes in PCOS. However, deterioration of glucose tolerance status might be observed particularly in morbidly obese PCOS patients. It is highly likely that, similar to healthy individuals, the risk of diabetes development depends on individual patient characteristics such as BMI, age, ethnicity, and family history of diabetes as well as individual characteristics of the OCP combination. The use of OCPs containing antiandrogenic progestins might provide certain advantages in terms of cardiometabolic risk in PCOS. Finally, it remains to be determined prospectively how these variable effects of OCPs on insulin sensitivity and glucose tolerance status within a year translates into the longer-term use of these medications in PCOS.

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