Divergent effects of a combined hormonal oral contraceptive on insulin sensitivity in lean versus obese women

ObjectiveTo evaluate the effects of a commonly used combined hormonal oral contraceptive (OC) on carbohydrate metabolism in obese as compared with lean women.Design6-month prospective study.SettingClinical research center at an academic medical center.Patient(s)Premenopausal nondiabetic women with body mass index <25 kg/m2 (n = 15) or >30 kg/m2 (n = 14).Intervention(s)Ethinyl estradiol (35 μg) and norgestimate (0.18/0.215/0.25 mg) for 6 cycles.Main Outcome Measure(s)Insulin sensitivity by frequent sampling intravenous glucose tolerance test; other indices of insulin sensitivity (homeostatic model assessment of insulin sensitivity index [ISI HOMA], the Matsuda index); fasting lipid panel.Result(s)Insulin sensitivity changed from 6.62 ± 3.69 min−1/mIU/L (baseline) to 8.23 ± 3.30 min−1/mIU/L (6 months) in lean women, and from 4.36 ± 2.32 to 3.82 ± 2.32 min−1/mIU/L in obese women. Divergent effects on insulin sensitivity were also observed with ISI HOMA and the Matsuda index. Low-density lipoprotein increased by approximately 20 mg/dL in both the lean and obese groups.Conclusion(s)Lean and obese women exhibit differential changes in insulin sensitivity when given 6 months of a commonly used oral contraceptive. The mechanisms of these differences and whether these divergent effects persist in the long term require further investigation.