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

Abstract

Objective: To evaluate the effects of a commonly used combined hormonal oral contraceptive (OC) on carbohydrate metabolism in obese as compared with lean women.

Design: 6-month prospective study.

Setting: Clinical research center at an academic medical center.

Patient(s): Premenopausal nondiabetic women with body mass index <25 kg/m(2) (n = 15) or >30 kg/m(2) (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.

Trial registration: ClinicalTrials.gov NCT00205504.

Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1. Insulin Sensitivity during 6 months OC administration in Lean and Obese Groups (Mean ± SE)

P-values were for comparisons of insulin sensitivity time trends between lean and obese groups in repeated measures analysis. Insulin sensitivity assessments included (A) Si (insulin sensitivity) obtained from frequently sampled intravenous glucose tolerance test (FSIVGTT) at baseline and 6 months; (B) Matsuda index of insulin sensitivity obtained from oral glucose tolerance test at baseline, 3 and 6 months; (C) the insulin sensitivity index by homeostatic model assessment (ISI HOMA), using fasting glucose and insulin concentrations at baseline, 3 and 6 months. Lean and obese women exhibited statistically significantly different time trends in (A) Si (p=0.0494), (B) Matsuda index (p=0.0227), and (C) ISI HOMA (p=0.0128), during the 6 months of oral contraceptive use.