Elevated fasting glucose and triglycerides in combined oral contraceptive users compared to naturally cycling females

The effects of oral contraceptive pills (OCPs) on metabolism and body composition remain unclear. This study aimed to compare fasting glucose and lipid metabolism between naturally cycling (NAT) females, second-(OCP2), and third-generation (OCP3) OCP users during low-(LH) and high-hormone (HH) phases. Forty-nine healthy females (age: 21 ± 2 years, BMI: 23.5 ± 3.8 kg/m2) were assessed. Participants were assessed in two randomized fasting blood draws during: (1) LH phase (NAT: early follicular, OCP: placebo pill week), and (2) HH phase (NAT: mid-luteal, OCP: third week of active pill use) to assess glucose, insulin, and lipids. Dual-energy X-ray absorptiometry was performed to assess body composition. Glucose was higher in OCP2 (4.4 ± 0.3 mM, p = 0.002) and OCP3 (4.5 ± 0.3 mM, p < 0.001), compared to NAT (4.0 ± 0.5 mM), with no effect of hormone phase (p = 0.895); insulin was not different across groups or phases. Triglycerides were higher in OCP2 (0.9 ± 0.5 mM, p = 0.036) and OCP3 (0.9 ± 0.3 mM, p = 0.011), compared to NAT (0.6 ± 0.2 mM). Appendicular lean mass index was lower in OCP2 (6.5 ± 0.8 kg/m2, p = 0.030) and OCP3 (6.5 ± 0.5 kg/m2, p = 0.030) compared to NAT (7.2 ± 1.1 kg/m2). Findings suggest that OCP use associates with a distinct metabolic profile, potentially related to differences in lean mass, an important glucose sink.