Impact of Oral Contraceptives and Metformin on Advanced Lipid Phenotyping in PCOS
Iris T Lee, Daniel E Soffer, Alan T Remaley, Martin P Playford, Nehal N Mehta, Christos Coutifaris, Richard S Legro, Anuja DokrasAbstract
Context
Combined oral contraceptives (OCPs) and metformin are commonly used in patients with polycystic ovary syndrome (PCOS), who are at elevated risk of dyslipidemia and cardiovascular disease (CVD), but their effects on advanced lipid phenotyping remain unclear.
Objective
To examine the impact of OCPs and metformin on 1) lipoproteins, 2) apolipoproteins, and 3) cholesterol efflux capacity (CEC, marker of high-density lipoprotein [HDL] function)
Design
Secondary analysis of the COMET-PCOS randomized clinical trial
Setting
Two tertiary care reproductive endocrinology clinics
Patients or Other Participants
Patients with hyperandrogenic PCOS and elevated BMI with paired serum samples for lipoprotein/apolipoprotein analysis (n=180) and cholesterol efflux capacity (n=129)
Intervention(s)
24 weeks of metformin, OCP, or OCP + metformin
Main Outcome Measure(s)
Change in HDL particles (HDL-P), low-density lipoprotein particles (LDL-P), triglyceride-rich lipoprotein particles (TRL-P); apolipoproteins A-I, B, and C-III; and CEC
Results
. HDL-P concentration increased in the OCP and OCP + metformin arms, while atherogenic small LDL-P increased slightly. Metformin had a largely neutral effect on advanced lipid phenotyping. CEC increased in the OCP arm, though this was attenuated when adjusting for change in ApoA-I (adjusted ratio of geometric means 1.08, 95% CI 0.99-1.17), which increased in all arms.
Conclusions
In patients with PCOS and high metabolic risk, OCP use resulted in improved HDL-C function and a mixed effect on lipoproteins and apolipoproteins, with no clear benefit from metformin. These findings do not support or refute the cardiovascular risk-benefit of OCP use in PCOS and highlight the need for studies evaluating long-term clinical outcomes.