Effects of estetrol/drospirenone versus ethinyl estradiol/drospirenone on glucose tolerance in women with polycystic ovary syndrome: A randomised controlled trial

Abstract Aims To compare the effects of estetrol/drospirenone ( E4 / DRSP ) and ethinyl estradiol/drospirenone ( EE / DRSP ) on glucose tolerance in women with polycystic ovary syndrome ( PCOS ). Materials and Methods This open‐label, randomised crossover trial was conducted from January 2024 to January 2025. Women with PCOS , diagnosed according to the modified 2003 Rotterdam criteria, received three cycles of either E4 15 mg/ DRSP 3 mg or EE 30 mcg/ DRSP 3 mg. After a 2‐month washout, participants crossed over to the alternate regimen for three further cycles. Glucose tolerance (via 75 g oral glucose tolerance test [ OGTT ]), insulin levels and homeostatic model assessment for insulin resistance ( HOMA ‐ IR ) were compared between treatments. Results Of 66 women enrolled, 61 completed both treatment phases. Baseline characteristics were comparable. No significant differences were observed in the mean changes in 2‐h OGTT ( E4 / DRSP : 4.65 mg/ dL [95% confidence interval ( CI ) −2.37 to 11.66] vs. EE / DRSP : 14.40 mg/ dL [95% CI 7.50–21.29]; p = 0.05; upper boundary for non‐inferiority margin of 14.29), 1‐h insulin levels (−1.04 μU / mL [95% CI −25.94 to 23.86] vs. −0.77 μU / mL [95% CI −25.24 to 23.70]; p = 0.99; upper boundary for non‐inferiority margin of 50.72) or HOMA ‐ IR (0.28 [95% CI −0.24 to 0.80] vs. 0.60 [95% CI 0.09–1.11]; p = 0.39; upper boundary for non‐inferiority margin of 1.06). Conclusion E4/DRSP was not inferior to EE/DRSP in its effects on glucose tolerance, insulin levels and HOMA‐IR, supporting its use as a potential oral contraceptive option in women with PCOS.