Effects of estetrol/drospirenone vs drospirenone-only on thrombin generation in women with polycystic ovary syndrome: a randomized, double-blind, controlled trial.

BACKGROUND

Combined oral contraceptives are first-line treatment for polycystic ovary syndrome (PCOS); however, venous thromboembolism risk remains a concern. Estetrol/drospirenone (E4/DRSP) has a more favorable thrombin generation assay (TGA) profile than ethinyl estradiol-based combined oral contraceptives, but direct comparison with progestin-only pills is lacking.

OBJECTIVES

This study aimed to compare the effects of E4/DRSP and DRSP-only on TGA parameters, hyperandrogenic symptoms, and vaginal bleeding patterns in women with PCOS.

METHODS

In a randomized, double-blind, controlled trial, women with PCOS aged 18 to 40 years at Siriraj Hospital, Thailand (May-December 2025) were assigned in a 1:1 ratio to E4/DRSP or DRSP-only for 12 weeks. The primary outcome was change in TGA parameters measured with and without thrombomodulin (TM). Secondary outcomes were vaginal bleeding patterns, modified Ferriman-Gallwey score, acne severity, and treatment satisfaction.

RESULTS

Both regimens increased endogenous thrombin potential and peak height on TGA, without TM (E4/DRSP: 1699 to 1888; DRSP-only: 1836 to 2085 nM·min; within-group P ≤ .017) and with TM (both P = .001), with no between-group differences (all P > .05). The endogenous thrombin potential-TM ratio rose in both groups, with no between-group difference (E4/DRSP: median +0.14; DRSP-only: +0.13; between-group P = .74). DRSP-only had fewer scheduled bleeding days across 3 cycles, whereas E4/DRSP reduced modified Ferriman-Gallwey score for hirsutism (P < .001). Waist-to-hip ratio, acne, and treatment satisfaction were comparable, with no serious adverse events.

CONCLUSION

E4/DRSP and DRSP-only had comparable effects on thrombin generation and TM-mediated anticoagulation in women with PCOS. E4/DRSP reduced hirsutism, supporting its consideration as a treatment option for PCOS.