Internal medicine

Pathology

Adverse effect

Placebo

Metrorrhagia

Menstrual cycle

Regimen

Population

Obstetrics

Alternative medicine

Breakthrough bleeding

Family planning

Gynecology

Sexual intercourse

Drospirenone

Research methodology

Hormone

Medicine

Environmental health

BJOG An International Journal of Obstetrics & Gynaecology

To assess the contraceptive efficacy, bleeding pattern and safety of a combined oral contraceptive containing estetrol (E4) 15 mg and drospirenone (DRSP) 3 mg.Multicenter, open-label, phase 3 trial.Sixty-nine sites in Europe and Russia.Sexually active women aged 18-50 years with regular menstrual cycles and body mass index ≤35 kg/m2 .E4/DRSP was administered in a 24 active/4 placebo regimen for up to 13 cycles. Visits were scheduled during Cycles 2, 4, 7 and 10 and after completing treatment during which adverse events (AEs) were collected. Participants recorded medication intake, vaginal bleeding/spotting, use of other contraceptive methods and sexual intercourse on a daily diary.Pearl Index (PI) for women 18-35 years (overall and method-failure), bleeding pattern and AEs.A total of 1553 women aged 18-50 years, including 1353 from 18 to 35 years old, received the study medication. PI was 0.47 pregnancies/100 woman-years (95% CI 0.15-1.11); method failure PI was 0.29 pregnancies/100 woman-years (95% CI 0.06-0.83). Scheduled bleeding/spotting occurred in 91.9-94.4% of women over Cycles 1 to 12 and lasted a median of 4-5 days per cycle. The percentage of women with unscheduled bleeding/spotting episodes decreased from 23.5% in Cycle 1 to <16% from Cycle 6 onwards. The most common AEs were headache (7.7%), metrorrhagia (5.5%), vaginal haemorrhage (4.8%) and acne (4.2%). One treatment-related serious AE was reported, a lower extremity venous thromboembolism. One-hundred and forty-one (9.1%) women discontinued study participation because of treatment-related adverse events.E4/DRSP provides effective contraception, a predictable bleeding pattern and a favourable safety profile.A phase 3 trial with E4/DRSP shows high contraceptive efficacy, a predictable bleeding pattern and favourable safety profile.

Estetrol‐Drospirenone combination oral contraceptive: a clinical study of contraceptive efficacy, bleeding pattern and safety in Europe and Russia