Bleeding pattern and cycle control with estetrol-containing combined oral contraceptives: results from a phase II, randomised, dose-finding study (FIESTA)

Abstract

Objectives: This study aims to assess vaginal bleeding patterns and cycle control of oral contraceptives containing estetrol (E4) combined with either drospirenone (DRSP) or levonorgestrel (LNG).

Study design: An open-label, multicentre, randomised, dose-finding study lasting six cycles in healthy women aged 18-35 years was used. Four treatments (15 mg or 20 mg E4, combined with either 3 mg DRSP or 150 mcg LNG) were administered in a 24/4-day regimen. A marketed dosing regimen of estradiol valerate with dienogest (E2V/DNG) served as reference since it contains (like E4) a natural oestrogen.

Results: A total of 396 women were randomised, of whom 389 received study medication, and 316 completed the study. By cycle 6, the frequencies of unscheduled bleeding and/or spotting and absence of withdrawal bleeding were the lowest in the 15 mg E4/DRSP group (33.8% and 3.5%, respectively). In the E2V/DNG reference group, these frequencies were 47.8% and 27.1%, respectively. By cycle 6, the frequency of women with absence of withdrawal bleeding was <20% for all E4 treatment groups: 3.5-3.8% combined with DRSP and 14.0-18.5% combined with LNG. By cycle 6, unscheduled intracyclic bleeding was reported by <20% of women in the 20 mg E4/LNG group (18.9%) and in the 15 mg E4/DRSP group (16.9%).

Conclusion: This study showed that, of the four treatment modalities investigated, the 15 mg E4/DRSP combination has the most favourable bleeding pattern and cycle control.

Implications: Due to its favourable bleeding pattern and cycle control, the 15 mg E4/DRSP combination is the preferred combination for further phase III clinical development.

Keywords: Bleeding pattern; Cycle control; Dienogest; Estetrol; Estradiol valerate.