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

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.