Estetrol combined with drospirenone: an oral contraceptive with high acceptability, user satisfaction, well-being and favourable body weight control.

OBJECTIVES: This study evaluated acceptability, user satisfaction, body weight control and general well-being of estetrol (E4) combined with either drospirenone (DRSP) or levonorgestrel (LNG). METHODS: In this open-label, multi-centre, dose-finding, 6-cycle study, 396 healthy women of reproductive age were randomised into five treatment groups in a 24/4-day regimen: 15 mg or 20 mg E4 combined with either 3 mg DRSP or 150 µg LNG, and as reference estradiol valerate (E2V) combined with dienogest (DNG). Data on acceptability, user well-being, satisfaction and body weight were collected. RESULTS: The number of completers was the highest in the 15 mg E4/DRSP group (91.1%), and the lowest for 20 mg E4/LNG (70.1%). The largest proportion of treatment satisfaction was reported for 15 mg E4/DRSP (73.1%), and the lowest for 15 mg E4/LNG (50.6%). The number of women willing to continue with the assigned study treatment was the highest in the 15 mg E4/DRSP group (82.1%) and the lowest for 20 mg E4/LNG (58.3%). Well-being with E4/DRSP combinations was statistically significantly better than with E4/LNG combinations: OR (95% CI) 2.00 (1.13; 3.53) and 1.93 (1.06; 3.56) for 15 and 20 mg E4, respectively, and comparable to E2V/DNG. Proportion of women with a 2 kg or more weight loss after 3 and 6 cycles was the highest in the 15 mg E4/DRSP group (30.7 and 36.7%, respectively). CONCLUSIONS: The present study shows that 15 mg estetrol combined with 3 mg DRSP is associated with a high-user acceptability and satisfaction, and with a favourable body weight control.

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.