A multicenter, double-blind, randomized trial on the bleeding profile of a drospirenone-only pill 4 mg over nine cycles in comparison with desogestrel 0.075 mg

PURPOSE: A typical compliance problem in the use of traditional progestin-only pills is the irregular bleeding pattern and the strict daily intake. Desogestrel 75 mg has a 12-h missed-pill window; however, its poor cycle control limits a more common use. METHODS: A drospirenone (DRSP)-only pill was developed to improve the bleeding profile. SETTING: A phase III study in healthy women aged 18–45 years was performed to compare the bleeding profile and safety of a DRSP-only pill in a regime of 24 days of 4 mg of DRSP tablets followed by 4 days of placebo versus desogestrel 0.075 mg per day continuously over nine cycles. POPULATION: A total of 858 women with 6691 drospirenone and 332 women with 2487 desogestrel treatment cycles were analyzed. MAIN OUTCOME MEASURES: The primary end point was the proportion of women with unscheduled bleeding/spotting in each cycle from cycles 2 to 9 and cumulative in cycles 2–4 and cycles 7–9. RESULTS: In each cycle, up to cycle 7, the proportion of women with unscheduled bleeding was statistically significantly lower in the DRSP group than in the DSG group (p = 0.0001, Chi-square test). CONCLUSIONS: This report describes the improvement in bleeding profile of women using the new DRSP-only oral contraceptive in comparison to DSG, providing a better quality of live and adherence to the contraceptive method. EudraCT Registration Number: 2011-002396-42. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00404-019-05340-4) contains supplementary material, which is available to authorized users.