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

Arch Gynecol Obstet. 2019 Dec;300(6):1805-1812. doi: 10.1007/s00404-019-05340-4. Epub 2019 Nov 14.


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.

Keywords: Bleeding; Cycle control; Drospirenone only pill.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Androstenes / administration & dosage*
  • Contraception / methods
  • Contraceptives, Oral / administration & dosage*
  • Desogestrel / administration & dosage*
  • Double-Blind Method
  • Female
  • Humans
  • Metrorrhagia / prevention & control*
  • Middle Aged
  • Young Adult


  • Androstenes
  • Contraceptives, Oral
  • Desogestrel
  • drospirenone

Associated data

  • EudraCT/2011-002396-42