Drospirenone-Containing Oral Contraceptive Pills and the Risk of Venous Thromboembolism: An Assessment of Risk in First-Time Users and Restarters

Drug Saf. 2017 Jul;40(7):583-596. doi: 10.1007/s40264-017-0525-2.


Introduction: The effects of drospirenone-containing combined oral contraceptives (COCs) on the risk of venous thromboembolism (VTE) remain controversial due to the challenge in distinguishing between first-time users and restarters, and their different underlying VTE risks, in healthcare databases.

Objectives: The aim of this study was to describe the challenge of studying the risk of VTE among first-time users of drospirenone-containing COCs in a healthcare database and assess the risk among first-time users and restarters.

Methods: We used data from the Clinical Practice Research Datalink to construct two cohorts. The first-time user cohort included all women aged 16-45 years who received a first ever prescription of drospirenone- or levonorgestrel-containing COCs between May 2002 and March 2015. The restarter cohort included those who were restarting a COC after a period of non-use of ≥6 months. Cox proportional hazards models adjusted for high dimensional propensity scores were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).

Results: The final cohorts included 55,139 first-time users (3582 drospirenone and 51,557 levonorgestrel) and 162,959 restarters (23,191 drospirenone and 139,768 levonorgestrel). The adjusted HR of VTE associated with drospirenone versus levonorgestrel was 3.19 (95% CI 1.12-9.08) for first-time users and 1.96 (95% CI 1.12-3.41) for restarters.

Conclusions: We found an elevated risk of VTE associated with drospirenone-containing COCs in comparison with levonorgestrel-containing COCs in both cohorts. While left truncation of healthcare databases is a concern for the identification of first-time users, the use of a more explicit cohort of restarters suggests a doubling of VTE risk with drospirenone-containing COCs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Androstenes / administration & dosage
  • Androstenes / adverse effects*
  • Cohort Studies
  • Contraceptives, Oral, Combined / administration & dosage
  • Contraceptives, Oral, Combined / adverse effects*
  • Drug Administration Schedule
  • Female
  • Humans
  • Levonorgestrel / administration & dosage
  • Levonorgestrel / adverse effects
  • Middle Aged
  • Proportional Hazards Models
  • Risk Factors
  • Venous Thromboembolism / chemically induced*
  • Young Adult


  • Androstenes
  • Contraceptives, Oral, Combined
  • Levonorgestrel
  • drospirenone