Risk of venous thromboembolism from oral contraceptives containing gestodene and desogestrel versus levonorgestrel: A meta-analysis and formal sensitivity analysis

Sean Hennessy, Jesse A. Berlin, Judith L. Kinman, David J. Margolis, Sue M. Marcus, Brian L. Strom

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

Abstract

Controversy exists regarding whether oral contraceptives (OCs) containing desogestrel and gestodene are associated with an increased risk of venous thromboembolism (VTE) versus OCs containing levonorgestrel. We were interested in synthesizing the available data, exploring explanations for mixed results, and characterizing the degree of uncontrolled confounding that could have produced a spurious association. We performed a meta-analysis and formal sensitivity analysis of studies that examined the relative risk of VTE for desogestrel and gestodene versus levonorgestrel. Twelve studies, all observational, were included. The summary relative risk (95% CI) was 1.7 (1.3-2.1; heterogeneity p = 0.09). If real, the incremental risk of VTE would be about 11 per 100,000 women per year. An association was present when accounting for duration of use and when restricted to the first year of use in new users. However, in the sensitivity analysis, the association abated in many, but not all, scenarios in which an unmeasured confounding factor increased the risk of VTE three to fivefold and in nearly all examined scenarios in which the factor increased the risk 10-fold. The summary relative risk of 1.7 does not appear to be caused by depletion of susceptibles, but is sensitive to a modest degree of unmeasured confounding. Whether such confounding occurred is unknown. However, given this sensitivity, this issue probably cannot be settled unequivocally with observational data. In the absence of a definitive answer, this apparent increased risk, together with its uncertainty and small magnitude and its important consequences, should be considered when selecting an OC for a given woman.

Original languageEnglish (US)
Pages (from-to)125-133
Number of pages9
JournalContraception
Volume64
Issue number2
DOIs
StatePublished - 2001

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynecology

Keywords

  • Desogestrel
  • Gestodene
  • Levonorgestrel
  • Meta-analysis
  • Oral contraceptives
  • Venous thromboembolism

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