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Risk of venous thromboembolism among users of oral contraceptives: a review of two recently published studies
  1. Samuel Shapiro, FCP(SA), FRCP(E), Visiting Professor of Epidemiology (also Emeritus Director, Slone Epidemiology Center, Boston University, Boston, MA, USA)1 and
  2. Jügen Dinger, MD, PhD, Director2
  1. Department of Epidemiology, University of Cape Town, Cape Town, South Africa
  2. Berlin Center for Epidemiology and Health Research, Berlin, Germany
  1. Correspondence to Professor Samuel Shapiro, Department of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa. E-mail: samshap{at}


Background Two recent studies, a cohort study from Denmark, and a case-control study from The Netherlands, have reported increased risks of venous thromboembolism (VTE) among users of oral contraceptives (OCs) containing desogestrel, gestodene, drospirenone and cyproterone, relative to the use of levonorgestrel.

Critique In the Danish study the comparisons were not valid. (1) VTE risk is highest soon after commencement of OC use, and duration of use was underestimated for levonorgestrel users, but not for drospirenone users; for the remaining compounds duration was only slightly underestimated. The underestimation for levonorgestrel resulted in systematic overestimation of the relative risks for the compared OCs. (2) Duration was also incorrectly estimated: only the duration of current use, not duration of all episodes of use was relevant to VTE risk. (3) Confounding was not adequately controlled.

In The Netherlands study the comparisons were not valid. (1) The relative risk for drospirenone versus levonorgestrel was not statistically significant. (2) Extensive publicity had been given to the risk of VTE among users of desogestrel, gestodene, drospirenone and cyproterone: information bias and detection bias were therefore likely. (3) Inadequate allowance was made for duration of use. (4) The combination of two different control groups, both of them likely to have been biased, into a single category was not valid.

Conclusion The best evidence continues to suggest that the increased risk of VTE in OC users is a class effect, dependent on the estrogen dose and duration of use, and independent of the progestogen used.

  • combined oral contraceptives
  • progestogen
  • risk assessment
  • venous thromboembolism

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