Association between the current use of low-dose oral contraceptives and cardiovascular arterial disease: a meta-analysis

J Clin Endocrinol Metab. 2005 Jul;90(7):3863-70. doi: 10.1210/jc.2004-1958. Epub 2005 Apr 6.


Context: The long-term cardiovascular safety of widely used oral contraceptives (OCs) is still debated, and no meta-analysis assesses the modern use of OCs and the associated cardiovascular risks.

Objective: We aimed to assess the risk of cardiovascular diseases associated with current use of low-dose combined OCs.

Data sources: All studies published between January 1980 and October 2002 were searched using MEDLINE, BIOSIS, and Scientific Citations.

Study selection: Original studies were selected independently by two investigators (J.P.B., P.A.E.) based on inclusion criteria: low-dose combined OC (<50 mug of ethinyl-estradiol); more than 10 cases in low-dose users; clear definition of cases; concurrent controls; and control for age. A third investigator (J.E.N.) adjudicated disagreements. From 2715 identified articles, 14 independent studies were included.

Data extraction: All data were abstracted by one investigator (J.P.B.) in a systematic manner. Classification of OCs and types of exposure were directly abstracted from studies. Current use was defined as use at the time of the event or within 3 months. Only peer-reviewed studies with definition of events as definite or possible, based on prespecified criteria, were included.

Data synthesis: The summary risk estimates associated with current use of low-dose OCs were 1.84 [95% confidence interval (CI) = 1.38, 2.44] for myocardial infarctions and 2.12 (95% CI = 1.56, 2.86) for ischemic strokes. The overall summary odds ratio for both outcomes was 2.01 (95% CI = 1.63, 2.48). Second generation OCs were associated with a significant increased risk of both myocardial infarction and ischemic stroke events [1.85 (95% CI = 1.03,3.32) and 2.54 (95% CI = 1.96,3.28), respectively]; and third-generation OCs, for ischemic stroke outcome only [2.03 (95% CI = 1.15,3.57)].

Conclusions: In conclusion, a rigorous meta-analysis of the literature suggests that current use of low-dose OCs significantly increases the risk of both cardiac and vascular arterial events, including a significant risk of vascular arterial complications with third generation OCs.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Brain Ischemia / etiology*
  • Contraceptives, Oral / adverse effects*
  • Female
  • Humans
  • Myocardial Infarction / etiology*
  • Odds Ratio
  • Stroke / etiology*


  • Contraceptives, Oral