Third generation oral contraceptives have greater risk of venous thrombosis than second generation contraceptives

Sapp, Aaron V. MD
Lindbloom, Erik J. MD, MSPH

University of Missouri-Columbia, Columbia, MO, USA

Abstracted from:Kemmeren JA, Algra A, Grobbee DE. Third generation oral contraceptives and risk of venous thrombosis: meta-analysis. BMJ 2001; 323 (7305): 131-134 .

Evidence-based Healthcare 6(1):p 35, March 2002.

BACKGROUND

There may be more risk of developing venous thrombosis from third generation oral contraceptives (those containing desogestrel, gestodene, or norgestimate) compared to second generation contraceptives. A previous meta-analysis reported a relative risk of 1.9, but did not examine confounding or biases in the studies upon which it was based.

OBJECTIVE

To identify factors associated with increased venous thrombosis risk among users of third generation oral contraceptives, including biases and confounding.

METHOD

Review and meta-analysis.

LITERATURE REVIEW

MEDLINE (October 1995 to December 2000); hand searching of studies in English; input from specialists.

INCLUSION CRITERIA

All cohort and case-control studies of women diagnosed with venous thrombosis or thromboembolism conducted in Western countries prior to November 1995 with data enabling calculation of relative risk and confidence intervals. Later studies were excluded due to changes in oral contraceptive prescribing. Of 114 studies identified, 12 were included with three additional papers providing analyses of earlier results.

OUTCOMES

Venous thrombosis risk.

ANALYSIS

Data were extracted and odds ratios and heterogeneity statistics calculated.

MAIN RESULTS

After accounting for biases and confounding, the risk of venous thrombosis was higher in those taking third- compared to second generation contraceptives (adjusted OR: 1.7; 95% CI: 1.4 to 2.0). The risk was even greater for first time users (OR: 3.1; 95% CI: 2.0 to 4.6). Risk differences were not affected by age, diagnosis, duration of contraceptive use, or whether studies were financed by pharmaceutical companies.

AUTHORS' CONCLUSIONS

Women who use third generation contraceptives have a higher risk of venous thrombosis compared to those who use second generation contraceptives. The results cannot be attributed to biases and confounding alone.