Third generation oral contraceptives and risk of venous thrombosis: meta-analysis.
OBJECTIVE
To evaluate quantitatively articles that compared effects of second and third generation oral contraceptives on risk of venous thrombosis.


METHODS
Meta-analysis.


METHODS
Cohort and case-control studies assessing risk of venous thromboembolism among women using oral contraceptives before October 1995.


METHODS
Pooled adjusted odds ratios calculated by a general variance based random effects method. When possible, two by two tables were extracted and combined by the Mantel-Haenszel method.


RESULTS
The overall adjusted odds ratio for third versus second generation oral contraceptives was 1.7 (95% confidence interval 1.4 to 2.0; seven studies). Similar risks were found when oral contraceptives containing desogestrel or gestodene were compared with those containing levonorgestrel. Among first time users, the odds ratio for third versus second generation preparations was 3.1 (2.0 to 4.6; four studies). The odds ratio was 2.5 (1.6 to 4.1; five studies) for short term users compared with 2.0 (1.4 to 2.7; five studies) for longer term users. The odds ratio was 1.3 (1.0 to 1.7) in studies funded by the pharmaceutical industry and 2.3 (1.7 to 3.2) in other studies. Differences in age and certainty of diagnosis of venous thrombosis did not affect the results.


CONCLUSIONS
This meta-analysis supports the view that third generation oral contraceptives are associated with an increased risk of venous thrombosis compared with second generation oral contraceptives. The increase cannot be explained by several potential biases.
Kemmeren
J M
JM
Julius Centre for General Practice and Patient Oriented Research, University Medical Centre Utrecht, PO Box 85500, 3508 GA Utrecht, Netherlands.
Algra
A
A
Grobbee
D E
DE
D000328:Adult; D015982:Bias; D016022:Case-Control Studies; D015331:Cohort Studies; D003280:Contraceptives, Oral, Synthetic / Q000009:adverse effects*; D005260:Female; D006801:Humans; D045167:Progesterone Congeners / Q000009:adverse effects*; D018570:Risk Assessment; D012307:Risk Factors; D013923:Thromboembolism / Q000139:chemically induced; D020246:Venous Thrombosis / Q000139:chemically induced*
D003280:Contraceptives, Oral, Synthetic; D045167:Progesterone Congeners