Type of progestogen in combined oral contraceptives and risk of myocardial infarction

Type of progestogen in combined oral contraceptives and risk of myocardial


P. O’Brien

Westside Contraceptive Services, London, UK

Objectives: In 1980s and 1990s new progestogens were introduced to

combine oral contraceptives (COC) that induce a lipid profile suggesting

possible reduction in arterial diseases. We systematically review the data on

acute myocardial infarction.

Design and Methods: Medline was searched for case-control and cohort

studies that provide results comparing the newer progestogens desogestrel,

gestodene, norgestimate or drosperinone with levonorgestrel or norethisterone,

combined with ethinyl estradiol 35 mcg or less. Odds ratios (OR) were taken

directly from the reports or calculated from the available data. Studies were

pooled, using the general variance based method and fixed effect model. We

quantified characteristics of studies that might have affected results and

explored heterogeneity through stratification. A test of asymmetry of funnel

plot was performed for publication bias.

Results: Seven studies were identified, all case-controlled, one in

abstract only, involving 1932 women with acute myocardial infarction and 10,753

controls. One study found a statistically lower risk with the later progestogens.

The combined OR comparing newer to older progestogens was 0.76 (95% confidence

limits 0.50 to 1.14; p=0.16; test for heterogeneity p=0.22). The OR for

community and hospital controls did not differ (test for heterogeneity p=0.7).

Stratifying by region, the OR for newer versus older progestogens was 0.62 (0.37

to 1.06) for studies conducted in Continental Europe, and 1.29 (0.65 to 2.59)

for studies in U.K. (test for heterogeneity between regions p=0.1). The source

of funding did not influence the result (test for heterogeneity p=0.3). There

was no evidence of publication bias (p=0.6). A meta-analysis of the crude ORs (OR

0.74, 6 studies) was a little higher than the combined adjusted OR (0.64, same 6

studies), which suggests slight prescribing bias of newer OCs to women at

greater risk of myocardial infarction. The adjusted unbiased estimates were used

in this review.

Conclusion: While there was a tendency towards lower risk of

myocardial infarction with newer progestogens, in this large dataset the

difference was not statistically significant. When taken together the absence of

effect of past use and the apparent lack of benefit on risk of stroke, the

combined evidence suggests the lipid changes induced by the newer progestogens

have at most minimal clinical benefits for arterial diseases.

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