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