Oral Contraceptives and Risk of Myocardial Infarction

Abstract & Commentary

By Leon Speroff, MD, Editor, Professor of Obstetrics and Gynecology Oregon Health and Science University, Portland, is Editor for OB/GYN Clinical Alert.

Synopsis: A Swedish cohort study finds no increase in risk of myocardial infarction associated with low-dose oral contraceptives.

Source: Margolis KL, et al. A prospective study of oral contraceptive use and risk of myocardial infarction among Swedish women. Fertil Steril. 2007;88:310-316.

Margolis and colleagues analyzed data from a large prospective study of a cohort of 48,321 Swedish women who are part of the Women's Lifestyle and Health Cohort Study.1 Of the women who took part, 16.6% had never used oral contraceptives, 69.3% were former users, and 14.1% were current users (more than half were age 35 and older). There were 214 cases of myocardial infarction (24 fatal) during 11 years of follow-up.

Table 1
  Cases Relative Risk Adjusted for Risk Factors
Former users 156 1.0 (0.7-1.4)
Current users 11 0.7 (0.4-1.4)
First use after age 30 10 1.0 (0.5-1.9)

The risk of myocardial infarction among current users was not elevated in smokers, but the conclusion was limited by small numbers. There was no trend for an increase in risk with duration of use. The authors concluded that low-dose (less than 50 µg ethinyl estradiol) oral contraceptives are not associated with an increased risk of myocardial infarction.

Commentary

The Women's Lifestyle and Health Cohort Study is a prospective cohort study of 106,841 Norwegian and Swedish women, started in 1991, specifically designed to assess the long-term health effects of hormonal contraceptives. All previous cohort studies date back to oral contraceptive use with higher doses of estrogen in the 1970s and 1980s. For example, in the report from the Nurses' Health Study in 1988, an increased risk of myocardial infarction was found in current users.2

Case-control studies of low-dose estrogen oral contraceptives have concluded that an increased risk of arterial disease occurs only in women who have hypertension or are smokers.3-7 The cohort studies don't help us with this important issue because the numbers are too small for definitive analyses of subgroups. Nevertheless, British and Finnish cohorts were reported to have increased risks of developing myocardial infarction in oral contraceptive users who smoked.8, 9

This new study supports the conventional wisdom of the last decade that low-dose oral contraceptives do not increase risk of myocardial infarction or stroke in healthy, nonsmoking women, regardless of age. Screening for hypertension is especially important in that it is the major risk factor for stroke associated with oral contraceptive use. With no hypertension, the effect of smoking in women under age 35 is too small to be measured. It is currently believed that with medical control of blood pressure and close follow-up (blood pressure monitoring every 3 months), nonsmoking women under age 35 and otherwise healthy can use low-dose oral contraception. There is no reason to doubt that these conclusions apply as well to the transdermal and vaginal methods of steroid contraception.

References

  1. Margolis KL, et al. Fertil Steril. 2007;88:310-316.
  2. Stampfer MJ, et al. A prospective study of past use of oral contraceptive agents and risk of cardiovascular diseases. New Engl J Med. 1988;319:1313-1317.
  3. Croft P, Hannaford PC. Risk factors for acute myocardial infarction in women: evidence from the Royal College of General Practitioners' oral contraceptive study. Br Med J. 1989;298:165-168.
  4. Sidney S, et al. Myocardial infarction in users of low-dose oral contraceptives. Obstet Gynecol. 1996;88:939-944.
  5. Lewis MA, et al. The use of oral contraceptives and the occurrence of acute myocardial infarction in young women. Results from the Transnational Study on Oral Contraceptives and the Health of Young Women. Contraception. 1997;56:129-140.
  6. WHO Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. Acute myocardial infarction and combined oral contraceptives: results of an international multicentre case-control study. Lancet. 1997;349:1202-1209.
  7. Tanis BC, et al. Oral contraceptives and the risk of myocardial infarction. New Eng J Med. 2001;345:1787-1793.
  8. Mant J, et al. Risk of myocardial infarction, angina and stroke in users of oral contraceptives: an updated analysis of a cohort study. Br J Obstet Gynaecol. 1998;105:890-896.
  9. Salonen JT. Oral contraceptives, smoking and risk of myocardial infarction in young women: a longitudinal population study in eastern Finland. Acta Med Scand. 1982;212:141-144.