Postmenopausal estrogen and progestin use and the risk of cardiovascular disease

N Engl J Med. 1996 Aug 15;335(7):453-61. doi: 10.1056/NEJM199608153350701.


Background: Estrogen therapy in postmenopausal women has been associated with a decreased risk of heart disease. There is little information, however, about the effect of combined estrogen and progestin therapy on the risk of cardiovascular disease.

Methods: We examined the relation between cardiovascular disease and postmenopausal hormone therapy during up to 16 years of follow-up in 59,337 women from the Nurses' Health Study, who were 30 to 55 years of age at base line. Information on hormone use was ascertained with biennial questionnaires. From 1976 to 1992, we documented 770 cases of myocardial infarction or death from coronary disease in this group and 572 strokes. Proportional-hazards models were used to calculate relative risks and 95 percent confidence intervals, adjusted for confounding variables.

Results: We observed a marked decrease in the risk of major coronary heart disease among women who took estrogen with progestin (multivariate adjusted relative risk, 0.39; 95 percent confidence interval, 0.19 to 0.78) or estrogen alone (relative risk, 0.60; 95 percent confidence interval, 0.43 to 0.83), as compared with women who did not use hormones [corrected]. However, there was no significant association between stroke and use of combined hormones (multivariate adjusted relative risk, 1.09; 95 percent confidence interval, 0.66 to 1.80) or estrogen alone (relative risk, 1.27; 95 percent confidence interval, 0.95 to 1.69).

Conclusions: The addition of progestin does not appear to attenuate the cardioprotective effects of postmenopausal estrogen therapy.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Cardiovascular Diseases / epidemiology*
  • Cardiovascular Diseases / prevention & control
  • Drug Therapy, Combination
  • Estrogen Replacement Therapy*
  • Estrogens / therapeutic use*
  • Estrogens, Conjugated (USP) / administration & dosage
  • Female
  • Follow-Up Studies
  • Humans
  • Middle Aged
  • Postmenopause / drug effects*
  • Progestins / therapeutic use*
  • Proportional Hazards Models
  • Risk
  • United States / epidemiology


  • Estrogens
  • Estrogens, Conjugated (USP)
  • Progestins