Estrogen-progestin replacement therapy and breast cancer risk: the Women's Health Study (United States)

Cancer Causes Control. 2002 Nov;13(9):847-54. doi: 10.1023/a:1020617415381.


Objective: While there is substantial evidence that unopposed estrogen use increases the risk of breast cancer, there are limited data from epidemiologic studies on the impact of estrogen-progestin combinations. We therefore examined estrogen-progestin replacement therapy and breast cancer risk in the Women's Health Study.

Methods: We investigated postmenopausal hormone (PMH) use among 17,835 apparently healthy postmenopausal women aged > or =45 years, and followed them prospectively for an average of 5.9 years. Breast cancer occurred in 411 women.

Results: The multivariate relative risks of all breast cancer associated with never use of PMH, use of estrogen replacement therapy (ERT), and use of estrogen-progestin replacement therapy (HRT) were 1.00 (referent), 0.96 (95% CI 0.65-1.42), and 1.37 (95% CI 1.05-1.78). The increase in risk among users of HRT was largely limited to those women who had used estrogen-progestin replacement therapy for five years or more, and to those women who were on continuous rather than cyclic progestin combinations. Higher doses of estrogen, but not progestin, were associated with increased breast cancer risk, compared with lower doses.

Conclusions: These prospective data suggest that use of estrogen-progestin replacement therapy imparts an increased risk of breast cancer in comparison with never use of PMH.

Publication types

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

MeSH terms

  • Breast Neoplasms / epidemiology*
  • Confounding Factors, Epidemiologic
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Estrogen Replacement Therapy / adverse effects*
  • Estrogens, Conjugated (USP) / adverse effects
  • Female
  • Humans
  • Linear Models
  • Middle Aged
  • Multivariate Analysis
  • Proportional Hazards Models
  • Prospective Studies
  • Risk Assessment
  • Time Factors
  • United States / epidemiology


  • Estrogens, Conjugated (USP)