Combined estrogen and progestin hormone replacement therapy in relation to risk of breast cancer in middle-aged women

JAMA. 1995 Jul 12;274(2):137-42.


Objective: To determine the risk of breast cancer in relation to the use of combined estrogen and progestin hormone replacement therapy (HRT).

Design: A population-based case-control study.

Setting: The general female population of King County in western Washington State.

Participants: Middle-aged (50 to 64 years) women, including 537 patients with incident primary breast cancer diagnosed between January 1, 1988, and June 30, 1990, who were ascertained through the Seattle-Puget Sound Surveillance, Epidemiology, and End Results cancer registry and 492 randomly selected control women without a history of breast cancer.

Main outcome measure: Breast cancer risk in relation to use of menopausal hormones.

Results: Menopausal hormones of some type had been used by 57.6% of breast cancer cases and 61.0% of comparison women. The women who had ever taken combined estrogen-progestin HRT, representing 21.5% of cases and 21.3% of controls, were not at increased risk of breast cancer (relative odds [RO] = 0.9; 95% confidence interval [CI], 0.7 to 1.3). Compared with nonusers of menopausal hormones, those who used estrogen-progestin HRT for 8 or more years had, if anything, a reduced risk of breast cancer (RO = 0.4; 95% CI, 0.2 to 1.0).

Conclusions: On the whole, the use of estrogen with progestin HRT does not appear to be associated with an increased risk of breast cancer in middle-aged women. Nonetheless, since the use of combined estrogen-progestin HRT has only recently become prevalent, future investigations must assess whether breast cancer incidence is altered many years after estrogen-progestin HRT has been initiated, particularly among long-term users.

Publication types

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

MeSH terms

  • Breast Neoplasms / chemically induced
  • Breast Neoplasms / epidemiology*
  • Case-Control Studies
  • Drug Therapy, Combination
  • Estrogen Replacement Therapy / adverse effects*
  • Estrogens / adverse effects*
  • Estrogens / therapeutic use
  • Female
  • Humans
  • Logistic Models
  • Middle Aged
  • Progestins / adverse effects*
  • Progestins / therapeutic use
  • Proportional Hazards Models
  • Risk Factors


  • Estrogens
  • Progestins