Estrogen plus progestin therapy and breast cancer in recently postmenopausal women

Ross L. Prentice, Rowan T. Chlebowski, Marcia L. Stefanick, Joann E. Manson, Mary Pettinger, Susan L. Hendrix, F. Allan Hubbell, Charles Kooperberg, Lewis H. Kuller, Dorothy S. Lane, Anne McTiernan, Mary Jo O'Sullivan, Jacques E. Rossouw, Garnet L. Anderson

Research output: Contribution to journalArticlepeer-review

124 Scopus citations


The Women's Health Initiative trial found a modestly increased risk of invasive breast cancer with daily 0.625-mg conjugated equine estrogens plus 2.5-mg medroxyprogesterone acetate, with most evidence among women who had previously received postmenopausal hormone therapy. In comparison, observational studies mostly report a larger risk increase. To explain these patterns, the authors examined the effects of this regimen in relation to both prior hormone therapy and time from menopause to first use of postmenopausal hormone therapy ("gap time") in the Women's Health Initiative trial and in a corresponding subset of the Women's Health Initiative observational study. Postmenopausal women with a uterus enrolled at 40 US clinical centers during 1993-1998. The authors found that hazard ratios agreed between the two cohorts at a specified gap time and time from hormone therapy initiation. Combined trial and observational study data support an adverse effect on breast cancer risk. Women who initiate use soon after menopause, and continue for many years, appear to be at particularly high risk. For example, for a woman who starts soon after menopause and adheres to this regimen, estimated hazard ratios are 1.64 (95% confidence interval: 1.00, 2.68) over a 5-year period of use and 2.19 (95% confidence interval: 1.56, 3.08) over a 10-year period of use.

Original languageEnglish (US)
Pages (from-to)1207-1216
Number of pages10
JournalAmerican journal of epidemiology
Issue number10
StatePublished - May 2008
Externally publishedYes


  • Breast neoplasms
  • Clinical trials as topic
  • Cohort studies
  • Estrogens
  • Hormone replacement therapy
  • Postmenopause
  • Progestins

ASJC Scopus subject areas

  • Epidemiology


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