Postmenopausal hormone therapy and the risks of coronary heart disease, breast cancer, and stroke

Semin Reprod Med. 2014 Nov;32(6):419-25. doi: 10.1055/s-0034-1384624. Epub 2014 Oct 16.


The principal findings are briefly reviewed from the Women's Health Initiative trials of the most commonly used postmenopausal hormone regimens in the United States-conjugated equine estrogens and these same estrogens plus medroxyprogesterone acetate. A more detailed review is presented for three major clinical outcomes: coronary heart disease (CHD), the primary trial outcome for which a major benefit was hypothesized; invasive breast cancer, the primary safety outcome for which some adverse effect was expected; and stroke which surfaced as an important adverse effect with both regimens, and one that is influential in decisions concerning the continued use of postmenopausal estrogens alone. The review for these outcomes includes an update on interactions of treatment effects with study subject characteristics and exposures and with prerandomization biomarker levels. It also includes a focus on timing issues that are important to the understanding of treatment effects. Specifically, with combined estrogen plus progestin, CHD risk was elevated early with the elevation dissipating after a few years of treatment, whereas breast cancer elevations increased during the treatment period, and climbed to about a threefold increase following 5 years of adherence. Importantly, breast cancer risk elevations appear to be higher among women who initiate treatment at the menopause, or soon thereafter, compared with women having a longer gap time. Stroke effects, on the contrary, did not seem to vary appreciably with these timing issues. The adverse effect was evidently localized to ischemic strokes, for which there was an approximate 50% increase with either regimen. The rather limited knowledge concerning the biomarkers and biological pathways that mediate the hormone therapy effects on these diseases is also briefly reviewed.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Aged
  • Aged, 80 and over
  • Brain Ischemia / chemically induced*
  • Brain Ischemia / epidemiology
  • Breast Neoplasms / chemically induced*
  • Breast Neoplasms / epidemiology
  • Coronary Disease / chemically induced*
  • Coronary Disease / epidemiology
  • Drug Therapy, Combination / adverse effects
  • Estrogen Replacement Therapy / adverse effects*
  • Estrogens / adverse effects
  • Estrogens, Conjugated (USP) / adverse effects
  • Evidence-Based Medicine*
  • Female
  • Humans
  • Medroxyprogesterone Acetate / adverse effects
  • Middle Aged
  • Progestins / adverse effects
  • Risk Factors
  • Stroke / chemically induced*
  • Stroke / epidemiology
  • United States / epidemiology


  • Estrogens
  • Estrogens, Conjugated (USP)
  • Progestins
  • Medroxyprogesterone Acetate