Hormone Therapy Use and Risk of Chronic Disease in the Nurses' Health Study: A Comparative Analysis With the Women's Health Initiative

Am J Epidemiol. 2017 Sep 15;186(6):696-708. doi: 10.1093/aje/kwx131.


Observational studies and randomized controlled trials of menopausal hormone therapy (HT) and chronic disease risk appear to have divergent results for cardiovascular disease. However, differences may be related to a modifying effect of age, time since menopause, and HT formulation. In the Nurses' Health Study (NHS) (enrolling during 1980-1994 and following participants until 2002), we investigated associations between the use of oral conjugated equine estrogens (CEE) (0.625 mg/day) plus medroxyprogesterone acetate (MPA) (<10 mg/day) or oral CEE alone and cardiovascular disease, cancer, all-cause mortality, and other major endpoints among postmenopausal women, aged 50-79 years at HT initiation. Among women aged 50-59 years at HT initiation, associations of CEE alone or CEE+MPA with most clinical outcomes were highly concordant between NHS and Women's Health Initiative (WHI). However, for myocardial infarction, results for CEE+MPA were in the direction of risk elevation in WHI and in the direction of risk reduction in NHS. When examined according to years since menopause onset (<10 years) rather than age group, results were nonsignificant and concordant for both studies. Because few women in the NHS initiated HT after age 60 years, we did not examine associations in this group. Discrepancies between NHS and WHI could largely be attributed to differences in the age structure of the populations and age at HT initiation.

Keywords: Nurses’ Health Study; Women's Health Initiative; cardiovascular disease; chronic disease; epidemiologic methods; hormone therapy; randomized controlled trials.

Publication types

  • Comparative Study

MeSH terms

  • Aged
  • Cardiovascular Diseases / chemically induced
  • Cardiovascular Diseases / mortality
  • Cause of Death
  • Chronic Disease / mortality*
  • Comparative Effectiveness Research
  • Estrogen Replacement Therapy / methods
  • Estrogen Replacement Therapy / mortality*
  • Estrogens, Conjugated (USP) / administration & dosage
  • Estrogens, Conjugated (USP) / adverse effects*
  • Female
  • Humans
  • Medroxyprogesterone Acetate / administration & dosage
  • Medroxyprogesterone Acetate / adverse effects*
  • Menopause
  • Middle Aged
  • Neoplasms / chemically induced
  • Neoplasms / mortality
  • Postmenopause / drug effects*
  • Risk Factors
  • State Medicine
  • Time Factors
  • Women's Health


  • Estrogens, Conjugated (USP)
  • Medroxyprogesterone Acetate