Postmenopausal hormone replacement therapy: scientific review

Topic: Risk, prevention and care in population studies

Recent results of the Women's Health Initiative (WHI) and the Heart and Estrogen/progestin Replacement Study (HERS) are included for reported outcomes. Studies were excluded if the population was selected according to prior events or presence of conditions associated with higher risks for targeted outcomes. Data synthesis Meta-analyses of observational studies indicated summary relative risks (RRs) for coronary heart disease (CHD) incidence and mortality that were significantly reduced among current HRT users only, although risk for incidence was not reduced when only studies that controlled for socioeconomic status were included. Stroke incidence but not mortality was significantly increased among HRT users in the meta-analysis and the WHI. The meta-analysis indicated that risk was significantly elevated for thromboembolic stroke (RR, 1.20; 95% CI, 1.01-1.40) but not subarachnoid or intracerebral stroke. Risk of venous thromboembolism among current HRT users was increased overall (RR, 2.14; 95% CI, 1.64-2.81) and was highest during the first year of use (RR, 3.49; 95% CI, 2.33-5.59) according to a meta-analysis of 12 studies. Protection against osteoporotic fractures is supported by a meta-analysis of 22 estrogen trials, cohort studies, results of the WHI, and trials with bone density outcomes. Current estrogen users have an increased risk of breast cancer that increases with duration of use.

Key findings

• Recent results of the Women's Health Initiative (WHI) and the Heart and Estrogen/progestin Replacement Study (HERS) are included for reported outcomes.
• Studies were excluded if the population was selected according to prior events or presence of conditions associated with higher risks for targeted outcomes.
• Data synthesis Meta-analyses of observational studies indicated summary relative risks (RRs) for coronary heart disease (CHD) incidence and mortality that were significantly reduced among current HRT users only, although risk for incidence was not reduced when only studies that controlled for socioeconomic status were included.
• Stroke incidence but not mortality was significantly increased among HRT users in the meta-analysis and the WHI.
• The meta-analysis indicated that risk was significantly elevated for thromboembolic stroke (RR, 1.20; 95% CI, 1.01-1.40) but not subarachnoid or intracerebral stroke.

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Study details

• Study designmeta-analysis
• Evidence strengthHigh

Read the original

• DOI: 10.1001/jama.288.7.872
• PubMed: 12186605
• Original source →

May need a subscription Unpaywall, Europe PMC and OpenAlex found no free copy of the full text (checked 10 Oct 2026), so the publisher may charge for it. The PubMed abstract is free.

@article{nelson2002-12186605,
  author  = {Nelson, H. D. and Humphrey, L. L. and Nygren, P. and Teutsch, S. M. and Allan, J. D.},
  title   = {{Postmenopausal hormone replacement therapy: scientific review}},
  journal = {JAMA},
  year    = {2002},
  doi     = {10.1001/jama.288.7.872},
  pmid    = {12186605},
  url     = {https://doi.org/10.1001/jama.288.7.872}
}

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• Estrogen replacement therapy and risk of Alzheimer disease Archives of internal medicine · 1996-10-01 · usefulness score 57/100 · How common it is

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