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Cited by 612Menopause: Health Impacts and TreatmentsHormonal and reproductive studiesEstrogen and related hormone effects

Hormone therapy for preventing cardiovascular disease in post-menopausal women

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Boardman, Henry MP, Hartley, Louise, Eisinga, Anne, Main, Caroline, Roqué i Figuls, Marta, Bonfill Cosp, Xavier, Gabriel Sanchez, Rafael, Knight, Beatrice·2015·Cochrane Database of Systematic Reviews
DOI 10.1002/14651858.cd002229.pub4PMC PMC10183715
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Abstract

BACKGROUND: Evidence from systematic reviews of observational studies suggests that hormone therapy may have beneficial effects in reducing the incidence of cardiovascular disease events in post-menopausal women, however the results of randomised controlled trials (RCTs) have had mixed results. This is an updated version of a Cochrane review published in 2013. OBJECTIVES: To assess the effects of hormone therapy for the prevention of cardiovascular disease in post-menopausal women, and whether there are differential effects between use in primary or secondary prevention. Secondary aims were to undertake exploratory analyses to (i) assess the impact of time since menopause that treatment was commenced (≥ 10 years versus < 10 years), and where these data were not available, use age of trial participants at baseline as a proxy (≥ 60 years of age versus < 60 years of age); and (ii) assess the effects of length of time on treatment. SEARCH METHODS: We searched the following databases on 25 February 2014: Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE and LILACS. We also searched research and trials registers, and conducted reference checking of relevant studies and related systematic reviews to identify additional studies. SELECTION CRITERIA: RCTs of women comparing orally administered hormone therapy with placebo or a no treatment control, with a minimum of six months follow-up. DATA COLLECTION AND ANALYSIS: Two authors independently assessed study quality and extracted data. We calculated risk ratios (RRs) with 95% confidence intervals (CIs) for each outcome. We combined results using random effects meta-analyses, and undertook further analyses to assess the effects of treatment as primary or secondary prevention, and whether treatment was commenced more than or less than 10 years after menopause. MAIN RESULTS: We identified six new trials through this update. Therefore the review includes 19 trials with a total of 40,410 post-menopausal women. On the whole, study quality was good and generally at low risk of bias; the findings are dominated by the three largest trials. We found high quality evidence that hormone therapy in both primary and secondary prevention conferred no protective effects for all-cause mortality, cardiovascular death, non-fatal myocardial infarction, angina, or revascularisation. However, there was an increased risk of stroke in those in the hormone therapy arm for combined primary and secondary prevention (RR 1.24, 95% CI 1.10 to 1.41). Venous thromboembolic events were increased (RR 1.92, 95% CI 1.36 to 2.69), as were pulmonary emboli (RR 1.81, 95% CI 1.32 to 2.48) on hormone therapy relative to placebo.The absolute risk increase for stroke was 6 per 1000 women (number needed to treat for an additional harmful outcome (NNTH) = 165; mean length of follow-up: 4.21 years (range: 2.0 to 7.1)); for venous thromboembolism 8 per 1000 women (NNTH = 118; mean length of follow-up: 5.95 years (range: 1.0 to 7.1)); and for pulmonary embolism 4 per 1000 (NNTH = 242; mean length of follow-up: 3.13 years (range: 1.0 to 7.1)).We performed subgroup analyses according to when treatment was started in relation to the menopause. Those who started hormone therapy less than 10 years after the menopause had lower mortality (RR 0.70, 95% CI 0.52 to 0.95, moderate quality evidence) and coronary heart disease (composite of death from cardiovascular causes and non-fatal myocardial infarction) (RR 0.52, 95% CI 0.29 to 0.96; moderate quality evidence), though they were still at increased risk of venous thromboembolism (RR 1.74, 95% CI 1.11 to 2.73, high quality evidence) compared to placebo or no treatment. There was no strong evidence of effect on risk of stroke in this group. In those who started treatment more than 10 years after the menopause there was high quality evidence that it had little effect on death or coronary heart disease between groups but there was an increased risk of stroke (RR 1.21, 95% CI 1.06 to 1.38, high quality evidence) and venous thromboembolism (RR 1.96, 95% CI 1.37 to 2.80, high quality evidence). AUTHORS' CONCLUSIONS: Our review findings provide strong evidence that treatment with hormone therapy in post-menopausal women overall, for either primary or secondary prevention of cardiovascular disease events has little if any benefit and causes an increase in the risk of stroke and venous thromboembolic events.

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  • Subsequent re-analyses of the Women's Health Initiative data revealed cardiometabolic benefits of MHT in women aged 50-59.

    “subsequent re-analyses of the WHI data revealed cardiometabolic benefits of MHT in women aged 50-59 (216–218).”

    From Metabolic impact of endogenously produced estrogens by adipose tissue in females and males across the lifespan (2025) · cites this paper as [217]

    The Discussion (Summary of main results; page unavailable) reports improved overall survival and coronary heart disease outcomes when hormone therapy began within 10 years of menopause or before age 60, and notes a similar WHI trend. It does not establish benefits specifically for women aged 50–59 from WHI re-analyses, and it reports increased venous thromboembolism risk even with earlier treatment. (LLM, conf=0.85)

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Research works printed but not linked: 3

  1. Miller J, Chan B, Nelson H. Postmenopausal Estrogen Replacement and Risk for VenousThromboembolism: A Systematic Review and Meta-Analysis for the U.S. Preventive Services Task Force. Annals of Internal Medicine 2002;136:680-90.
  2. Hemminki E, McPherson K. Impact of postmenopausal hormone therapy on cardiovascular events and cancer: pooled data from clinical trials. Bmj. Jul 19 1997;315(7101):149-153.
  3. Resch H, Pietschmann P, Krexner E, Woloszczuk W, Willvonseder R. Effects of one-year hormone replacement therapy on peripheral bone mineral content in patients with osteoporotic spine fractures. Acta endocrinologica. Jul 1990;123(1):14-18.

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Authors
Boardman, H. M., Hartley, L., Eisinga, A., Main, C., Roqué i Figuls, M., Bonfill Cosp, X., Gabriel Sanchez, R., & Knight, B.
Affiliations
  • John Radcliffe Hospital (GB)
  • University of Warwick (GB)
  • National Institute for Health and Care Research (GB)
  • Cancer Research UK Clinical Trials Unit (GB)
  • CIBER Epidemiología y Salud Pública (CIBERESP); Iberoamerican Cochrane Centre, Biomedical Research Institute Sant Pau (IIB Sant Pau); Sant Antoni Maria Claret 171 Edifici Casa de Convalescència Barcelona Catalunya Spain 08041
  • CIBER Epidemiología y Salud Pública (CIBERESP) - Universitat Autònoma de Barcelona; Iberoamerican Cochrane Centre - Biomedical Research Institute Sant Pau (IIB Sant Pau); Sant Antoni Maria Claret, 167 Pavilion 18 (D-13) Barcelona Catalunya Spain 08025
  • Hospital Universitario de la Paz, Universidad Autónoma de Madrid; Instituto de Investigacion IdiPAZ, Red Espanola de Investigacion Cardiovascular RD/12/0042/0008; Diego De Leon 62 Planta 9 Madrid Spain 28006
  • University of Exeter (GB)
ORCID
Venue
Cochrane Database of Systematic Reviews
Publisher
Wiley
Published
2015-03-10
Volume
2015
Issue
8
Pages
CD002229-CD002229
ISSN
  • 1361-6137 (ISSN-L)
  • 1465-1858
DOI
10.1002/14651858.cd002229.pub4
PMC
PMC10183715
OpenAlex
W1927817986
Cited by
612
References
230
Citations by year
2026: 35 · 2025: 57 · 2024: 69 · 2023: 64 · 2022: 42 · 2021: 63 · 2020: 46 · 2019: 60 · 2018: 48 · 2017: 50 · 2016: 32 · 2015: 26 · 2014: 14 · 2013: 1
FWCI
7.83
Type
journal article
Language
en
Open access
Locations
  • Cochrane Database of Systematic Reviews (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
Keywords
hormone therapy, postmenopausal women, cardiovascular disease prevention, primary prevention, secondary prevention, stroke risk, venous thromboembolism, myocardial infarction, all-cause mortality, cardiovascular mortality, time since menopause, treatment duration, oral hormone therapy, menopause, cardiovascular risk factors, cardiovascular risk reduction
MeSH terms
Adult, Aged, Aged, 80 and over, Cardiovascular Diseases, Cause of Death, Female, Humans, Middle Aged, Primary Prevention, Estrogen Replacement Therapy, Postmenopause, Hormone Replacement Therapy, Stroke, Venous Thromboembolism, Secondary Prevention

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