Hormone therapy for preventing cardiovascular disease in post-menopausal women

  • Comment
  • Review
  • Intervention


  • Caroline Main,

    Corresponding author
    1. Peninsula College of Medicine and Dentistry, Peninsula Technology Assessment Group (PenTAG), Exeter, UK
    • Caroline Main, Peninsula Technology Assessment Group (PenTAG), Peninsula College of Medicine and Dentistry, Noy Scott House, Barrack Road, Exeter, EX2 5DW, UK. carriemain24@gmail.com.

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  • Beatrice Knight,

    1. University of Exeter Medical School, NIHR Exeter Clinical Research Facilt, Exeter, UK
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  • Tiffany Moxham,

    1. Florida Atlantic University, Wimberly Library, Boca Raton, Florida, USA
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  • Rafael Gabriel Sanchez,

    1. Hospital Universitario de la Paz, Universidad Autónoma de Madrid, Instituto de Investigacion IdiPAZ, Red Espanola de Investigacion Cardiovascular RD/12/0042/0008, Madrid, Spain
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  • Luis Maria Sanchez Gomez,

    1. Instituto de Salud Carlos III, Agencia de Evaluacion Tecnologias Sanitarias, Madrid, Spain
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  • Marta Roqué i Figuls,

    1. CIBER Epidemiología y Salud Pública (CIBERESP), Iberoamerican Cochrane Centre, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Catalunya, Spain
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  • Xavier Bonfill Cosp

    1. CIBER Epidemiología y Salud Pública (CIBERESP), Spain - Universitat Autònoma de Barcelona, Iberoamerican Cochrane Centre, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Catalonia, Spain
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Evidence from systematic reviews of observational studies suggest that hormone replacement therapy (HT) may have beneficial effects in reducing the incidence of cardiovascular disease (CVD) events in post-menopausal women. This is an updated version of a Cochrane review first published in 2005 (Gabriel-Sanchez 2005).


To assess the effects of HT for the prevention of CVD in post-menopausal women, and whether there are differential effects between use of single therapy alone compared to combination HT and use in primary or secondary prevention.

Search methods

We searched the following databases to April 2010: Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library, MEDLINE, EMBASE and LILACS.

Selection criteria

Randomised controlled trials (RCTs) of women comparing orally administered HT with placebo with a minimum of six-months follow-up.

Data collection and analysis

Two authors independently assessed study quality and extracted data. Risk Ratios (RR) with 95% confidence intervals were calculated for each outcome. Results were combined using fixed-effect meta-analyses, and where possible, further stratified analyses conducted to assess the effect of time on treatment. Additionally, univariate meta-regression analyses were undertaken to assess whether length of trial follow-up, single or combination treatment, or whether treatment for primary or secondary prevention were potential predictors for a number of CVD outcomes in the trials.

Main results

Four new trials were identified through the update; one trial included in the previous review was excluded. Therefore the review included 13 trials with a total of 38,171 post-menopausal women. Overall, single and combination HT in both primary and secondary prevention conferred no protective effects for all cause mortality, CVD death, non-fatal MI, or angina. There were no significant differences in the number of coronary artery by-pass procedures or angioplasties performed between the trial arms. However there was an increased risk of stroke for both primary and secondary prevention when combination and single HT was combined, RR 1.26 (95% CI 1.11 to 1.43), in venous thromboembolic events, RR 1.89 (95% CI 1.58 to 2.26) and in pulmonary embolism RR 1.84 (95% CI 1.42 to 2.37) relative to placebo. The associated numbers needed-to-harm (NNH) were 164, 109 and 243 for stroke, venous thromboembolism and pulmonary embolism respectively. 

Authors' conclusions

Treatment with HT in post-menopausal women for either primary or secondary prevention of CVD events is not effective, and causes an increase in the risk of stroke, and venous thromboembolic events. HT should therefore only be considered for women seeking relief from menopausal symptoms. Short-term HT treatment should be at the lowest effective dose, and used with caution in women with predisposing risk factors for CVD events.

Plain language summary

Hormone therapy for preventing cardiovascular disease in both healthy post-menopausal women and those with pre-existing cardiovascular disease

Hormone therapy (HT) is used for controlling menopausal symptoms. It has also been used for the management and prevention of cardiovascular disease (CVD) in older post-menopausal women. The present review assessed the clinical effects of using HT for six-months or more. Thirteen randomised controlled trials (involving 38171 women aged 42 - 91) compared oral HT (oestrogen, with or without progestogen) with placebo. Most participants were post-menopausal American women, and the mean age in most studies was over 60 years. The length of time women were on treatment varied across the trials from 11.9 months to 7.1 years.

Overall, results showed no evidence that HT provides any protective effects against the development of CVD, either in healthy women or women with pre-existing heart disease. Rather, in relatively healthy post-menopausal women both single (oestrogen alone) and combination HT (oestrogen plus progestogen) significantly increased the risk of stroke and obstruction of a vein by a blood clot (venous thrombo-embolism). Combination HT, additionally, significantly increased the risk of suffering from a non-fatal heart attack or blood clots on the lungs (pulmonary embolism). Among women with existing CVD, combination HT significantly increased the risk of both venous thrombo-embolism and pulmonary embolism, but not stroke.

Laički sažetak

Hormonska terapija za prevenciju kardiovaskularnih bolesti i kod zdravih postmenopauzalnih žena i postmenopauzalnih žena s postojećim kardiovaskularnim bolestima

Hormonska terapija koristi se za kontroliranje menopauzalnih simptoma. Također se koristi za liječenje i prevenciju kardiovaskularnih bolesti u starijih postmenopauzalnih žena.  Ovaj Cochrane sustavni pregled analizirao je kliničke učinke hormonske terapije u trajanju od 6 mjeseci ili dulje. U literaturi je pronađeno 13 randomiziranih kontroliranih ispitivanja (s ukupno 38171 žena u dobi od 42 do 91 godina) u kojima je uspoređena hormonska terapija (estrogen, s ili bez progesterona) s placebom. V Većina ispitanica bile su postmenopauzalne žene iz Amerike i srednja dob ispitanica u većini studija bila je iznad 60 godina.  Duljina terapije razlikovala se među studijama, od 11,9 mjeseci do 7,1 godina.

Nakon analize svih pronađenih studija, rezultati nisu pokazali dokaze da hormonska terapije omogućuje ikakav zaštitni učinak protiv razvoja kardiovaskularnih bolesti, niti u zdravih žena niti u žena s već postojećom srčanom bolešću. Naprotiv, u relativno zdravih postmenopauzalnih žena koje su dobivale sam estrogen ili kombiniranu hormonsku terapiju (estrogen plus progesteron) značajno je smanjen rizik moždanog udara i venske opstrukcije krvnim ugrušcima (venska tromboembolija).  Nadalje, kombinirana hormonska terapija dodatno je povećala rizik od ne-fatalnog srčanog udara ili plućne embolije. Među ženama s postojećim kardiovaskularnim bolestima kombinirana hormonska terapija značajno je povećala rizik venske tromboembolije i plućne embolije, ali ne i moždanog udara.

Bilješke prijevoda

Hrvatski Cochrane ogranak
Prevela: Livia Puljak