Effect of hormone replacement therapy on cardiovascular events in recently postmenopausal women: randomised trial
By L. Schierbeck, L. Rejnmark, C. Tofteng, L. Stilgren, P. Eiken, L. Mosekilde, L. Køber, J. Jensen. British medical journal, 2012
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Objective To investigate the long term effect of hormone replacement therapy on cardiovascular outcomes in recently postmenopausal women. Design Open label, randomised controlled trial. Setting Denmark, 1990-93. Participants 1006 healthy women aged 45-58 who were recently postmenopausal or had perimenopausal symptoms in combination with recorded postmenopausal serum follicle stimulating hormone values. 502 women were randomly allocated to receive hormone replacement therapy and 504 to receive no treatment (control). Women who had undergone hysterectomy were included if they were aged 45-52 and had recorded values for postmenopausal serum follicle stimulating hormone. Interventions In the treatment group, women with an intact uterus were treated with triphasic estradiol and norethisterone acetate and women who had undergone hysterectomy received 2 mg estradiol a day. Intervention was stopped after about 11 years owing to adverse reports from other trials, but participants were followed for death, cardiovascular disease, and cancer for up to 16 years. Sensitivity analyses were carried out on women who took more than 80% of the prescribed treatment for five years. Main outcome measure The primary endpoint was a composite of death, admission to hospital for heart failure, and myocardial infarction. Results At inclusion the women on average were aged 50 and had been postmenopausal for seven months. After 10 years of intervention, 16 women in the treatment group experienced the primary composite endpoint compared with 33 in the control group (hazard ratio 0.48, 95% confidence interval 0.26 to 0.87; P=0.015) and 15 died compared with 26 (0.57, 0.30 to 1.08; P=0.084). The reduction in cardiovascular events was not associated with an increase in any cancer (36 in treated group v 39 in control group, 0.92, 0.58 to 1.45; P=0.71) or in breast cancer (10 in treated group v 17 in control group, 0.58, 0.27 to 1.27; P=0.17). The hazard ratio for deep vein thrombosis (2 in treated group v 1 in control group) was 2.01 (0.18 to 22.16) and for stroke (11 in treated group v 14 in control group) was 0.77 (0.35 to 1.70). After 16 years the reduction in the primary composite outcome was still present and not associated with an increase in any cancer. Conclusions After 10 years of randomised treatment, women receiving hormone replacement therapy early after menopause had a significantly reduced risk of mortality, heart failure, or myocardial infarction, without any apparent increase in risk of cancer, venous thromboembolism, or stroke. Trial registration ClinicalTrials.gov NCT00252408.
Subfields: Endocrinology, Diabetes and Metabolism, Obstetrics and Gynecology, Public Health, Environmental and Occupational Health
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Citations in the corpus
- Cardiovascular Risks Associated with Gender and Aging (2019, background): “There have been reported cardioprotective benefits in women when estrogen replacement is introduced in early menopause, suggesting that there may be a “critical window” for estrogen replacement therapy [134,135].”
- The protective role of estrogen and estrogen receptors in cardiovascular disease and the controversial use of estrogen therapy (2017, background): “Another randomized study in women (45–58 years old) also showed a significantly reduced risk of mortality, heart failure, or myocardial infarction if HRT was initiated early after menopause [121].”
- Guidelines for the Prevention of Stroke in Women: A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association (2014, background): “Stroke rates did not differ between groups.(258) Transdermal estradiol may represent a safer alternative than oral estrogens, because treatment does not appear to increase the risk of VTE and stroke and may reduce the risk of MI compared with nonusers.”
- Treatment of Symptoms of the Menopause: An Endocrine Society Clinical Practice Guideline. (2015, background): “A randomized osteoporosis trial that did not have CHD as a predefined primary endpoint reported that 10 years of MHT treatment in women 50 years old at study onset was associated with the reduction of a composite safety endpoint (death, hospital admission for MI, or heart failure) (103).”