Does Hormone Replacement Therapy Protect Against Cardiovascular Events?

Does Hormone Replacement Therapy Protect Against Cardiovascular Events?

Women who initiated hormone replacement therapy (HRT) soon after beginning menopause and who continued treatment for 10 years had significantly reduced risk of myocardial infarction (MI), heart failure, or death with no increased risk of cancer, venous thromboembolism, or stroke, according to findings from a randomized controlled trial conducted using data from the Danish Osteoporosis Prevention Study (DOPS).1

Since the primary results of the Women’s Health Initiative (WHI) study were presented in 2002,2 controversy has surrounded the use of HRT in postmenopausal women. Before 2002, HRT was characterized as having significant cardiovascular and skeletal benefits, with any adverse effects being offset by its benefits. However, the WHI study findings showed that HRT not only had no cardiovascular benefits but also modestly increased the risk of stroke, venous thromboembolism, and breast cancer.2 These conflicting findings have caused speculation about whether the timing of HRT initiation affects cardiovascular risk.

In this latest DOPS study, 1006 healthy women aged 45 to 58 years who were recently postmenopausal or who had perimenopausal symptoms confirmed by postmenopausal serum follicle stimulating hormone values were randomized to either HRT or no treatment.1 Twenty years of treatment was planned, but after publication of the WHI study results, researchers advised participants to discontinue HRT. The primary endpoint encompassed a trio of factors—death, MI, or heart failure.

During 10 years of randomized treatment plus 6 years of follow-up, death, MI, or heart failure occurred in 33 women who received HRT and 53 women who had no treatment. Of these 86 women, 11 had heart failure (3, HRT group; 8, control group), 16 had MI (5, HRT group; 11, control group), and 67 died (27, HRT group; 40, control group). There was no difference between the HRT and the control groups in the number of women who had a stroke (19 vs 21, respectively), venous thromboembolism (4 vs 5, respectively), or pulmonary embolism (1 vs 3, respectively). The rates of breast cancer were also similar between groups (24, HRT group; 26, control group), but women younger than 50 who received HRT had a significantly reduced risk of breast cancer.

According to the study authors, these results imply that long-term use of HRT, when started soon after menopause, does not increase the risk of adverse cardiovascular events, specifically death, MI, or heart failure. In this study, however, synthetic 17-beta-estradiol was used; in the WHI study, conjugated equine estrogen was used. This difference in medication, along with variations in patient characteristics, may account for the disparities in results between this DOPS study and the WHI study, suggested the study authors.1

Pertinent Points:
- Beginning HRT soon after menopause significantly reduced the risk of the combined endpoint of mortality, myocardial infarction, or heart failure.
- Early initiation and prolonged use (> 10 years) of HRT was not associated with an increased risk of breast cancer or stroke.


1. Schierbeck LL, Rejnmark L, Tofteng CL, et al. Effect of hormone replacement therapy on cardiovascular events in recently postmenopausal women: randomised trial. BMJ. 2012;345:e6409.
2. Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative randomized controlled trial. JAMA. 2002;288:321-333.
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