Hormone therapy for preventing cardiovascular disease in post-menopausal women.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of randomized controlled trials
PubMed 25754617 · doi:10.1002/14651858.CD002229.pub4
What was done
This updated Cochrane systematic review and random-effects meta-analysis evaluated randomized controlled trials comparing oral hormone therapy against placebo or no treatment (minimum follow-up 6 months) for cardiovascular disease prevention in post-menopausal women. Searches were updated through February 25, 2014 across CENTRAL, MEDLINE, EMBASE, and LILACS. Primary analyses assessed primary versus secondary prevention, while exploratory subgroup analyses examined initiation timing (<10 versus ≥10 years post-menopause, or age <60 versus ≥60 years).
What was found
The review included 19 trials totaling 40,410 post-menopausal women. Overall, hormone therapy conferred no protective effect against all-cause mortality, cardiovascular death, non-fatal myocardial infarction, angina, or revascularisation. Hormone therapy significantly increased the risk of stroke (RR 1.24, 95% CI 1.10 to 1.41; absolute risk increase 6 per 1,000, NNTH = 165), venous thromboembolism (RR 1.92, 95% CI 1.36 to 2.69; absolute risk increase 8 per 1,000, NNTH = 118), and pulmonary embolism (RR 1.81, 95% CI 1.32 to 2.48; absolute risk increase 4 per 1,000, NNTH = 242). In subgroup analyses of women starting therapy <10 years post-menopause, lower mortality (RR 0.70, 95% CI 0.52 to 0.95) and coronary heart disease (RR 0.52, 95% CI 0.29 to 0.96) were observed alongside elevated venous thromboembolism (RR 1.74, 95% CI 1.11 to 2.73). Starting therapy ≥10 years post-menopause showed no mortality or coronary benefit, with increased stroke (RR 1.21, 95% CI 1.06 to 1.38) and venous thromboembolism (RR 1.96, 95% CI 1.37 to 2.80).
Why it matters
Oral hormone therapy should not be used for primary or secondary prevention of cardiovascular disease due to an absence of overall benefit and clinically meaningful increases in stroke and thromboembolic events.
Limits
The findings are heavily dominated by the three largest included trials. The review was restricted to oral hormone therapy and cannot be generalized to transdermal or non-oral preparations. Findings regarding timing of initiation rely on secondary and exploratory subgroup analyses supported by moderate-quality evidence.