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Review
. 2008 Aug;29(16):2031-41.
doi: 10.1093/eurheartj/ehn299. Epub 2008 Jul 3.

Association between hormone replacement therapy and subsequent arterial and venous vascular events: a meta-analysis

Gillian M Sare  1 , Laura J Gray, Philip M W Bath
Affiliations
Review

Association between hormone replacement therapy and subsequent arterial and venous vascular events: a meta-analysis

Gillian M Sare et al. Eur Heart J. 2008 Aug.

Abstract

Aims: Randomized controlled trials (RCTs) have shown that the risk of stroke and venous thromboembolism (VTE) is increased with hormone replacement therapy (HRT); the effect on coronary heart disease (CHD) remains unclear.

Methods and results: RCTs of HRT were identified. Event rates for cerebrovascular disease [stroke, TIA (transient ischaemic attack)], CHD (myocardial infarction, unstable angina, sudden cardiac death), and VTE (pulmonary embolism, deep vein thrombosis) were analysed. Sensitivity analyses were performed by type of HRT (mono vs. dual) and subject age. 31 trials (44 113 subjects) were identified. HRT was associated with increases in stroke (odds ratio, OR, 1.32, 95% confidence intervals, CI, 1.14-1.53) and VTE (OR 2.05, 95% CI 1.44-2.92). In contrast, CHD events were not increased (OR 1.02, 95% CI 0.90-1.11). Ordinal analyses confirmed that stroke severity was increased with HRT (OR 1.31, 95% CI 1.12-1.54). Although most trials included older subjects, age did not significantly affect risk. The addition of progesterone to oestrogen doubled the risk of VTE.

Conclusion: HRT is associated with an increased risk of stroke, stroke severity, and VTE, but not of CHD events. Although most trials studied older patients, increased risk was not related to age. Combined HRT increases the risk of VTE compared with oestrogen monotherapy.

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Figures

Figure 1
Figure 1
Flowchart for inclusion and exclusion of trials of hormone replacement therapy.
Figure 2
Figure 2
Funnel plots assessing publication bias showing the distribution of odds ratios for trials of cerebrovascular disease, coronary heart disease and venous thromboembolic disease.
Figure 3
Figure 3
Forrest plots of the effect of hormone replacement therapy. Shaded squares represent the weighting of each trial in the analysis: (A) Cerebrovascular events (including stroke and TIA); (B) coronary heart disease events (including myocardial infarction); (C) venous thromboembolism (including pulmonary embolism, deep vein thrombosis and cerebral sinus thrombosis).
Figure 3
Figure 3
Forrest plots of the effect of hormone replacement therapy. Shaded squares represent the weighting of each trial in the analysis: (A) Cerebrovascular events (including stroke and TIA); (B) coronary heart disease events (including myocardial infarction); (C) venous thromboembolism (including pulmonary embolism, deep vein thrombosis and cerebral sinus thrombosis).
Figure 4
Figure 4
Tabulated results of pre-specified sensitivity analysis for cerebrovascular disease, coronary heart disease, and venous thromboembolism. Odds ratios and 95% confidence intervals are plotted on a log scale with no effect at 0.
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Comment in

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