Association between hormone replacement therapy and subsequent stroke: a meta-analysis
BMJ 2005; 330 doi: https://doi.org/10.1136/bmj.38331.655347.8F (Published 10 February 2005) Cite this as: BMJ 2005;330:342- Philip M W Bath, Stroke Association professor of stroke medicine (philip.bath{at}nottingham.ac.uk)⇑1,
- Laura J Gray, medical statistician1
- 1 Division of Stroke Medicine, Institute of Neuroscience, Queen's Medical Centre, University of Nottingham, Nottingham NG7 2UH
- Correspondence to: P M W Bath
- Accepted 1 December 2004
Abstract
Abstract Objectives To review completed trials assessing effect of hormone replacement therapy on subsequent risk of stroke, assessing stroke by pathological type, severity, and outcome.
Design Systematic review of randomised controlled trials identified from the Cochrane Library, Embase, and Medline; reviews; and reference lists of relevant papers.
Studies reviewed 28 trials, with 39 769 subjects, were identified.
Review measures Rates for cerebrovascular events analysed with a random effects model. Sensitivity analyses for heterogeneity included phase of prevention (primary or secondary), type of hormone replacement therapy (oestrogen alone or combined with progesterone), type of oestrogen (estradiol or conjugated equine oestrogen), size of trial (< 5000 or > 5000 patients), length of follow up (£ 3 years or > 3 years), sex (women only or men only), and trial quality (high or low).
Results Hormone replacement therapy was associated with significant increases in total stroke (odds ratio 1.29 (95% confidence interval 1.13 to 1.47), n = 28), non-fatal stroke (1.23 (1.06 to 1.44), n = 21), stroke leading to death or disability (1.56 (1.11 to 2.20), n = 14), ischaemic stroke (1.29 (1.06 to 1.56), n = 16), and a trend to more fatal stroke (1.28 (0.87 to 1.88), n = 22). It was not associated with haemorrhagic stroke (1.07 (0.65 to 1.75), n = 17) or transient ischaemic attack (1.02 (0.78 to 1.34), n = 22). Statistical heterogeneity was not present in any analysis.
Conclusions Hormone replacement therapy was associated with an increased risk of stroke, particularly of ischaemic type. Among subjects who had a stroke, those taking hormone replacement therapy seemed to have a worse outcome. Hormone replacement therapy cannot be recommended for the primary or secondary prevention of stroke.
Footnotes
Details of the search strategy used, of the trials identified in the search, and of references w1-w40 are on bmj.coma
Contributors PMWB conceived of the study, collated data, and drafted the paper and is guarantor. LJG collated data, performed statistical analyses, and revised the paper.
Funding PMWB is Stroke Association professor of stroke medicine. LJG is funded, in part, by the Stroke Association (TSA 01/03) and BUPA Foundation. The Division of Stroke Medicine receives core funding from the Stroke Association.
Competing interests None declared
Ethical approval None required.