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For Menopausal Hormone Therapy and Stroke Risk, Timing Makes a Difference

New NHS results corroborate previous findings about HT and stroke risk while providing reassurance for young menopausal women using HT for fewer than 5 years.

Previous results from the Nurses’ Health Study (NHS; Ann Intern Med 2000; 133:933) and the Women’s Health Initiative (WHI; JAMA 2003; 289:2673 and Circulation 2006; 113:2425) have shown that menopausal hormone therapy is associated with a 30% to 40% higher risk for stroke. In a new NHS analysis of data from questionnaires completed in 2004, investigators evaluated timing of HT initiation, duration of use, and estrogen dose as factors in determining risk for various types of stroke. Because vasomotor symptoms are most likely to be bothersome in young menopausal women and to diminish over time, for the analysis of HT duration, the authors focused on women who were within 4 years of menopause or were younger than 55.

Current use of estrogen-alone HT or combined HT was associated with age-adjusted relative risks for total stroke of 1.33 (95% confidence interval, 1.13–1.55) and 1.17 (95% CI, 0.96–1.42), respectively. RRs were generally similar for ischemic, hemorrhagic, nonfatal, and fatal strokes. Timing of HT with respect to onset of menopause did not change these risks appreciably. Despite a limited sample size for the analysis of HT duration, use of HT for fewer than 5 years was not associated with significant elevations in risk for stroke, particularly among women who were younger than 55. Estrogen dose correlated with stroke risk: For a 0.3-mg dose of conjugated equine estrogen, no excess risk was observed. In contrast, doses of 0.625 mg and 1.25 mg were associated with adjusted RRs of 1.54 and 1.62, respectively.

Comment: These results agree with prior NHS and WHI findings, which showed that HT use is associated with a small elevation in stroke risk regardless of age or time after onset of menopause. However, NHS and WHI researchers alike have found that HT use by young menopausal women is associated with a lower risk for heart disease. Among young menopausal women, excess risk for stroke (if any) seems particularly modest, especially when duration of HT use is limited and low estrogen doses are employed.

— Andrew M. Kaunitz, MD

Published in Journal Watch Women's Health June 5, 2008

Citation(s):

Grodstein F et al. Postmenopausal hormone therapy and stroke: Role of time since menopause and age at initiation of hormone therapy. Arch Intern Med 2008 Apr 28; 168:861.

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