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Role of Time Since Menopause and Age at Initiation of Hormone Therapy

Arch Intern Med. 2008;168(8):861-866.

Background  We evaluated stroke risk associated with hormone therapy (HT) in younger women, in recently menopausal women, and in older women.

Methods  Prospective, observational analyses were performed in postmenopausal participants of the Nurses' Health Study, from 1976 to 2004, with biennial mailed questionnaires. Proportional hazards models were used to calculate multivariable-adjusted relative risks (RRs) and 95% confidence intervals (CIs).

Results  We found a significantly increased risk of stroke for women currently taking HT (estrogen alone: RR, 1.39; 95% CI, 1.18-1.63; and estrogen with progestin: RR, 1.27; 95% CI, 1.04-1.56), a finding that is nearly identical to that of the Women's Health Initiative. This increased risk was observed for women initiating HT at young ages or near menopause and at older ages or more than 10 years after menopause. Short-term (<5 years) HT initiated at younger ages was not associated with a clear increase in stroke; however, this apparently null result was based on a small number of cases. The incidence of stroke was relatively low in younger women, and the attributable risk in women aged 50 through 54 years indicated approximately an additional 2 cases of stroke per 10 000 women per year taking hormones. We found a strong relationship between dose of oral conjugated estrogen and stroke, with RRs of 0.93, 1.54, and 1.62 for doses of 0.3, 0.625, and 1.25 mg, respectively (P for trend, <.001).

Conclusions  Hormone therapy is associated with an increased risk of stroke, and this increased risk does not appear to be related to the timing of the initiation of HT. In younger women, with lower stroke risk, the attributable risk of stroke owing to hormone use is modest and might be minimized by lower doses and shorter treatment duration.

Author Affiliations: Channing Laboratory (Drs Grodstein, Manson, and Stampfer), Division of Aging (Dr Grodstein), and Division of Preventive Medicine (Drs Manson and Rexrode), Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, and Department of Epidemiology, Harvard School of Public Health (Drs Grodstein, Manson, and Stampfer), Boston, Massachusetts.

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