Hormone Therapy Linked to Stroke Regardless of Timing

By Peggy Peck

BOSTON, 29 April 2008 -- Women on hormone therapy are at increased risk of stroke, whether they start shortly before or a decade after menopause, researchers here said.
Women who used estrogen alone had an increased stroke risk of almost 40% compared with the risk faced by women who didn't use hormones, and when estrogen was combined with progestin, the risk increased by 27%, Francine Grodstein, Sc.D., of the Harvard School of Public Health, and colleagues reported in the April 28 issue of Archives of Internal Medicine.
Their analysis of data from the 121,700-woman Nurses' Health Study showed that, for women ages 50 through 54, the attributable risk was about two additional cases of stroke per 10,000 women per year taking hormones.
Moreover, they found a strong dose-dependent response. Relative risk was 0.93 for 0.3 mg of oral conjugated estrogen and escalated to 1.54 when the dose was 0.625 -- the dose used in the Women's Health Initiative study -- and 1.62 at a dose of 1.25 mg (P for trend <0.001).
The authors said there was no higher risk of stroke for hormone therapy initiated at a younger age with a duration of less than five years, but they cautioned that "this apparently null result was based on a small number of cases."
The results, the authors said, were virtually identical to those seen in the Women's Health Initiative study, and Wyeth, the maker of Premarin (conjugated estrogen) and Prempro (estrogen/progestin) concurred with that statement.
The Women's Health Initiative tested both Prempro and Premarin in healthy women for primary prevention of cardiovascular events but the trial was halted when its data safety monitoring board found that hormone use increased, rather than decreased, cardiovascular and cerebrovascular events and was associated with an increased risk of breast cancer.
Wyeth said the study reported today did not break new ground, noting that the increased stroke risk was already included in current labeling for all hormone therapy products.
The company also said that hormone therapy was "the most effective FDA-approved treatment for menopausal symptoms and the benefits of hormone therapy may outweigh the risks for many symptomatic menopausal women."
The Nurses' Health Study began in 1976 with an enrollment of 121,700 women ages 30 to 55 who returned mailed questionnaires that included detailed information on hormone use, menopause status, and cardiovascular risk factors.
Data on health and lifestyle are updated with biennial follow-up questionnaires. On each of the follow-ups, women are asked about postmenopausal hormone therapy, including use within the previous month, duration of use, and type of hormones taken. Data on dose of conjugated estrogen were first collected in 1980.
The current analysis included information on strokes that were identified between study enrollment and June 1, 2004. Nonfatal strokes were confirmed by a review of medical records.
When the data were adjusted for stroke risk factors as well as for dietary factors, physical activity, aspirin use, and vitamin supplementation the relative risk for total stroke was 1.43 (95% CI 1.19 to 1.71 for estrogen alone) and 1.45 (95% CI 1.18 to 1.80 for estrogen/progestin).
For women who began hormone therapy near menopause the relative risk for estrogen alone was 1.20 (95% CI 1.106 to 1.58) and for those who started 10 years or more after menopause the relative risk was 1.31 (95% CI 1.06 to 1.63).
For women taking estrogen/progestin just before menopause the relative risk was 1.22 (95% CI 0.95 to 1.55) and for those who waited 10 years or longer after menopause it was 1.18 (95% CI 0.87 to 1.60).
For men and women the risk of stroke increases with age, so it was not surprising that the lowest stroke risk in the Nurses' Health Study was observed in women younger than 50, who had an attributable risk of 0.93 per 10,000 person years of hormone therapy, the researchers said.
But from there the risk steadily increased so that women 65 or older had an attributable risk of 7.2 cases per 10,000 person years of hormone therapy.
Primary source: Archives of Internal MedicineSource reference: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; 168: 861-866.