Postmenopausal hormone replacement therapy decreased the risk for stroke and stroke-related death in white women
ACP J Club. 1993 July-Aug;119:29. doi:10.7326/ACPJC-1993-119-1-029
Finucane FF, Madans JH, Bush TL, Wolf PH, Kleinman JC. Decreased risk of stroke among postmenopausal hormone users. Results from a national cohort. Arch Intern Med. 1993 Jan 11;153:73-9.
To assess the risk for stroke and mortality from stroke in white women who used postmenopausal hormones (PMHs).
A cohort study of women in the first National Health and Nutrition Examination Survey (NHANES I) with mean follow-up of 12 years.
1910 of 2371 eligible, white, postmenopausal women aged 55 to 74 years enrolled in NHANES I from 1971 to 1975. Women who reported no history of stroke at entry and had no missing follow-up data were included.
Assessment of risk factors
An interview and physical examination at baseline assessed history of diabetes, hypertension, and myocardial infarction; smoking status; education level; income-poverty ratio; physical activity; systolic blood pressure; and body mass index. PMH use ("ever used" or "never used") was determined during the first follow-up interview (1982 to 1984) from participants (n = 1474) or from proxies for participants who were deceased or incapacitated (n = 436).
Main outcome measures
Stroke and mortality from stroke were determined from health care facility records and death certificates collected during 3 follow-up periods to 1987.
250 incident cases of stroke were identified. 33 women (8.3%) who had ever used PMHs and 217 women (14.3%) who had never used PMHs had strokes. The age-adjusted incidence rate for stroke was 82 per 10 000 follow-up years for ever used compared with 124 per 10 000 follow-up years for never used. The relative risk (RR) for stroke, adjusted for all risk factors, from PMH use was 0.69 (95% CI 0.47 to 1.00). 5 of the 86 deaths (6%) in the PMH ever-used group and 59 of the 535 deaths (11%) in the never-used group were caused by stroke (RR for mortality from stroke, adjusted for all risk factors, from PMH use was 0.37 [CI 0.14 to 0.92]). When adjusted for other risk factors, PMH use was associated with a 31% reduction in stroke incidence and a 63% reduction in mortality from stroke. When proxy responses were excluded, the protective effects of PMH were reduced (RR for mortality from stroke, 0.86 [CI 0.28 to 2.66], and RR for stroke incidence, 0.82 [CI 0.46 to 1.47]).
Postmenopausal hormone use was associated with decreased risks for stroke and mortality from stroke in white, postmenopausal women.
Source of funding: Public Health Service.
For article reprint: Dr. J.H. Madans, Office of Analysis and Epidemiology, National Center for Health Statistics, 6525 Belcrest Road, Hyattsville, MD 20782, USA. FAX 301-436-5202.
Many studies have shown a reduced risk for coronary heart disease in women who use postmenopausal estrogen (1), but there is conflicting evidence whether estrogens also lower the risk for stroke. This study by Finucane and colleagues suggests that hormone replacement substantially reduces the risk for stroke in older women (most were > 65 years old). The long follow-up and information on risk factors (including socioeconomic variables) are the strengths of this study, but the data on exposure and definition of stroke pose potential problems. Relatives or other proxies who provided information on women who died or were incapacitated may have underestimated hormone use among patients with stroke, exaggerating the protective effects of estrogen. The dramatic reduction (63%) in stroke mortality among "ever users" seems surprising because many ever users probably had brief and distant exposure to estrogens. In contrast, the Nurses' Health Study found similar risks for total and ischemic stroke in current, former, and "never users" of estrogen (2). Although the differences between the studies may indicate a greater benefit in older women (3), they may also reflect bias or unmeasured confounding in the current study.
This study does provide reassurance that estrogen replacement is not likely to increase the risk for stroke, as formerly thought. Ongoing studies, including a large randomized trial of hormone replacement, may clarify some of these unresolved risks and benefits. Until then, clinicians should emphasize the proven benefits of estrogen (relief of menopausal and urogenital symptoms, prevention of osteoporosis, and improved lipid profile) and be reassured that the potential cardiovascular benefits appear much greater than the possible risks (endometrial or breast cancer) of therapy.
David Atkins, MD, MPH
University of WashingtonSeattle, Washington, USA