title: Hormone replacement therapy and the risk of subarachnoid hemorrhage in postmenopausal women.
abstract: OBJECT The incidence of subarachnoid hemorrhage (SAH) increases after menopause. Anecdotal data suggest that hormone replacement therapy (HRT) may reduce the rate of SAH and aneurysm formation in women. The goal of this study was to determine the effect of HRT on occurrence of SAH in a large prospective cohort of postmenopausal women. METHODS The data were analyzed for 93, 676 women 50-79 years of age who were enrolled in the observational arm of the Women's Health Initiative Study. The effect of HRT on risk of SAH was determined over a period of 12 ± 1 years (mean ± SD) using Cox proportional hazards analysis after adjusting for potential confounders. Additional analysis was performed to identify the risk associated with "estrogen only" and "estrogen and progesterone" HRT among women. RESULTS Of the 93, 676 participants, 114 (0.1%) developed SAH during the follow-up period. The rate of SAH was higher among women on active HRT compared with those without HRT used (0.14% vs 0.11%, absolute difference 0.03%, p < 0.0001). In unadjusted analysis, participants who reported active use of HRT were 60% more likely to suffer an SAH (RR 1.6, 95% CI 1.1-2.3). Compared with women without HRT use, the risk of SAH continued to be higher among women reporting active use of HRT (RR 1.5, 95% CI 1.0-2.2) after adjusting for age, systolic blood pressure, cigarette smoking, alcohol consumption, body mass index, race/ethnicity, diabetes, and cardiovascular disease. The risk of SAH was nonsignificantly higher among women on "estrogen only" HRT (RR 1.4, 95% CI 0.91-2.0) than "estrogen and progesterone" HRT(RR 1.2, 95% CI 0.8-2.1) after adjusting for the above-mentioned confounders. CONCLUSIONS Postmenopausal women, particularly those at risk for SAH due to presence of unruptured aneurysms, family history, or cardiovascular risk factors, should be counseled against use of HRT.
authors.affiliation: Zeenat Qureshi Stroke Institute, St. Cloud, Minnesota.
authors.forename: Adnan I
authors.initials: AI
authors.lastname: Qureshi
authors.affiliation: Zeenat Qureshi Stroke Institute, St. Cloud, Minnesota.
authors.forename: Ahmed A
authors.initials: AA
authors.lastname: Malik
authors.affiliation: Zeenat Qureshi Stroke Institute, St. Cloud, Minnesota.
authors.forename: Omar
authors.initials: O
authors.lastname: Saeed
authors.affiliation: Zeenat Qureshi Stroke Institute, St. Cloud, Minnesota.
authors.forename: Archie
authors.initials: A
authors.lastname: Defillo
authors.affiliation: Zeenat Qureshi Stroke Institute, St. Cloud, Minnesota.
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Sherr
authors.affiliation: Zeenat Qureshi Stroke Institute, St. Cloud, Minnesota.
authors.forename: M Fareed K
authors.initials: MF
authors.lastname: Suri
mesh_terms: D000368:Aged; D000428:Alcohol Drinking / Q000009:adverse effects / Q000453:epidemiology; D015331:Cohort Studies; D015897:Comorbidity; D015914:Estrogen Replacement Therapy / Q000009:adverse effects*; D004967:Estrogens / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D011374:Progesterone / Q000627:therapeutic use; D011446:Prospective Studies; D012306:Risk; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects / Q000453:epidemiology; D013345:Subarachnoid Hemorrhage / Q000453:epidemiology*; D016019:Survival Analysis
chemical_list: D004967:Estrogens; D011374:Progesterone
keywords: HRT = hormone replacement therapy; RR = relative risk; SAH = subarachnoid hemorrhage; SE = standard error; WHI = Women’s Health Initiative; estrogen replacement; hormone replacement therapy; intracranial aneurysm; postmenopausal women; subarachnoid hemorrhage; vascular disorders