Hormone replacement therapy and the risk of subarachnoid hemorrhage in postmenopausal women

Abstract

T he risk of intracranial aneurysm formation and subarachnoid hemorrhage (SAH) is higher in postmenopausal women compared with premenopausal women. 8,13,18,19,28 Reduced levels of estrogen in postmenopausal women may increase the risk of aneurysm formation and rupture by reduction in collagen and elastin content and reduced elasticity of arterial walls. 3 In an experimental intracranial aneurysm mouse model, estrogen prevented aneurysmal rupture in ovariectomized mice. 30The protective effect of estrogen seemed to occur through activation of estrogen receptor-b, a predominant subtype of estrogen receptor in human intracranial aneurysms and cerebral arteries. Hormone replacement therapy (HRT) was associated with reduced risk of spontaneous SAH in postmenopausal women in most 19,22 but not all case control studies. 25 The Women's Health Initiative (WHI) randomized trial 33 assessed the effect of estrogen plus progestin on ischemic and hemorrhagic stroke in 608 women 50-79 years of age with an average follow-up of 5.6 years. There was a nonsignificant protective effect on hemorrhagic stroke (HR 0.82, 95% CI 0.43-1.56). However, the study was underpowered because there were only 10 SAH events among the randomized patients. A meta-analysis 24 found a small nonsignificant protective effect of HRT on risk of SAH (HR 0.8, 95% CI 0.57-1.04).We performed this study to determine the effect of abbreviatioNs HRT = hormone replacement therapy; RR = relative risk; SAH = subarachnoid hemorrhage; SE = standard error; WHI = Women's Health Initiative. obJective 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 h...

MRI Characterization in the Acute Phase of Experimental Subarachnoid Hemorrhage

“…The relationship between gender and cerebral hemorrhage has been examined previously both clinically (52, 53) and experimentally (54-56). We previously found that acute hydrocephalus occurs more frequently in female rats after SAH (6).…”

“…The peak incidence of aneurysmal SAH occurs in the 7 th decade in women and the 6 th decade in men (59). Estrogen deficiency, such as after menopause, is associated with increased risk for SAH (60) and hormone replacement therapy is associated with decreased risk SAH as well as ameliorating subsequent brain injury (52, 58, 61). However, no significant difference of overall outcomes after aneurysmal SAH was found between women and men in another study, despite differences in age and aneurysm characteristics (53).…”

Relationship between Estrogen Hormone and Rupture of Cerebral Aneurysm in Premenopausal Women

“…There is increasing evidence that the timing of HRT initiation may play a crucial role in determining chronic heart disease risk among estrogen users. And, significant drawback is that long-term HRT may increase the risk of breast cancer and meningioma in women 1,7,9,13,17,21,24,35) . There are some limitations to our study design.…”

“…Because the incidence of SAH is higher after menopause than before, it has been suggested that the estrogen hormone might be protective against the aneurysm formation and SAH 5,10,11,17,[20][21][22]27,28,30) . However, the benefit of postmenopausal estrogen hormone replacement therapy (HRT) for aneurysm formation and rupture is not clear 13,21,24,35) . We hypothesize that decreases in both circulating estrogen hormone level and cerebrovascular estrogen hormone receptor density may contribute to an increased risk of aneurysm formation and rupture.…”

Menopausal hormone therapy: modern state of the problem

“…В случае монотерапии эстрогеном повышается риск гиперплазии и рака эндометрия, который нивелируется при приеме комбинации эстрогена с адекватной дозировкой микронизированного прогестерона [15]. Применение МГТ в более старшем возрасте, старше 60 лет или более 10 лет от начала менопаузы, сопряжено с возникновением дополнительных рисков, которые включают в себя инфаркт миокарда, инсульт и деменцию [12,13]. Таким образом, применение МГТ в сроки более 10 лет от начала менопаузы влечет за высокие собой риски, которые в большинстве случаев перевешивают пользу.…”