Association of Reproductive Life Span and Age at Menopause With the Risk of Aneurysmal Subarachnoid Hemorrhage

Abstract

Background and Objectives:Subarachnoid hemorrhage from cerebral aneurysm remains a devastating disease with high mortality and morbidity. Cerebral aneurysm and its rupture are more prevalent in post-menopausal women and have been postulated to be hormonally influenced. The goal of this study was to investigate the associations of female-specific factors, including reproductive life span, age at menarche, and age at menopause, with the incidence of aneurysmal subarachnoid hemorrhage (aSAH) in women.Methods:Participants in the Nurses’ Health Study were followed from 1980 or the time of reaching menopause until 2018, Only women with natural menopause or surgical menopause due to bilateral oophorectomy were included. Reproductive life span was defined by subtracting the age at menarche from the age at menopause. Multivariable stratified proportional hazards models were used to study reproductive life span, age at menarche and age at menopause with the incidence of aSAH. Multivariable models were adjusted for age, race, smoking, hysterectomy, hypertension, hyperlipidemia, body mass index, hormone therapy use, oral contraceptive use, and parity.Results:A total of 97,398 postmenopausal women with reproductive lifespan data were included, with 138 participants developed aneurysmal subarachnoid hemorrhage which was confirmed on medical record review by a physician. A shorter reproductive lifespan (≤35 years) was associated with a two-fold higher incidence of aSAH after multivariable adjustment (HR=2.0 [95%CI 1.4-2.8]). Early age at menopause (age<45) was similarly associated with a higher risk of aSAH (HR=2.1 [95%CI 1.4-3.1]), but age at menarche was not. The use of oral contraceptives and postmenopausal hormone therapy were not associated with the incidence of aSAH.Discussion:An earlier age at menopause, as well as a shorter reproductive life span duration (≤35 years), were associated with a higher risk of incident aSAH in women. No associations were noted for age at menarche, parity, oral contraceptive use or postmenopausal therapy use.