Abstract P474: Sex-Specific Prevention of Stroke Through Reproductive Risk Factors and Sex Hormone Effects (STOP STROKE): Preliminary Findings

Abstract

Background: There are known associations between sex-specific reproductive health factors such as reproductive lifespan and stroke risk. The relation of endogenous sex hormones, specifically sex hormone binding globulin (SHBG), to stroke risk remains uncertain, however, despite some data showing an inverse association between SHBG and stroke. We conducted a pilot case-control study to evaluate SHBG as a stroke risk factor, to report SHBG levels in the period immediately after acute ischemic stroke (AIS), and to demonstrate the feasibility of collecting data on sex hormones and reproductive history in this study population. Methods: In STOP STROKE, postmenopausal women were enrolled from a single large healthcare system in the northeast between July 2020 and May 2022. Case participants were postmenopausal women ≥50 years old newly admitted with AIS to a large stroke center; controls were postmenopausal women without a history of stroke recruited from an outpatient clinic in the same healthcare system. Among others, exclusion criteria included use of menopausal hormone therapy within 10 years, prior stroke, surgical menopause, and history of hormone-related cancers. We ascertained data on stroke risk factors and collected blood samples between 24 and 72 hours after stroke onset or at the time of enrollment for controls. Serum SHBG was measured using enzyme-linked immunosorbent assays. Following descriptive analyses, age- and BMI-adjusted SHBG levels were compared between cases and controls using multiple linear regression. Multiple logistic regression was then performed to assess associations between SHBG, clinical risk factors, and the outcome of AIS, with covariates chosen a priori based on prior literature. Results: In total, 32 cases and 30 controls were enrolled; median age was 69.0 years (IQR 64.5-82.0) for cases vs. 62.0 (IQR (59.0-68.0) for controls. The mean SHBG of AIS cases was 68.8 (SD 36.1) nmol/L compared to 56.6 (SD 30.0) nmol/L among controls (p=0.16). In models adjusted for age and body mass index (BMI), SHBG was similar between cases and controls (beta = 3.0, 95%CI -15.0 - 21.1, p=0.74). Adjusted for age, BMI, history of hypertension, history of diabetes, and age at menarche and menopause, there was a positive association between SHBG and AIS (OR 1.04, 95%CI 1.004-1.071, p=0.03). Conclusions: Our pilot study demonstrates the feasibility of enrolling newly admitted AIS patients and controls among postmenopausal women in the catchment area of our comprehensive stroke center. To understand initial findings of a positive association between SHBG and AIS, work is ongoing to measure estrogens and androgens at study baseline and all hormones in follow-up specimens (3-6 months post stroke).