Increased P450 aromatase levels in post-menopausal women after acute ischemic stroke

Abstract

Background: Sex differences in stroke have been attributed to the neuroprotective effects of estrogen, yet most clinical trials of estrogen supplementation for stroke prevention have failed. The contribution of sex hormones to stroke outcome remains a subject of debate. Aromatization of testosterone to estradiol in neural tissue leads to sexual differentiation. Emerging data suggests aromatase activity increases in response to brain injury, and increased aromatase expression is seen in the ischemic penumbra in animal models. The objective of this study was to examine the levels of endogenous sex steroids after acute ischemic stroke and determine if levels of sex steroids were associated with acute stroke outcomes.Methods: Peripheral blood from ischemic stroke patients was collected under an approved IRB within 24 hours of symptom onset. 17 β estradiol, testosterone and aromatase levels were measured in the serum of both men and women. Hormone levels were compared in men vs. women in stroke and control groups and correlated with outcomes (NIHSS and change in the modified Rankin Scale (mRS), defined as difference of premorbid and discharge mRS) using multivariate regression.Results: We found no significant change in estradiol levels 24 hours after stroke in men (p = 0.86) or women (p = 0.10). In men, testosterone significantly decreased after stroke as compared with controls (1.83 ± 0.12 vs 2.86 ± 0.65, p = 0.01). Aromatase levels were significantly higher in women after stroke as compared with controls (2.27 ± 0.22 vs 0.97 ± 0.22, p = 0.002), but not in men (p = 0.84). Estradiol levels positively correlated with higher NIHSS at the time of admission, (r = 0.62, p = 0.0001) and higher change in mRS, (r = 0.38, p = 0.02) in women. Similar correlations between estradiol levels with NIHSS, (r = 0.34, p = 0.02) and change in mRS, r = 0.3, p = 0.04, was seen in men.Conclusions: Higher estradiol levels correlated with worse acute stroke outcomes, regardless of the sex. Testosterone levels decreased after stroke in men. As seen in animal models, aromatase levels increase after acute ischemic stroke, but this was only true for older women. These indicate an active aromatization process in post-menopausal women after acute ischemic stroke. We speculate that aromatase mediated local production of estradiol may occur in the female brain after acute ischemic stroke.

Application of Multimodal Magnetic Resonance Imaging in Green Channel of Acute and Hyperacute Ischemic Stroke

“…(2) Neurological function: three months before and three months after treatment, the National Institutes of Health Stroke Scale (NIHSS) [12] score was used to evaluate, with a total score of 0-42, which included visual field, consciousness level, facial paralysis, upper and lower limb movement, ataxia, and the score was positively proportional to the degree of neurological impairment. (3) Prognosis and outcome: 3 months before and 3 months after treatment, the Modified Rankin Scale (mRS) [13] was applied, with a total score of 6. Death was rated 6 points.…”