Background: Ischemic stroke is a sexually dimorphic disease. Sex differences in stroke have been attributed to neuroprotective effects of estrogen, yet most clinical trials of estrogen supplementation have shown detrimental effects. The role of sex hormones in stroke is still a subject of debate. Aromatization of testosterone to estradiol in neural tissue leads to sexual differentiation. Emerging data suggests similar aromatase activity in response to brain injury, as increased aromatase expression is seen in ischemic penumbra in animals. Administration of aromatase inhibitors exacerbates damage in experimental stroke models. However, studies on sex steroids in humans are sorely lacking. Objective of this study was to investigate the contributions of sex steroids to the etiology of sex differences in stroke.
Methods: 253 patients admitted to Hartford Hospital for focal neurological deficit were consented for 24hour blood draw from symptom onset. Stroke was confirmed by CTscan/MRI brain. Patients with intracerebral or subarachnoid hemorrhage, age<56 years, were excluded from the study. Controls were patients with transient ischemic attack/seizure. ELISA was run for estradiol, testosterone &P450 aromatase levels in serum.
Results: In age matched men & women, no difference in estradiol levels was seen. For testosterone, main effect of sex, F(1,3)=26,p<0.001 & sex by stroke interaction F(1,3)=4.7,p<0.03 was seen. There was a significant effect of stroke, F(1,3)=9.3,p<0.003 & sex by stroke interaction, F(1,3)=5.8,p<0.01 in aromatase levels (*).
Conclusions:Aromatase levels increase in post-menopausal women after acute ischemic stroke. This may indicate increased aromatase activity as testosterone levels also decreased as compared with controls. Local production of estradiol may occur in the injured female brain mediated by aromatase as seen in prior animal studies. Ongoing work will assess functional outcomes and correlation with hormonal levels.