Background and Purpose- Although exogenous hormone therapy (HT) use has been associated with increased risk of ischemic stroke in postmenopausal women, it remains unknown whether sex hormone levels contribute to ischemic stroke risk. We aimed to estimate associations between plasma sex hormone levels and ischemic stroke risk, by HT status, in a nested case-control study of postmenopausal women from the NHS (Nurses' Health Study). Methods- Women with confirmed incident ischemic stroke (n=419) were matched with controls (n=419) by age, HT use, and other factors. Plasma estradiol and testosterone levels were measured using liquid chromatography tandem mass spectrometry; SHBG (sex hormone-binding globulin) was assayed by electrochemiluminescence immunoassay. Associations of total and free estradiol and testosterone, the estradiol/testosterone ratio, and SHBG with ischemic stroke were estimated using conditional logistic regressions stratified by HT status with adjustment for matching and cardiovascular risk factors. Results- Current HT users had different hormone profiles from never/past users. No clear linear trends were observed between estradiol (total or free) levels or the estradiol/testosterone ratio and ischemic stroke risk among either current users (Ptrend>0.1) or never/past users (Ptrend>0.6). For both current and never/past users, the associations between some of the sex hormones and ischemic stroke differed by body mass index categories (Pinteraction≤0.04). For women with a body mass index <25 kg/m2, a higher estradiol/testosterone ratio was associated with significantly elevated ischemic stroke risk among current users (Ptrend=0.01), and higher levels of total and free estradiol were significantly associated with higher ischemic stroke risk among never/past users (Ptrend≤0.04). Testosterone and SHBG were not associated with ischemic stroke in either current or never/past users. Conclusions- Our findings do not support a role of sex hormone levels in mediating ischemic stroke risk among postmenopausal women. Replications in additional larger studies are required.

中文翻译：

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绝经后妇女的血浆雌二醇和睾丸激素水平及缺血性卒中。

背景与目的-尽管外源激素治疗（HT）的使用与绝经后妇女缺血性中风的风险增加有关，但性激素水平是否有助于缺血性中风的风险尚不清楚。我们的目的是通过NHS的绝经后妇女嵌套病例对照研究（Nurses的健康研究）通过HT状态评估血浆性激素水平与缺血性中风风险之间的关联。方法-通过年龄，HT使用和其他因素，将确诊为缺血性中风的妇女（n = 419）与对照组（n = 419）进行匹配。使用液相色谱串联质谱法测定血浆雌二醇和睾丸激素水平；SHBG（性激素结合球蛋白）通过电化学发光免疫测定法进行测定。总和游离雌二醇和睾丸激素的关联，雌二醇/睾丸激素比率和缺血性中风的SHBG均采用条件性逻辑回归（以HT状态分层，并调整了匹配因素和心血管危险因素）进行估算。结果-当前的HT使用者与从未/过去的使用者具有不同的激素谱。在当前使用者（Ptrend> 0.1）或从不/过去使用者（Ptrend> 0.6）之间，未观察到雌二醇（总水平或游离水平）或雌二醇/睾丸激素比率与缺血性中风风险之间没有明确的线性趋势。对于当前用户和从未/过去/过去用户，某些性激素与缺血性卒中之间的关联因体重指数类别而异（互动≤0.04）。对于体重指数<25 kg / m2的女性，当前使用者中较高的雌二醇/睾丸激素比例与缺血性中风风险显着相关（Ptrend = 0.01），从未/过去使用者中较高的总雌二醇和游离雌二醇水平与较高的缺血性卒中风险显着相关（Ptrend≤0.04）。当前或从不/过去的使用者中，睾丸激素和SHBG与缺血性卒中无关。结论-我们的研究结果不支持性激素水平在绝经后妇女中介导的缺血性中风风险中的作用。需要在其他更大的研究中进行重复。