From the Division of Women's Health (J.H., M.C.J., K.M.R.), Department of Medicine, Brigham and Women's Hospital, Boston, MA.
Division of Preventive Medicine (J.H.L., M.C.J., J.E.M., K.M.R.), Department of Medicine, Brigham and Women's Hospital, Boston, MA.
Stroke. 2020 Apr;51(4):1297-1300. doi: 10.1161/STROKEAHA.119.028588. Epub 2020 Feb 14.
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 (>0.1) or never/past users (>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 (≤0.04). For women with a body mass index <25 kg/m, a higher estradiol/testosterone ratio was associated with significantly elevated ischemic stroke risk among current users (=0.01), and higher levels of total and free estradiol were significantly associated with higher ischemic stroke risk among never/past users (≤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.
背景与目的-尽管外源性激素治疗（HT）的使用与绝经后妇女缺血性中风的风险增加有关，但性激素水平是否与缺血性中风风险相关仍不清楚。我们旨在通过 NHS（护士健康研究）中绝经后妇女的巢式病例对照研究，估计 HT 状态与血浆性激素水平与缺血性中风风险之间的关系。方法- 经证实患有缺血性中风的女性（n=419）与对照组（n=419）按年龄、HT 使用情况和其他因素进行匹配。使用液相色谱串联质谱法测量血浆雌二醇和睾酮水平；使用电化学发光免疫分析法测定 SHBG（性激素结合球蛋白）。使用条件逻辑回归估计总雌二醇和游离雌二醇和睾酮、雌二醇/睾酮比以及 SHBG 与缺血性中风的关系，该回归按 HT 状态分层，并进行了匹配和心血管危险因素的调整。结果- 当前 HT 用户的激素谱与从未/过去使用者不同。在当前使用者（>0.1）或从未/过去使用者（>0.6）中，雌二醇（总或游离）水平或雌二醇/睾酮比与缺血性中风风险之间均未观察到明显的线性趋势。对于当前和从未/过去使用者，一些性激素与缺血性中风之间的关联因体重指数类别而异（≤0.04）。对于 BMI<25kg/m 的女性，当前使用者中雌二醇/睾酮比较高与缺血性中风风险显著升高相关（=0.01），而从未/过去使用者中总雌二醇和游离雌二醇水平较高与缺血性中风风险显著相关（≤0.04）。在当前或从未/过去使用者中，睾酮和 SHBG 均与缺血性中风无关。结论- 我们的研究结果不支持性激素水平在介导绝经后妇女缺血性中风风险中的作用。需要在更多的大型研究中进行重复验证。
