Department of Immunology, Genetics and Pathology, Science for Life Laboratory (T.J., W.E.E., T.K., A.J.), Uppsala University, Sweden.
Centre for Women's Mental Health during the Reproductive Lifespan - Womher (T.J.), Uppsala University, Sweden.
Stroke. 2022 Oct;53(10):3107-3115. doi: 10.1161/STROKEAHA.121.038659. Epub 2022 Jun 23.
Millions of women worldwide use exogenous hormones as oral contraceptives or hormone replacement therapy. Still, time-dependent and long-term consequences of exogenous hormones on stroke risk remains unclear.
We examined the association between self-reported oral contraceptive and hormone replacement therapy use and stroke risk in 257 194 women from the UK Biobank, born between 1939 and 1970. Outcomes included any type of stroke, ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage. Exposures were analyzed as time-varying variables in Cox regression models.
During first year of oral contraceptive use, an increased event rate of any stroke was observed (hazard ratio [HR], 2.49 [95% CI, 1.44-4.30]), while the hazards were found to be comparable during remaining years of use (HR, 1.00 [95% CI, 0.86-1.14]), compared with nonusers. Similarly, first year of hormone replacement therapy use was associated with higher hazard rates of any stroke (HR, 2.12 [95% CI, 1.66-2.70]), as well as cause-specific stroke, including ischemic stroke (HR, 1.93 [95% CI, 1.05-3.57]) and subarachnoid hemorrhage (HR, 2.17 [95% CI, 1.25-3.78]), which remained increased for any stroke during remaining years of use (HR, 1.18 [95% CI, 1.05-1.31]), and after discontinuation (HR, 1.16 [95% CI, 1.02-1.32]).
Oral contraceptive use and hormone replacement therapy were associated with an increased risk of stroke, especially during the first year of use, possibly due to immediate changes in hemostatic balance. This study provides new insights on the effects of hormone exposure on stroke risk and provide evidence of not only an overall risk but also a pronounced effects seen in the beginning of treatment.
全世界数以百万计的女性使用外源性激素作为口服避孕药或激素替代疗法。然而，外源性激素对中风风险的时间依赖性和长期影响仍不清楚。
我们在英国生物库中检查了 257194 名出生于 1939 年至 1970 年之间的女性中自我报告的口服避孕药和激素替代疗法使用与中风风险之间的关联。结果包括任何类型的中风、缺血性中风、脑出血和蛛网膜下腔出血。在 Cox 回归模型中，将暴露作为时变变量进行分析。
在使用口服避孕药的第一年，任何类型中风的发生率均升高（危险比 [HR]，2.49 [95%置信区间，1.44-4.30]），而在剩余的使用年限中，风险比则相当（HR，1.00 [95%置信区间，0.86-1.14]），与非使用者相比。同样，使用激素替代疗法的第一年与任何类型中风的风险率升高相关（HR，2.12 [95%置信区间，1.66-2.70]），以及特定原因的中风，包括缺血性中风（HR，1.93 [95%置信区间，1.05-3.57]）和蛛网膜下腔出血（HR，2.17 [95%置信区间，1.25-3.78]），而在剩余的使用年限中，任何类型中风的风险比仍在增加（HR，1.18 [95%置信区间，1.05-1.31]），并且在停药后（HR，1.16 [95%置信区间，1.02-1.32]）。
口服避孕药的使用和激素替代疗法与中风风险增加相关，尤其是在使用的第一年，这可能是由于止血平衡的即时变化所致。这项研究提供了关于激素暴露对中风风险影响的新见解，并提供了不仅总体风险的证据，而且还提供了在治疗开始时明显的效果的证据。
