From the Amsterdam UMC (S.M.Z.), The Netherlands; University Hospital of Essen (A.N.S., B.S., R.J., U.S., P.D.), Essen; Center for Translational Neuroscience and Behavioral Science (C-TNBS) (A.N.S., R.J., U.S., P.D.), University of Duisburg-Essen, Germany; and Mayo Clinic (K.D.F., G.L.), Rochester, MN.
Neurology. 2023 Apr 18;100(16):e1673-e1679. doi: 10.1212/WNL.0000000000206888. Epub 2023 Feb 8.
Female hormone therapy (oral contraception in female patients of reproductive age and menopausal hormone therapy in postmenopausal patients) is not withheld from patients with cerebral cavernous malformations (CCMs), although the effects of these drugs on the risk of intracranial hemorrhage are unknown. We investigated the association between female hormone therapy and intracranial hemorrhage in female patients with CCM in 2 large prospective, multicenter, observational cohort studies.
We included consecutive patients with a CCM. We compared the association between use of female hormone therapy and the occurrence of intracranial hemorrhage due to the CCM during up to 5 years of prospective follow-up in multivariable Cox proportional hazards regression. We performed an additional systematic review through Ovid MEDLINE and Embase from inception to November 2, 2021, to identify comparative studies and assess their intracranial hemorrhage incidence rate ratio according to female hormone therapy use.
Of 722 female patients, aged 10 years or older at time of CCM diagnosis, 137 used female hormone therapy at any point during follow-up. Female hormone therapy use (adjusted for age, mode of presentation, and CCM location) was associated with an increased risk of subsequent intracranial hemorrhage (46/137 [33.6%] vs 91/585 [15.6%] and adjusted hazard ratio 1.56, 95% CI 1.09-2.24; = 0.015). Use of oral contraceptives in female patients aged 10-44 years adjusted for the same factors was associated with a higher risk of subsequent intracranial hemorrhage (adjusted hazard ratio 2.00, 95% CI 1.26-3.17; = 0.003). Our systematic literature search showed no studies reporting on the effect of female hormone therapy on the risk of intracranial hemorrhage during follow-up.
Female hormone therapy use is associated with a higher risk of intracranial hemorrhage from CCMs. These findings raise questions about the safety of female hormone therapy in clinical practice in patients with CCM. Further studies evaluating clinical factors raising risk of thrombosis may be useful to determine which patients may be most susceptible to intracranial hemorrhage.
This study provides Class III evidence that female hormone therapy use is associated with a higher risk of intracranial hemorrhage in patients with CCM.
女性激素疗法（生殖年龄女性患者的口服避孕药和绝经后患者的绝经激素疗法）不会对脑动静脉畸形（CCM）患者禁用，尽管这些药物对颅内出血风险的影响尚不清楚。我们在 2 项大型前瞻性、多中心、观察性队列研究中，调查了女性 CCM 患者中女性激素疗法与颅内出血之间的关联。
我们纳入了连续的 CCM 患者。我们比较了在长达 5 年的前瞻性随访中，多变量 Cox 比例风险回归中使用女性激素疗法与 CCM 导致的颅内出血之间的关联。我们通过 Ovid MEDLINE 和 Embase 进行了额外的系统综述，从开始到 2021 年 11 月 2 日，以确定比较研究，并根据女性激素疗法的使用情况评估其颅内出血发生率比。
在 722 名年龄在 10 岁或以上的女性 CCM 患者中，有 137 名患者在随访期间的任何时候使用女性激素疗法。女性激素疗法的使用（按年龄、表现方式和 CCM 位置调整）与随后颅内出血的风险增加相关（46/137 [33.6%] vs 91/585 [15.6%]和调整后的危险比 1.56，95%CI 1.09-2.24；=0.015）。对于按相同因素调整的 10-44 岁女性患者，使用口服避孕药与随后颅内出血的风险增加相关（调整后的危险比 2.00，95%CI 1.26-3.17；=0.003）。我们的系统文献检索没有发现报告女性激素疗法对随访期间颅内出血风险影响的研究。
女性激素疗法的使用与 CCM 引起的颅内出血风险增加相关。这些发现引发了关于 CCM 患者在临床实践中女性激素疗法安全性的问题。进一步评估增加血栓形成风险的临床因素的研究可能有助于确定哪些患者最容易发生颅内出血。
本研究提供了 III 级证据，表明女性激素疗法的使用与 CCM 患者颅内出血风险增加相关。
