背景:已显示使用含雌激素的绝经期激素治疗会影响中枢神经系统(CNS)肿瘤的风险。然而,目前尚不清楚孕激素成分如何影响风险,以及连续治疗方案与循环治疗方案对风险的影响是否不同.
结果:从2000年到2018年,丹麦女性全国队列中的嵌套病例对照研究持续了19年。该队列包括789,901名年龄在50至60岁的女性,没有事先诊断中枢神经系统肿瘤,癌症,或使用更年期激素治疗的禁忌症。有关女性激素类药物累积暴露的信息是基于处方。统计分析包括教育水平,使用抗组胺药,以及使用抗哮喘药物作为协变量。随访期间,1,595名妇女被诊断出患有脑膜瘤,1,167名患有神经胶质瘤。整个队列中个体的中位(第一至第三四分位数)随访时间为10.8年(5.0年至17.5年)。与从不使用相比,暴露于雌激素-孕激素或仅孕激素均与脑膜瘤的风险增加有关。风险比(HR)1.21;(95%置信区间(CI)[1.06,1.37]p=0.005)和HR1.28;(95%CI[1.05,1.54]p=0.012),分别。神经胶质瘤的相应HR为HR1.00;(95%CI[0.86,1.16]p=0.982)和HR1.20;(95%CI[0.95,1.51]p=0.117)。连续雌激素-孕激素显示脑膜瘤的HR较高1.34;(95%CI[1.08,1.66]p=0.008)比循环治疗1.13;(95%CI[0.94,1.34]p=0.185)。先前在诊断前5至10年使用雌激素-孕激素与脑膜瘤的相关性最强,HR1.26;(95%CI[1.01,1.57]p=0.044),而目前/最近使用孕激素对脑膜瘤1.64;(95%CI[0.90,2.98]p=0.104)和神经胶质瘤1.83;(95%CI[0.98,3.41]p=0.057)均产生最高的HR.作为一项观察性研究,可能会发生残余混杂。
结论:使用连续的,但循环雌激素-孕激素与脑膜瘤风险增加无关.没有证据表明使用雌激素-孕激素会增加神经胶质瘤的风险。仅使用孕激素与脑膜瘤和潜在神经胶质瘤的风险增加有关。需要进一步的研究来评估我们的发现,并研究长期仅使用孕激素的方案对中枢神经系统肿瘤风险的影响。
BACKGROUND: Use of estrogen-containing menopausal hormone therapy has been shown to influence the risk of central nervous system (CNS) tumors. However, it is unknown how the progestin-component affects the risk and whether continuous versus cyclic treatment regimens influence the risk differently.
RESULTS: Nested
case-control studies within a nationwide cohort of Danish women followed for 19 years from 2000 to 2018. The cohort comprised 789,901 women aged 50 to 60 years during follow-up, without prior CNS tumor diagnosis, cancer, or contraindication for treatment with menopausal hormone therapy. Information on cumulative exposure to female hormonal drugs was based on filled prescriptions. Statistical analysis included educational level, use of antihistamines, and use of anti-asthma drugs as covariates. During follow-up, 1,595 women were diagnosed with meningioma and 1,167 with glioma. The median (first-third quartile) follow-up time of individuals in the full cohort was 10.8 years (5.0 years to 17.5 years). Compared to never-use, exposure to estrogen-progestin or progestin-only were both associated with increased risk of meningioma, hazard ratio (HR) 1.21; (95% confidence interval (CI) [1.06, 1.37] p = 0.005) and HR 1.28; (95% CI [1.05, 1.54] p = 0.012), respectively. Corresponding HRs for glioma were HR 1.00; (95% CI [0.86, 1.16] p = 0.982) and HR 1.20; (95% CI [0.95, 1.51] p = 0.117). Continuous estrogen-progestin exhibited higher HR of meningioma 1.34; (95% CI [1.08, 1.66] p = 0.008) than cyclic treatment 1.13; (95% CI [0.94, 1.34] p = 0.185). Previous use of estrogen-progestin 5 to 10 years prior to diagnosis yielded the strongest association with meningioma, HR 1.26; (95% CI [1.01, 1.57] p = 0.044), whereas current/recent use of progestin-only yielded the highest HRs for both meningioma 1.64; (95% CI [0.90, 2.98] p = 0.104) and glioma 1.83; (95% CI [0.98, 3.41] p = 0.057). Being an observational study, residual confounding could occur.
CONCLUSIONS: Use of continuous, but not cyclic estrogen-progestin was associated with increased meningioma risk. There was no evidence of increased glioma risk with estrogen-progestin use. Use of progestin-only was associated with increased risk of meningioma and potentially glioma. Further studies are warranted to evaluate our findings and investigate the influence of long-term progestin-only regimens on CNS tumor risk.