应用沙利度胺在214例育龄期女性风湿病患者中的生殖系统安全性评价

Evaluation of reproductive system safety of thalidomide in 214 women of childbearing age with rheumatic diseases

目的:观察沙利度胺在治疗育龄期女性风湿免疫患者中月经紊乱及卵巢储备功能等生殖系统方面的不良反应,为临床用药安全提供参考。方法:回顾2018年1月—2023年6月在南昌大学第一附属医院风湿免疫科就诊使用了沙利度胺具有完整资料的18~45岁女性患者,观察沙利度胺使用期间的经期紊乱及抗缪勒管激素(AMH)水平,分析其可能对生殖系统功能产生的不良影响及危险因素。结果:纳入214例患者,平均年龄(34.81±6.45)岁,服用沙利度胺剂量为25~75 mg·d^(-1),累积剂量为750~81000 mg,服用时间为1~36个月,使用后育龄期女性周期紊乱率高达79.59%,其中闭经率18.37%。单因素分析结果显示累积剂量和使用时间与AMH下降显著相关(P<0.05),并且AMH≤2 ng·mL^(-1)的患者停用沙利度胺后月经恢复率62.5%,而AMH>2 ng·mL^(-1)的患者停用沙利度胺后月经恢复率达100%。两组月经恢复时间都在1~2个月内。Pearson相关分析显示AMH与沙利度胺日剂量(r=-0.522,P<0.05)、累积剂量(r=-0.807,P<0.05)和使用时间(r=-0.761,P<0.05)呈负线性相关。Cox回归分析显示沙利度胺累积剂量>9 g是发生生殖系统不良事件的独立危险因素(HR=19.014,P<0.001)。结论:育龄期女性使用沙利度胺发生月经紊乱及卵巢储备功能下降的发生率高,因此育龄期女性使用沙利度胺需要评估生育风险、监测卵巢储备功能,防止卵巢功能丧失导致闭经,影响生育能力和生活质量。

Objective:To observe the adverse reactions of thalidomide in the reproductive system,such as menstrual disorders and ovarian reserve function,in women of childbearing age with rheumatic immune diseases and provide references for the safety of clinical medication.Methods:A retrospective analysis was conducted on female patients aged 18~45 years with complete data who visited the Rheumatology and Immunology Department of the First Affiliated Hospital of Nanchang University and received thalidomide treatment from January 2018 to June 2023.The occurrence of menstrual disorders and levels of anti-Müllerian hormone(AMH)during thalidomide use were observed to analyze the potential adverse effects on reproductive system function and risk factors.Results:A total of 214 patients were included,with an average age of(34.81±6.45)years.The dosage of thalidomide ranged from 25 to 75 mg·d^(-1),with a cumulative dose ranging from 750 to 81000 mg.The treatment duration ranged from 1 to 36 months.The rate of menstrual cycle disorders in women of childbearing age during thalidomide use was as high as 79.59%,with a rate of amenorrhea of 18.37%.Univariate analysis showed a significant correlation between cumulative dose,treatment duration,and decreased AMH levels(P<0.05).The menstrual recovery rate after discontinuation of thalidomide was 62.5%in patients with AMH≤2 ng·mL^(-1),while it was 100%in patients with AMH>2 ng·mL^(-1).The menstrual recovery time for both groups was within 1~2 months.Pearson correlation analysis showed a negative linear correlation between AMH and daily dose of thalidomide(r=-0.522,P<0.05),cumulative dose(r=-0.807,P<0.05),and treatment duration(r=-0.761,P<0.05).Cox regression analysis showed that a cumulative dose of thalidomide>9 g was an independent risk factor for adverse events in the reproductive system(HR=19.014,P<0.001).Conclusion:The incidence of menstrual disorders and decreased ovarian reserve function is high in women of childbearing age using thalidomide.Therefore,the reproductive risks should be evaluated,and ovarian reserve function should be monitored to prevent ovarian dysfunction leading to amenorrhea and affecting fertility and quality of life.