TRIPTORELIN FOR OVARY PROTECTION IN LUPUS

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。在美国，大约有30，000名儿童被诊断患有系统性红斑狼疮（SLE），这是一种多器官自身免疫性疾病，女性占显著优势。对于SLE的严重疾病表现，需要使用环磷酰胺静脉化疗，其副作用包括性腺毒性。没有药物被批准用于保护SLE患者免受化疗相关的性腺损伤。环磷酰胺的性腺毒性作用在年龄超过30岁的男性和女性中最为明显，他们在环磷酰胺治疗后有70%的卵巢早衰风险，可能是因为他们具有与年龄相关的卵巢储备较小。年轻女性发生卵巢功能明显衰竭的风险要小得多，约为11%。促性腺激素释放激素激动剂（GNRH-a），如曲普瑞林，可显著降低环磷酰胺治疗后成人SLE患者卵巢早衰（POF）的发生率。保护卵巢的生物学基础是，在卵巢活动短暂增加后，可能导致对性腺毒素的脆弱性增加，曲普瑞林可诱导完全卵巢抑制（COS），使卵巢对环磷酰胺性腺毒性相对耐受。曲普瑞林在SLE中的安全性尚未得到充分研究。既往病例报告提示GnRH-a可能加重SLE疾病活动并促进自身免疫。曲普瑞林保护卵巢的最佳剂量和诱导SLE儿童COS所需的确切时间间隔尚不清楚。目前尚不确定POF发病率降低的青少年女性是否也会从曲普瑞林中获益。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Approximately 30,000 children in the US are diagnosed with Systemic Lupus Erythematosus (SLE), a multiorgan autoimmune disease with striking female preponderance. For severe disease manifestations of SLE intravenous chemotherapy using cyclophosphamide is required, whose side effects include gonadotoxicity. No drugs have been approved to protect patients with SLE from chemotherapy associated gonadal damage. The gonadotoxic effects of cyclophosphamide are most apparent among males and women over the age of 30 years who have a 70% risk of premature ovarian failure after cyclophosphamide therapy, likely because they have an age-related smaller ovarian reserve. The risks of developing overt ovarian failure among young females is much smaller at around 11%. Gonadotropin releasing hormone agonists (GNRH-a), such as triptorelin, may significantly decrease the incidence of premature ovarian failure (POF) after cyclophosphamide in adult SLE. The biologic basis for protecting ovaries is that, after a brief episode of increased ovarian activity, likely leading to increased vulnerability to gonadotoxins, triptorelin can induce complete ovarian suppression (COS), making ovaries relatively resistant to cyclophosphamide gonadotoxicity. The safety of triptorelin in SLE has not been well examined. Previous case reports suggest that GnRH-a may worsen SLE disease activity and promote autoimmunity. The optimal dose of triptorelin for ovarian protection and the exact time interval necessary to induce a COS in children with SLE are unknown. It is uncertain whether adolescent females with their decreased incidence of POF would also benefit from triptorelin.