TRIPTORELIN FOR OVARY PROTECTION IN LUPUS

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。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，以女性为主。对于病情严重的SLE患者，需要使用环磷酰胺静脉化疗，其副作用包括促性腺毒性。目前还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。环磷酰胺的促性腺毒性作用在30岁以上的男性和女性中最为明显，他们在环磷酰胺治疗后卵巢早衰的风险为70%，可能是因为他们的卵巢储备能力与年龄相关。年轻女性发生明显卵巢功能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triptorelin，可显著降低成人SLE患者环磷酰胺后卵巢早衰（POF）的发生率。保护卵巢的生物学基础是，在短暂的卵巢活动增加后，可能导致对促性腺毒素的易感性增加，雷triprelin可以诱导卵巢完全抑制（COS），使卵巢相对抵抗环磷酰胺的促性腺毒性。triptorelin治疗SLE的安全性尚未得到很好的研究。以往的病例报告表明，GnRH-a可能加重SLE疾病活动性并促进自身免疫。雷普利林对卵巢保护的最佳剂量和SLE儿童诱导COS所需的确切时间间隔尚不清楚。目前尚不确定的是，降低POF发病率的青春期女性是否也会受益于雷普托雷林。

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.