TRIPTORELIN FOR OVARY PROTECTION IN CHILDHOOD ONSET LUPUS

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。这项研究的长期目标是通过治疗干预开发保护系统性红斑狼疮(SLE)儿童性腺功能的治疗方法，其有益效果已被高质量的临床证据证实。环磷酰胺是儿童系统性红斑狼疮最常用的免疫抑制剂，但目前还没有针对环磷酰胺引起的性腺毒性的预防性治疗。本研究希望确定曲普瑞林预防性腺毒性的安全性、剂量和化疗前达到完全抑制卵巢(COS)所需的时间，并获得其为年轻女性SLE提供卵巢保护的初步证据。这一应用的中心假设是，曲普瑞林可以安全地实现COS，并可以有效地保护需要用环磷酰胺进行促性腺激素化疗的青少年女性SLE患者的卵巢功能。这一假说是基于成人系统性红斑狼疮患者支持性研究的结果提出的。这项调查的基本原理是，找到更有效的干预措施来保护卵巢功能，避免过早绝经，将转化为生育率的提高，心血管疾病、骨质疏松症和更年期其他长期健康并发症的风险因素减少；这反过来将降低与系统性红斑狼疮相关的总体社会成本。

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. The long-term goal of this study is to develop therapies for protecting the gonadal function of children with systemic lupus erythematosus (SLE) through therapeutic interventions whose beneficial effects have been verified by high-quality clinical evidence. Cyclophosphamide is the most frequently used immunosuppressive agent for children with SLE but there are no approved prophylactic treatments against gonadotoxicity caused by cyclophosphamide. This study hopes to determine the safety of the drug triptorelin when used as a prophylactic against gonadotoxicity, its dose and the time necessary to achieve complete ovarian suppression (COS) prior to chemotherapy, as well as obtain preliminary evidence of its efficacy to provide ovarian protection for young females with SLE. The central hypothesis of this application is that triptorelin can safely achieve COS and may effectively preserve ovarian function of adolescent females with SLE requiring gonadotoxic chemotherapy with cyclophosphamide. This hypothesis has been formulated based on the results of supportive studies in adult patients with SLE. The rationale that underlies the investigation is that identification of more effective interventions to preserve ovarian function and avoid premature menopause will translate into increased fertility, fewer risk factors of cardiovascular disease, osteoporosis and other long-term health complications of menopause; this in turn, will lower the overall societal costs associated with SLE.