TRIPTORELIN FOR OVARY PROTECTION IN CHILDHOOD ONSET 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。本研究的长期目标是通过治疗干预开发出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所证实。环磷酰胺是儿童SLE患者最常用的免疫抑制剂，但目前尚无批准的针对环磷酰胺引起的性腺毒性的预防性治疗方法。本研究希望确定药物triptorelin作为预防促性腺毒性的安全性、剂量和化疗前实现卵巢完全抑制（COS）所需的时间，并获得其对年轻SLE女性卵巢保护功效的初步证据。本应用的中心假设是，雷普妥林可以安全地实现COS，并可能有效地保护需要环磷酰胺促性腺毒性化疗的SLE青少年女性的卵巢功能。这一假设是基于对成年SLE患者的支持性研究结果而提出的。这项研究的基本原理是，确定更有效的干预措施，以保持卵巢功能和避免过早绝经，将转化为提高生育能力，减少心血管疾病、骨质疏松症和其他更年期长期健康并发症的风险因素；反过来，这将降低与SLE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.