TRIPTORELIN FOR OVARY PROTECTION IN LUPUS

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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.