Gonadotropin Releasing Hormone Agonists May Minimize Cyclophosphamide Associated Gonadotoxicity in SLE and Autoimmune Diseases

ObjectiveSince young women undergoing cyclophosphamide pulse therapy may suffer premature ovarian failure (POF) in almost 50% of cases, we examined the ability of GnRH-a administration to minimize the gonadotoxicity associated with cyclophosphamide pulse therapy (CPT).MethodsRetrospective analysis of medical charts of 44 women (age 16-38 years) who received CPT for autoimmune diseases. In 33 patients a monthly depot injection of GnRH-a was started before the alkylating agent. The ovarian function [spontaneous menstrual bleeding, hormonal profile, (FSH, LH, E2, progesterone) pelvic sonography, and conceptions] was evaluated, 1 to 10 years after CPT.ResultsIn the GnRH-a group, 30 women resumed cyclic ovarian function; 1 (a 37-year-old patient) developed POF (3%), and 2 were lost to follow-up. In the control (no GnRH-a) group, 5 of 11 patients suffered POF (45%). The mean age in the study group was 25.6 ± 5.2 years compared with 29.3 ± 5.8 years in the control group, and the mean cumulative cyclophosphamide dose was 9.9 g compared to 10.9 g, respectively. The difference in the long-term POF remained significant even after adjusting the groups for comparable age and cumulative cyclophosphamide doses.ConclusionGnRH-a decreases cyclophosphamide-associated gonadotoxicity and POF in young women with systemic lupus erythematosus and other autoimmune diseases. Therefore this treatment should be considered and recommended to every young woman before gonadotoxic chemotherapy.