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

Objective

Since 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).

Methods

Retrospective 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.

Results

In 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.

Conclusion

GnRH-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.

Keywords: connective tissue disease, systemic lupus erythematosus, systemic sclerosis, GnRH-a, gonadotoxicity, premature ovarian failure