Use of a gonadotropin‐releasing hormone analog for protection against premature ovarian failure during cyclophosphamide therapy in women with severe lupus

Objective Cyclophosphamide (CYC) therapy for systemic lupus erythematosus (SLE), a disease predominantly affecting women of childbearing age, causes an unacceptably high incidence of irreversible premature ovarian failure (POF). This study was performed to evaluate the effectiveness of depot leuprolide acetate, a synthetic gonadotropin‐releasing hormone analog (GnRH‐a), for protection against POF during CYC therapy. Methods Young women with severe SLE treated in a standardized protocol of monthly intravenous bolus CYC were offered treatment with GnRH‐a (depot leuprolide acetate; a 3.75‐mg monthly injection during the standard CYC regimen). Patients treated with GnRH‐a were compared with controls individually matched by age (±5 years) and by cumulative CYC dose (±5 gm). Reproductive status was determined after a minimum followup of 3 years after CYC therapy. The primary outcome was time to POF. Paired summary statistical analyses, Kaplan‐Meier survival estimates, and Cox regression analyses were performed to assess differences in outcome between groups. Results POF developed in 1 of 20 women treated with GnRH‐a (5%) compared with 6 of 20 controls (30%) matched by age and cumulative CYC dose (matched odds ratio 0.09, P < 0.05). Kaplan‐Meier estimates demonstrated improved cumulative ovarian protection over time in the GnRH‐a–treated group ( P = 0.04). Conclusion Treatment with GnRH‐a during CYC therapy was associated with a significant reduction of POF in young women with severe SLE.