Effect of a gonadotropin-releasing hormone analog for ovarian function preservation after intravenous cyclophosphamide therapy in systemic lupus erythematosus patients: a retrospective inception cohort study.

Abstract

To determine the effect of leuprolide acetate, a synthetic gonadotropin-releasing hormone analog (GnRH-a) on ovarian function preservation in systemic lupus erythematosus (SLE) patients treated with cyclophosphamide (CYC) in clinical practice. We enrolled 30 premenopausal female SLE patients who fulfilled the 1997 American College of Rheumatology revised criteria and were treated with intravenous CYC (IVCY) in 2008-2017. We used Kaplan-Meier survival estimates to compare the GnRH-a-treated patients and those not treated with GnRH-a as controls. We performed Cox regression analyses to identify factors associated with premature ovarian failure (POF), incidences of cardiovascular events, strokes and osteoporosis after IVCY therapy. After a mean follow-up of 41months, POF developed in one of the 16 GnRH-a-treated patients (6%) versus seven of the 14 controls (50%). Significantly improved cumulative ovarian protection over time was observed in the GnRH-a-treated group (P=0.030). The hazard model analysis showed that treatment with GnRH-a during IVCY therapy is an independent factor associated with POF after IVCY therapy (adjusted hazards ratio=0.12, 95% CI 0.01-0.67, P=0.013) but not incidences of cardiovascular events, strokes or osteoporosis. The combined use of GnRH-a with IVCY therapy was associated with a significant reduction of POF among premenopausal women with SLE, suggesting that the addition of GnRH-a can be a strategy to prevent POF among premenopausal women with SLE after IVCY therapy.