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

Int J Rheum Dis. 2018 Jun;21(6):1287-1292. doi: 10.1111/1756-185X.13318.

Abstract

Objective: 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.

Methods: 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.

Results: After a mean follow-up of 41 months, 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.

Conclusion: 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.

Keywords: cyclophosphamide; gonadotropin-releasing hormone analog; premature ovarian failure; systemic lupus erythematosus.

MeSH terms

  • Administration, Intravenous
  • Adult
  • Cardiovascular Diseases / epidemiology
  • Case-Control Studies
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / adverse effects*
  • Female
  • Fertility Agents, Female / adverse effects
  • Fertility Agents, Female / therapeutic use*
  • Fertility Preservation / adverse effects
  • Fertility Preservation / methods*
  • Humans
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / adverse effects*
  • Incidence
  • Infertility, Female / chemically induced
  • Infertility, Female / epidemiology
  • Infertility, Female / physiopathology
  • Infertility, Female / prevention & control*
  • Kaplan-Meier Estimate
  • Leuprolide / adverse effects
  • Leuprolide / therapeutic use*
  • Lupus Erythematosus, Systemic / drug therapy*
  • Lupus Erythematosus, Systemic / epidemiology
  • Lupus Erythematosus, Systemic / immunology
  • Multivariate Analysis
  • Osteoporosis / epidemiology
  • Ovary / drug effects*
  • Ovary / physiopathology
  • Premenopause
  • Primary Ovarian Insufficiency / chemically induced
  • Primary Ovarian Insufficiency / epidemiology
  • Primary Ovarian Insufficiency / physiopathology
  • Primary Ovarian Insufficiency / prevention & control*
  • Proportional Hazards Models
  • Stroke / epidemiology
  • Time Factors
  • Treatment Outcome
  • Young Adult

Substances

  • Fertility Agents, Female
  • Immunosuppressive Agents
  • Cyclophosphamide
  • Leuprolide