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

Arthritis Rheum. 2005 Sep;52(9):2761-7. doi: 10.1002/art.21263.


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.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Cyclophosphamide / adverse effects*
  • Data Interpretation, Statistical
  • Female
  • Fertility Agents, Female / therapeutic use*
  • Follicle Stimulating Hormone / blood
  • Humans
  • Immunosuppressive Agents / adverse effects*
  • Leuprolide / therapeutic use*
  • Lupus Erythematosus, Systemic / blood
  • Lupus Erythematosus, Systemic / complications
  • Lupus Erythematosus, Systemic / drug therapy*
  • Ovary / drug effects
  • Ovary / physiopathology
  • Primary Ovarian Insufficiency / blood
  • Primary Ovarian Insufficiency / chemically induced
  • Primary Ovarian Insufficiency / prevention & control*
  • Survival Analysis
  • Treatment Outcome


  • Fertility Agents, Female
  • Immunosuppressive Agents
  • Cyclophosphamide
  • Follicle Stimulating Hormone
  • Leuprolide