Risk factors for ovarian failure in patients with systemic lupus erythematosus receiving cyclophosphamide therapy

Arthritis Rheum. 1998 May;41(5):831-7. doi: 10.1002/1529-0131(199805)41:5<831::AID-ART9>3.0.CO;2-1.


Objective: To determine the incidence of ovarian failure after cyclophosphamide (CYC) treatment for systemic lupus erythematosus (SLE) and to identify the risk factors for this complication.

Methods: The records of 70 premenopausal female SLE patients treated with CYC were reviewed retrospectively. Information on demographic features, autoantibody profiles, and CYC treatment was obtained, and comparisons were made between those who developed ovarian failure and those who did not. Data on the CYC-treated patients were also compared with data on 2 control groups of non-CYC-treated SLE patients.

Results: Eighteen patients developed ovarian failure after CYC treatment, for an overall incidence of 26%. The incidence of ovarian failure showed a linear trend of increase with increasing age at the start of CYC (P = 0.007). The cumulative CYC dose was significantly higher in the patients with ovarian failure than in those without (28.3 gm versus 15.4 gm; P = 0.004). The risk of ovarian failure also showed a linear trend of increase with increasing cumulative CYC dose (P < 0.001). Using multiple logistic regression, the age at the time of CYC treatment initiation (beta = 0.37, SE = 0.11, P = 0.001) and the cumulative dose of CYC received (beta = 0.69, SE = 0.29, P = 0.02) were found to be independent risk factors for CYC-induced ovarian failure.

Conclusion: In our population of female SLE patients, CYC-induced ovarian toxicity is a significant problem, particularly in patients above the age of 40. The age at the start of CYC therapy and the cumulative dose are the major determinants for the development of this complication. For older patients with SLE in whom the use of CYC is warranted, a shorter course and lower dosage should be considered.

MeSH terms

  • Adult
  • Age Factors
  • Amenorrhea / chemically induced*
  • Antirheumatic Agents / adverse effects*
  • Cyclophosphamide / adverse effects*
  • Female
  • Humans
  • Incidence
  • Lupus Erythematosus, Systemic / blood
  • Lupus Erythematosus, Systemic / drug therapy*
  • Lupus Erythematosus, Systemic / pathology
  • Middle Aged
  • Primary Ovarian Insufficiency / chemically induced*
  • Retrospective Studies
  • Risk Factors


  • Antirheumatic Agents
  • Cyclophosphamide