Risk for sustained amenorrhea in patients with systemic lupus erythematosus receiving intermittent pulse cyclophosphamide therapy

Ann Intern Med. 1993 Sep 1;119(5):366-9. doi: 10.7326/0003-4819-119-5-199309010-00003.


Objective: To determine the risk for secondary amenorrhea after pulse cyclophosphamide therapy in premenopausal women with systemic lupus erythematosus.

Design: Controlled, retrospective clinical study.

Setting: Government referral-based research hospital.

Patients: Thirty-nine women younger than 40 years treated with pulse cyclophosphamide therapy for active lupus nephritis or neuropsychiatric lupus. Sixteen women who received pulses of intravenous methylprednisolone were controls.

Interventions: Sixteen patients received pulse cyclophosphamide (0.5 to 1.0 g/m2 body surface area) monthly for a total of 7 doses (short-CY), and 23 patients received 15 or more doses (long-CY). Control patients were treated with monthly pulses of methylprednisolone (1.0 g/m2) for a total of nine doses.

Measurements: Rates of amenorrhea were evaluated according to duration of treatment (number of doses) and age at the initiation of pulse therapy.

Results: Two of 16 patients (12%) in the Short-CY group and 9 of 23 (39%) in the long-CY group developed sustained amenorrhea (P = 0.07). Rates of sustained amenorrhea (short- and long-CY) according to age at the start of pulse therapy were: < or = 25 years, 2/16 (12%); 26 to 30 years, 4/15 (27%); > or = 31 years, 5/8 (62%) (P = 0.04). The increased risk for sustained amenorrhea in patients treated with long-CY was most evident in patients older than 25 years (short-CY [2/12] compared with long-CY [7/11]; P = 0.03). Three other patients with short-CY had reversal of amenorrhea fewer than 12 months after cessation of therapy. Amenorrhea was not observed in any of the 16 control patients.

Conclusions: Intermittent pulse cyclophosphamide therapy in patients with systemic lupus erythematosus is associated with sustained amenorrhea, which is related to both age and number of doses of cyclophosphamide.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Age Factors
  • Amenorrhea / chemically induced*
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / adverse effects*
  • Drug Administration Schedule
  • Female
  • Fertility / drug effects
  • Humans
  • Lupus Erythematosus, Systemic / drug therapy*
  • Lupus Nephritis / drug therapy
  • Ovary / drug effects
  • Retrospective Studies
  • Risk Factors


  • Cyclophosphamide