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Risk for Sustained Amenorrhea in Patients with Systemic Lupus Erythematosus Receiving Intermittent Pulse Cyclophosphamide Therapy

Dimitrios T. Boumpas, MD; Howard A. Austin, MD; Ellen M. Vaughan, RN; Cheryl H. Yarboro, RN; John H. Klippel, MD; and James E. Balow, MD
[+] Article and Author Information

From the National Institute of Diabetes and Digestive and Kidney Diseases; the Nursing Department, Clinical Center; the National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland. Request for Reprints: Dimitrios T. Boumpas, MD, National Institutes of Health (NIH), Building 10, Room 3N-112, Bethesda, MD 20892. Acknowledgments: The authors thank Lisa A. Miller for her help during the preparation of the manuscript.


Copyright 2004 by the American College of Physicians


Ann Intern Med. 1993;119(5):366-369. doi:10.7326/0003-4819-119-5-199309010-00003
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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: 25 years, 2/16 (12%); 26 to 30 years, 4/15 (27%); 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.

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