Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


Association of Low-Dose Pulsed Intravenous Cyclophosphamide Therapy and Amenorrhea in 62 Patients with Systemic Lupus Erythematosus: A Case-Control Study.

Baba1,  Sayumi, Katsumata4,  Yasuhiro, Kawaguchi2,  Yasushi, Takagi1,  Kae, Gono1,  Takahisa, Okamoto1,  Yuko, Ota1,  Yuko

Tokyo Women's Medical University, Tokyo, Japan
Tokyo Women's Medical University, Tokyo, Japan
Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan
Tokyo Women's Medical University

Purpose:

Amenorrhea is a serious adverse effect associated with cyclophosphamide (CY). Although low-dose intravenous CY (IVCY) regimen has been proposed to reduce its various adverse effects in the treatment for major organ involvements in systemic lupus erythematosus (SLE), the beneficial effect of low-dose IVCY on amenorrhea has not been fully elucidated. We aimed to clarify the incidence of amenorrhea following low-dose IVCY and the association between amenorrhea and clinical parameters.

Methods:

We performed a case-control study on women younger than 45 years who were treated with low-dose IVCY (500 mg/body/pulse) plus steroid or steroid alone (0.8–1.0 mg/kg/day of predonisolone) for active SLE in our university hospital from 2000 through 2009. Patients with pre-existing amenorrhea and patients who dropped out from our follow-up were also excluded. We conducted a questionnaire survey about secondary amenorrhea and reviewed medical records from cases and controls. Amenorrhea was defined as lack of menses for at least 3 months. Sustained amenorrhea was defined as lack of menses for at least 12 months without resumption during the study period.

Results:

Twenty-nine and 33 patients who were treated with low-dose IVCY (IVCY group) and steroid alone (steroid group) returned the questionnaire, respectively. The median cumulative dose of CY in the IVCY group was 1000 mg. All the patients in both groups were successfully treated and discharged. Amenorrhea developed more frequently in patients in the IVCY group than the steroid group (59% vs. 14%; p= 0.02; OR 3.5; 95% CI 1.3–11.0). The incidence of sustained amenorrhea was not statistically different between the groups (14% vs. 3%; p= 0.18). 'Age over 40 years at initiation of treatment' was the strongest risk factor for developing amenorrhea by the univariate analysis: Patients over 40 years of age had higher incidence of amenorrhea than younger patients (p= 0.005; OR 9.0; 95% CI 1.7–46.5) when both groups were analyzed as a whole. IVCY was also associated with amenorrhea (p= 0.02; OR 3.5; 95% CI 1.3–11.0). Sustained amenorrhea developed in 4 patients in the IVCY group and 1 patient in the steroid group and all these patients were in their forties. In contrast, menses resumed in all the patients younger than 40 years old irreverent to the treatment. The multivariate logistic regression demonstrated that 'age over 40 years at initiation of treatment' was significantly associated with amenorrhea (p= 0.004; OR 10.2; 95% CI 2.1–78.5). IVCY was weakly associated with amenorrhea without statistical significance (p= 0.07; OR 2.9; 95% CI 0.9–9.7).

Conclusions:

Our data suggested that the strongest risk factor for developing amenorrhea in SLE patients treated with high-dose steroids with or without low-dose IVCY is 'age over 40 years at initiation of treatment.' In addition, even low-dose IVCY might also increase the risk for developing amenorrhea. Patients younger than 40 years old had minimum risk for sustained amenorrhea irreverent to treatment regimen. Higher risk of IVCY for sustained amenorrhea should be seriously pre-considered in patients over 40 years of age.

To cite this abstract, please use the following information:
Baba, Sayumi, Katsumata, Yasuhiro, Kawaguchi, Yasushi, Takagi, Kae, Gono, Takahisa, Okamoto, Yuko, et al; Association of Low-Dose Pulsed Intravenous Cyclophosphamide Therapy and Amenorrhea in 62 Patients with Systemic Lupus Erythematosus: A Case-Control Study. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :447
DOI: 10.1002/art.28216

Abstract Supplement

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2010 ACR/ARHP