Objective: To identify predictors of intravenous cyclophosphamide (IC) induced sustained amenorrhea, especially in young premenopausal women with systemic lupus erythematosus (SLE).
Methods: The cumulative dose resulting in sustained amenorrhea in 50 and 90% of the treated women (D50 and D90) and predictors of sustained amenorrhea at various ages were determined with Kaplan-Meier plots and Cox regressions in a consecutively enrolled cohort of 67 premenopausal women with SLE who received a pulsed IC regimen (monthly doses of 0.75-1.00 g/m2) for nephritis (n = 59) or other indications (n = 8).
Results: Twenty-one of 67 women developed sustained amenorrhea of > 12 months' duration. Age was the strongest determinant of this adverse event. For women in the upper age tertile (>or= 32 years old), D50 was 8 g/m2 and D90 was 12 g/m2, and no strong protective or predisposing factors were identified. Conversely, only 5 of 44 women <or= 31 years old at initiation of IC developed sustained amenorrhea. In these young women the risk was modulated by the prior SLE disease duration (risk increased 1.28-fold per year; p = 0.002), the presence of anti-U1RNP antibodies (relative risk 9.5; p = 0.016), and the presence of anti-Ro antibodies (relative risk 13.5; p = 0.021). In multivariate modeling, anti-U1RNP and disease duration were still significant (p < 0.05).
Conclusion: Sustained amenorrhea is difficult to avoid in women 32 years or older, even with very short IC courses, and alternative regimens should be considered. In younger women treated with a monthly IC regimen, sustained amenorrhea may occur predominantly in those with the recognized adverse predictors of this complication.