Predictors of sustained amenorrhea from pulsed intravenous cyclophosphamide in premenopausal women with systemic lupus erythematosus.

Abstract

To identify predictors of intravenous cyclophosphamide (IC) induced sustained amenorrhea, especially in young premenopausal women with systemic lupus erythematosus (SLE). 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). 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). 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.