Predictors of sustained amenorrhea from pulsed intravenous cyclophosphamide in premenopausal women with systemic lupus erythematosus
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Ioannidis, J. P.
Katsifis, G. E.
Tzioufas, A. G.
Moutsopoulos, H. M.
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peer-reviewed
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J Rheumatol
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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.
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Adult, Age Factors, Amenorrhea/chemically induced/*diagnosis/epidemiology, Antirheumatic Agents/administration & dosage/*adverse effects, Cohort Studies, Cyclophosphamide/administration & dosage/*adverse effects, Female, Greece/epidemiology, Humans, Injections, Intravenous, Lupus Erythematosus, Systemic/complications/*drug therapy/epidemiology, Predictive Value of Tests, *Premenopause, Pulse Therapy, Drug, Risk Factors
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http://www.ncbi.nlm.nih.gov/pubmed/12375322
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en
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Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής