Ovarian failure and flares of systemic lupus erythematosus

Objective. To study the effects of ovarian failure on disease flares in sys temic lupus erythematosus (SLE). Methods. Fifty-four female premenopausal SLE patients who were under the ag e of 45 years and treated with continuous oral cyclophosphamide (CYC) for n o more than 12 months were studied. All patients had been followed up for > 5 years following CYC treatment. Demographic characteristics, clinical and serologic profiles, and information concerning disease flares were recorded . Comparison of the number of severe and mild/moderate flares during the fi rst 5 years after CYC treatment was made between patients who de, eloped CY C-induced ovarian failure and those who did not. Results, Fourteen SLE patients had documented ovarian failure with hypoestr ogenemia within 2 years after CYC treatment. Compared with the menstruating group of patients, those who developed ovarian failure were significantly older at the time of CYC therapy (mean 37.9 versus 25.5 years; P < 0.001), but otherwise no significant differences in organ manifestations and autoan tibody profiles between the 2 groups were observed. Both the ovarian failur e group and menstruating group of patients had similar SLE Disease Activity Index scores at the time of CYC treatment (mean 15.6 versus 17.7; P = 0.16 ), and had comparable treatment durations (mean 8.2 versus 7.8 months; P = 0.68) and cumulative doses of CYC (mean 20.4 versus 17.9 grams; P = 0.34). Flares of SLE were uncommon during the first year following CYC administrat ion. However, during the 5-year followup period, patients who developed CYC -induced ovarian failure had significantly fewer severe flares (mean 0.014 versus 0.075 flares/patient-year; P = 0.01) and smaller total number of fla res (mean 0.128 versus 0.250 flares/patient-year; P = 0.03) when compared w ith those who were still menstruating, Conclusion. This study provides an Important clinical observation to suppor t the notion that ovarian failure with hypoestrogenemia Is protective again st lupus flares and emphasizes the importance of estrogen status in the det ermination of disease activity in SLE.