Objective: To study the effects of ovarian failure on disease flares in systemic lupus erythematosus (SLE).
Methods: Fifty-four female premenopausal SLE patients who were under the age of 45 years and treated with continuous oral cyclophosphamide (CYC) for no 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 first 5 years after CYC treatment was made between patients who developed CYC-induced ovarian failure and those who did not.
Results: Fourteen SLE patients had documented ovarian failure with hypoestrogenemia 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 autoantibody profiles between the 2 groups were observed. Both the ovarian failure 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 administration. 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 flares (mean 0.128 versus 0.250 flares/patient-year; P = 0.03) when compared with those who were still menstruating.
Conclusion: This study provides an important clinical observation to support the notion that ovarian failure with hypoestrogenemia is protective against lupus flares and emphasizes the importance of estrogen status in the determination of disease activity in SLE.