Background Systemic lupus erythematosus (SLE) is commonly treated with broad immunosuppression, including cyclophosphamide. Use of this agent can result in ovarian toxicity leading to premature menopause. Ovarian failure is associated with concomitant hypothyroidism. We hypothesized that hypothyroidism might be a marker for ovarian autoimmunity because organ-specific autoimmune diseases tend to occur together. We undertook this study to determine whether anti-ovarian antibodies are associated with premature ovarian failure among SLE women who received cyclophosphamide.
Methods All SLE women with a history of cyclophosphamide therapy were identified in the Lupus Registry and Repository (LFRR). All subjects were shown to meet the revised ACR classification criteria. Premature menopause was defined as spontaneous lack of menstrual periods prior to age 45. Anti-ovarian antibodies were measured by ELISA (Anti-Ovarian Ab ELISA, IBL, Minneapolis, catalog # IB9184). Data were analyzed by Students T test and chi square testing. The protocol received ethical approval from the University of Oklahoma Health Sciences Center and Oklahoma Medical Research Foundation IRBs.
Results Among ~3000 SLE women enrolled in the LFRR who had received cyclophosphamide, we found 169 with menopause before age 45 along with 73 who underwent menopause after age 45 and 16 patients over age 45 who were still having menstrual periods at the time of evaluation. Thus, there were a total of 89 SLE women who did not have premature menopause. Mean anti-ovarian antibodies in the 169 with premature ovarian failure was 16.2 units (SD=20.3), while the mean among those without premature menopause was 17.4 units (SD=21.7). These values were not statistically different between the groups. 11 of 169 (6.5%) prematurely menopausal SLE women had a positive result and 8 of 89 (8.9%) without premature menopausal were positive (2=0.53, p=0.46, OR=1.02 (95% CI 0.95–1.1).
Conclusions Anti-ovarian antibodies were present at low levels (~10% positivity) among women with SLE. However, the presence of these antibodies was not related to premature ovarian failure after cyclophosphamide.
Funding Source(s): NIH grants AR053483, AI082714, GM104938. VA grant BX0011451
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