Background/Purpose: Treatment of systemic lupus erythematosus (SLE) with cyclophosphamide is associated with premature menopause, especially those at an older age of treatment and those receiving a higher cumulative dose.  We hypothesized that reduced ovarian reserve caused by ovarian autoimmunity would be associated with premature ovarian failure among SLE patients treated with cyclophosphamide. We undertook this study to test this hypothesis.   Treatment of systemic lupus erythematosus (SLE) with cyclophosphamide is associated with premature menopause, especially those at an older age of treatment and those receiving a higher cumulative dose.  We hypothesized that reduced ovarian reserve caused by ovarian autoimmunity would be associated with premature ovarian failure among SLE patients treated with cyclophosphamide. We undertook this study to test this hypothesis.

Methods: All SLE women with a history of cyclophosphamide therapy were identified in the Lupus Registry and Repository (LFRR).  The subjects met the revised ACR classification criteria.  Spontaneous lack of menstrual periods prior to age 45 was defined as premature menopause.  Anti-ovarian antibodies were measured by ELISA (Anti-Ovarian Ab ELISA, IBL, Minneapolis, catalog # IB9184).  We used Student’s T test and chi square testing for data analyses.  Approval was obtained from local Institutional Review Boards.

Results: Among ~3000 SLE women enrolled in the LFRR, 258 had received cyclophosphamide.  Of these 169 had menopause before age 45, while 73 underwent menopause after age 45.  16 patients were over age 45 and still having menstrual periods at the time of evaluation.  Thus, there were a total of 89 SLE women who did not have premature menopause.  Among the 169 with premature ovarian failure the mean anti-ovarian antibody level 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.  Considering categorical results, 11 of 169 (6.5%) SLE women with premature menopause had a positive result while 8 of 89 (8.9%) without premature menopause were positive (Χ²=0.53, p=0.46, OR=1.02 (95% CI 0.95-1.1)).

Conclusion: A small percentage of SLE patients treated with cyclophosphamide had anti-ovarian antibodies in their serum.   Nonetheless, the presence of these antibodies was not related to premature menopause.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/anti-ovarian-antibodies-are-not-associated-with-premature-menopause-in-sle-treated-with-cyclophophosphamide/