Adjunctive GnRH-a treatment attenuates depletion of ovarian reserve associated with cyclophosphamide therapy in premenopausal SLE patients

Abstract

Background: We measured antimullerian hormone (AMH), a marker of ovarian reserve, in women with lupus treated with cyclophosphamide (CYC) (group I), CYC plus gonadotropin-releasing hormone agonist (GnRH-a) (group II) or neither (group III). We hypothesized that AMH would be diminished in women exposed to CYC versus women receiving adjunctive GnRH-a treatment or no CYC exposure. Methods: Forty-eight premenopausal lupus patients were retrospectively divided into three treatment groups: CYC alone (group I, n = 11), CYC + GnRH-a (group II, n = 10) and neither (group III, n = 27). Serum AMH levels between groups were compared using a nonparametric test (Wilcoxon rank-sum). Multiple linear regression adjusting for age was performed. Results: AMH (ng/mL) levels at the last collection were significantly lower in group I versus group III (mean ± SD: 0.18 ± 0.20 group I vs 1.33 ± 1.59 group III; p = 0.015), and versus group II (mean ± SD: 0.86 ± 1.06; p = 0.018). When centered on age 30 years, average AMH levels for group I, group II and group III were 0.20, 0.44 and 1.00, respectively. When adjusted for age, AMH between all groups was significantly different (p<0.0001). Conclusion: Posttreatment AMH levels were significantly higher among patients receiving CYC + GnRH-a compared to CYC alone, suggesting that GnRH-a coadministration mitigates CYC-induced ovarian injury.

Keywords::

• Antimullerian hormone
• cyclophosphamide
• primary ovarian insufficiency
• systemic lupus erythematosus

Declaration of Interest: There are no conflicting interests among any authors to declare. This work was supported by The Pilot and Collaborative Grant Program, Michigan Institute for Clinical and Health Research (MICHR) UL1RR024986 (to W. Marder). W. Marder was supported by K12HD001438 from National Institutes of Health and the Elizabeth Caroline Crosby Research Fund. E.C. Somers was supported by UL1RR024986 from the National Center for Research Resources. This work was also supported in part by the Herbert and Carol and Amster Lupus Research Fund, and the Michael and Marcia Klein Lupus Research Fund.