Antimullerian hormone, but not follicle stimulating hormone, reflects decline in ovarian reserve associated with oral cyclophosphamide use in Wegener's granulomatosis for the WGET research group

Abstract

OBJECTIVE: Our aim was to determine the effect of cyclophosphamide (CYC) on ovarian reserve markers antimullerian hormone (AMH) and follicle stimulating hormone (FSH) in patients with Wegener's Granulomatosis (WG). DESIGN: Case control study of stored plasma. MATERIALS AND METHODS: Patients in Wegener's Granulomatosis Etanercept Trial (WGET) received cyclophosphamide (CYC) for severe WG and methotrexate for limited WG. The first and last available plasma samples from the 42 women who were under age 50 at WGET enrollment were analyzed in duplicate for FSH (ELISA Calbiotech) and AMH (ELISA DSLabs). Linear regression analysis and Wilcoxon rank sum tests were performed. RESULTS: While the change in AMH during the study was closely correlated with the dose of CYC received (0.8 ng/mL decline per 10 gms CYC, p=0.009), change in FSH did not correlate with CYC dose. Furthermore, AMH, but not FSH, exhibited a significant decline in patients receiving CYC compared to no CYC.Table 1Change in AMH & FSH from baseline to end of study.CYC in WGETNo CYC in WGETParameterNMean ± std.NMean ± std.p-valueRaw Change of AMH (last visit - baseline)∗Baseline AMH<0.5 ng/mL excluded.11-2.15 ± 1.9460.36 ± 0.890.011Raw Change of FSH (last visit - baseline)†Oral contraceptive pill & GnRH agonist users excluded.227.40 ± 18.4410-1.73 ± 14.080.347∗ Baseline AMH<0.5 ng/mL excluded.† Oral contraceptive pill & GnRH agonist users excluded. Open table in a new tab CONCLUSIONS: In this study, AMH was more closely linked to CYC ovarian damage than FSH. FSH testing was not obtained in the early follicular phase, so was influenced by endogenous estradiol and progesterone during the ovarian cycle of ovulating women. In the oncofertility setting, where patients are not routinely seen in the early follicular phase and may be taking oral contraceptives, AMH is a superior marker of ovarian function.