Standard treatment for severe granulomatosis with polyangiitis (GPA, previously Wegener’s granulomatosis) is daily oral cyclophosphamide (CYC), a cytotoxic agent associated with ovarian failure. In this study we assessed the rate of diminished ovarian reserve in women with GPA who received CYC versus methotrexate (MTX).
Patients in the Wegener’s Granulomatosis Etanercept Trial received either daily CYC or weekly MTX and were randomized to etanercept or placebo. For all women under 50, plasma samples taken at baseline or early in the study were evaluated against samples taken later in the study to compare levels of anti-Müllerian hormone (AMH) and follicle stimulating hormone (FSH), endocrine markers of remaining egg supply. Diminished ovarian reserve was defined as AMH<1.0ng/ml.
Of 42 women in this analysis (mean age 35), 24 had CYC exposure prior to enrollment and 28 received the drug during the study. At study entry, women with prior CYC exposure had significantly lower AMH, higher FSH, and a higher rate of early menstruation cessation. For women with normal baseline ovarian function, 6/8 who received CYC during the trial developed diminished ovarian reserve, compared to 0/4 who did not receive CYC (p<0.05). Changes in AMH correlated inversely with cumulative CYC dose (p=0.01), with a 0.74ng/ml decline in AMH for each 10g of CYC.
Daily oral CYC, even when administered for less than 6 months, causes diminished ovarian reserve, as indicated by low AMH levels. These data highlight the need for alternative treatments for GPA in women of childbearing age.