Dr. Allen has received consultant fees, speaking fees, and/or honoraria (less than $10,000) from Genentech.
Ovarian reserve diminished by oral cyclophosphamide therapy for granulomatosis with polyangiitis (Wegener's)†
Article first published online: 29 NOV 2011
Copyright © 2011 by the American College of Rheumatology
Arthritis Care & Research
Volume 63, Issue 12, pages 1777–1781, December 2011
How to Cite
Clowse, M. E. B., Copland, S. C., Hsieh, T.-C., Chow, S.-C., Hoffman, G. S., Merkel, P. A., Spiera, R. F., Davis, J. C., McCune, W. J., Ytterberg, S. R., St.Clair, E. W., Allen, N. B., Specks, U., Stone, J. H. and WGET Research Group (2011), Ovarian reserve diminished by oral cyclophosphamide therapy for granulomatosis with polyangiitis (Wegener's). Arthritis Care Res, 63: 1777–1781. doi: 10.1002/acr.20605
ClinicalTrials.gov identifier: NCT00005007.
- Issue published online: 29 NOV 2011
- Article first published online: 29 NOV 2011
- Accepted manuscript online: 30 AUG 2011 10:12AM EST
- Manuscript Accepted: 16 AUG 2011
- Manuscript Received: 20 APR 2011
- NIH National Institute of Arthritis and Musculoskeletal and Skin Diseases). Grant Number: N01-AR-9-2240
- FDA Office of Orphan Products. Grant Number: FD-R-001652-01
- General Clinical Research Center grants from the NIH National Center for Research Resources to Johns Hopkins University School of Medicine. Grant Number: M01-RR0-2719
- Boston University. Grant Number: M01-RR0-00533
- University of Michigan. Grant Number: M01-RR-0042
- Duke University. Grant Number: M01-RR-30
- Charles Hammond Research Fund of Duke University Medical Center's Department of Obstetrics and Gynecology
Standard treatment for severe granulomatosis with polyangiitis (Wegener's) (GPA) 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 ages <50 years, 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 an AMH level of <1.0 ng/ml.
Of 42 women in this analysis (mean age 35 years), 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 of 8 who received CYC during the trial developed diminished ovarian reserve, compared to 0 of 4 who did not receive CYC (P < 0.05). Changes in AMH correlated inversely with cumulative CYC dose (P < 0.01), with a 0.74 ng/ml decline in AMH level for each 10 gm 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.