Ovarian reserve diminished by oral cyclophosphamide therapy for granulomatosis with polyangiitis (Wegener's)

Megan E B Clowse, Susannah C. Copland, Tsung Cheng Hsieh, Shein Chung Chow, Gary S. Hoffman, Peter A. Merkel, Robert F. Spiera, John C. Davis, W. Joseph McCune, Steven R Ytterberg, E. William St.Clair, Nancy B. Allen, Ulrich Specks, John H. Stone

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Abstract

Objective. 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). Methods. 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-Mü llerian 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. Results. 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. Conclusion. 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.

Original languageEnglish (US)
Pages (from-to)1777-1781
Number of pages5
JournalArthritis Care and Research
Volume63
Issue number12
DOIs
StatePublished - Dec 2011

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Granulomatosis with Polyangiitis
Cyclophosphamide
Hormones
Therapeutics
Follicle Stimulating Hormone
Methotrexate
Ovarian Reserve
Menstruation
Cytotoxins
Ovum
Placebos

ASJC Scopus subject areas

  • Rheumatology
  • Medicine(all)

Cite this

Clowse, M. E. B., Copland, S. C., Hsieh, T. C., Chow, S. C., Hoffman, G. S., Merkel, P. A., ... Stone, J. H. (2011). Ovarian reserve diminished by oral cyclophosphamide therapy for granulomatosis with polyangiitis (Wegener's). Arthritis Care and Research, 63(12), 1777-1781. https://doi.org/10.1002/acr.20605

Ovarian reserve diminished by oral cyclophosphamide therapy for granulomatosis with polyangiitis (Wegener's). / Clowse, Megan E B; Copland, Susannah C.; Hsieh, Tsung Cheng; Chow, Shein Chung; Hoffman, Gary S.; Merkel, Peter A.; Spiera, Robert F.; Davis, John C.; McCune, W. Joseph; Ytterberg, Steven R; St.Clair, E. William; Allen, Nancy B.; Specks, Ulrich; Stone, John H.

In: Arthritis Care and Research, Vol. 63, No. 12, 12.2011, p. 1777-1781.

Research output: Contribution to journalArticle

Clowse, MEB, Copland, SC, Hsieh, TC, Chow, SC, Hoffman, GS, Merkel, PA, Spiera, RF, Davis, JC, McCune, WJ, Ytterberg, SR, St.Clair, EW, Allen, NB, Specks, U & Stone, JH 2011, 'Ovarian reserve diminished by oral cyclophosphamide therapy for granulomatosis with polyangiitis (Wegener's)', Arthritis Care and Research, vol. 63, no. 12, pp. 1777-1781. https://doi.org/10.1002/acr.20605
Clowse, Megan E B ; Copland, Susannah C. ; Hsieh, Tsung Cheng ; Chow, Shein Chung ; Hoffman, Gary S. ; Merkel, Peter A. ; Spiera, Robert F. ; Davis, John C. ; McCune, W. Joseph ; Ytterberg, Steven R ; St.Clair, E. William ; Allen, Nancy B. ; Specks, Ulrich ; Stone, John H. / Ovarian reserve diminished by oral cyclophosphamide therapy for granulomatosis with polyangiitis (Wegener's). In: Arthritis Care and Research. 2011 ; Vol. 63, No. 12. pp. 1777-1781.
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abstract = "Objective. 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). Methods. 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-M{\"u} llerian 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. Results. 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. Conclusion. 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.",
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AU - Clowse, Megan E B

AU - Copland, Susannah C.

AU - Hsieh, Tsung Cheng

AU - Chow, Shein Chung

AU - Hoffman, Gary S.

AU - Merkel, Peter A.

AU - Spiera, Robert F.

AU - Davis, John C.

AU - McCune, W. Joseph

AU - Ytterberg, Steven R

AU - St.Clair, E. William

AU - Allen, Nancy B.

AU - Specks, Ulrich

AU - Stone, John H.

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N2 - Objective. 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). Methods. 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-Mü llerian 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. Results. 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. Conclusion. 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.

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