GnRH antagonist-induced ovarian suppression does not protect the ovarian reserve from cyclophosphamide chemotherapy in tumour-bearing mice
- 1Development and Stem Cell Program, Department of Anatomy and Developmental Biology, Biomedicine Discovery Institute, Monash University
- 2Division of Research, Peter MacCallum Cancer Centre, University of Melbourne
- 3Sir Peter MacCallum Department of Oncology, University of Melbourne
Abstract
Background: Gonadotropin-releasing hormone (GnRH) analogues are used clinically to induce ovarian suppression during chemotherapy treatment and are proposed to protect the ovaries from chemotherapy-induced damage, yet their efficacy and underlying mechanisms remain uncertain. While most preclinical and clinical studies have focused on GnRH agonists, far less is known about the effects of GnRH antagonists in this context, despite their more rapid and direct suppression of gonadotrophin signaling.
Materials and methods: We used the GnRH antagonist degarelix to induce ovarian suppression in an orthotopic tumour-bearing mouse model. We then evaluated whether degarelix protected against cyclophosphamide-induced ovarian damage in reproductively young and aged mice receiving one or two chemotherapy doses. Ovarian function was assessed by quantifying ovarian volume, corpora lutea number (a marker of ovulation), and serum anti-Müllerian hormone (AMH) levels, as well as follicle enumeration and histological assessment of ovarian fibrosis.
Results: Degarelix suppressed ovulatory activity, as indicated by reduced corpora lutea number and ovarian volume. However, degarelix was associated with increased ovarian fibrosis in young mice treated with single-dose cyclophosphamide and failed to protect the ovarian reserve following either single or two doses of cyclophosphamide in both age groups. Moreover, degarelix did not prevent reductions in circulating AMH, with all treatment groups displaying reduced AMH levels compared with controls in young mice.
Conclusions: Together, our findings do not support a protective effect of GnRH antagonist treatment against cyclophosphamide-induced ovarian damage.
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BibTeX
@article{lewis2026gnrh,
title = {{GnRH antagonist-induced ovarian suppression does not protect the ovarian reserve from cyclophosphamide chemotherapy in tumour-bearing mice}},
author = {Yasmin M Lewis and Daniella Herszberg and Kate Fowler and Michael Hun and Emmaline Brown and Sherene Loi and Amy L Winship and Karla J Hutt},
journal = {Frontiers in Endocrinology},
year = {2026},
month = oct,
doi = {10.3389/fendo.2026.1959150},
url = {https://www.frontiersin.org/articles/10.3389/fendo.2026.1959150/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - GnRH antagonist-induced ovarian suppression does not protect the ovarian reserve from cyclophosphamide chemotherapy in tumour-bearing mice
AU - Yasmin M Lewis
AU - Daniella Herszberg
AU - Kate Fowler
AU - Michael Hun
AU - Emmaline Brown
AU - Sherene Loi
AU - Amy L Winship
AU - Karla J Hutt
PY - 2026
DA - 2026/10/27
JO - Frontiers in Endocrinology
DO - 10.3389/fendo.2026.1959150
UR - https://www.frontiersin.org/articles/10.3389/fendo.2026.1959150/full
AB - Background: Gonadotropin-releasing hormone (GnRH) analogues are used clinically to induce ovarian suppression during chemotherapy treatment and are proposed to protect the ovaries from chemotherapy-induced damage, yet their efficacy and underlying mechanisms remain uncertain. While most preclinical and clinical studies have focused on GnRH agonists, far less is known about the effects of GnRH antagonists in this context, despite their more rapid and direct suppression of gonadotrophin signaling. Materials and methods: We used the GnRH antagonist degarelix to induce ovarian suppression in an orthotopic tumour-bearing mouse model. We then evaluated whether degarelix protected against cyclophosphamide-induced ovarian damage in reproductively young and aged mice receiving one or two chemotherapy doses. Ovarian function was assessed by quantifying ovarian volume, corpora lutea number (a marker of ovulation), and serum anti-Müllerian hormone (AMH) levels, as well as follicle enumeration and histological assessment of ovarian fibrosis. Results: Degarelix suppressed ovulatory activity, as indicated by reduced corpora lutea number and ovarian volume. However, degarelix was associated with increased ovarian fibrosis in young mice treated with single-dose cyclophosphamide and failed to protect the ovarian reserve following either single or two doses of cyclophosphamide in both age groups. Moreover, degarelix did not prevent reductions in circulating AMH, with all treatment groups displaying reduced AMH levels compared with controls in young mice. Conclusions: Together, our findings do not support a protective effect of GnRH antagonist treatment against cyclophosphamide-induced ovarian damage.
SN - 1664-2392
ER -