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A novel model to study the impact of gender-affirming therapy on bone in young male mice

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Title: A novel model to study the impact of gender-affirming therapy on bone in young male mice
Authors: Verlinden, Lieve, Calvo Blanco, Sandra, Liekens, Toke, Stockmans, Ingrid, Moermans, Karen, Schollaert, Dieter, Vercruysse, Chris, Fiers, Tom, Reyns, Tim, Narinx, Nick, De Waal, Tom, Antonio, Leen, Dmitriev, Ruslan, Claessens, Frank, Vanderschueren, Dirk, Carmeliet, Geert, Dubois, Vanessa, Stegen, Steve
Source: JOURNAL OF BONE AND MINERAL RESEARCH ; ISSN: 0884-0431 ; ISSN: 1523-4681
Publication Year: 2026
Collection: Ghent University Academic Bibliography
Subject Terms: Medicine and Health Sciences, Biology and Life Sciences, gender-affirming therapy, estrogen, bone, puberty suppression, transgender, ANDROGEN DEPRIVATION, RAT MODEL, ESTRADIOL, MASS, RECEPTOR, HORMONE, SERUM, MEN
Description: Transgender individuals are increasingly seeking gender-affirming therapy. For children and adolescents, this typically involves puberty suppression followed by hormone treatment. However, potential long-term adverse effects on the growing skeleton remain poorly characterized, largely due to the lack of appropriate preclinical animal models. Existing models often rely on surgical puberty suppression and, in the case of estradiol (E2) administration, cause a high bone mass-phenotype that is not observed in the clinical setting. To address this, we developed a novel preclinical mouse model that mimics the medical approach used in transgirls and analyzed the effects of gender-affirming therapy on bone. Four-week-old male mice were treated with the gonadotropin-releasing hormone analogue degarelix (DGX) for pharmacological puberty suppression. After 4 weeks, E2 was administered at different doses, and bone properties were analyzed after an additional 8 weeks. DGX treatment effectively suppressed sex steroid signaling, leading to reduced bone mass and strength, which were dose-dependently restored by E2. While high E2 doses resulted in an excessive increase in bone mass, thereby precluding further mechanistic study, lower doses resulted in a bone phenotype resembling that of native females. At the cellular level, DGX-mediated puberty suppression resulted in increased bone resorption that exceeded bone formation, and also caused an accumulation of marrow adipocytes. Subsequent low-dose E2 administration reduced bone resorption, stimulated bone formation, and prevented the increase in bone marrow adiposity. In summary, we established and validated a mouse model that accurately mimics gender-affirming therapy initiated during early puberty and enables the study of its effects on bone.
Document Type: article in journal/newspaper
File Description: application/pdf
Language: English
Relation: https://biblio.ugent.be/publication/01KFDC01XR225VQKJR1YY2FHJ8; https://doi.org/10.1093/jbmr/zjag009; https://biblio.ugent.be/publication/01KFDC01XR225VQKJR1YY2FHJ8/file/01M1H21GT24WEZN5G8DRKC5V5A
DOI: 10.1093/jbmr/zjag009
Availability: https://biblio.ugent.be/publication/01KFDC01XR225VQKJR1YY2FHJ8
https://hdl.handle.net/1854/LU-01KFDC01XR225VQKJR1YY2FHJ8
https://doi.org/10.1093/jbmr/zjag009
https://biblio.ugent.be/publication/01KFDC01XR225VQKJR1YY2FHJ8/file/01M1H21GT24WEZN5G8DRKC5V5A
Rights: info:eu-repo/semantics/openAccess
Accession Number: edsbas.F240DAB8
Database: BASE
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  – Url: https://biblio.ugent.be/publication/01KFDC01XR225VQKJR1YY2FHJ8#
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  Label: Title
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  Data: A novel model to study the impact of gender-affirming therapy on bone in young male mice
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  Data: <searchLink fieldCode="AR" term="%22Verlinden%2C+Lieve%22">Verlinden, Lieve</searchLink><br /><searchLink fieldCode="AR" term="%22Calvo+Blanco%2C+Sandra%22">Calvo Blanco, Sandra</searchLink><br /><searchLink fieldCode="AR" term="%22Liekens%2C+Toke%22">Liekens, Toke</searchLink><br /><searchLink fieldCode="AR" term="%22Stockmans%2C+Ingrid%22">Stockmans, Ingrid</searchLink><br /><searchLink fieldCode="AR" term="%22Moermans%2C+Karen%22">Moermans, Karen</searchLink><br /><searchLink fieldCode="AR" term="%22Schollaert%2C+Dieter%22">Schollaert, Dieter</searchLink><br /><searchLink fieldCode="AR" term="%22Vercruysse%2C+Chris%22">Vercruysse, Chris</searchLink><br /><searchLink fieldCode="AR" term="%22Fiers%2C+Tom%22">Fiers, Tom</searchLink><br /><searchLink fieldCode="AR" term="%22Reyns%2C+Tim%22">Reyns, Tim</searchLink><br /><searchLink fieldCode="AR" term="%22Narinx%2C+Nick%22">Narinx, Nick</searchLink><br /><searchLink fieldCode="AR" term="%22De+Waal%2C+Tom%22">De Waal, Tom</searchLink><br /><searchLink fieldCode="AR" term="%22Antonio%2C+Leen%22">Antonio, Leen</searchLink><br /><searchLink fieldCode="AR" term="%22Dmitriev%2C+Ruslan%22">Dmitriev, Ruslan</searchLink><br /><searchLink fieldCode="AR" term="%22Claessens%2C+Frank%22">Claessens, Frank</searchLink><br /><searchLink fieldCode="AR" term="%22Vanderschueren%2C+Dirk%22">Vanderschueren, Dirk</searchLink><br /><searchLink fieldCode="AR" term="%22Carmeliet%2C+Geert%22">Carmeliet, Geert</searchLink><br /><searchLink fieldCode="AR" term="%22Dubois%2C+Vanessa%22">Dubois, Vanessa</searchLink><br /><searchLink fieldCode="AR" term="%22Stegen%2C+Steve%22">Stegen, Steve</searchLink>
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  Data: JOURNAL OF BONE AND MINERAL RESEARCH ; ISSN: 0884-0431 ; ISSN: 1523-4681
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  Data: 2026
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  Data: Ghent University Academic Bibliography
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  Data: <searchLink fieldCode="DE" term="%22Medicine+and+Health+Sciences%22">Medicine and Health Sciences</searchLink><br /><searchLink fieldCode="DE" term="%22Biology+and+Life+Sciences%22">Biology and Life Sciences</searchLink><br /><searchLink fieldCode="DE" term="%22gender-affirming+therapy%22">gender-affirming therapy</searchLink><br /><searchLink fieldCode="DE" term="%22estrogen%22">estrogen</searchLink><br /><searchLink fieldCode="DE" term="%22bone%22">bone</searchLink><br /><searchLink fieldCode="DE" term="%22puberty+suppression%22">puberty suppression</searchLink><br /><searchLink fieldCode="DE" term="%22transgender%22">transgender</searchLink><br /><searchLink fieldCode="DE" term="%22ANDROGEN+DEPRIVATION%22">ANDROGEN DEPRIVATION</searchLink><br /><searchLink fieldCode="DE" term="%22RAT+MODEL%22">RAT MODEL</searchLink><br /><searchLink fieldCode="DE" term="%22ESTRADIOL%22">ESTRADIOL</searchLink><br /><searchLink fieldCode="DE" term="%22MASS%22">MASS</searchLink><br /><searchLink fieldCode="DE" term="%22RECEPTOR%22">RECEPTOR</searchLink><br /><searchLink fieldCode="DE" term="%22HORMONE%22">HORMONE</searchLink><br /><searchLink fieldCode="DE" term="%22SERUM%22">SERUM</searchLink><br /><searchLink fieldCode="DE" term="%22MEN%22">MEN</searchLink>
– Name: Abstract
  Label: Description
  Group: Ab
  Data: Transgender individuals are increasingly seeking gender-affirming therapy. For children and adolescents, this typically involves puberty suppression followed by hormone treatment. However, potential long-term adverse effects on the growing skeleton remain poorly characterized, largely due to the lack of appropriate preclinical animal models. Existing models often rely on surgical puberty suppression and, in the case of estradiol (E2) administration, cause a high bone mass-phenotype that is not observed in the clinical setting. To address this, we developed a novel preclinical mouse model that mimics the medical approach used in transgirls and analyzed the effects of gender-affirming therapy on bone. Four-week-old male mice were treated with the gonadotropin-releasing hormone analogue degarelix (DGX) for pharmacological puberty suppression. After 4 weeks, E2 was administered at different doses, and bone properties were analyzed after an additional 8 weeks. DGX treatment effectively suppressed sex steroid signaling, leading to reduced bone mass and strength, which were dose-dependently restored by E2. While high E2 doses resulted in an excessive increase in bone mass, thereby precluding further mechanistic study, lower doses resulted in a bone phenotype resembling that of native females. At the cellular level, DGX-mediated puberty suppression resulted in increased bone resorption that exceeded bone formation, and also caused an accumulation of marrow adipocytes. Subsequent low-dose E2 administration reduced bone resorption, stimulated bone formation, and prevented the increase in bone marrow adiposity. In summary, we established and validated a mouse model that accurately mimics gender-affirming therapy initiated during early puberty and enables the study of its effects on bone.
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  Data: https://biblio.ugent.be/publication/01KFDC01XR225VQKJR1YY2FHJ8; https://doi.org/10.1093/jbmr/zjag009; https://biblio.ugent.be/publication/01KFDC01XR225VQKJR1YY2FHJ8/file/01M1H21GT24WEZN5G8DRKC5V5A
– Name: DOI
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  Data: 10.1093/jbmr/zjag009
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  Data: https://biblio.ugent.be/publication/01KFDC01XR225VQKJR1YY2FHJ8<br />https://hdl.handle.net/1854/LU-01KFDC01XR225VQKJR1YY2FHJ8<br />https://doi.org/10.1093/jbmr/zjag009<br />https://biblio.ugent.be/publication/01KFDC01XR225VQKJR1YY2FHJ8/file/01M1H21GT24WEZN5G8DRKC5V5A
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  Data: info:eu-repo/semantics/openAccess
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  Data: edsbas.F240DAB8
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        Value: 10.1093/jbmr/zjag009
    Languages:
      – Text: English
    Subjects:
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        Type: general
      – SubjectFull: Biology and Life Sciences
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      – SubjectFull: gender-affirming therapy
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