Impact of gender-affirming treatment on bone health in transgender and gender diverse youth

Ciancia, Silvia; Dubois, Vanessa; Cools, Martine

doi:10.1530/ec-22-0280

Cited by 13 publications

(7 citation statements)

References 68 publications

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“…Puberty blockers have previously been considered a fully reversible treatment. Over the last decade, however, reports about adverse effects on bone density-leading in adult-hood to increased risk of fracture and kyphosis-have caused some practitioners to reconsider this view [18,19]. In the current study adverse effects on bone health (7/49; 14.3%) and on cardiovascular health (via weight gain, 5/49; 10.2%) have emerged as two key areas of concern.…”

Section: Discussionmentioning

confidence: 85%

“…The physical effects of GnRH agonists have long been thought to be fully reversible: when ceased, puberty recommences. Recent data suggest a negative impact of long-term puberty suppression on bone mineral density (p. 1) [18,19]. Far less is known, however, about the effects of puberty suppression on cognitive, psychosocial and psychosexual development and mental health functioning [19][20][21].…”

mentioning

confidence: 99%

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Developmental Pathway Choices of Young People Presenting to a Gender Service with Gender Distress: A Prospective Follow-Up Study

et al. 2023

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This prospective case-cohort study examines the developmental pathway choices of 79 young people (13.25–23.75 years old; 33 biological males and 46 biological females) referred to a tertiary care hospital’s Department of Psychological Medicine (December 2013–November 2018, at ages 8.42–15.92 years) for diagnostic assessment for gender dysphoria (GD) and for potential gender-affirming medical interventions. All of the young people had attended a screening medical assessment (including puberty staging) by paediatricians. The Psychological Medicine assessment (individual and family) yielded a formal DSM-5 diagnosis of GD in 66 of the young people. Of the 13 not meeting DSM-5 criteria, two obtained a GD diagnosis at a later time. This yielded 68 young people (68/79; 86.1%) with formal diagnoses of GD who were potentially eligible for gender-affirming medical interventions and 11 young people (11/79; 13.9%) who were not. Follow-up took place between November 2022 and January 2023. Within the GD subgroup (n = 68) (with two lost to follow-up), six had desisted (desistance rate of 9.1%; 6/66), and 60 had persisted on a GD (transgender) pathway (persistence rate of 90.9%; 60/66). Within the cohort as a whole (with two lost to follow-up), the overall persistence rate was 77.9% (60/77), and overall desistance rate for gender-related distress was 22.1% (17/77). Ongoing mental health concerns were reported by 44/50 (88.0%), and educational/occupational outcomes varied widely. The study highlights the importance of careful screening, comprehensive biopsychosocial (including family) assessment, and holistic therapeutic support. Even in highly screened samples of children and adolescents seeking a GD diagnosis and gender-affirming medical care, outcome pathways follow a diverse range of possibilities.

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Section: Discussionmentioning

confidence: 85%

mentioning

confidence: 99%

Developmental Pathway Choices of Young People Presenting to a Gender Service with Gender Distress: A Prospective Follow-Up Study

et al. 2023

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“…(10) Previous work showed that puberty suppression in transgender adolescents increased fat mass and decreased lean mass and that subsequent GAH shaped body composition toward the experienced gender. (11) With regard to bone, several studies recently reviewed in Ciancia and colleagues (12) reported a decrease in areal bone mineral density (aBMD) Z-scores after GnRHa administration, which was only partially restored after GAH administration. However, long-term outcome data in transgender individuals who started medical transition from the earliest stages of puberty onward are lacking.…”

Section: Introductionmentioning

confidence: 99%

Testosterone Restores Body Composition, Bone Mass, and Bone Strength Following Early Puberty Suppression in a Mouse Model Mimicking the Clinical Strategy in Trans Boys

Dubois,

Ciancia,

Doms

et al. 2023

Journal of Bone and Mineral Research

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Transgender youth increasingly present at pediatric gender services. Some of them receive long‐term puberty suppression with gonadotropin‐releasing hormone analogues (GnRHa) before starting gender‐affirming hormones (GAH). The impact of GnRHa use started in early puberty on bone composition and bone mass accrual is unexplored. It is furthermore unclear whether subsequent GAH fully restore GnRHa effects and whether the timing of GAH introduction matters. To answer these questions, we developed a mouse model mimicking the clinical strategy applied in trans boys. Prepubertal 4‐week‐old female mice were treated with GnRHa alone or with GnRHa supplemented with testosterone (T) from 6 weeks (early puberty) or 8 weeks (late puberty) onward. Outcomes were analyzed at 16 weeks and compared with untreated mice of both sexes. GnRHa markedly increased total body fat mass, decreased lean body mass, and had a modest negative impact on grip strength. Both early and late T administration shaped body composition to adult male levels, whereas grip strength was restored to female values. GnRHa‐treated animals showed lower trabecular bone volume and reduced cortical bone mass and strength. These changes were reversed by T to female levels (cortical bone mass and strength) irrespective of the time of administration or even fully up to adult male control values (trabecular parameters) in case of earlier T start. The lower bone mass in GnRHa‐treated mice was associated with increased bone marrow adiposity, also reversed by T. In conclusion, prolonged GnRHa use started in prepubertal female mice modifies body composition toward more fat and less lean mass and impairs bone mass acquisition and strength. Subsequent T administration counteracts GnRHa impact on these parameters, shaping body composition and trabecular parameters to male values while restoring cortical bone architecture and strength up to female but not male control levels. These findings could help guide clinical strategies in transgender care. © 2023 American Society for Bone and Mineral Research (ASBMR).

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“…Previously, a decrease in areal bone mineral density (aBMD) Z-scores were reported after GnRHa administration, which were partially restored after GAHT (13).…”

Section: Introductionmentioning

confidence: 99%

“…While much of what we know about GAHT in humans has focused on cardiovascular health and metabolic risk (13), the effect of delayed or prolonged pubertal suppression transitioned into GAHT on bone health is underappreciated. Previously, a decrease in areal bone mineral density (aBMD) Z-scores were reported after GnRHa administration, which were partially restored after GAHT (14).…”

Section: Introductionmentioning

confidence: 99%

Bone quality following peripubertal growth in a mouse model of transmasculine gender-affirming hormone therapy

Henry,

Cruz,

Goulet

et al. 2023

Preprint

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During peri-puberty, bone growth and the attainment peak bone mass is driven predominantly by sex steroids. This is important when treating transgender youth, who have become increasingly present at pediatric clinics. Analogues of gonadotropin-releasing hormone (GnRH) are commonly prescribed to transgender youth prior to starting gender-affirming hormone therapy (GAHT). However, the impact of GnRH agonists on long bones with the addition of GAHT is relatively unknown. To explore this, we developed a trans-masculine model by introducing either GnRHa or vehicle treatment to female-born mice at a pre-pubertal age. This treatment was followed by male GAHT (testosterone, T) or control treatment three weeks later. Six weeks after T therapy, bone quality was compared between four treatment groups: Control (vehicle only), GnRHa-only, GnRHa + T, and T-only. Bone length/size, bone shape, mechanical properties, and trabecular morphology were modulated by GAHT. Independent of GnRHa administration, mice treated with T had shorter femurs, larger trabecular volume and increased trabecular number, higher trabecular bone mineral density, and wider superstructures on the surface of bone (e.g., third trochanters) when compared to control or GnRHa-only mice. In conclusion, prolonged treatment of GnRHa with subsequent GAHT treatment directly affect the composition, parameters, and morphology of the developing long bone. These findings provide insight to help guide clinical approaches to care for transgender youth.

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Impact of gender-affirming treatment on bone health in transgender and gender diverse youth

Cited by 13 publications

References 68 publications

Developmental Pathway Choices of Young People Presenting to a Gender Service with Gender Distress: A Prospective Follow-Up Study

Developmental Pathway Choices of Young People Presenting to a Gender Service with Gender Distress: A Prospective Follow-Up Study

Testosterone Restores Body Composition, Bone Mass, and Bone Strength Following Early Puberty Suppression in a Mouse Model Mimicking the Clinical Strategy in Trans Boys

Bone quality following peripubertal growth in a mouse model of transmasculine gender-affirming hormone therapy

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