Evidence map›Paper›PMID 40438403›Full record

SynthesisFrontiers in endocrinology2025

Use of gonadotropin-releasing hormone agonists in transgender and gender diverse youth: a systematic review.

Gianluca Tornese, Raffaella Di Mase, Jessica Munarin, Silvia Ciancia, Fabiana Santamaria, Daniela Fava, Egidio Candela, Donatella Capalbo, Carla Ungaro, Nicola Improda and 17 more

Registry-linked trialAbstract readSystematic Review
In one paragraph

Synthesis in Frontiers in endocrinology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07481942 (Body Composition Adaptations Following Initiation of Gender-Affirming Hormone Therapy in Transgender Populations.), which is not on this map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT07481942 completednot on this map

Body Composition Adaptations Following Initiation of Gender-Affirming Hormone Therapy in Transgender Populations.

TypeobservationalSponsorCelia BañulsRan2017 to 2025Enrolled70ConditionsTransgenderArmsgender affirming hormone therapy
3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

27 authors.

Gianluca TorneseInstitute for Maternal and Child Health IRCCS "Burlo Garofolo", Trieste, Italy.
Raffaella Di MasePediatric Endocrinology Unit, Department of Mother and Child, University Hospital Federico II, Naples, Italy.
Jessica MunarinRegina Margherita Children's Hospital, Pediatric Endocrinology, Department of Public Health and Pediatric Sciences, University of Turin, Turin, Italy.
Silvia CianciaDepartment of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium.
Fabiana SantamariaPediatric Endocrinology Unit, Department of Mother and Child, University Hospital Federico II, Naples, Italy.
Daniela FavaDepartment of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genoa, Italy.
Egidio CandelaPediatric Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
Donatella CapalboPediatric Endocrinology Unit, Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy.
Carla UngaroMaternal and Child Unit, Local Health Unit, ASL Napoli 1 Centro, Naples, Italy.
Nicola ImprodaNeuro-Endocrine Diseases and Obesity Unit, Department of Neurosciences, Santobono-Pausilipon Children's Hospital, Naples, Italy.
Pierluigi DianaDepartment of Medicine and Surgery, University of Parma, Parma, Italy.
Patrizia MatarazzoRegina Margherita Children's Hospital, Pediatric Endocrinology, Department of Public Health and Pediatric Sciences, University of Turin, Turin, Italy.
Laura GuazzarottiEndocrinology Unit, Pediatric Department, University of Padua, Padua, Italy.
Tommaso ToschettiDepartment of Medicine and Surgery, University of Parma, Parma, Italy.
Vanessa SambatiDepartment of Medicine and Surgery, University of Parma, Parma, Italy.
Gianluca TamaroInstitute for Maternal and Child Health IRCCS "Burlo Garofolo", Trieste, Italy.
Giulia BrescianiInstitute for Maternal and Child Health IRCCS "Burlo Garofolo", Trieste, Italy.
Maria Rosaria LicenziatiNeuro-Endocrine Diseases and Obesity Unit, Department of Neurosciences, Santobono-Pausilipon Children's Hospital, Naples, Italy.
Maria Elisabeth StreetDepartment of Medicine and Surgery, University of Parma, Parma, Italy.
Tommaso AversaDepartment of Human Pathology of Adulthood and Childhood, University of Messina, Messina, Italy.
Maurizio DelvecchioDepartment of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.
Maria Felicia FaienzaPediatric Unit, Department of Precision and Regenerative Medicine and Ionian Area, University of Bari "A. Moro", Bari, Italy.
Lorenzo IughettiUniversity of Modena and Reggio Emilia, Modena, Italy.
Valeria CalcaterraPediatric and Adolescent Unit, Department of Internal Medicine, University of Pavia, Pavia, Italy.
Luisa de SanctisRegina Margherita Children's Hospital, Pediatric Endocrinology, Department of Public Health and Pediatric Sciences, University of Turin, Turin, Italy.
Mariacarolina SalernoPediatric Endocrinology Unit, Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy.
Roberto FranceschiDepartment of Pediatrics, Santa Chiara Hospital of Trento, Azienda Provinciale per i Servizi Sanitari della Provincia Autonoma di Trento, Trento, Italy.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Introduction: Puberty suppression using gonadotropin-releasing hormone agonists (GnRHa) is a reversible medical intervention that halts endogenous puberty, allowing transgender and gender-diverse (TGD) adolescents to avoid the development of secondary sexual characteristics that may cause psychological distress. This pause in pubertal progression provides time to explore gender identity or facilitates alignment with affirmed gender in those with an established identity. While widely used, long-term evidence on the efficacy and safety of GnRHa in this population remains limited. This systematic review aims to synthesize current data on the benefits and potential risks of GnRHa in TGD adolescents. Methods: We conducted a comprehensive literature search across PubMed, EMBASE, Cochrane Library, and other databases, covering studies published from February 2011 to February 2024. Eligible studies included adolescents under 18 with gender dysphoria or incongruence treated with GnRHa, reporting outcomes related to efficacy or side effects. Fifty-one studies met inclusion criteria, and data on physical health, mental health, bone density, fertility, and adverse events were extracted and assessed using the GRADE approach. Results: Of the 51 studies, 22 were rated as moderate to high-quality evidence. GnRHa effectively suppressed puberty and secondary sex characteristics. Effects on growth and body composition varied; bone mineral density declined during treatment, particularly in AMAB individuals. Mental health improved significantly, including reduced depression, anxiety, and suicidality-especially when GnRHa was followed by gender-affirming hormone therapy (GAHT). Quality of life improved over time, while body dissatisfaction often persisted during suppression and improved after GAHT or surgery. No moderate- or high-quality evidence was found on fertility, sexual function, or cancer risk. Conclusion: GnRHa is effective in halting puberty and improving mental health in TGD adolescents. However, key clinical and ethical considerations-such as bone health monitoring, fertility counseling, psychological support, and informed decision-making-must guide treatment. Long-term safety remains uncertain, particularly regarding skeletal health, reproductive outcomes and cancer risk. A precision medicine approach and co-produced longitudinal studies are essential to support safe, individualized care. Systematic review registration: https://www.crd.york.ac.uk, identifier CRD42024528334.

Indexed as

Gender DysphoriaGonadotropin-Releasing HormonePubertyTransgender PersonsAdolescentFemaleHumansMaleGonadotropin-Releasing Hormoneadolescencegender dysphoria (GD)gender incongruenceGnRH analog (GnRHa)LHRH analogtransgender and gender diverse (TGD)transgender and gender diverse youth

Identifiers

PMID40438403
PMCPMC12116301

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.