ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2021
Behavioral and neurobiological effects of GnRH agonist treatment in mice-potential implications for puberty suppression in transgender individuals.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 40 citations in OpenAlex.
- Pubertal Triptorelin Exposure Alters Hypothalamic Reproductive-Metabolic Integration in a Sex-Specific Manner.Biology · 2026Article
- Characteristics of Executive Function in School-Aged Girls With Idiopathic Central Precocious Puberty.Brain and behavior · 2026Article
- History of and evidence for puberty suppression as intervention for children experiencing gender dysphoria.The Medico-legal journal · 2026Article
- The Cass Review and Gender-Related Care for Young People in Canada: A Commentary on the Canadian Paediatric Society Position Statement on Transgender and Gender-Diverse Youth.Archives of sexual behavior · 2025Article
- Sex-specific and developmental effects of early life adversity on stress reactivity are rescued by postnatal knockdown of 5-HTNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- Reproductive Health in Trans and Gender Diverse Patients: Effects of transmasculine gender-affirming hormone therapy on future reproductive capacity: clinical data, animal models, and gaps in knowledge.Reproduction (Cambridge, England) · 2024Review
- Androgen Inhibition of Reproductive Neuroendocrine Function in Females and Transgender Males.Endocrinology · 2024Review
- 5-HTBiological psychiatry · 2024Article
- The Utility of Preclinical Models in Understanding the Bone Health of Transgender Individuals Undergoing Gender-Affirming Hormone Therapy.Current osteoporosis reports · 2023Review
- Brain mitochondrial diversity and network organization predict anxiety-like behavior in male mice.Nature communications · 2023Article
- Alterations in the inferior fronto-occipital fasciculus - a specific neural correlate of gender incongruence?Psychological medicine · 2023Article
- Chronic periadolescent leuprolide exposure affects the development of reproductive physiology and behavior of female and male rats differently, but both mature after treatment termination.Biology of sex differences · 2023Article
- Association between pre-treatment IQ and educational achievement after gender-affirming treatment including puberty suppression in transgender adolescents.Clinical child psychology and psychiatry · 2022Article
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 1 country.
Funding
Abstract
In the United States, ~1.4 million individuals identify as transgender. Many transgender adolescents experience gender dysphoria related to incongruence between their gender identity and sex assigned at birth. This dysphoria may worsen as puberty progresses. Puberty suppression by gonadotropin-releasing hormone agonists (GnRHa), such as leuprolide, can help alleviate gender dysphoria and provide additional time before irreversible changes in secondary sex characteristics may be initiated through feminizing or masculinizing hormone therapy congruent with the adolescent's gender experience. However, the effects of GnRH agonists on brain function and mental health are not well understood. Here, we investigated the effects of leuprolide on reproductive function, social and affective behavior, cognition, and brain activity in a rodent model. Six-week-old male and female C57BL/6J mice were injected daily with saline or leuprolide (20 μg) for 6 weeks and tested in several behavioral assays. We found that leuprolide increases hyperlocomotion, changes social preference, and increases neuroendocrine stress responses in male mice, while the same treatment increases hyponeophagia and despair-like behavior in females. Neuronal hyperactivity was found in the dentate gyrus (DG) of leuprolide-treated females, but not males, consistent with the elevation in hyponeophagia and despair-like behavior in females. These data show for the first time that GnRH agonist treatment after puberty onset exerts sex-specific effects on social- and affective behavior, stress regulation, and neural activity. Investigating the behavioral and neurobiological effects of GnRH agonists in mice will be important to better guide the investigation of potential consequences of this treatment for youth experiencing gender dysphoria.
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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.