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Establishment of Rat Models Mimicking Gender-affirming Hormone Therapies
Published on: January 10, 2025
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The GnRH Agonist Triptorelin Causes Reversible, Focal, and Partial Testicular Atrophy in Rats, Maintaining Sperm
Alberto Marcos1, Maria Cruz Rodríguez Del Cerro1, Rosa María Fernández2,3
1Department of Psychobiology, Universidad Nacional de Educación a Distancia, 28040 Madrid, Spain.
International Journal of Molecular Sciences
|July 29, 2025
Summary
Gonadotropin-releasing hormone (GnRH) agonist triptorelin delayed puberty in rats, causing reversible testicular changes but preserving fertility. This suggests triptorelin may be suitable before estrogen therapy for transgender girls.
Area of Science:
- Reproductive endocrinology
- Translational research
- Pediatric endocrinology
Background:
- Pubertal delay is a clinical concern in transgender youth.
- GnRH agonists are used to suppress puberty.
- Understanding reproductive effects is crucial for patient care.
Purpose of the Study:
- To establish a rat model for studying the reproductive effects of GnRH agonist triptorelin in peripubertal transgender girls.
- To assess testicular maturation and fertility in rats treated with triptorelin during key pubertal stages.
Main Methods:
- 30 Sprague Dawley rats were divided into three groups (control, short-term triptorelin, long-term triptorelin) from P30 to P95.
- Triptorelin or vehicle was administered at specific time points (P30, P50, P71).
- Plasma testosterone, testicular histology, and epididymal sperm were analyzed.
Main Results:
- Triptorelin treatment significantly reduced testosterone levels, indicating delayed puberty.
- Testes were smaller in treated rats, with focal atrophy in seminiferous tubules (1-30% parenchyma).
- Despite atrophy, all treated rats maintained mature sperm in the epididymis, preserving fertility.
Conclusions:
- Triptorelin-induced pubertal delay is partially reversible and compatible with spermatogenesis and fertility.
- The GnRH agonist triptorelin may be a viable option before estrogen therapy for transgender girls.
- This rat model provides insights into the reproductive consequences of GnRH agonist use in this population.
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