The GnRH Agonist Triptorelin Causes Reversible, Focal, and Partial Testicular Atrophy in Rats, Maintaining Sperm Production

TL;DR

Triptorelin, a hormone treatment, causes temporary testicular shrinkage in rats but does not fully stop sperm production, suggesting it could be safe for transgender girls undergoing gender transition.

Contribution

The study introduces a rat model to evaluate the effects of triptorelin on testicular maturation and fertility during pubertal delay.

Findings

Triptorelin treatment reduced testosterone levels in rats, indicating delayed puberty.

Testicular atrophy was focal and partial, with most seminiferous tubules maintaining spermatogenesis.

Sperm production was preserved in all treated rats, ensuring fertility.

Abstract

We aim to provide a translational model to investigate the reproductive consequences of pubertal delay using the GnRH agonist triptorelin in transgender girls, tested in particular on testicular maturation in peripubertal rats. A total of 30 Sprague Dawley rats were utilized, with 10 subjects assigned to each of three groups from day P30 postpartum (prepubertal) until day P95 (postpubertal), mimicking treatment timing in patients. Rats received triptorelin at three time points (P30, P50, and P71), or only at P30 and P50. Control rats were injected with vehicle. Plasma testosterone levels were determined using MRM analysis. Testes and epididymides were examined histologically. There were significantly lower testosterone levels at postnatal day 48 in treated rats, indicating delayed puberty, with further reductions by day 69. By day 93, testosterone levels had recovered in rats given vehicle at P71 but remained low in the triptorelin-continuous group, suggesting the reversibility of the treatment. Treated rats had smaller testes; however, the majority of the testicular parenchyma was unaffected, with most seminiferous tubules displaying complete spermatogenesis. However, focal atrophic changes were observed in 1–30% of the parenchyma. One-third of the short-term group and half of the long-term group were classified as atrophic. Despite these changes, all treated rats had mature sperm in the epididymis, ensuring their fertility. In conclusion, triptorelin treatment promotes a decline in testosterone levels accompanied by discrete atrophy of the seminiferous tubules, which is partially reversible and compatible with sperm production and fertility preservation. Triptorelin could be an appropriate treatment prior to estrogen therapy for patients seeking gender transition.

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