Testosterone replacement therapy and spermatogenesis in reproductive age men.
Level 5 - mechanism / opinion, no new human data
Narrative review synthesizing mechanisms and clinical management without systematic methodology or primary human data.
PubMed 40346275 · doi:10.1038/s41585-025-01032-8
What was done
This narrative review examined the mechanistic and clinical effects of testosterone replacement therapy (TRT) on the hypothalamic-pituitary-gonadal axis, its suppression of spermatogenesis in reproductive-age men, post-cessation recovery kinetics, adjunctive medical therapies for fertility preservation, and the potential role of newer short-acting formulations.
What was found
The abstract provides a qualitative overview and reports no numerical data. Exogenous androgens suppress gonadotropin secretion, reduce intratesticular testosterone, and impair spermatogenesis. While sperm production often resumes after TRT cessation, recovery kinetics are highly variable. Therapies such as aromatase inhibitors, selective estrogen receptor modulators, and exogenous gonadotropins (hCG, FSH) can preserve or restore spermatogenesis in select men. Newer short-acting formulations (such as oral testosterone undecanoate and nasal gel) may result in incomplete axis suppression and partially spare spermatogenesis.
Why it matters
It clarifies the mechanisms of TRT-induced infertility and highlights clinical management options—including alternative medications and short-acting androgen delivery systems—for hypogonadal men who wish to maintain fertility.
Limits
As a narrative review, the abstract provides no primary data, systematic search protocol, sample sizes, or quantitative effect estimates. Long-term fertility outcomes, comparative efficacy of preservation protocols, and the clinical fertility rates associated with newer short-acting formulations are not quantitatively detailed.