Preserving spermatogenesis in testosterone deficiency: innovations in replacement and stimulatory therapies.
Level 5 - mechanism / opinion, no new human data
Narrative review summarizing clinical literature without systematic review methodology.
PubMed 41522318 · doi:10.21037/tau-2025-480
What was done
This narrative review summarizes clinical advances and therapeutic modalities since 2013 aimed at treating testosterone deficiency while preserving fertility. The review evaluates short-acting testosterone therapies (intranasal testosterone and oral testosterone undecanoate), concomitant administration of low-dose human chorionic gonadotropin (hCG) alongside testosterone replacement, and selective estrogen receptor modulators (enclomiphene citrate).
What was found
The abstract provides qualitative observations without quantitative metrics or effect sizes: - Intranasal testosterone normalizes serum testosterone while maintaining follicle-stimulating hormone (FSH) and luteinizing hormone (LH) within reference ranges. - Oral testosterone undecanoate maintains FSH and LH within normal limits (reduced relative to baseline), though semen parameter data remain limited. - Concomitant low-dose hCG preserves intratesticular testosterone and sustains sperm production during exogenous testosterone administration. - Enclomiphene citrate stimulates endogenous testosterone production via the hypothalamic-pituitary-gonadal axis while preserving spermatogenesis.
Why it matters
Standard exogenous testosterone replacement typically suppresses gonadotropins and induces oligospermia or azoospermia. Outlining alternative modalities and combination regimens provides clinical pathways to manage hypogonadal symptoms in men who desire current or future fertility.
Limits
This is a narrative overview rather than a systematic review or meta-analysis, introducing potential selection bias. The abstract reports no numerical values, confidence intervals, or sample sizes. Semen parameter evidence for oral formulations remains sparse, and long-term fertility and safety endpoints across these strategies require further validation in larger clinical trials.
Cited by
- supports Intratesticular testosterone is the primary mediator of spermatogenesis in the testes.
- supports Co-administration of hCG and recombinant FSH during testosterone therapy maintains testicular size, function, and spermatogenesis.