Diagnosis and treatment of hypogonadism in men seeking to preserve fertility - what are the options?

Long-acting forms of testosterone replacement therapy (TRT) lead to infertility and are inappropriate for patients wishing to conceive.

• TRT is described as the most common treatment utilised for male hypogonadism.
• The infertility effect of long-acting TRT makes it unsuitable for patients seeking to preserve fertility.
• This limitation prompted review of alternative treatment options for this patient population.

Gonadotropin releasing hormone (GnRH) can successfully induce spermatogenesis but is impractical to administer.

• GnRH was identified as an alternative treatment option for hypogonadal men wishing to preserve fertility.
• Despite its efficacy in inducing spermatogenesis, the administration method was deemed impractical.
• These practical limitations restrict its clinical utility as a routine treatment option.

Aromatase inhibitors have limited use in hypogonadal men seeking fertility due to the adverse effect of inducing osteopenia.

• Aromatase inhibitors were evaluated as an alternative treatment option for hypogonadism in men wishing to conceive.
• The induction of osteopenia was identified as a significant limiting adverse effect.
• This safety concern restricts the widespread use of aromatase inhibitors in this patient population.

Nasal TRT may be a viable treatment option for hypogonadal men seeking fertility preservation, but evidence is currently limited to small sample sizes.

• Nasal TRT was identified as a potential alternative to systemic TRT for patients wishing to remain fertile.
• Its efficacy has so far only been demonstrated in small sample sizes, limiting the strength of conclusions.
• Further research with larger populations is implicitly needed to confirm its role in this indication.

Clomiphene citrate and exogenous gonadotropins are safe, offer good symptom control, and can successfully induce fertility in hypogonadism patients.

• Both clomiphene citrate and exogenous gonadotropins were reviewed as alternative treatment options to long-acting TRT.
• These treatments were found to provide good symptom control in addition to fertility preservation.
• They were identified as the most favourable alternatives among the options reviewed for hypogonadal men seeking to conceive.
• The review of literature assessed safety and efficacy across both treatment modalities.

Male hypogonadism results from disruption at one or more levels of the hypothalamic-pituitary-gonadal (HPG) axis.

• Male hypogonadism is described as a clinical syndrome resulting in low testosterone levels.
• The syndrome frequently leads to infertility.
• Disruption can occur at the level of the hypothalamus, pituitary, or gonads.
• This pathophysiology informs the rationale for the various treatment approaches reviewed.