Pharmacological management of testosterone deficiency in men current advances and future directions

ABSTRACT

Introduction

Testosterone deficiency (TD) is relatively common in aging men, affecting around 2% of the general population. Testosterone replacement therapy (TRT) represents the most common medical approach for subjects who are not interested in fathering.

Areas covered

This review summarizes advances in TRT, including approved or non-approved pharmacological options to overcome TD. When possible, a meta-analytic approach was applied to minimize subjective and biased interpretations of the available data.

Expert opinion

During the last decade, several new TRT formulations have been introduced on the market, including oral, transdermal, and parenteral formulations. Possible advantages and limitations have been discussed appropriately. Anti-estrogens, including selective estrogen modulators or aromatase inhibitors still represent further possible off-label options. However, long-term side effects on sexual function and bone parameters constitute major limitations. Glucagon-like peptide 1 analogues can be an alternative option in particular for massive obesity-associated TD. Weight loss obtained through lifestyle modifications including diet and physical exercise should be encouraged in all overweight and obese patients. A combination of TRT and lifestyle changes can be considered in those subjects in whom a reversal of the condition cannot be expected in a reasonable time frame.

KEYWORDS:

• Testosterone
• hypogonadism
• late onset hypogonadism
• erectile dysfunction
• weight loss

Article highlights

• New FDA-approved oral T formulations, based on the self-emulsifying delivery system technology, allow a better pharmacokinetic profile when compared to the older oral preparation.

• According to available evidence nasal T preparation is less often associated with side effects such as hematocrit increase or suppression of the hypothalamus pituitary testis axis. More controlled trials are advisable to confirm these preliminary results.

• Data derived from the use of anti-estrogens such as selective estrogens receptor modulators (SERM) or aromatase inhibitors are still conflicting.

• GLP-1 analogues represent a new putative tool for the treatment of functional hypogonadism in particular for massive obesity-associated hypogonadism.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was funded by Next Generation EU grant DM 1557 11.10.2022.