Developments and challenges for new and emergent preparations for male hypogonadism treatment

ABSTRACT

Introduction

The specific role of testosterone (T) replacement therapy in patients with late onset hypogonadism is still conflicting. Several available preparations have been developed to restore either fertility and normal testosterone (T) levels (secondary hypogonadism) or just T levels (primary hypogonadism).

Areas covered

Advantages and limitations related to available new treatments will be discussed in detail. In addition, possible news related to preparations in the pipeline will be discussed.

Expert opinion

The selection of a specific T preparation should be adequately discussed with each subject. Transdermal T preparations are those that can preserve, after a unique morning administration, the circadian rhythmicity of T secretion. Conversely, short-acting preparations (such as oral or intranasal) need two- or three-times daily administration, potentially reducing patient compliance. Long acting T preparations, such as injectable T undecanoate have the advantage of bimestrial or trimestral administration, reducing the required number of administrations. The use of non-steroidal selective androgen receptor modulators (SARM), a heterogeneous class of compounds selectively acting on androgen receptor targets, remains investigational due to the lack of the full spectrum of T’s action and the possible risk of side effects, despite their potential use in the treatment of muscle wasting and osteoporosis.

KEYWORDS:

• Erythrocytosis
• hypogonadism
• testosterone
• testosterone replacement therapy
• prostate

Article highlights

• Although the suggested cutoffs to start testosterone treatment, in symptomatic men, differ among available guidelines, European position emphasized that 12 nM represents the best threshold.

• Preliminary results with nasal testosterone showing a minor effect on erythropoiesis, need to be confirmed.

• New oral formulations with self-emulsifying delivery system have shown good results but these preparations are not available in Europe.

• Data related to developing preparations including kisspeptin or neurokinin-B agonists or IL1 antagonist are too preliminary.

• An accurate discussion with each individual patient on the advantages and disadvantages of each testosterone preparations, to allow a metered prescription is mandatory.

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

A reviewer on this manuscript has disclosed they received speaker honoraria from Besins and Bayer in relation to hypogonadism and testosterone prescribing. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

We acknowledge co-funding from Next Generation EU, in the context of the National Recovery and Resilience Plan, Investment PE8 – Project Age-It: “Ageing Well in an Ageing Society”. This resource was co-financed by the Next Generation EU [DM 1557 11.10.2022]. The views and opinions expressed are only those of the authors and do not necessarily reflect those of the European Union or the European Commission. Neither the European Union nor the European Commission can be held responsible for them.