Considerations when treating male pubertal delay pharmacologically

ABSTRACT

Introduction

Delayed puberty , usually affects psychosocial well-being. Patients and their parents show concern about genital development and stature. The condition is transient in most of the patients; nonetheless, the opportunity should not be missed to diagnose an underlying illness.

Areas covered

The etiologies of pubertal delay in males and their specific pharmacological therapies are discussed in this review.

Expert opinion

High-quality evidence addressing the best pharmacological therapy approach for each etiology of delayed puberty in males is scarce, and most of the current practice is based on small case series or unpublished experience. Male teenagers seeking attention for pubertal delay most probably benefit from medical treatment to avoid psychosocial distress. While watchful waiting is appropriate in 12- to 14-year-old boys when constitutional delay of growth and puberty (CGDP) is suspected, hormone replacement should not be delayed beyond the age of 14 years . When hypogonadism is diagnosed, hormone replacement should be proposed by the age of 12 years . Testosterone replacement has been used for decades and is fairly standardized. Aromatase inhibitors have arisen as an interesting alternative . Gonadotrophin therapy seems more physiological in patients with central hypogonadism, but its efficacy and timing still need to be established.

KEYWORDS:

• Aromatase inhibitor
• constitutional delay of growth and puberty (CDGP)
• gonadotrophin-releasing hormone (GnRH)
• human chorionic gonadotrophin (hCG)
• hypergonadotrophic hypogonadism
• hypogonadotrophic hypogonadism
• letrozole
• recombinant follicle-stimulating hormone (r-FSH)
• testosterone enanthate
• testosterone undecanoate

Article highlights

• Scarce high-quality evidence exists about the best pharmacological therapy approach for delayed puberty in males.

• Constitutional delay of puberty, an extreme of normal pubertal onset, is the most frequent cause of pubertal delay. Nevertheless, male teenagers seeking attention for pubertal delay most probably benefit from medical treatment to avoid psychosocial distress.

• In any case, testosterone replacement should be indicated by the age of 14 years in order to maximise height potential and peak bone mass.

• When primary or central hypogonadism is diagnosed, hormone replacement should be proposed by the age of 12 years, after functional hypogonadism has been ruled out.

• Testosterone replacement regimens have been used for decades and are fairly standardised.

• Aromatase inhibitors are an alternative for patients with constitutional delay of puberty and short stature. However, evidence based on robust clinical trials is lacking.

• In patients with central hypogonadism, gonadotrophin therapy would be the aetiological therapy, but its relative efficacy and most appropriate timing require clinical trials with long follow-up.

Declaration of Interest

RAR has received honoraria from CONICET (Argentina) for technology services using the AMH ELISA and royalties derived from an agreement between INSERM (France) and Beckman-Coulter-Immunotech for the development of an AMH ELISA kit, until 2020, as well as lecture honoraria from Novo Nordisk and Sandoz, and travel grants from Biosidus, Merck, Novo Nordisk, Pfizer and Sandoz.

Reviewers Disclosure

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

Additional information

Funding

This work was partially funded by Fondo para la Investigación Científica y Tecnológica (FONCYT, Argentina), grant numbers PIDC 32/2017 and PICT 2972/2018.