Testosterone Undecanoate Replacement Therapy in Boys With Pubertal Delay or Confirmed Hypogonadism

Introduction: The absence of clinical signs of pubertal maturation, i.e. pubertal delay, is a relatively frequent reason for consultation in boys. In cases where it is necessary, the treatment to be established is the administration of testosterone with the aim of provoking the development of secondary sexual characteristics and optimizing growth.

Problem: Currently, the most commonly used treatment is empirical, with im depot testosterone at increasing doses over a period of 2 to 3 years. The most commonly used formulation, testosterone enanthate, comes in ampoules of 250 mg in 1 ml of vehicle. The usual administration regimen begins with approximately 50-60 mg im every 4 weeks (1/4 of the ampoule), increasing the dose by approximately 50-60 mg (1/4 ampoule) every 6 months until the full dose of 250 mg (1 ampoule) is reached every 4 weeks. The pharmacokinetic profile has not been described to see if it mimics the physiological progressive increase in testosterone levels at normal puberty. The pharmacokinetic profile of testosterone enanthate in adults shows supraphysiological serum testosterone concentrations the first week after the medication is administered, with a progressive drop to subphysiological levels in the fourth week.

In adults, testosterone undecanoate is used as a first-line medication. Its presentation in ampoules with 1000 mg in 4 ml, of im administration every 12 weeks, is considered equivalent to testosterone enanthate 250 mg every 4 weeks. In adults, the circulating levels of testosterone obtained with the formulation of testosterone undecanoate show a profile within physiological ranges, more stable between doses than that observed with testosterone enanthate. Testosterone undecanoate im has not been tested in adolescents.

Hypothesis: The hypothesis of this work is that the initial administration of 1 ml (~250 mg) of testosterone undecanoate (1000 mg/4 ml) via im every 12 weeks for 6 months, with a progressive increase of 1 ml (~250 mg) every 6 months until reaching 4 ml (1000 mg) per dose is safe and effective in causing normal progress in pubertal development of secondary sex characteristics and growth in males with pubertal delay.

Objective: The general objective of this study is to evaluate whether a quarterly administration regimen of im testosterone undecanoate, in boys with anorchia, hypogonadism or pubertal delay induces the progression in the development of secondary sexual characteristics, the speed of growth and the acquisition of bone mass in accordance with physiological pubertal development, and maintain blood testosterone levels similar to those seen during spontaneous pubertal maturation.