The Role of Long-Acting Parenteral Testosterone Undecanoate Compound in the Induction of Secondary Sexual Characteristics in Males with Hypogonadotropic Hypogonadism
Authors: Giagulli Vito A. , Triggiani Vincenzo , Carbone Maria D. , Corona Giovanni , Tafaro Emilio , Licchelli Brunella , Guastamacchia Edoardo 
Published: October 2011

ABSTRACT

Introduction
Androgens are able to induce the development of secondary sexual characteristics in male patients suffering from hypogonadism. So far, the most common method of administering testosterone to induce puberty in these patients has been via the injection of testosterone ester formulations. Moreover, some evidence has showed that the length of polymorphism Cytosine-Adenine-Guanine (CAG) trinucleotide repeats present in androgen receptor (AR) gene might co-regulate the effectiveness of testosterone therapy.

Aim
The aim of this study is to evaluate the effectiveness of a long-acting injectable testosterone undecanoate (TU) formulation for the induction of secondary sexual characteristics in young males with hypogonadotropic hypogonadism (HH).

Main Outcome Measures
We studied the different stages of puberty development that occur progressively according to the continuous increase in serum testosterone levels and, secondly, whether these changes might be modulated by the length of CAG repeats.

Methods
Nine male subjects over the age of 17 that had not undergone pubertal development because of HH were enrolled in this study and compared with 15 control males. Of these patients, 6/9 suffered from idiopathic HH and 3/9 experienced hypogonadism related to β-thalassemia (BT). All patients underwent a clinical examination and a determination of follicle-stimulating hormone, luteinizing hormone, sex hormone binding globulin (SHBG), and total testosterone (T) serum levels; the free fraction (FT) and biologically active fraction of testosterone were also determined. The number of CAG triplets present in the AR gene was obtained for each patient. For treatment, HH patients received an oral TU (Andriol, 120 mg/day) for 3 months, followed by intramuscular injection of parenteral TU (Nebid, 1,000 mg) every 14 weeks for 1 year, then every 12 weeks for a second year. Serum T and SHBG levels were assayed 3 months after the start of oral TU treatment and also in the 10th week following the start of the second round of intramuscular TU injections (e.g., the eighth month). Levels were also determined 12, 18, and 24 months after the start of the parenteral TU treatments.

Results
Serum levels of T, SHBG, FT, and BT increased in all of the patients receiving oral TU and parental TU treatments, and this was accompanied by a development of secondary sexual characteristics. For treated patients with &gt;24 CAG triples vs. the HH subjects with ≤24 CAG triplets, a slight delay in the appearance of the most advanced phases of puberty and a slightly reduced final penis length were observed, suggesting that AR CAG polymorphism might co-regulate the effectiveness of T treatment.

Conclusions
Long-acting parental TU was able to induce the puberty in our group of HH patients, even though additional studies are needed to elucidate the possible role of CAG repeats’ length for the development of secondary sexual characteristics in young men with HH.