Central body fat changes in men affected by post-surgical hypogonadotropic hypogonadism undergoing testosterone replacement therapy are modulated by androgen receptor CAG polymorphism

Abstract

Background and aims: Little is known about the effect of androgen receptor (AR) gene CAG repeat polymorphism in conditioning body composition changes after testosterone replacement therapy (TRT). In this study, we aimed to clarify this aspect by focussing our attention on male post-surgical hypogonadotropic hypogonadism, a condition often associated with partial or total hypopituitarism.

Methods and results: Fourteen men affected by post-surgical hypogonadotropic hypogonadism and undergoing several replacement hormone therapies were evaluated before and after TRT. Dual-energy X-ray absorptiometry (DEXA)-derived body composition measurements, pituitary-dependent hormones and AR gene CAG repeat polymorphism were considered. While testosterone and insulin-like growth factor-1 (IGF-1) levels increased after TRT, cortisol concentration decreased. No anthropometric or body composition parameters varied significantly, except for abdominal fat decrease. The number of CAG triplets was positively and significantly correlated with this abdominal fat decrease, while the opposite occurred between the latter and Δ-testosterone. No correlation of IGF-1 or cortisol variation (Δ-) with Δ-abdominal fat was found. At multiple linear regression, after correction for Δ-testosterone, the positive association between CAG triplet number and abdominal fat change was confirmed.

Conclusions: In male post-surgical hypogonadotropic hypogonadism, shorter length of AR CAG repeat tract is independently associated with a more marked decrease of abdominal fat after TRT.

Keywords: Androgen receptor; Body composition; Dual-energy X-ray absorptiometry; Hypogonadotropic hypogonadism; Hypopituitarism; Testosterone.