Androgen Receptor Gene CAG Repeat Polymorphism Regulates the Metabolic Effects of Testosterone Replacement Therapy in Male Postsurgical Hypogonadotropic Hypogonadism

Aim. To evaluate the independent role of androgen receptor (AR) gene CAG repeat polymorphism on metabolic effects of testosterone replacement therapy (TRT) in male postsurgical hypogonadotropic hypogonadism, a condition frequently associated with hypopituitarism and in which the TRT-related metabolic effects are combined with those deriving from concomitant administration of metabolically active pituitary-function replacement therapies. Methods. 15 men affected by postsurgical hypogonadotropic hypogonadism were evaluated before and after TRT. Cardiovascular risk factors (CVRFs), pituitary-dependent hormones, and AR gene CAG repeat polymorphism were considered. Results. Testosterone, insulin-like growth factor 1 (IGF-1), and estradiol were the only hormones, which varied significantly between the two phases. All CVRFs significantly improved after TRT. The number of CAG triplets was positively and significantly correlated with all the variations (Δ-) of CVRFs (except for a significant negative correlation with Δ-high-density lipoprotein); the opposite occurred between the latter and Δ-testosterone. No correlation between Δ-IGF-1 or estradiol and Δ-CVRFs was found. At multiple linear regression, after correction for Δ-testosterone, nearly all the associations between the number of CAG triplets and Δ-CVRFs were confirmed. Conclusions. In male postsurgical hypogonadotropic hypogonadism, shorter AR gene CAG tract length seems to yield greater metabolic improvement after TRT, independently of the effects of concomitant pituitary-function replacement therapies

Effects of testosterone replacement therapy on bone metabolism in male post-surgical hypogonadotropic hypogonadism: focus on the role of androgen receptor CAG polymorphism

Introduction and aim The relationship between androgen receptor (AR) CAG polymorphism and bone metabolism is highly controversial. We, therefore, aimed to evaluate the independent role of AR CAG repeat polymorphism on bone metabolism improvement induced by testosterone replacement therapy (TRT) in male post-surgical hypogonadotropic hypogonadism, a condition frequently associated with hypopituitarism and in which the effects of TRT have to be distinguished from those resulting from concomitant administration of pituitary function replacing hormones. Methods 12 men affected by post-surgical hypogonadotropic hypogonadism [mean duration of hypogonadism 8.3 +/- 2.05 (SD) months] were retrospectively assessed before and after TRT (from 74 to 84 weeks after the beginning of therapy). The following measures were studied: parameters of bone metabolism [serum markers and bone mineral density (BMD)], pituitary dependent hormones and genetic analysis (AR CAG repeat number). Results Total testosterone, estradiol, free T4 (FT4) and insulin-like growth factor-1 (IGF-1) increased between the two phases, while follicle stimulating hormone (FSH) decreased. While serum markers did not vary significantly between the two phases, BMD improved slightly but significantly in all the studied sites. The number of CAG triplets correlated negatively and significantly with all the variations (Delta-) of BMDs. Conversely, Delta-testosterone correlated positively and significantly with all studied Delta-BMDs, while Delta-FSH, Delta-estradiol, Delta-FT4, and Delta-IGF-1 did not correlate significantly with any of the Delta-BMDs. Multiple linear regression analysis, after correction for Delta-testosterone, showed that CAG repeat length was negatively and significantly associated with Delta-BMD of all measured sites. Conclusions Our data suggest that, in post-surgical male hypogonadotropic hypogonadism, shorter AR CAG tract is independently associated with greater TRT-induced improvement of BMD

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

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. © 2014 Elsevier B.V. All rights reserved