Male hypogonadism is a testicular dysfunction due to congenital and acquired causes affecting the hypothalamic-pituitary unit (central hypogonadism, CH) or the testis. Since Sanger sequencing has been developed, various genes have been implicated in the pathogenesis of congenital CH. Subsequently, this panel of genes has greatly increased with the advent of next-generation sequencing (NGS). Furthermore, several mechanisms of inheritance have been discovered, including digenic or oligogenic transmission. Novel mechanisms involving GnRH pulsatility and the kisspeptin system are also emerging. Among them, the role of anti-Müllerian hormone (AMH) and insulin-like growth factor 1 (IGF1) in GnRH neuron firing has recently been supported by in vitro and in vivo studies. The comprehension of these mechanisms may be helpful to elucidate the apparently idiopathic forms.
The etiology of hypogonadism also recognizes testicular causes. Dysmetabolic hypogonadism is an often undiagnosed emerging disease in patients with obesity or diabetes mellitus. New therapeutic strategies such as the very-low-calorie ketogenic diet (VLCKD) or antidiabetic drugs seem to be effective in improving the function of the hypothalamic-pituitary-testicular axis in patients with metabolic diseases.
However, to better understand the pathogenesis of hypogonadism it is necessary to recognize that the boundaries between congenital and acquired causes are not clear-cut. A complex genetic background (eg, inheritance of variance of uncertain significance in heterozygosity) can increase the susceptibility to developing hypogonadism following exposure to specific stimuli (eg, low body weight, obesity; exposure to stress, aging, etc.).
This research topic of Frontiers in Endocrinology, Reproduction section, aims to collect studies describing recent advances in the genetic background of male hypogonadism, novel etiopathogenetic hypothesis (including the role of AMH and IGF1), the relationship between body weight, diabetes mellitus, and hypogonadism, and the impact of different types of diets and antidiabetic treatments on recovery from metabolic hypogonadism, to offer the basis for an updated and evidence-based classification of male hypogonadism.
Male hypogonadism is a testicular dysfunction due to congenital and acquired causes affecting the hypothalamic-pituitary unit (central hypogonadism, CH) or the testis. Since Sanger sequencing has been developed, various genes have been implicated in the pathogenesis of congenital CH. Subsequently, this panel of genes has greatly increased with the advent of next-generation sequencing (NGS). Furthermore, several mechanisms of inheritance have been discovered, including digenic or oligogenic transmission. Novel mechanisms involving GnRH pulsatility and the kisspeptin system are also emerging. Among them, the role of anti-Müllerian hormone (AMH) and insulin-like growth factor 1 (IGF1) in GnRH neuron firing has recently been supported by in vitro and in vivo studies. The comprehension of these mechanisms may be helpful to elucidate the apparently idiopathic forms.
The etiology of hypogonadism also recognizes testicular causes. Dysmetabolic hypogonadism is an often undiagnosed emerging disease in patients with obesity or diabetes mellitus. New therapeutic strategies such as the very-low-calorie ketogenic diet (VLCKD) or antidiabetic drugs seem to be effective in improving the function of the hypothalamic-pituitary-testicular axis in patients with metabolic diseases.
However, to better understand the pathogenesis of hypogonadism it is necessary to recognize that the boundaries between congenital and acquired causes are not clear-cut. A complex genetic background (eg, inheritance of variance of uncertain significance in heterozygosity) can increase the susceptibility to developing hypogonadism following exposure to specific stimuli (eg, low body weight, obesity; exposure to stress, aging, etc.).
This research topic of Frontiers in Endocrinology, Reproduction section, aims to collect studies describing recent advances in the genetic background of male hypogonadism, novel etiopathogenetic hypothesis (including the role of AMH and IGF1), the relationship between body weight, diabetes mellitus, and hypogonadism, and the impact of different types of diets and antidiabetic treatments on recovery from metabolic hypogonadism, to offer the basis for an updated and evidence-based classification of male hypogonadism.
