AUTHOR=Pivonello Rosario , Menafra Davide , Riccio Enrico , Garifalos Francesco , Mazzella Marco , de Angelis Cristina , Colao Annamaria 

TITLE=Metabolic Disorders and Male Hypogonadotropic Hypogonadism

JOURNAL=Frontiers in Endocrinology

VOLUME=Volume 10 - 2019

YEAR=2019

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2019.00345

DOI=10.3389/fendo.2019.00345

ISSN=1664-2392

ABSTRACT=Several studies highlight that testosterone deficiency is associated and predicts increased risk of developing metabolic disorders, and, that it is highly prevalent in obesity, metabolic syndrome and type-2 diabetes mellitus. Models of gonadotropin releasing hormone deficiency and androgen deprivation in patients with prostate cancer suggest that hypogonadotropic hypogonadism might contribute to onset or further worsen metabolic conditions by means of increased fat mass and insulin resistance. Nevertheless, in functional hypogonadism, such as late onset hypogonadism, the relationship between hypogonadotropic hypogonadism and metabolic disorders is bidirectional, and a vicious circle between the two components has been documented. The mechanisms underlying the crosstalk between testosterone deficiency and metabolic disorders include increased visceral adipose tissue and insulin resistance, leading to development of metabolic disorders, which in turn contribute to a further reduction of testosterone, determined by insulin resistance- and possibly pro-inflammatory cytokine-mediated, decrease of sex hormone binding globulin, resulting in increased  free testosterone available for aromatization in visceral adipose tissue, a subsequent decrease in free testosterone, due to the excess of visceral adipose tissue and aromatization, and reduced gonadotropin secretion induced by estradiol, inflammatory mediators, leptin resistance, and insulin resistance, with determination of substantial Hypo-H. The majority of studies focusing on the effects of testosterone replacement therapy on metabolic profile reported a beneficial effect on anthropometric parameters, body composition, cholesterol levels, and glycemic control. Consistently, several studies demonstrated that correction of metabolic disorders, in particular with compounds displaying a greater impact on body weight and insulin resistance, improved gonadotropins and testosterone levels. The aim of the current review is to provide a comprehensive overview on the relationship between hypogonadotropic hypogonadism and metabolism, by clarifying the independent role of testosterone deficiency in the pathogenesis of metabolic disorders, and by describing the relative role of testosterone deficiency and metabolic impairment, in the context of the bidirectional relationship between hypogonadism and metabolic diseases documented in functional hypogonadotropic hypogonadism. These aspects will be assessed by describing metabolic profile in men with hypogonadotropic hypogonadism, and androgenic status in men with metabolic disorders; afterwards, the reciprocal effects of testosterone replacement and corrective interventions on metabolic derangements will be reported.