Role of androgens in energy metabolism affecting on body composition, metabolic syndrome, type 2 diabetes, cardiovascular disease, and longevity: lessons from a meta-analysis and rodent studies

Abstract

Testosterone is a sex hormone produced by testicular Leydig cells in males. Blood testosterone concentrations increase at three time-periods in male life-fetal, neonatal (which can be separated into newborn and infant periods), and pubertal stages. After peaking in the early 20s, the blood bioactive testosterone level declines by 1-2% each year. It is increasingly apparent that a low testosterone level impairs general physical and mental health in men. Here, this review summarizes recent systematic reviews and meta-analyses of epidemiological studies in males (including cross-sectional, longitudinal, and androgen deprivation studies, and randomized controlled testosterone replacement trials) in relation to testosterone and obesity, body composition, metabolic syndrome, type 2 diabetes, cardiovascular disease, and longevity. Furthermore, underlying mechanisms are discussed using data from rodent studies involving castration or androgen receptor knockout. This review provides an update understanding of the role of testosterone in energy metabolism. Abbreviations AR: androgen receptor; CV: cardiovascular; FDA: US Food and Drug Administration; HFD: high-fat diet; KO: knockout; MetS: metabolic syndrome; RCT: randomized controlled trial; SHBG: sex hormone binding globulin; SRMA: systematic review and meta-analysis; TRT: testosterone replacement therapy; T2DM:type 2 diabetes mellitus.

Emerging role of testosterone in pancreatic β cell function and insulin secretion

“…However, in most of these smaller studies, testosterone deficiency was moderate, diabetes was already well-controlled or the population was heterogeneous, and testosterone deficiency was not the primary driver of T2D development. Overall, systematic reviews and meta-analyses are consistent with a beneficial effect of testosterone therapy in improving glucose homeostasis in men with T2D and primary hypogonadism (reviewed in Harada 2018).…”

Vascular Pathways of Testosterone: Clinical Implications

“…Testosterone was initially considered to be harmful to the cardiovascular system, as men have a high prevalence of CVD and cardiovascular morbidity and mortality are over 2-fold greater in men compared to women [42]. However, several clinical and epidemiological studies have challenged this idea.…”

“…elevated fasting glucose), raised blood pressure, dyslipidaemia (i.e. elevated triglyceride levels and low high-density lipoprotein (HDL) cholesterol levels) and obesity [42,49]. The molecular mechanisms behind this complex clinical condition can be explained by the bidirectional mechanism between hypogonadism and obesity-a mechanism that involves not only adipocytes but Leydig cells and hypothalamic hormones responsible for pituitary-testicular axis control.…”

“…The main criterion for the diagnosis of hypogonadism is the low blood T level in men, which impairs general physical and mental health status and is diagnosed in~2% of elderly men. Total and free T levels of less than 11 nmol/L and 0.22 nmol/L, respectively, are the minimum criteria for the hypogonadism diagnosis in Europe [42,60]. In 2013, a review performed by Corona et al (2013) about male hypogonadism suggested that TRT was able to improve central obesity in subjects with MeSy, and glucometabolic control in patients with MeSy and T2DM.…”

Association of plasma total testosterone level and metabolic syndrome in adult males

“…Low testosterone level has strongly correlated with body fat accumulation and abdominal obesity in men (8). Testosterone is a sex hormone in males which is produced by testicular Leydig cells (9). It increases lipolysis and decreases visceral fat, while lack of testosterone leads to insulin resistance due to increased fatty acids (10).…”