Androgens and Cardiometabolic Health

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madman

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ABSTRACT

Introduction:
Cardiometabolic syndrome (CMS), as a bunch of metabolic disorders mainly characterized by type 2 diabetes mellitus (T2DM), hypertension, atherosclerosis, central adiposity, and abdominal obesity triggering androgen deficiency, is one of the most critical threats to men. Although many significant preclinical and clinical findings explain CMS, new approaches toward common pathophysiological mechanisms and reasonable therapeutic targets are lacking.

Aim: To gain a further understanding of the role of androgen levels in various facets of CMS such as the constellation of cardiometabolic risk factors including central adiposity, dyslipidemia, insulin resistance, diabetes, and arterial hypertension and to define future directions for the development of effective therapeutic modalities.

Methods: Clinical and experimental data were searched through scientific literature databases (PubMed) from 2009 to October 2019.

Main Outcome Measure: Evidence from basic and clinical research was gathered with regard to the causal impact and therapeutic roles of androgens on CMS.

Results: There are important mechanisms implicated in androgen levels and the risk of CMS. Low testosterone levels have many signs and symptoms on cardiometabolic and glycometabolic risks as well as abdominal obesity in men.

Clinical Implications: The implications of the findings can shed light on future improvements in androgen levels and add potentially predictive risk for CMS, as well as T2DM, abdominal obesity to guide clinical management in the early stage.

Strengths & Limitations: This comprehensive review refers to the association between androgens and cardiovascular health. A limitation of this study is the lack of large, prospective population-based studies that analyze the effects of testosterone treatment on CMS or mortality.

Conclusion: Low testosterone levels have several common features with metabolic syndrome. Thus, testosterone may have a preventive role in the progress of metabolic syndrome and subsequent T2DM, abdominal obesity, and cardiovascular disease and likely affect aging men's health mainly through endocrine and vascular mechanisms. Further studies are necessary to evaluate the therapeutic interventions directed at preventing CMS in men.






INTRODUCTION

Cardiometabolic syndrome (CMS) is a group of metabolic disorders that occur together, increasing the risk of obesity, type 2 diabetes mellitus (T2DM), hypertension, hyperlipidemia, atherosclerosis.1,2 The most common cardiometabolic factors are hypertension, insulin resistance (IR), abdominal obesity, hypercholesterolemia, and low high-density lipoprotein (HDL)-cholesterol levels. 3 CMS is an essential cause of the formation and progression of cardiovascular diseases (CVDs).4,5 CVDs triggers are primarily malnutrition, lack of physical activity, and metabolic syndromes (MetS) such as hypertension, obesity, T2DM, and risk factors to cardiometabolic disease.6 The prevalence of MetS was 17%among people over 40 years old, 29.7% for people between 40 and 49 years old, 37.5% between 50 and 59 years old, and over 44% among people aged ≥ 60 years.7 Definitions of MetS and its components have widely varied depending on several organizations.8 The “World Health Organization” and the most commonly used criteria “International Diabetes Federation” were adopted in 2005,8 and the “National Cholesterol Education Program Adult Treatment Panel III” was adopted in 2005 (Table 1).9 In the determination of MetS, the appearance of 3 of 5 risk factors is required: 1) abdominal obesity (measured by waist circumference), 2) fasting glucose (≥ 5.6 mmol/L), 3) HDL cholesterol (<1.0 mmol/L), 4) tri-glycerides (≥ 1.7 mmol/L, 5) blood pressure (≥ 130/≥ 85 mmHg) (Table 1).8 Based on “The National Health and Nutrition Examination Survey” data from 2001 to 2012, the prevalence of MetS in men increased with advanced age.





In this review, we focused on recent discoveries in the relationship between androgens (T and dihydrotestosterone [DHT]) and androgen receptors (ARs), their contribution to cardiometabolic health, and their potential role on CMS. The relationship between all these important factors and T deficit, as well as the mutual association among CMS, CVD, and hypogonadism, was highlighted.






ANDROGEN HORMONES AND THEIR RECEPTORS


*Androgens in CMS
*Abdominal Obesity
*Type 2 Diabetes Mellitus
*Hypertension
*Atherosclerosis
*Dyslipidemia
*Inflammation






Despite many investigations regarding the cardiac, metabolic, and hormonal effects of androgens, there is still a need for a better understanding of precise mechanisms of androgens for improving all components of the CMS. Ongoing research might provide the knowledge required to fully understand the different responses to androgens in the CMS.
 

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Table 1. Parameters defining metabolic syndrome
Screenshot (2294).png
 
Figure 1. The actions of androgens via androgen receptors (ARs). DHT ¼ dihydrotestosterone; HSP ¼ heat shock protein.
Screenshot (2296).png
 
Figure 3. The age-specific reference ranges for testosterone (T).
Screenshot (2298).png

Figure 4. The pathophysiological mechanisms linking low testosterone (T) and sex hormone-binding globulin (SHBG) concentrations to cardiometabolic syndrome (CMS).
 
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