The Effects of Androgens on Cardiometabolic Syndrome: Current Therapeutic Concepts

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 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 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. Kirlangic OF, Yilmaz-Oral D, Kaya-Sezginer E, et al. The Effects of Androgens on Cardiometabolic Syndrome: Current Therapeutic Concepts. Sex Med 2020;8:132-155.

Keywords: Androgen Receptors; Androgen Replacement Therapy; Cardiometabolic Syndrome; Hypogonadism; Testosterone; Type 2 Diabetes Mellitus.

Figure 1

The actions of androgens via androgen receptors (ARs). DHT = dihydrotestosterone; HSP = heat shock protein.

Figure 2

Interactions between cardiometabolic syndrome (CMS) components and testosterone (T).

Figure 3

The age-specific reference ranges for testosterone (T).

Figure 4

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