Testosterone: a vascular hormone in health and disease

Abstract

Coronary heart disease is a leading cause of premature death in men. Epidemiological studies have shown a high prevalence of low serum testosterone levels in men with cardiovascular disease (CVD). Furthermore, a low testosterone level is associated in some but not in all observational studies with an increase in cardiovascular events and mortality. Testosterone has beneficial effects on several cardiovascular risk factors, which include cholesterol, endothelial dysfunction and inflammation: key mediators of atherosclerosis. A bidirectional relationship between low endogenous testosterone levels and concurrent illness complicates attempts to validate causality in this association and potential mechanistic actions are complex. Testosterone is a vasoactive hormone that predominantly has vasodilatory actions on several vascular beds, although some studies have reported conflicting effects. In clinical studies, acute and chronic testosterone administration increases coronary artery diameter and flow, improves cardiac ischaemia and symptoms in men with chronic stable angina and reduces peripheral vascular resistance in chronic heart failure. Although the mechanism of the action of testosterone on vascular tone in vivo is not understood, laboratory research has found that testosterone is an L-calcium channel blocker and induces potassium channel activation in vascular smooth muscle cells. Animal studies have consistently demonstrated that testosterone is atheroprotective, whereas testosterone deficiency promotes the early stages of atherogenesis. The translational effects of testosterone between in vitro animal and human studies, some of which have conflicting effects, will be discussed in this review. We review the evidence for a role of testosterone in vascular health, its therapeutic potential and safety in hypogonadal men with CVD, and some of the possible underlying mechanisms.

Testosterone replacement attenuates mitochondrial damage in a rat model of myocardial infarction

“…In cultured endothelial cells, the activation of PKC could influence liver kinase B1 (LKB1) to stimulate AMPK (Xie et al 2006). Testosterone can modulate Ca2+ channels of the cell membrane directly (Kelly & Jones 2013). The modulation of Ca2+ channels will also change intracellular Ca2+ concentrations.…”

Roles of the Androgen – Androgen Receptor System in Vascular Angiogenesis

“…Androgen actions on vascular function and inflammation may include the modulation of gene transcription via the AR and AR-mediated activation of a rapid intracellular signaling pathway 57) . Vascular endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) are pivotal cellular components of the vascular structure that play important roles in vascular health and disease.…”

Basaal wetenschappelijk bewijs voor de link tussen erectiele disfunctie en cardiometabole disfunctie

“…Uit de meeste klinische studies blijkt dat een lagere testosteronspiegel gecorreleerd is met ED, CVZ, DM2 en metabole ziekten [28][29][30]. Ofschoon deze associatie sterk is en opvallend, is een oorzakelijk verband niet bewezen, aangezien het bewijs meestal voortkomt uit retrospectieve en observationele klinische studies.…”

“…De beschikbare klinische data tonen aan, zij het niet geheel consistent, dat TRT bij hypogonadale mannen de viscerale adipositas en insulineresistentie kan verminderen en de lipide-en ontstekingsprofielen kan verbeteren [30,36]. Het lage testosterongehalte en deze metabole stoornissen vormen hierbij een vicieuze cirkel, waarbij de beide factoren elkaar versterken, met name bij mannen met centrale adipositas door de hormonale activiteit van het viscerale vet als endocrien orgaan: toenemende aromatisatie van testosteron tot oestradiol in adipocyten leidt tot een stijging van het oestradiolgehalte, hetgeen vervolgens de testosteronproductie onderdrukt door inhibitie van de hypofysaire secretie van de gonadotrofinen.…”