androgen
deprivation therapy results in unfavorable changes in body composition, insulin resistance, and dyslipidemia and predisposes
men to develop atherosclerosis and an increased risk of cardiovascular mortality
The hypogonadal–obesity cycle hypothesis was originally proposed by Cohen in 1999 to explain the relationship between low
testosterone levels and metabolic disease. It was based on the finding that obesity impairs testosterone levels by increasing
the aromatization of testosterone to estradiol, while low testosterone levels promote increased fat deposition
adipocytokines contribute to low testosterone levels as well as to the processes
underlying metabolic syndromes and type 2 diabetes
The presence of estradiol and the adipocytokines TNF-α, IL6, and leptin (as a result of leptin resistance in obesity)
inhibits the hypothalamic–pituitary–testicular axis response to decreasing androgen levels
An increasing number of studies have illustrated the potential for applying metabolomics to the field of androgen
research
As early as the 1940s, the therapeutic use of testosterone was
reported to improve angina pectoris in men with coronary artery disease
most of the epidemiological studies reported
increased cardiovascular risk and mortality in men with low testosterone levels
long-term testosterone replacement
appears to be a safe and effective means of treating hypogonadal elderly men
a recent interventional trial showed that testosterone treatment was associated with decreased mortality
when compared with no testosterone treatment in an observational cohort of men with low testosterone levels
a number of short-term studies conducted support the notion that testosterone therapy reduces the cardiovascular
risk
The majority of animal studies support the hypothesis that the actions of testosterone on vascular relaxation are both endothelium-dependent
and -independent vasodilatory effects
Endothelial-dependent actions of testosterone increase the expression or activity of
endothelial nitric oxide synthase and enhance nitric oxide production, which in turn activates cyclic guanosine monophosphate
to induce vasorelaxation in smooth muscle cells
Endothelial-independent mechanisms of testosterone are believed to occur
primarily via inhibition of voltage-operated Ca2+ channels and/or activation of K+ channels in smooth muscle cells
Testosterone may also inhibit intracellular Ca2+ influx via store-operated Ca2+ channels by blocking the response to prostaglandin F2α
testosterone has demonstrated anti-inflammatory effects
to protect against atherogenesis in animal studies
both genomic AR activation to modulate gene transcription and non-genomic activation to modulate the rapid intracellular
signaling pathways of ion channels may mediate testosterone effects on vascular function and inflammation.
Butenandt & Ruzicka first showed how testosterone
is synthesized and responsible for masculine characteristics in the early 1930s
Awesome review on the current understanding of Testosterone and Diabetes, metabolic syndrome, and CVD. This article even goes into the literature on androgen receptors.
Study found that PCOS was associated with increased glycolysis, reduced kreb's cycle activity, and decreased gluconeogenesis. Also found a decrease in the BCAA/AAA ratio.