Introduction:
The main androgen in men is testosterone, which controls sexual traits and physical composition. Estradiol and dihydrotestosterone are produced during the conversion of testosterone to these bioactive metabolites. Early adulthood is the time when circulating testosterone peaks, and it steadily decreases as people become older. Older men have lower testosterone levels and dihydrotestosterone levels than younger men. Lower testosterone levels are linked to an increased frequency of cardiovascular events in middle-aged and older males. Lower levels of testosterone and dihydrotestosterone are also linked to greater cardiovascular mortality in middle-aged and older men. The decrease of cholesterol buildup, the control of inflammation, and the enhancement of endothelial function are a few potential testosterone-related mechanisms of action.
Greater levels of high-density lipoprotein (HDL) cholesterol and lower levels of blood pressure, blood triglycerides, and glucose are among the cardiovascular disease risk factors that are associated with higher levels of endogenous testosterone in men. The use of lower amounts of exogenous testosterone is becoming more common due to the notion that supplementation is beneficial for well-being, despite the fact that hypogonadism in males is also negatively connected with health.
What Is the Physiology Behind Androgens and Cardiovascular Disease?
The main androgen or male sex hormone in adult males, testosterone, controls secondary sexual traits, body composition, and sexual maturity. Testosterone is converted into two key bioactive metabolites: estradiol, a ligand for estrogen receptors, and dihydrotestosterone (DHT), a more potent androgen receptor ligand. Testosterone is largely made by the testicles, which are stimulated by the pituitary gland's luteinizing hormone, which is then controlled by the hypothalamus's gonadotropin-releasing hormone. The central components of the hypothalamic-pituitary-testicular axis are subject to negative feedback control by testosterone and estradiol.
What Are the Consequences of Adrenal Deficiency?
Androgens have a variety of functions in the body, and androgen insufficiency in men leads to a variety of symptoms and signs, including:
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Fat storage.
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Loss of muscle mass.
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Osteopenia or osteoporosis.
Other symptoms and indicators include lethargy, weariness, and poor focus. The local conversion of testosterone to dihydrotestosterone by the enzyme 5-reductase in tissues like the prostate and skin amplifies the effects of testosterone. Some of the testosterone effects, such as those on bone and adipose tissue, are mediated by the enzyme aromatase, turning testosterone into estradiol.
What Are the Effects of Male Aging on Adrenal Gland?
In early adulthood, circulating testosterone increases, gradually falling as people get older. As a result, elderly men have lower levels of testosterone and dihydrotestosterone than younger men. Observational studies have indicated that testosterone and dihydrotestosterone levels fall over time in aged males, whereas luteinizing hormone and sex hormone binding globulin levels rise. This event raises the possibility that, in certain men, testicular endocrine activity declines over time. It is uncertain, nevertheless, whether older men with symptoms of androgen shortage and lower levels of testosterone in the blood than younger men are genuinely experiencing an androgen deficiency state. Dihydrotestosterone and estradiol, the bioactive metabolites of testosterone, have been linked to longer leukocyte telomere length in men, a marker of slower biological aging.
What Are the Risk Factors Associated With Androgen Deficiency and Cardiovascular Disease?
Obesity and Age:
Growing older is a known risk factor for chronic conditions like cardiovascular disease (CVD) and death. All significant cardiovascular risk calculators include age as a factor. Similar to age, obesity is a significant cardiovascular risk factor that may be controlled due to its tight ties to insulin resistance and diabetes risk. Observational studies that reveal a decrease in cardiovascular events and death in obese people (mean age 48 years) after bariatric surgery serve as an example of this. Therefore, aging and obesity are risk factors for cardiovascular disease and are both linked to decreased circulating testosterone concentrations.
What Are the Systemic Effects of Testosterone on the Cardiovascular System?
A pro-atherosclerotic environment is encouraged by low testosterone, which raises the risk of coronary artery disease. According to some studies, testosterone acts as a vasodilator and an endothelium-healing hormone in a variety of body parts, including the coronary arteries. According to recent studies, testosterone plays a significant role in reducing the generation of inflammatory cytokines that affect atherosclerotic profiles, such as tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6. Although a lower atherosclerotic profile is thought to be connected to a decrease in inflammatory cytokines, more research is necessary to understand this mechanism fully.
Additionally, testosterone has demonstrated anti-atherosclerotic activity by reducing the buildup of aortic cholesterol. It has been established that the androgen receptor is not responsible for the fatty deposition inside the aorta that is linked to low endogenous testosterone. Aromatase activity and estrogen receptor alpha activation are partially responsible for the atherosclerotic profile associated with low testosterone, while the exact mechanism is yet unknown. Men with heart failure also have lower levels of systemic testosterone, with the severity of the condition being inversely correlated with these lower levels. Despite the lack of a clear, direct mechanism of action, some evidence links low testosterone to the progression of heart failure's adverse symptoms, including diminished capacity for activity, decreased muscle mass, exhaustion or dyspnea, and cachexia (it is a complicated metabolic syndrome characterized by muscle mass loss with or without fat loss related to an underlying illness).
How Does Testosterone Replacement Therapy Help in Androgen Deficiency?
The physiological hormone testosterone is essential for males to function normally. Physiological testosterone administered over an extended period of time to mouse models has demonstrated atheroprotective effects by raising the HDL fraction of cholesterol (the anti-atherosclerotic cholesterol). The beneficial effect of testosterone in raising HDL fraction can be attributed to its conversion into 17-beta estradiol via aromatase activity in adipose tissue, which then activates estrogen alpha-receptors. Therefore, more testosterone results in greater conversion into estrogen and a healthier lipid profile.
An elevated risk of myocardial infarction has been linked to the use of testosterone replacement treatment in males with pre-existing cardiac disease. Furthermore, in recent studies, testosterone replacement medication has been related to an increase in cardiovascular mortality and other events in men with a history of coronary artery disease.
Conclusion:
Male testosterone, the main androgen, has been found to decrease significantly with age. Multiple illness states in men have been connected to the aging-related reduction in both serum and total testosterone. This natural biochemical drop in testosterone has been associated with a number of conditions, most notably cardiac failure and ischemic heart disease.
Higher levels of endogenous androgens in the blood that are still within the normal range are associated with a lower risk of cardiovascular disease and mortality. The advantages of testosterone therapy for males with pathological hypogonadism probably outweigh the potential risks of cardiovascular side effects. However, it is still unknown how exogenous androgens used in testosterone treatment, which aims to maintain normal circulating androgen concentrations, would affect the cardiovascular system. The evidence gap in hypogonadal men's clinical treatment should be acknowledged, and men who need testosterone therapy can be individually assessed and managed for cardiovascular risk factors and disease.
