Welcoming low testosterone as a cardiovascular risk factor

Abstract

Male hypogonadism now has a new spectrum of complications. They are mainly cardiometabolic in nature. Low serum testosterone levels are a risk factor for diabetes, metabolic syndrome, inflammation and dyslipidemia. These metabolic and inflammatory complications are not without consequences. Recent studies have shown low serum testosterone levels to be an independent risk factor of cardiovascular and all-cause mortality. It is time to welcome low serum testosterone levels as a cardiovascular risk factor. Testosterone is the predominant sex hormone in man. A young man produces 3-10 mg of testosterone daily that results in serum levels of 300-1000 ng per 100 ml. The traditional consequences of male hypogonadism are well known. These include decreased libido, erectile dysfunction, decreased muscle mass and strength, increased fat mass, changes in mood and energy, osteoporosis and decreased sexual hair. 1 However, for the past two decades, many studies have found an association between low serum testosterone levels and various cardiovascular (CV) risk factors. In addition, some epidemiological studies have also linked low testosterone levels with CV and all-cause mortality. In this review, we will briefly touch upon the various CV risk factors that have been linked to low serum testosterone in men. Diabetes and metabolic syndromeLow testosterone levels have been associated with diabetes and metabolic syndrome. Epidemiological studies have reported that low testosterone levels are an independent risk factor for type-2 diabetes.2 Interestingly, concentrations of free and bioavailable testosterone even in the low-normal range are associated with diabetes, after adjusting for adiposity.3 Similarly, low total testosterone levels independently predict development of the metabolic syndrome in middle-aged men. 4 Interventional trials have shown that testosterone administration results in an increased glucose uptake by the muscles, thereby improving insulin sensitivity. 5 One study even showed an improvement in HbA1c in hypogonadal men with type-2 diabetes who received testosterone. 6 Another study showed that testosterone replacement inhibits incorporation of triglycerides in visceral fat (which is the most active depot metabolically and contributes to insulin resistance).7 In addition, androgen deprivation in men with prostate cancer is associated with hyperglycemia and metabolic syndrome, 8,9 and the degree of hyperglycemia is directly related to the duration of castration.10 Thus, even low-normal levels of testosterone appear to be a risk factor for metabolic dysregulation. Hyperlipidemia and inflammationIn contrast to the belief of many physicians that androgen administration leads to an adverse lipid profile, research shows that physiological testosterone replacement is at least neutral (if not beneficial) to lipids. Hence, it should be differentiated from non-aromatizable androgens that do result in harm-

An old emperor finds new clothing: rejuvenation in our time

“…This regular association in observational studies has become overinterpreted as a risk factor (rather than a consequence), leading to prediction of beneficial (rather than adverse) effects of testosterone treatment. [42][43][44][45] This complacency led to a misplaced focus on prostate cancer as the major risk of testosterone treatment in older men. 35,36 This paper saliently highlights the important principle that relatively small adverse effects involving the most common cause of death-cardiovascular disease-overwhelms even substantial benefits on less common or non-fatal disorders.…”

Cardiovascular risk, metabolic profile, and body composition in adult males with congenital adrenal hyperplasia due to 21-hydroxylase deficiency

“…Longstanding undertreatment with elevation of adrenal androgens may also reduce insulin sensitivity (8,9) and induce hypogonadism with low testosterone values by gonadotropin suppression. Hypogonadotropic hypogonadism has been shown to be a risk factor for the metabolic syndrome and T2DM and to increase cardiovascular mortality (10). Inadequate mineralocorticoid therapy for aldosterone deficiency may also have negative impact on the vascular system (11).…”

Workplace noise exposure and serum testosterone in men enrolled in the 1999-2004 National Health and Nutrition Examination Survey

“…A follow-up study of 8,538 employed men in the US estimated that hypogonadal employees had greater health care costs and disability leave/medical absenteeism than the eugonadal employees (49). Cardiometabolic complications alone make low testosterone an important biomarker for morbidity and mortality in men (50), and meta-analyses have reported a significantly higher risk of cardiovascular disease-related and all-cause mortality among testosterone-deficient men (18,19). Given that the pharmacological treatment of hypogonadism with testosterone replacement therapy, however safe, may still be associated with some adverse effects (51), environmental risk factors for low testosterone, such as noise, should be explored, and preventive measures established as needed.…”