Various diseases and clinical conditions are associated with low T or hypogonadism. Obesity, diabetes, hypertension, hyperlipidemia, osteoporosis, and chronic obstructive pulmonary disease occur more frequently in hypogonadal males. It remains unclear whether low T levels are a consequence of these diseases or a cause of their etiology.
Testosterone was believed to increase the risk for heart disease based on the relative incidence of heart disease among men versus women. The 2003 IOM report identified no clear association between testosterone and cardiovascular disease. Since this report, epidemiological evidence has confirmed that testosterone has a positive association with high density lipids (HDL) cholesterol and an inverse relationship with hyperlipidemia, hypertension, and prothrombotic factors.
A systemic review of 35 cross-sectional studies was conclusive regarding no evidence to support a positive correlation between testosterone and coronary artery disease (CAD). Most studies reported an inverse relationship: low levels of testosterone were associated with an increased prevalence of CAD. Studies have demonstrated that testosterone can have a positive effect on reducing risk factors for cardiovascular disease.[4,5] Inverse relationships were reported between body mass index (BMI), waist circumference, waist/hip ratio, serum leptin, low-density lipoprotein (LDL) cholesterol, triglyceride and fibrinogen levels, and increased risk for CAD. There is preliminary evidence of potential benefits of testosterone replacement therapy (TRT) in men with CAD.
Low T levels have been linked to type 2 diabetes. The Endocrine Society recommends testosterone assessment in all men with type 2 diabetes. The Kuopio Ischemic Heart Disease Risk Factor Study, conducted in Finland, discovered that nondiabetic males were twice as likely to develop diabetes within 11 years if they were in the lowest quartile for testosterone levels. The Hypogonadism in Males (HIM) study reported that diabetic males were twice as likely to have low T levels compared with nondiabetic males. Data from the National Health Nutrition Survey (NHANES) III survey indicate that men in the lowest free testosterone quartile were 4 times as likely to have diabetes, compared with males in the highest free testosterone quartile. It is estimated that 33%–50% of diabetic men experience hypogonadism.
Hypogonadism has been related to type 2 but not type 1 diabetes. This suggests that hypogonadism is not specifically directly related to hyperglycemia. This relationship between hypogonadism and type 2 diabetes is a result of the comorbidity of obesity and metabolic syndrome that results in insulin insensitivity, rather than the lack of insulin production.
Obesity and Metabolic Syndrome
Health risks associated with obesity include an increased risk for type 2 diabetes, hypertension, and CAD. Approximately 83% of diabetic patients are overweight (BMI between 25 and 29.9 kg/m2) or obese (BMI > 30 kg/m2). Obese males have low free T levels and reduced SHBG levels. An inverse relationship has been identified between total testosterone levels and BMI. Free testosterone levels decrease as BMI increases. Serum total and free testosterone levels have an inverse relationship with visceral fat mass. Hypogonadism is positively correlated to the degree of obesity. Obese males who lose weight may experience improve testosterone levels.
Metabolic syndrome is defined as a person having central obesity in addition to any 2 of these 4 factors: hypertension (≥ 130/85 mmHg), reduced HDL (< 40 mg/dL in males), raised triglycerides (≥ 150 mg/dL), or raised fasting plasma glucose (≥ 100 mg/dL). Positive correlations have been identified between metabolic syndrome and levels of testosterone; therefore, it is not surprising that hypogonadism is associated with metabolic syndrome.
Low T levels were correlated with insulin resistance, increased fat mass, and decreased lean muscle resulting in increased adipose tissue. Testosterone assists in the development of pluripotent stem cells into myocytes and inhibits adipogenesis. Deficient testosterone levels facilitate adipocyte proliferation, with an increase in fat mass and decrease in lean muscle. Animal studies have supported the finding that insulin resistance is correlated with decrease in testosterone secretion by the Leydig cell of the testes.
Osteoporosis is an underrecognized condition in men. In the United States, 10%–20% of men over the age of 50 develop osteoporosis. Causes of osteoporosis include Cushing's syndrome, sedentary lifestyle, overuse of corticosteroids, low calcium intake, smoking, and low T or hypogonadism.
Testosterone levels have been positively associated with bone mineral density (BMD). Men with low BMD have significantly lower testosterone levels than do men with normal BMD. This linkage between testosterone levels and BMD proposes that testosterone can have both a preventive and restorative effect on BMD. The suspicion of or definitive diagnosis of osteoporosis in men is an indication to explore testosterone as a causative and treatable factor in male osteoporosis.
Testosterone replacement therapy (TRT) in hypogonadal males has been reported to increase BMD and trabecular connectivity in interventional studies. These therapeutic results enable males to maintain physical function and prevent frailty.
Mood and Cognition
Low T has been inversely associated with mood alterations, memory, and cognitive ability. Testosterone has been associated with antisocial behavior, risk behavior, unemployment, and marital status.
Journal for Nurse Practitioners. 2012;8(10):778-786. © 2012 Elsevier Science, Inc.