Male hypogonadism: A clinically important indicator of systemic health issues

Hypogonadism is highly prevalent in ageing men, who are also more likely to experience systemic health conditions such as diabetes and cardiovascular disease. Studies report that up to 39% of men aged ≥ 45 have low levels of testosterone, but despite the high prevalence of testosterone deficiency, the condition is under-diagnosed and under-treated.1

Until recently, hypogonadism has largely been seen as a condition that impairs quality of life and sexual function, and the perception that it is primarily a sexual condition may have contributed to its under-diagnosis and under-treatment.² However, there is increasing evidence that hypogonadism has broad adverse health effects and that improved diagnosis and treatment of testosterone deficiency is clinically important for improving men’s long-term health and longevity.¹

Mortality

There is now data showing that low testosterone levels are associated with an increased risk of mortality in ageing men. For example, a United States study reported that male veterans aged > 40 with low testosterone levels (total testosterone < 250 ng/dL or 8.7 nmol/L), were 88% more likely to die in the 4.3 year follow-up period than those with normal testosterone levels. The study controlled for factors such as age and mortality risk.³

Metabolic conditions

There is strong evidence of an association between low testosterone and chronic metabolic conditions, particularly type 2 diabetes mellitus and the metabolic syndrome. Amongst type 2 diabetic men of all ages, one in three are testosterone deficient.⁴ Prevalence varies between 20% and 64% for diabetic men of different ages, with increasing prevalence amongst older men.⁵ Prevalence also increases amongst diabetic men who are obese.⁴ In addition, diabetes has been shown to progress more quickly in men with low testosterone levels.⁶

Metabolic syndrome, a condition which often precedes type 2 diabetes, is characterised by the co-occurrence of several metabolic abnormalities, including insulin resistance, obesity, hypertension and abnormal lipid profiles. There is evidence that hypogonadism is an independent risk factor for the development of metabolic syndrome.⁷ One study, which followed participants for 11 years, showed that non-diabetic hypogonadal men were four times more likely to develop metabolic syndrome than eugonadal men. Men with metabolic syndrome also have a 5.7–7.4 times increased risk of hypogonadism.¹

In addition, data shows associations between the metabolic abnormalities that characterise metabolic syndrome and testosterone levels.¹ Studies have consistently shown an inverse relationship between testosterone levels and insulin concentrations.^8,9 They have also shown an inverse relationship between low testosterone and body mass index (BMI), waist–hip ratio and percentage body fat. It has been proposed that these changes in body composition may mediate the association between hypogonadism and insulin resistance, as changes in body composition may alter lipid profiles.¹Metabolic syndrome increases the risk of cardiovascular disease three-fold, another condition associated with low testosterone levels.⁷

Cardiovascular disease

While long-term studies of cardiovascular morbidity and mortality are lacking, there is evidence that low testosterone levels adversely affect male cardiovascular health. Low testosterone is associated with numerous markers of cardiovascular ill-health, and studies have shown inverse associations between testosterone levels and pro-thrombotic factors, hypertension and hyperlipidaemia.¹

Cross-sectional data show an inverse relationship between testosterone and risk of coronary artery disease. Data from intervention studies show that increasing testosterone levels with testosterone replacement therapy improves markers of coronary artery disease, chronic heart failure and ischaemic heart disease. Parameters – including brachial artery vasoreactivity, coronary vascular tone, exercise capacity and time to 1 mm electrocardiographic ST segment depression – have improved in response to testosterone replacement therapy in several small studies.¹ Furthermore, androgen deprivation therapy has been shown to increase cardiovascular risk.⁷

Muscle, bone and physical function

Evidence that testosterone levels are associated with altered body composition (including muscle mass and bone density) and physical capacity is mounting. It suggests that many of the manifestations of ageing that increase male frailty and reduce physical function are associated with low testosterone. Evidence further suggests that testosterone replacement therapy may improve symptoms of frailty in ageing men with low testosterone.¹

Studies have reported inverse associations between testosterone and bone mineral density, and also decreasing bone mineral density with androgen deprivation therapy.¹

Total testosterone was positively associated with muscle mass in a cross-sectional study. Several randomised studies of the effects of testosterone replacement therapy have reported increased muscle mass, bone mineral density and/or muscle strength with increasing testosterone concentrations.¹

Sexual health

Testosterone deficiency typically results in sexual dysfunction. Reduced libido is the most common symptom, as testosterone regulates the male sex drive and low levels of testosterone cause sexual desire to diminish. However, in rare cases (< 5%), testosterone deficiency and erectile dysfunction may be comorbid. It is therefore recommended that all men presenting with erectile dysfunction are screened for testosterone deficiency.¹⁰

Improving the diagnosis and treatment of hypogonadism

Historically, treatment of hypogonadism in males has aimed to restore sexual function and sense of wellbeing. However, partly because hypogonadism has been perceived as a disease of sexual dysfunction, it has remained under-diagnosed and under-treated.² The growing body of evidence that hypogonadism increases the risk of mortality, frailty and chronic disease has spurred recognition of the need to improve the diagnosis and treatment of hypogonadism to improve systemic health in men.¹

Evidence suggests that prompt diagnosis and treatment of testosterone deficiency can reduce insulin resistance and delay the progression of type 2 diabetes in hypogonadal men. There is also mounting evidence that increasing testosterone levels may reduce male cardiovascular risk and improve body composition.^1,7Diagnosing and treating hypogonadism is therefore of increasing clinical importance, as it offers a new avenue for improving men’s systemic health and longevity.¹

More information

For more information on testerone deficiency in men, see Testosterone Deficiency.

References

Miner MM, Seftel AD. Testosterone and ageing: What have we learned since the Institute of Medicine report and what lies ahead? Int J Clin Prac. 2007;61(4):622-32.
Rice D, Brannigan RE, Campbell RK, et al. Men’s health, low testosterone and diabetes: Individualized treatment and a multidisciplinary approach [online]. American Association of Diabetes Educators; 3 October 2008 [cited 20 March 2010]. Available from URL: http://www.diabeteseducator.org/export/sites/aade/_resources/pdf/Mens_Health_White_Paper.pdf
Shores MM, Matsumoto AM, Sloan KL, Kivlahan DR. Low serum testosterone and mortality in male veterans. Arch Intern Med. 2006;166(15):1660-5.
Allan C. Fact sheet: Diabetes and sexual and reproductive health [online]. Clayton, VIC: Andrology Australia; August 2008 [cited 23 March 2010]. Available from URL: www.andrologyaustralia.org/docs/Factsheet_Diabetes_08.pdf
Kalyani RR, Dobs AS. Androgen deficiency, diabetes and the metabolic syndrome in men. Curr Opin Endocrinol Diabetes Obes. 2007;14(3):226-34.
Miner MM, Sadovsky R. Evolving issues in male hypogonadism: Evaluation, management and comorbidities. Cleve Clin J Med. 2007;74 Suppl 3:S38-46.
Kapoor D, Jones TH. Androgen deficiency as a predictor of metabolic syndrome in aging men: An opportunity for intervention? Drugs Aging. 2008;25(5):357-69.
Selvin E, Feinleib M, Zhang L, et al. Androgens and diabetes in men: results from the Third National Health and Nutrition Examination Survey (NHANES III). Diabetes Care. 2007;30(2):234-8.
Kapoor D, Goodwin E, Channer KS, Jones TH. Testosterone replacement therapy improves insulin resistance, glycaemic control, visceral adiposity and hypercholesterolaemia in hypogonadal men with type 2 diabetes. Eur J Endocrinol. 2006;154(6):899-906.
Conway AJ, Handelsman DJ, Lording DW, et al. Use, misuse and abuse of androgens. The Endocrine Society of Australia consensus guidelines for androgen prescribing. Med J Aust. 2000;172(5):220-4.