Testosterone deficiency, or hypogonadism, is a clinical syndrome resulting from a failure of the testes to produce physiological levels of testosterone (androgen deficiency), sperm, or both, because of disruption of one or more levels of the hypothalamic-pituitary-gonadal axis.1 Hypogonadism can occur in men of any age, however, there is a progressive decline in testosterone levels as men age. Late-onset hypogonadism (LOH; age-related hypogonadism) is a clinical and biochemical syndrome associated with advancing age and characterised by symptoms and a deficiency in serum testosterone levels below the young healthy adult male reference range of approximately 12–35 nmol/L (350–1000 ng/dL).2
Unlike the clearly defined decrease in hormone levels associated with female menopause, the decline in androgen levels with advancing age in men is gradual and variable, and the late-onset hypogonadism is more appropriate than the colloquial terms "male menopause" or "andropause" to refer to the annual decrease in testosterone levels of 0.5% to 2% which occur with advancing age, independent of chronic conditions associated with aging.3
Testosterone deficiency has many causes, including but not limited to age, metabolic syndrome, obesity, and Type II diabetes. This common disorder has an uncertain prevalence, with studies estimating it affects between 5.6% and 50% of the male population. The increasing life expectancy, aging population, and lifestyle factors are expected to increase these figures even further.4
The AMS (Aging Males’ Symptoms) scale is a 17-point self-rating questionnaire designed to help assess the symptoms of testosterone deficiency and monitor treatment-related changes if a diagnosis of testosterone deficiency (hypogonadism) is confirmed and testosterone replacement therapy initiated.
When testosterone deficiency is defined on the basis of a combination of testosterone level or measurement and signs and symptoms according to the current Endocrine Society guidelines,1 other population-based studies have estimated an overall prevalence in men aged 30 years and over of 5.6%, rising to 18.4% among 70-year olds.7 Approximately 40% of men aged 45 years or over (mean age 60.5 years; range 45–96 years) screened in primary care had hypogonadism (defined as testosterone <300 ng/dL), with significantly higher rates in men with hypertension, hyperlipidemia, obesity, diabetes, prostate disease, and asthma or chronic obstructive pulmonary disease.8 However, despite hypogonadism affecting a substantial proportion of the adult male population, only a small proportion are being treated for hypogonadism and the condition is probably underdiagnosed.6
Estimates of Men in Europe at Risk of Testosterone Deficiency (hypogonadism)
(numbers in millions; estimates made around 2006)
|Region||Age 50–64||Age 65–79||Age 80+|
|Whole European Union||42.53||29.61||9.63|
Figures from Carruthers M. The Aging Male 2009; 12(1):21-28
The essential role of testosterone in the health and well-being of males is well established. Testosterone is responsible for typical male sexual characteristics and is required for a healthy life physically and psychologically, enabling and maintaining erectile function, libido, and overall sexual satisfaction. Testosterone also helps to maintain body composition and bone mass, positive mood, and physical energy. Accordingly, the health consequences of hypogonadism can be quite wide-ranging, and include fatigue, depression, erectile dysfunction, loss of libido, loss of facial and body hair, decrease in muscle mass, development of gynaecomastia, and osteoporosis.1
Low testosterone can be diagnosed by an assessment of symptoms and a blood test to measure testosterone levels. If tests confirm hypogonadism, a range of different testosterone replacement therapies and formulations are available to normalise testosterone levels.1
There are clearly established links between hypogonadism and low mood, cardiovascular risk, diabetes and metabolic syndrome, osteoporosis, and other chronic illnesses.
Low testosterone values are also associated with increased mortality, even after adjusting for age, comorbidities, and other clinical covariates.
Reduced survival in men with low testosterone levels
Unadjusted Kaplan-Meier survival curves for the three testosterone level groups in men aged 40 years and older.
Normal = ≥2 measurements of >250 ng/dL; Low = ≥2 measurements of <250 ng/dL; Equivocal = ≥1 low and ≥ 1 normal testosterone levels.
Adapted from Shores MM, et al. Archives of Internal Medicine 2006; 166:1660-5
Testosterone replacement therapy can improve libido, mood, increase bone density, and improve body composition and quality of life in hypogonadal men. Treatment may also improve insulin resistance, reduce central obesity, and improve other risk factors for cardiovascular disease.1
- Bhasin S, Cunningham GR, Hayes FJ, Matsumoto AM, Snyder PJ, Swerdloff RS, Montori VM; Task Force, Endocrine Society. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2010 Jun;95(6):2536-59. doi: 10.1210/jc.2009-2354. Review.
- ISA, ISSAM, EAU, EAA and ASA recommendations: investigation, treatment and monitoring of late-onset hypogonadism in males. Wang C, Nieschlag E, Swerdloff RS, Behre H, Hellstrom WJ, Gooren LJ, Kaufman JM, Legros JJ, Lunenfeld B, Morales A, Morley JE, Schulman C, Thompson IM, Weidner W, Wu FC. Aging Male. 2009 Mar;12(1):5-12. doi: 10.1080/13685530802389628
- Seftel AD. Male hypogonadism. Part I: Epidemiology of hypogonadism. Int J Impot Res 2006; 18(2):115-20
- Jia H. Review of health risks of low testosterone and testosterone administration. World Journal of Clinical Cases. 2015;3(4):338. doi:10.12998/wjcc.v3.i4.338.
- Tajar et al. J Clin Endocrinol Metab. 2010, 95(4):1810–1818
- Dandona P, Rosenberg M. A practical guide to male hypogonadism in the primary care setting. Int J Clin Pract 2010;64(6):682-696
- Araujo AB, Esche GR, Kupelian V, et al. Prevalence of symptomatic androgen deficiency in men. J Clin Endocrinol Metab 2007; 92(11):4241-7
- Mulligan T, Frick MF, Zuraw QC, et al. Prevalence of hypogonadism in males aged at least 45 years: the HIM study. Int J Clin Pract 2006; 60(7):762-9