Risk factors for hypogonadism

Functional hypogonadism (testosterone deficiency) is a highly prevalent and under-diagnosed condition associated both with ageing and common medical comorbidities,1 as summarised in the table below. Although the prevalence of hypogonadism increases with advancing age, it can also occur in younger men.2 Hypogonadism has been associated with a high risk of obesity and a high prevalence of stress.3-5

While the typical decline of serum testosterone (T) concentrations with ageing is considerable, there is evidence that specific changes in health and lifestyle such as increased BMI are accompanied by accelerated loss of serum T.6-14 it is critical for health care professionals to recognise the association between high body fat and a reduction in plasma testosterone concentrations.14 Therefore, testosterone levels should be measured in men with excess body fat and/or large waist size, regardless of age.15,16,17

Although some risk factors for low testosterone are non-modifiable, improving lifestyle habits (such as making healthier food choices, regularly exercising, moderating alcohol consumption and reducing stress) may reduce the risk of hypogonadism.9,18,19

Table: Risk factors for hypogonadism.

Risk Factor Comment
Obesity Prevalence of hypogonadism in obese men has been shown to be around 29-45% however, one study with 33 men showed this to be up to 79% in morbidly obese men who required bariatric surgery.20-23
Abdominal obesity Nearly 50% of men with a waist circumference of 94 cm or higher have low testosterone, rising to 87% in those with a waist circumference of more than 120 cm.24

More than 1 in 3 (38%) men aged 20-59 have abdominal obesity and low testosterone.5

Younger men (age 20-39 years) with a large waist circumference (>102 cm or >40 inches) have a 6-fold increase risk of low testosterone.5

Among men with both abdominal obesity and erectile dysfunction, nearly 70% have low testosterone.25
Diabetes Prevalence of hypogonadism in type 2 diabetic men has been shown to be around 45-69% however, one study with 110 men showed this to be up to 79%.21,26,27
Metabolic syndrome Up to 35% of men with metabolic syndrome have hypogonadism.28-31
Heart disease 1 in 5 men" (this is in line with our disease core claims) - the number differs depending on which type of testosterone they measured in this paper32

In men with heart disease, hypogonadism has been associated with a "two-fold" (as per our core claim) increased risk of death.31
Stress Nearly half of men with erectile dysfunction who report having a high degree of life/work stress have low testosterone.4
Erectile dysfunction Among men with erectile dysfunction, over one third (36%) have low testosterone levels.4

Low testosterone can cause erectile dysfunction and/or non-responsiveness to treatment with PDE5i (phosphodiesterase 5 inhibitors).6,32
Chronic diseases Chronic diseases such as liver disease, kidney disease and rheumatoid arthritis are associated with low testosterone.33,34
Normal ageing Testosterone levels decline with age in most men.
 
  • After the age of 40 years:
    • total testosterone decreases on average -4 ng/dL (-0.124 nmol/L) per year7 or 0.4% - 2% per
      year.8,18
    • bioavailable testosterone decreases on average -2 to -3% per year.8
  • In older men (over 60 years of age):
    • The average rate of decline in total testosterone levels is approximately 110 ng/dL per decade after the peak in young adulthood.35
Medications Certain medications, especially opioids,36 selective serotonin reuptake inhibitors (SSRIs),37 statins38‐40 and glucocorticoid medications41 reduce testosterone levels.

5-alpha reductase inhibitors, which inhibit DHT synthesis, impair sexual function41-43 and also reduce testosterone levels.44
Pituitary disorders Pituitary dysfunction can impair the release of LH and FSH, which are hormones that affect normal testosterone and sperm production, respectively.45,46
Cancer and cancer treatment Cancer of the testes or pituitary tumors can lead to low testosterone production.45,46

Chemotherapy or radiation therapy can also interfere with testosterone production.45,46
Injury to the testes Damage to the testis can cause reduced testosterone production.45,46
Haemochromatosis A genetic disorder causing the body to absorb too much iron from the diet. Haemochromatosis can result in the deposition of iron in various body organs, including the hypothalamus, pituitary and testes, which impairs testosterone production.47,48

It is now recognised as a common disorder and 1 in 300 to 500 people of Europe may be at risk of developing iron overload.48
HIV/AIDS The HIV virus can cause low levels of testosterone by affecting the hypothalamus, pituitary and testes.45,46
Klinefelter’s syndrome A genetic chromosome disorder that can cause a deficiency in testosterone production, which affects between 1 in 500 and 1 in 1000 men45,46 This condition is largely undiagnosed or receives a late diagnosis in adulthood. It has been estimated that only 25% to 40% of subjects with 47,XXY Klinefelter syndrome are ever diagnosed.51
Hypothalamic disorder Abnormal development of the hypothalamus this is a risk factor for low testosterone (a.k.a. Kallman syndrome).45,46
Mumps orchitis A mumps infection that involves the testes as well as the saliva glands may result in long-term damage affecting testosterone production if it occurs during adolescence or adulthood.49
Undescended testes Failure of one or both of the testes to descend at birth (which occurs in up to 30% of boys born prematurely and approximately 2%–5% of boys born at term) may lead to a failure of the testes to develop properly if the condition does not correct itself naturally within the 6 months of life or if not corrected in early childhood.50

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