Risk factors for hypogonadism

Hypogonadism (testosterone deficiency) is a highly prevalent and under-diagnosed condition associated both with aging 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 In younger men, common causes of hypogonadism are obesity and stress.3-5

The increased prevalence of hypogonadism in older men is primarily related to an increased prevalence of obesity, type 2 diabetes, and chronic illness, not aging per se.6-14 In the current epidemic of obesity in all age groups,15,16 it is critical for health care professionals to know that excess body fat is a stronger risk factor for low testosterone than age.14 Therefore, testosterone levels should be measured in men with excess body fat and/or large waist size, regardless of age.17

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

Table: Risk factors for hypogonadism.

Risk FactorComment
Obesity45-79% of obese men have hypogonadism.20-23
Abdominal obesityNearly 40% of men with a waist circumference of 94 cm or higher have low testosterone.24

1 of 4 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
Diabetes50-81% of men with type 2 diabetes have hypogonadism.21,26-28
Metabolic syndromeUp to 35% of men with the metabolic syndrome have hypogonadism.29-31
Heart disease1 in 4 (24%) men with coronary heart disease have hypogonadism.32

In men with heart disease, hypogonadism nearly doubles the risk of death.32
StressNearly half of men who report having a high degree of life/work stress have low testosterone.4
Erectile dysfunctionAmong 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).
Chronic diseasesChronic diseases such as liver disease, kidney disease and rheumatoid arthritis are associated with low testosterone.33

In some cases, it is not clear whether the chronic illness is a cause or a consequence of low testosterone. It is possible that the causal relationship may be bi-directional.
Normal agingTestosterone 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.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.12
MedicationsCertain medications, especially opioids,35-38 selective serotonin reuptake inhibitors (SSRIs),39 statins40-42 and glucocorticoid medications43,44 reduce testosterone levels.

5-alpha reductase inhibitors, which inhibit DHT synthesis, impair sexual function45-47 and also reduce testosterone levels.48
Pituitary disordersPituitary dysfunction can impair the release of LH and FSH, which are hormones that affect normal testosterone and sperm production, respectively.49,50
Cancer and cancer treatmentCancer of the testes or pituitary tumors can lead to low testosterone production.

Chemotherapy or radiation therapy can also interfere with testosterone production.49,50
Injury to the testesTesticular damage can cause reduced testosterone production.49,50
HemochromatosisA genetic disorder causing the body to absorb too much iron from the diet. Hemochromatosis can result in the deposition of iron in various body organs, including the hypothalamus, pituitary and testes, which impairs testosterone production.49,50

It is now recognized as a common disorder and 1 in 200 people of northern Europe may be at risk of developing iron overload.50
HIV/AIDSThe HIV virus can cause low levels of testosterone by affecting the hypothalamus, pituitary and testes.49,50
Klinefelter’s syndromeA genetic deficiency in testosterone production. Affects between 1 in 500 and 1 in 1000 men.49,50
Hypothalamic disorderAbnormal development of the hypothalamus and is a risk factor for low testosterone (a.k.a. Kallmann's syndrome).49,50
Mumps orchitisA 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.49,50
Undescended testesFailure of one or both of the testes to descend at birth (which occurs in approximately 1 in 4 boys born prematurely and 1 in 20 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 first year of life or if not corrected in early childhood.49,50

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