Testosterone Deficiency in Men: Causes, Symptoms, Tests, Treatment and Prognosis

Testosterone deficiency is often part of the ageing process and therefore common in older men. It can also occur at any age as a result of conditions affecting the testicles, or the pituitary gland in the brain. Testosterone deficiency can be treated with testosterone replacement therapy. Any underlying cause for the testosterone deficiency will also need treatment. The outlook will depend on the underlying cause of testosterone deficiency.

In this article:
What is testosterone deficiency?
What causes testosterone deficiency?
How common is testosterone deficiency?
What are the symptoms of testosterone deficiency?
What are the tests for testosterone deficiency?
How is testosterone deficiency treated?
What is the outlook?

What is testosterone deficiency?

Testosterone deficiency occurs when the body is unable to make enough testosterone. It is sometimes called hypogonadism. Testosterone deficiency can significantly affect a man's health and quality of life.

Testosterone is the most important sex hormone in men. Its production is controlled by both the brain and the testicles (testes). The body starts to produce testosterone during puberty. From the age of about 30 years, testosterone levels normally start to decrease.

Testosterone is essential for developing and maintaining male characteristics. Testosterone also has effects on sexual function. Low testosterone levels also increase a man's risk of developing disease of the heart and blood vessels (cardiovascular disease), and increases the risk of early death. A low testosterone level can also significantly reduce a man's quality of life.

What causes testosterone deficiency?

Testosterone deficiency can be caused by normal ageing. However, there are many other different causes of testosterone deficiency. Some causes of testosterone deficiency can be inherited. Testosterone deficiency may be present at birth or it may develop later in life.

Being significantly overweight or obese at any age may be linked to testosterone deficiency.

Temporary testosterone deficiency may be caused by a physical illness, surgery or emotional stress. The testosterone level will go back to normal once the underlying problem has been treated.

Primary testosterone deficiency

Testosterone deficiency may be caused by a failure of the testicles (testes) to make enough testosterone (i.e. disruption of the testis). This is sometimes called primary testosterone deficiency (see figure 1 below). Common causes of primary testosterone deficiency include:

• Klinefelter's syndrome. A male normally has one X and one Y chromosome. In Klinefelter's syndrome, two or more X chromosomes are present in addition to one Y chromosome.
• Undescended testicles.
• Mumps orchitis.
• Haemochromatosis.
• Injury to the testicles.
• Cancer treatment. Both chemotherapy or radiotherapy can interfere with testosterone and sperm production.

Secondary testosterone deficiency

Testosterone deficiency can also be caused by a problem with parts of the brain (hypothalamus and pituitary gland) which make the hormones that stimulate the testicles to make testosterone. This is sometimes called secondary testosterone deficiency (see figure 1 below).

In secondary testosterone deficiency, the testicles are normal but don't function properly because of a problem with the pituitary gland or hypothalamus (i.e. disruption of the hypothalamus or pituitary gland). A number of conditions can cause secondary testosterone deficiency, including:

• Pituitary gland disorders.
• HIV/AIDS: can cause low levels of testosterone by affecting the hypothalamus, the pituitary gland and the testicles.
• Some medicines (such as opiate painkillers and some hormones): can affect testosterone production.

How common is testosterone deficiency?

Men are more likely to develop testosterone deficiency as they get older. It is also more common in men who are overweight and men who are in poor general health with long-term health conditions.

One large study in Europe found that testosterone deficiency affected about 2 in 100 men aged 40 to 79 years. Testosterone deficiency affected about 5 in 100 men aged 70 to 79 years.

What are the symptoms of testosterone deficiency?

In general, the symptoms and signs suggestive of testosterone deficiency in adult males are as listed in the table below.

Symptoms and Signs Suggestive of Testosterone Deficiency in Adult Men
More Specific Signs and Symptoms	Less Specific Signs and Symptoms
Reduced libido Erectile dysfunction (ED) Reduced intensity of orgasm and genital sensation Osteoporosis or low bone mineral density Decreased spontaneous erection Oligospermia or azoospermia Very small or shrinking testes Hot flushes, sweats Breast discomfort, gynecomastia Loss of pubic and axillary hair, reduced shaving	Decreased energy or vitality, increased fatigue Depressed mood Reduced muscle mass and strength Poor concentration and memory Sleep disturbance; increased sleepiness Mild anemia Increased body fat, body mass index Diminished physical or work performance

The table above show features of testosterone deficiency in adult males. However, individuals who develop this condition at other ages will show different symptoms, aside from the ones listed above, as explained below.

If an unborn male baby does not produce enough testosterone during pregnancy then the testicles won't develop properly and the baby may be born with either:

• Female genitals.
• Genitals that are neither clearly male nor clearly female (ambiguous genitals); or
• Underdeveloped male genitals.

If testosterone deficiency develops before puberty then it may also cause:

• Delayed puberty.
• Lack of deepening of the voice.
• Impaired growth of the penis and testicles.
• Excessive growth of the arms and legs compared with the trunk of the body.

In adult males, testosterone deficiency may cause (full list above):

• Erectile dysfunction.
• Infertility.
• Decrease in beard and body hair growth.
• Decrease in muscle mass.
• Development of breast tissue (gynaecomastia).
• Loss of bone density (osteoporosis).

As testosterone levels decrease in older men, some men experience symptoms similar to those of the menopause in women, such as:

• Excessive tiredness (fatigue).
• Decreased sex drive (reduced libido).
• Difficulty concentrating.
• Hot flushes.

What are the tests for testosterone deficiency?

Many older men with testosterone deficiency are never diagnosed. Often the general problems of tiredness, low sex drive and erectile dysfunction are thought to be due to the normal ageing process. Therefore many men don't go to see a doctor to see whether they have testosterone deficiency.

Testosterone deficiency is often identified if you see your doctor about decreased sex drive (reduced libido) or erectile dysfunction. Your doctor will arrange tests, which will include your blood testosterone level.

Men who don't respond to the medicines that are used to treat erectile dysfunction (such as sildenafil), should also have their testosterone level checked.

Figure 1: Primary and secondary testosterone deficiency. LH = luteinizing hormone, FSH = follicular stimulating hormone. Credit: British Society for Sexual Medicine (BSSM)

If tests confirm you have low testosterone, further testing can determine if a problem with your testicles (testes) or a pituitary gland abnormality is the cause. These further tests may include:

• Testing for other hormone levels (some pituitary gland disorders affect more than one hormone, like luteinizing hormone or the follicle stimulating hormone - see figure 1 above).
• Semen analysis.
• Pituitary computerised tomography (CT) scan or magnetic resonance imaging (MRI) scan.
• Genetic tests.
• Testicular biopsy.

How is testosterone deficiency treated?

Early detection in boys can help prevent problems from delayed puberty. Testosterone treatment can stimulate puberty and the development of sex characteristics such as increased muscle mass, beard and pubic hair growth, and growth of the penis.

Early diagnosis and treatment in adult men provide better protection against loss of bone density (osteoporosis) and cardiovascular disease. Treatment can also improve tiredness, general well-being, erectile dysfunction and sex drive.

The treatment for testosterone deficiency also depends on the underlying cause.

Testosterone replacement

When should testosterone replacement therapy be initiated? Your doctor or healthcare provider may want to initiate a trial of testosterone therapy if you have unquestionably low or borderline low testosterone levels and a consistent clinical features of testosterone deficiency.

Testosterone treatment is usually given in the form of a topical gel. Other forms of testosterone treatment include long-acting injections, using a patch applied to your scrotum or skin, subdermal pellets, and pills (buccal).

If you are using testosterone replacement therapy, you should see your doctor for regular check-ups to make sure it is working well and not causing any problems.

Other treatments

If testosterone deficiency is caused by a pituitary gland problem, treatment with pituitary hormones may stimulate sperm production and improve fertility. Testosterone replacement therapy can be used.

If a pituitary tumour is the cause of testosterone deficiency then this will require treatment, such as surgical removal, chemotherapy or radiotherapy, as well as replacement therapy with other hormones.

Although there's often no effective treatment to restore fertility in a man with primary testosterone deficiency, infertility treatments may be helpful.

What is the outlook?

Testosterone replacement therapy is effective, particularly in older men with no underlying condition. The outlook (prognosis) otherwise depends on the underlying cause.

Reference(s)
1). British Society for Sexual Medicine Guidelines (May 2017). Adult Testosterone Adult Testosterone Deficiency. Available online
2). Hackett G, Kirby M, Edwards D, et al: UK policy statements on testosterone deficiency. Int J Clin Pract. 2017 Mar71(3-4). doi: 10.1111/ijcp.12901. Epub 2017 Mar 20. Available online.
3). Hackett G: An update on the role of testosterone replacement therapy in the management of hypogonadism. Ther Adv Urol. 2016 Apr8(2):147-60. doi: 10.1177/1756287215617648. Epub 2015 Dec 9. Available online.
4). Livingston M, Kalansooriya A, Hartland AJ, et al: Serum testosterone levels in male hypogonadism: Why and when to check - A review. Int J Clin Pract. 2017 Nov71(11). doi: 10.1111/ijcp.12995. Epub 2017 Oct 5. Available online.