For healthcare professionals

Testosterone deficiency (hypogonadism)

What is testosterone deficiency?

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

Testosterone deficiency (hypogonadism) can occur in men of any age, however, there is a progressive decline in testosterone levels as men age.2 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).3

Download the latest UK Guidance on testosterone deficiency. Written by the BSSM (British Society for Sexual Medicine) panel.

Download

How important is it to treat testosterone deficiency?

There are clearly established links between testosterone deficiency (hypogonadism) and low mood, cardiovascular risk, diabetes and metabolic syndrome, osteoporosis, and other chronic illnesses4.

Low testosterone values are also associated with increased mortality, even after adjusting for age, comorbidities, and other clinical variables.5

Reduced survival in men with low testosterone levels

Reduced survival in men with low testosterone levels - Graph

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; known risk factors for cardiovascular disease.1

Symptoms, physical examination and blood tests

Signs and symptoms suggestive of testosterone deficiency (hypogonadism) in men1,7
Incomplete sexual development, eunuchoidism, aspermia
Reduced sexual desire (libido) and activity
Decreased spontaneous erections
Reduced muscle bulk and strength
Hot flushes, night sweats
Loss of body (axillary and pubic) hair, reduced shaving
Breast discomfort, gynaecomastia
Very small or shrinking testes
Inability to father children, low or zero sperm counts
Height loss, low trauma fracture, low bone mineral density (osteoporosis)
Other less specific symptoms and signs associated with testosterone deficiency (hypogonadism)1
Decreased energy, motivation, initiative, aggressiveness, self-confidence
Feeling sad or blue, depressed mood, dysthymia
Diminished physical or work performance
Poor concentration and memory
Increased body fat, body mass index
Insulin resistance
Sleep disturbance, increased sleepiness
Mild anaemia

The symptom most associated with testosterone deficiency (hypogonadism) is reduced libido, however other manifestations can also be associated with low testosterone, and a diagnosis of testosterone deficiency (hypogonadism) is made on the basis of low serum testosterone levels occurring in association with one or more of the symptoms and signs listed in the table.6,7

Download the latest UK Guidance on testosterone deficiency. Written by the BSSM (British Society for Sexual Medicine) panel.

Download

Measurement of testosterone levels in the diagnosis of testosterone deficiency

Values for normal testosterone ranges vary among laboratories depending on the commercial assay employed, and local values should be consulted when a diagnosis of testosterone deficiency (hypogonadism) is considered. There is no generally accepted lower limit of normal. However, a morning testosterone concentration in the blood of 12-35 nmol/L can be considered normal.1,8 Testosterone treatment might be recommended if this value is found to be below 12 nmol/L. There is general agreement that total testosterone levels above 12 nmol/L (346 ng/dL) or free testosterone levels above 250 pmol/L (72 pg/mL) do not require testosterone treatment.8

The British Society of Sexual Medicine (BSSM),9 European Association of Urology (EAU), International Society for the Study of the Aging Male (ISSAM), International Society of Andrology (ISA), European Academy of Andrology (EAA) and American Society of Andrology (ASA) suggest that serum total testosterone levels below 8 nmol/L (231 ng/dL) or free testosterone below 180 pmol/L (52 pg/mL) require testosterone replacement therapy.7 In addition, concentrations of the pituitary hormones can be measured. They provide information as to whether the testosterone deficiency (hypogonadism) is due to disorders of testicular function or of the hypothalamic-pituitary system.

Since symptoms of testosterone deficiency (hypogonadism) become manifest between 8 and 12 nmol/L (231–346 ng/dL), trials of treatment of at least 6 months can be considered in men with a clinical picture of testosterone deficiency (hypogonadism) and borderline testosterone levels when alternative causes of these symptoms have been excluded.6,7

Counselling your patient

The following should be discussed with your male patient prior to initiating testosterone replacement therapy:

  1. Fertility: Testosterone therapy may impair sperm quantity, quality and function.10 So it is important to determine if your patient would like preserve his fertility and/or father a child biologically in the near future as testosterone replacement therapy may not be an appropriate treatment option.
  2. Cardiovascular disease: Some studies have shown an increased risk of cardiovascular disease with testosterone replacement therapy, especially in older men.11,12 On the other hand, other studies have shown some potential benefit of testosterone replacement in hypogonadal men in terms of cardiovascular health,13 but the number of patients in these studies is too small to make such conclusions. More recent studies and meta analyses however have found that the risk of cardiovascular events was similar in hypogonadal men treated and not treated with testosterone.14 Your patient should therefore have a cardiovascular risk assessment prior to initiating testosterone therapy.
  3. Prostate health: Active prostate cancer is an absolute contraindication to initiating testosterone therapy. Recent studies have failed to show a causal link between testosterone and prostate cancer.10 Careful evaluation of your patient’s prostate heath by performing a digital rectal examination (DRE) and measurement of his serum PSA is necessary before commencing treatment.

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