Interpreting serum testosterone concentrations in diagnosis of male androgen deficiency

A low serum testosterone concentration must be interpreted in the context of the man’s clinical features. For a diagnosis, the following criteria for diagnosing male androgen deficiency must all be met:

  • symptoms or signs are consistent with male androgen deficiency
  • unequivocally low fasting early morning total serum testosterone concentration, confirmed by repeat measurement on a different day
  • hypothalamic–pituitary–testicular (HPT) axis dysfunction confirmed.

Serum testosterone concentrations have a wide diurnal variation and are highest in the morning. Samples must be taken between 8 am and 10 am1, after overnight fasting and confirmed by a repeat measurement on a different day.

Note: Low serum testosterone concentration must be confirmed by repeating the measurement.

Systemic illness temporarily lowers testosterone concentrations and can confound assessment of symptoms. Testosterone should not be measured during an acute illness or convalescence.

Note: Do not measure serum testosterone concentration during an acute illness or convalescence.

Reference ranges for total serum testosterone concentration vary because of factors such as assay method and age. Published ranges relate to mass spectrometry but at the time of writing most laboratories in Australia use immunoassays, so in practice, local reference ranges are used2.

Some conditions, such as obesity, diabetes and depression, and use of opioids or glucocorticoids, cause a mild reduction in total serum testosterone concentration that does not amount to androgen deficiency, and is generally managed by treating the underlying condition. This finding is referred to as functionally low total serum testosterone concentration. Serum gonadotrophin (luteinising hormone [LH] and follicle stimulating hormone [FSH]) concentrations are usually normal; this is consistent with mild functional central suppression of the HPT axis. The underlying conditions may also cause:

  • confounding symptoms that overlap with those of androgen deficiency (particularly the less specific features) but are not usually a result of the low testosterone concentration
  • reduced hepatic synthesis of sex hormone–binding globulin ([SHBG], the main protein that binds testosterone)—particularly in men with obesity, insulin resistance or glucocorticoid use. This can reduce the total serum testosterone concentration without necessarily affecting the amount of unbound (free) testosterone or having a clinical impact.

Some laboratories report free serum testosterone concentrations (calculated using the total serum testosterone and SHBG concentrations). Neither calculations nor reference ranges for free serum testosterone are established. A low free serum testosterone concentration (without a low total serum testosterone concentration) does not warrant testosterone therapy because evidence of clinical benefit is lacking.

If there is uncertainty about the interpretation of serum testosterone concentrations, seek specialist advice.

1 For shift workers or sleep-deprived men, measure testosterone shortly after waking.Return
2 When assayed by mass spectrometry (not immunoassay which is used by most laboratories), the lower limit for total serum testosterone in males aged 21 to 35 years with normal sexual and reproductive function is 10.4 nanomol/L and in healthy males aged 70 to 89 years is 6.4 nanomol/L. Reference ranges using mass spectrometry are less well defined for males aged 35 to 70 years.Return