Diagnosing Androgen Deficiency

Diagnosing Male Androgen Deficiency

The diagnosis of testosterone deficiency is a combination of both clinical features and serum testosterone measures - neither in isolation is consistently reliable.

Biochemical evaluation.

Biochemical evaluation of serum testosterone is confounded by numerous variables including:

  • Inter-individual variability in normal serum T
  • Poor assay performance characteristics
  • Inappropriate reference ranges

Because of the diurnal rhythm in hormone secretion in males blood samples should preferably be taken in the morning, when hormones levels are at their highest. Individual variations in serum testosterone levels can occur due to time of day, medication usage, stress, illness or recent surgery.

In general pathology laboratories today use fully automated, non extraction, competitive protein-binding immunoassays for determining serum androgens.

This method is quicker and less expensive than techniques such as extraction radioimmunoassay, gas chromatography or mass spectrometry. Numerous studies in Europe, USA and Australia have shown significant variances between analysers and laboratories in accurately determining serum testosterone results.

It is highly recommended that measurement of blood levels of testosterone, sex-hormone binding globulin (SHBG), luteinising hormone (LH) and follicle-stimulating hormone (FSH) be conducted using well-calibrated immunoassays to accurately reflect circulating hormone levels.

The total testosterone reference ranges commonly adopted for determination of -Y´normal¡, and ´low¡ testosterone are potentially misleading in the determination of androgen deficiency because the results do not take into account the effects of SHBG.

Endogenous testosterone in the circulation can be free (unbound), weakly bound to albumin, or tightly bound to SHBG. The free and albumin bound testosterone is available for use by the body, however the largest percentage (approximately 98-99%) is bound to SHBG and unavailable. Any increase in SHBG will decrease the amount of available testosterone.

SHBG is elevated by aging, smoking, high alcohol intake, insulin, oral estrogens, thyroxine, aging and some medications.

The Free Androgen Index (FAI), while not as yet a validated index in men, does make allowance for the effects of SHBG. The FAI is determined by the total testosterone level divided by the SHBG level multiplied by 100.

Bioavailable testosterone (BT), Calculated Free Testosterone (CFT) and Free Testosterone (FT) measurements employ alternative methods of analysis and do exhibit higher correlation than other total testosterone or FAI measurements. Because these tests involved assays not commonly employed at most laboratories they are not frequently requested by clinicians.

They can however be determined using total serum testosterone and SHBG measurements by mathematical calculations. A Free and Bioavailable Testosterone calculator is available at https://www.issam.ch/freetesto.htm.

Clinical features

Whether due to primary or secondary hypogonadism or ADAM (Androgen Deficiency in the Ageing Male) the signs and symptoms as a result of the androgen deficiency are consistent.

Individuals may exhibit some or all of the following:

  • Changes in mood (fatigue, depression, anger)
  • Decreased body hair (feminization)
  • Decreased bone mineral density and possible resulting osteoporosis
  • Decreased lean body mass and muscle strength
  • Decreased libido and erectile quality
  • Increased visceral fat
  • Oligospermia or azoospermia

The diagnosis of hypogonadism can be facilitated through the use of questionnaires such as the ADAM questionnaire (simple) or the AMS (Aging Males’ Symptoms) rating scale (detailed).

The ADAM questionnaire (Morley and Perry, 1999) is a 10 question yes/no checklist to a limited range of andropausal symptoms. It has limited use as a diagnostic tool due to its poor sensitivity and specificity.

Personal Assessment Tools

The German designed AMS questionnaire (Heinemann et al, 1999) is a validated 17 question self-rating symptoms based questionnaire. There are three key domains of assessment %Gβ%@ psychological (5 questions), somatic (7 questions) and sexual 5 questions). Responses to each question are assigned a rating 1-5 (none to extremely severe) and the total sum of all subscales provides a total score. Scores can range from a total low of 17 to a maximum of 85, with a complaint score measuring 50 considered severe.

It is well suited to assist in both the diagnosis and for the monitoring of treatment in patients using testosterone replacement therapy.

The AMS has been translated into 16 different languages and is the most applicable questionnaire currently available for determining symptoms associated with testosterone deficiency.

AMS questionnaire click here.

AMS evaluation form click here.

Once it has been determined that the patient is testosterone deficient and replacement is considered an option it is imperative that carcinoma of the prostate or breast cancer be excluded prior to initiating therapy. DRE (digital rectal examination) and determination of serum prostate-specific antigen (PSA) are mandatory in men over the age of 40 years.