Diagnosing Androgen Insufficiency

In 2002 The Princeton Consensus Statement provided a definitive classification of female androgen insufficiency as well as made recommendations regarding diagnosis and assessment of androgen deficiency states in women.

The androgen insufficient female was defined as:

  • Diminished sense of well-being, dysphoric mood and/or blunted motivation
  • Persistent, unexplained fatigue
  • Sexual function changes, including decreased libido, sexual receptivity and pleasure
  • (potential) bone loss, decreased muscle strength, changes in cognition/memory.

The statement set these symptoms against a background of women being estrogen replete, exclusion of other causes, and biochemical support using appropriate hormone assays.

Assessment of patients must include:

  • History, including sexual history

In terms of a sexual history it is vital that the practitioner knows his or her limits. If one has little or no training in sexual counselling referral is recommended. The important principle to practice is not to allow one’s own sexual prejudices or -Y΄hang-ups‘ to be judgemental; ensure the patient understand the issue of doctor-patient confidentiality; be sensitive and optimistic; on relationship issues encourage consultation with the partner present; allow extended time of consultations; understand that problems may not be revealed without specific enquiry, sensitive and embarrassing issues may not be readily volunteered.

  • Examination

It is important that a general ΄good female health‘ check be undertaken.
Routine screening includes: mammogram, PAP smear, cardiovascular parameters, fasting blood glucose, serum TSH, full blood examination and iron studies.

Further investigations of specific medical disorders such as transvaginal ultrasound/hysteroscopy for abnormal bleeding, diagnostic mammogram and FNA for breast lump(s), urodynamic testing for incontinence and DEXA for osteoporosis are warranted.

Psychological evaluation of mood, well-being and sexual function. See Physician Assessment Tools.

  • Biochemical investigation

Testosterone and SHBG levels are essential in the assessment of androgen insufficiency as a cause of loss of libido, mood and well-being. These measures are important regardless of menopausal status, age or ethnic background.

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 testosterone secretion blood samples should preferably be taken in the morning, when hormones levels are at their highest.

If the patient is pre-menopausal testosterone levels should be tested after day seven of the menstrual cycle. 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 ΄sensitive‘ immunoassays to accurately reflect circulating hormone levels.

The total testosterone reference ranges commonly adopted for determination of ΄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.

It is therefore essential that in females that the Free Androgen Index (FAI) or Calculated Free Testosterone (CFT) values be determined.

The FAI is a calculation correcting for testosterone that is bound to SHBG and more accurately indicates the amount of testosterone available for use.

All pathology laboratories will calculate the FAI according the formula below:

(Sensitive testosterone/SHBG)* 100 = FAI

If the FAI is less than 2 in the clinical setting of androgen deficiency testosterone therapy should be an option.

Bioavailable testosterone (BT), Calculated Free Testosterone (CFT) and Free Testosterone (FT) measurements employ alternative methods of analysis and do exhibit far higher correlation than total testosterone measurements alone.

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.