Free androgen index
Free Androgen Index or FAI is a ratio used to determine abnormal androgen status in humans. The ratio is the total testosterone level divided by the sex hormone binding globulin (SHBG) level, and then multiplying by a constant, usually 100. The concentrations of testosterone and SHBG are normally measured in nanomols per liter. FAI has no units.
The majority of testosterone in the blood does not exist as the free molecule. Instead around half is tightly bound to sex hormone binding globulin, and the other half is weakly bound to albumin. Only a small percentage is unbound, under 3% in females, and less than 0.7% in males. Since only the free testosterone is able to bind to tissue receptors to exert its effects, it is believed that free testosterone is the best marker of a person's androgen status. However, free testosterone is difficult and expensive to measure, and many laboratories do not offer this service.
The free androgen index is intended to give a guide to the free testosterone level, but it is not very accurate. Consequently, there are no universally agreed 'normal ranges', and levels slightly above or below quoted laboratory reference ranges may not be clinically significant.
Reference ranges depend on the constant in the calculation - 100 is used in the formula above, and the following suggested ranges are based on this. As with any laboratory measurement, however, it is vital that results are compared against the reference range quoted for that laboratory. Neither FAI nor free or total testosterone measurements should be interpreted in isolation; as a bare minimum, gonadotropin levels should also be measured.
As a guide, in healthy adult men typical FAI values are 30-150. Values below 30 may indicate testosterone deficiency, which may contribute to fatigue, erectile dysfunction, osteoporosis and loss of secondary sex characteristics. In women, androgens are most often measured when there is concern that they may be raised (as in hirsutism or the polycystic ovary syndrome). Typical values for the FAI in women are 7-10.
Various companies manufacture testing equipment and kits to measure this index. To test about 1 mL of blood is required.
Usefulness as a biochemical marker
Validity as a measure of free testosterone
Statistical analysis has shown FAI to be a poor predictor of bioavailable testosterone and of hypogonadism.
The Endocrine Society has taken a position against using the FAI to measure Free Testosterone in men:
The FAI is often used as a surrogate for FT, and the FAI correlates well with FT in women but not men. Because T production is regulated by gonadotropin feedback in men, changes in SHBG, which alter FT concentrations, will be compensated by autoregulation of T production but not so in women. In addition, much circulating T in women is derived from the peripheral conversion of adrenal dehydroepiandrosterone and dehydroepiandrosterone sulfate that also is not subject to feedback control. Because SHBG is present in such large excess in women (10–100:1), FT concentrations are driven primarily by SHBG abundance. In addition, T excess in women lowers SHBG concentrations, which raises the FT concentration and contributes to the strong correlation of 1/SHBG with FT.
The FAI has not been scientifically demonstrated to be a valid measurement of free testosterone in men:
The Free Androgen Index (FAI) was initially proposed as a measure for assessing the circulating testosterone availability in female hirsutism. The extension of its use, by a number of investigators, to males has not been formally justified.
Role in identifying polycystic ovary syndrome
The best single biochemical marker for polycystic ovary syndrome is a raised testosterone level, but "combination of SHBG and testosterone to derive a free testosterone value did not further aid the biochemical diagnosis of PCOS". Instead SHBG is reduced in obesity and so the FAI seems more correlated with the degree of obesity than with PCOS itself.
- Fraser, Marianne; Farrokh Sohrabi. "Free Androgen Index". Online Medical Encyclopedia. University of Rochester Medical Center. Retrieved 11 July 2014.
- Morris PD, Malkin CJ, Channer KS, Jones TH (August 2004). "A mathematical comparison of techniques to predict biologically available testosterone in a cohort of 1072 men" (PDF). Eur. J. Endocrinol. 151 (2): 241–9. doi:10.1530/eje.0.1510241. PMID 15296480.
- Rosner W, Auchus RJ, Azziz R, Sluss PM, Raff H (February 2007). "Position statement: Utility, limitations, and pitfalls in measuring testosterone: an Endocrine Society position statement". J. Clin. Endocrinol. Metab. 92 (2): 405–13. doi:10.1210/jc.2006-1864. PMID 17090633.
- The Free Androgen Index is not valid for adult males
- Robinson S, Rodin DA, Deacon A, Wheeler MJ, Clayton RN (March 1992). "Which hormone tests for the diagnosis of polycystic ovary syndrome?". Br J Obstet Gynaecol 99 (3): 232–8. doi:10.1111/j.1471-0528.1992.tb14505.x. PMID 1296589.
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- Ly LP, Handelsman DJ (March 2005). "Empirical estimation of free testosterone from testosterone and sex hormone-binding globulin immunoassays". Eur. J. Endocrinol. 152 (3): 471–8. doi:10.1530/eje.1.01844. PMID 15757865.
- Leo Vankrieken (May 1997). "Testosterone and the Free Androgen Index" (PDF). Diagnostic Products Corporation, Siemens Healthcare. Retrieved 2009-11-01.