Free Androgen Index (FAI / Testosterone:SHBG Ratio)

The free androgen index can be used to estimate physiologically active testosterone.

In most men and women, >50% of total circulating testosterone is bound to sex hormone-binding globulin, SHBG, and most of the rest is bound to albumin.^1-3 SHBG-bound testosterone is not readily available for intracellular complex formation because of SHBG's high binding affinity for testosterone.² Thus, testosterone-bound SHBG is considered to be biologically inactive. Albumin has a much lower binding affinity for testosterone but binds a significant portion of the total testosterone because albumin is present at much higher plasma concentrations than SHBG.^2,4 The rapid dissociation of “weakly bound” testosterone from albumin, together with a relatively long transit time of albumin through target tissue capillary beds, result in the availability of essentially all albumin-bound testosterone for steroid-receptor interaction.⁴ The sum of the free- and albumin-bound testosterone is often referred to as bioavailable testosterone. The concentration of testosterone in the various free and bound forms is essentially a function of total testosterone concentration and the relative concentrations of SHBG and albumin. It can be predicted that increased SHBG will decrease the concentration of both free and bioavailable testosterone for a given total testosterone concentration. The free androgen index can be used to estimate physiologically active testosterone.^2,3 This index is calculated as the ratio of total testosterone divided by SHBG (both expressed in the same units) and multiplied by 100 to yield numerical results comparable in free testosterone concentration.^2,5-7

1. Klee GG, Heser DW. Techniques to measure testosterone in the elderly. Mayo Clin Proc. 2000; 75(Suppl):S19-S25. PubMed 10959211

2. Wheeler MJ. The determination of bioavailable testosterone. Ann Clin Biochem. 1995; 32(Pt 4):345-357. PubMed 7486793

3. Gronowski AM, Landau-Levine M. Reproductive Endocrine Function. In: Burtis CA, Ashwood ER, eds. Tietz Textbook of Clinical Chemistry. 3rd ed. Philadelphia, Pa: WB Saunders Co;1999:1601-1641.

4. Manni A, Pardridge WM, Cefalu W, et al. Bioavailability of albumin-bound testosterone. J Clin Endocrinol Metab. 1985; 61(4):705-710. PubMed 4040924

5. Vermeulen A, Verdonck L, Kaufman JM. A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab. 1999; 84(10):3666-3672. PubMed 10523012

6. Blight LF, Judd SJ, White GH. Relative diagnostic value of serum non-SHBG-bound testosterone, free androgen index and free testosterone in the assessment of mild to moderate hirsutism. Ann Clin Biochem. 1989; (Pt 4):311-316. PubMed 2764484

7. Wilke TJ, Utley DJ, Total testosterone, free-androgen index, calculated free testosterone, and free testosterone by analog RIA compared in hirsute women and in otherwise-normal women with altered binding of sex-hormone-binding globulin. Clin Chem. 1987; 33(8):1372-1375. PubMed 3608155