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Free Androgen Index (FAI) is a ratio used to determine abnormal
androgen An androgen (from Greek ''andr-'', the stem of the word meaning "man") is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This in ...
status in humans. The ratio is the total
testosterone Testosterone is the primary sex hormone and anabolic steroid in males. In humans, testosterone plays a key role in the development of male reproductive tissues such as testes and prostate, as well as promoting secondary sexual characteris ...
level divided by the
sex hormone binding globulin Sex hormone-binding globulin (SHBG) or sex steroid-binding globulin (SSBG) is a glycoprotein that binds to androgens and estrogens. When produced by the Sertoli cells in the seminiferous tubules of the testis, it has also been called androg ...
(SHBG) level, and then multiplying by a constant, usually 100. The concentrations of testosterone and SHBG are normally measured in
nanomols per liter Molar concentration (also called molarity, amount concentration or substance concentration) is a measure of the concentration of a chemical species, in particular of a solute in a solution, in terms of amount of substance per unit volume of solu ...
. FAI has no unit. \text = 100 \times \left(\frac\right) 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 Albumin is a family of globular proteins, the most common of which are the serum albumins. All the proteins of the albumin family are water-soluble, moderately soluble in concentrated salt solutions, and experience heat denaturation. Albumins ...
. Only a small percentage is unbound, under 3% in males, and less than 0.7% in females. 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 (it requires a time-consuming
dialysis Dialysis may refer to: *Dialysis (chemistry), a process of separating molecules in solution **Electrodialysis, used to transport salt ions from one solution to another through an ion-exchange membrane under the influence of an applied electric pote ...
step), 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 (especially in males — see endocrine society commentary below). 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 Gonadotropins are glycoprotein hormones secreted by gonadotropic cells of the anterior pituitary of vertebrates. This family includes the mammalian hormones follicle-stimulating hormone (FSH) and luteinizing hormone (LH), the placental/ chori ...
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 Fatigue describes a state of tiredness that does not resolve with rest or sleep. In general usage, fatigue is synonymous with extreme tiredness or exhaustion that normally follows prolonged physical or mental activity. When it does not resolve ...
,
erectile dysfunction Erectile dysfunction (ED), also called impotence, is the type of sexual dysfunction in which the penis fails to become or stay erect during sexual activity. It is the most common sexual problem in men.Cunningham GR, Rosen RC. Overview of ma ...
, osteoporosis and loss of
secondary sex characteristics Secondary sex characteristics are features that appear during puberty in humans, and at sexual maturity in other animals. These characteristics are particularly evident in the sexually dimorphic phenotypic traits that distinguish the sexes of a ...
. In women, androgens are most often measured when there is concern that they may be raised (as in
hirsutism Hirsutism is excessive body hair on parts of the body where hair is normally absent or minimal. The word is from early 17th century: from Latin ''hirsutus'' meaning "hairy". It usually refers to a "male" pattern of hair growth in a female that ...
or the
polycystic ovary syndrome Polycystic ovary syndrome, or PCOS, is the most common endocrine disorder in women of reproductive age. The syndrome is named after the characteristic cysts which may form on the ovaries, though it is important to note that this is a sign and n ...
). Typical values for the FAI in women are 7-10.


Testing

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.''The Free Androgen Index is not valid for adult males ''
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Role in identifying polycystic ovary syndrome

The best single biochemical marker for
polycystic ovary syndrome Polycystic ovary syndrome, or PCOS, is the most common endocrine disorder in women of reproductive age. The syndrome is named after the characteristic cysts which may form on the ovaries, though it is important to note that this is a sign and n ...
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 Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's ...
and so the FAI seems more correlated with the degree of obesity than with PCOS itself.


References


External links

* * {{cite web , author=Leo Vankrieken , title=Testosterone and the Free Androgen Index , url=http://diagnostics.siemens.com/siemens/en_GLOBAL/gg_diag_FBAs/files/news_views/spring00/techreports/zb158-a.pdf , date=May 1997 , publisher=Diagnostic Products Corporation, Siemens Healthcare , access-date=2009-11-01 , archive-url=https://web.archive.org/web/20090611234913/http://diagnostics.siemens.com/siemens/en_GLOBAL/gg_diag_FBAs/files/news_views/spring00/techreports/zb158-a.pdf , archive-date=2009-06-11 , url-status=dead Testosterone