Free androgen index
Encyclopedia
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
, tall stature, 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.
The Endocrine Society has taken a position against using the FAI to measure Free Testosterone in men:
The FAI has not been scientifically demonstrated to be a valid measurement of free testosterone in men:
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.
Androgen
Androgen, also called androgenic hormone or testoid, is the generic term for any natural or synthetic compound, usually a steroid hormone, that stimulates or controls the development and maintenance of male characteristics in vertebrates by binding to androgen receptors...
status in humans. The ratio is the total testosterone
Testosterone
Testosterone is a steroid hormone from the androgen group and is found in mammals, reptiles, birds, and other vertebrates. In mammals, testosterone is primarily secreted in the testes of males and the ovaries of females, although small amounts are also secreted by the adrenal glands...
level divided by the sex hormone binding globulin
Sex hormone binding globulin
Sex hormone-binding globulin or sex steroid-binding globulin is a glycoprotein that binds to sex hormones, to be specific, testosterone and estradiol...
(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
Albumin
Albumin refers generally to any protein that is water soluble, which is moderately soluble in concentrated salt solutions, and experiences heat denaturation. They are commonly found in blood plasma, and are unique to other blood proteins in that they are not glycosylated...
. 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
Gonadotropin
Gonadotropins are protein hormones secreted by gonadotrope cells of the pituitary gland of vertebrates. This is a family of proteins, which include the mammalian hormones follitropin , lutropin , placental chorionic gonadotropins hCG and eCG and chorionic gonadotropin , as well as at least two...
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
Erectile dysfunction
Erectile dysfunction is sexual dysfunction characterized by the inability to develop or maintain an erection of the penis during sexual performance....
, tall stature, osteoporosis
Osteoporosis
Osteoporosis is a disease of bones that leads to an increased risk of fracture. In osteoporosis the bone mineral density is reduced, bone microarchitecture is deteriorating, and the amount and variety of proteins in bone is altered...
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
Hirsutism
Hirsutism or frazonism is the excessive hairiness on women in those parts of the body where terminal hair does not normally occur or is minimal - for example, a beard or chest hair. It refers to a male pattern of body hair and it is therefore primarily of cosmetic and psychological concern...
or the polycystic ovary syndrome
Polycystic ovary syndrome
Polycystic ovary syndrome is one of the most common female endocrine disorders. PCOS is a complex, heterogeneous disorder of uncertain aetiology, but there is strong evidence that it can to a large degree be classified as a genetic disease....
). 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.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 syndromePolycystic ovary syndrome
Polycystic ovary syndrome is one of the most common female endocrine disorders. PCOS is a complex, heterogeneous disorder of uncertain aetiology, but there is strong evidence that it can to a large degree be classified as a genetic disease....
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
Obesity is a medical condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health, leading to reduced life expectancy and/or increased health problems...
and so the FAI seems more correlated with the degree of obesity than with PCOS itself.