Free Androgen Index

Overview

The Free Androgen Index (FAI) is an important biochemical calculation used to assess biologically available testosterone in the bloodstream. As described in the document, FAI is derived from the ratio of total testosterone to sex hormone–binding globulin (SHBG). Because a significant portion of circulating testosterone is bound to SHBG and therefore inactive, this ratio offers a clearer picture of androgen activity than total testosterone alone.

FAI is particularly valuable in evaluating abnormal androgen status, especially among women. The document highlights its clinical usefulness in diagnosing conditions such as polycystic ovary syndrome (PCOS), hirsutism, acne, virilization, and Cushing’s syndrome. The index reflects the amount of testosterone free enough to exert biological effects in tissues, making it an essential marker in endocrine and reproductive evaluations.

The FAI formula is:

FAI = (Total Testosterone × 100) ÷ SHBG

FAI does not have units and is expressed only as a numerical ratio. Testing methodologies include immunoassay, electrochemiluminescence, and liquid chromatography–mass spectrometry (LC–MS). Blood collection requires 3–4 ml of venous blood in a red or green tube, preferably between 6–10 a.m. Serum should be separated within 2 hours for accurate results, with specimens stored refrigerated. EDTA plasma is considered unacceptable.

Symptoms

The document links abnormal Free Androgen Index levels to clinical symptoms associated with androgen excess or deficiency. These symptoms guide clinicians to investigate androgen activity through FAI testing.

Symptoms Suggesting Elevated Androgens (High FAI):

1. Hirsutism – excessive hair growth in women
2. Acne – persistent or severe breakouts
3. Virilization – features such as deepening voice or increased muscle mass
4. Symptoms of PCOS – menstrual irregularity, obesity, metabolic disturbances

Symptoms Suggesting Low Androgens (Low FAI):

1. Erectile dysfunction
2. Reduced sexual desire
3. Easy fatigue
4. Osteoporosis or decreased bone strength

These clinical manifestations reflect disturbances in androgen availability and justify evaluation using FAI measurements.

Causes

The document identifies several underlying conditions and physiological factors that can alter the Free Androgen Index by affecting testosterone production, SHBG levels, or both.

Causes of High FAI (Increased Androgen Availability):

1. PCOS – a major cause of hyperandrogenism in women
2. Cushing’s syndrome – leads to increased androgen production
3. Adrenal tumors – elevate adrenal androgen output
4. Ovarian tumors – can produce excess androgens
5. Abdominal obesity – lowers SHBG, increasing the calculated FAI
6. Reduced SHBG levels from metabolic or hormonal imbalances

Causes of Low FAI (Reduced Androgen Availability):

1. Decreased testosterone production
2. High SHBG levels
3. Hormonal or metabolic conditions affecting androgen binding

Analytical Causes (Test Limitations):

1. FAI is an indirect measure and not a true free testosterone measurement
2. SHBG assay variability can affect accuracy
3. FAI is not valid when SHBG is extremely low or extremely high
4. Abnormal albumin levels, such as in nephrotic syndrome, malnutrition, or liver cirrhosis, can alter interpretation

These causes highlight the need for careful evaluation of clinical and biochemical context.

Risk Factors

The document outlines several risk indicators associated with altered androgen levels that may necessitate FAI testing.

Risk Factors for Elevated FAI:

1. Women with PCOS
2. Presence of adrenal or ovarian tumors
3. Abdominal obesity
4. Conditions causing reduced SHBG
5. Endocrine disorders such as Cushing’s syndrome

Risk Factors for Altered or Uninterpretable FAI:

1. Extremely low or high SHBG levels
2. Individuals with abnormal albumin, including nephrotic syndrome
3. Malnutrition
4. Cirrhosis of the liver
5. Biological variability in SHBG and testosterone measurements

Understanding these risk factors helps determine when FAI is a reliable marker and when alternative methods such as equilibrium dialysis or LC–MS are preferred.

Prevention

Prevention in the context of FAI focuses on ensuring accurate sample collection, minimizing analytical errors, and selecting proper testing conditions as described in the document.

Testing & Sample Handling Prevention:

1. Collect 3–4 ml venous blood in a red or lithium-heparin green tube
2. Avoid EDTA plasma
3. Draw blood between 6–10 a.m. for hormonal stability
4. Separate serum within 2 hours of collection
5. Store samples refrigerated for optimal stability
   1. Ambient: 48 hours
   2. Refrigerated: 1 week
   3. Frozen: 2 months

Clinical Prevention Measures:

1. Evaluate SHBG levels before interpreting FAI
2. Use FAI cautiously in patients with abnormal albumin
3. Prefer LC–MS or equilibrium dialysis when precise free testosterone measurement is required
4. Correlate FAI with symptoms and clinical findings for accurate assessment