The free androgen index is a measure of the biologically active testosterone in the blood. It is a ratio of the total testosterone to the level of sex hormone-binding globulin (SHBG). About half of all testosterone in the blood is tightly bound to SHBG and the rest is either free or loosely bound to albumin. Only the portion that is free or bound to albumin is considered biologically active. The portion bound to SHBG is considered biologically inert. Thus, by calculating the ratio of total testosterone to SHBG, one can get a measurement of physiologically active testosterone in the blood. The free androgen index is expressed in the same units and multiplied by 100 to provide a number similar to the free testosterone concentration in blood. Normal free androgen index results are slightly higher than free testosterone levels, however. As a ratio, there are no units. The free androgen index may be a more accurate assessment of free testosterone in women than in men.
More about the relationship between Free Androgen Index and SHBG:
Sex hormone-binding globulin (SHBG) and the free androgen index (FAI) are closely related measures that provide insight into androgen status and metabolic health. Here is a summary of their relationship:
SHBG is a protein that binds to sex hormones like testosterone, regulating their bioavailability. Lower SHBG levels lead to higher levels of unbound or "free" testosterone. The FAI is calculated as (total testosterone / SHBG) x 100 and represents the percentage of total testosterone that is unbound and biologically active.[1]
An elevated FAI, resulting from low SHBG and/or high testosterone, is associated with adverse cardiometabolic risk factors such as insulin resistance, dyslipidemia, and systemic inflammation in both men and women.[2][4][5] In women, a high FAI is a key feature of polycystic ovary syndrome (PCOS) and is linked to reproductive issues like menstrual irregularities and hirsutism.[4]
Conversely, higher SHBG levels lead to lower FAI and are associated with a more favorable cardiometabolic profile.[2][5] Factors like obesity, insulin resistance, and certain medications can suppress SHBG production, raising FAI.[1][3] Age, genetics, and ethnicity also influence SHBG and FAI levels.[3][5]
In summary, SHBG and FAI are inversely related measures that reflect androgen bioavailability. Their levels are influenced by metabolic factors and have implications for reproductive and cardiometabolic health in both sexes.[1][2][3][4][5]
Normal Ranges for Free Androgen Index:
• Male:
− 20 to 29 years: 30.0−128.0
− 30 to 39 years: 24.0−122.0
− 40 to 49 years: 14.0−126.0
− Older than 49 years: 18.0−82.0
• Female:
− 20 to 49 years: 0.4−8.4
− Older than 49 years: 0.4−6.6
Sources:
https://www.labcorp.com/test-menu/25691/free-androgen-index-fai
https://www.labcorp.com/test-menu/35496/testosterone-free-direct
https://www.uptodate.com/contents/overview-of-androgen-deficiency-and-therapy-in-women
Citations:
[1] https://www.ahajournals.org/doi/10.1161/01.cir.0000157697.54255.ce
[2] https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/free-androgen-index
[3] https://www.endocrinologiapediatrica.org/modules.php?idarticulo=364&idlangart=EN&name=articulos
[4] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8279613/
[5] https://pubmed.ncbi.nlm.nih.gov/15769764/
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Elevated Free Androgen Index (FAI) in Men
Elevated FAI levels in men can signify various underlying conditions and metabolic disturbances.
Conditions Associated with Elevated FAI
- Hypogonadism (low testosterone production) can paradoxically lead to increased FAI due to decreased sex hormone-binding globulin (SHBG) levels.
- Obesity and insulin resistance are linked to lower SHBG, resulting in higher FAI despite normal total testosterone.
- Androgen-secreting tumors of the testes or adrenal glands can increase androgen levels and FAI.
Possible Reasons for Elevation
- Certain medications like glucocorticoids can suppress SHBG production, raising FAI.
- Chronic conditions like HIV/AIDS, hepatitis C, and liver disease can affect SHBG and androgen levels.
- Genetic factors and race (e.g., higher FAI in African American men) may play a role.
Potential Treatment Considerations
- Lifestyle modifications like weight loss and exercise can improve insulin sensitivity and SHBG levels.
- Medications to lower androgen levels or block their effects may be used for androgen-secreting tumors.
- Surgical removal of tumors may be necessary in some cases.
Other Biomarkers and Associations
- Insulin resistance markers like HOMA-IR and oral glucose tolerance test (OGTT) are inversely associated with total testosterone and SHBG.
- Obesity, as measured by body mass index (BMI), is inversely associated with total testosterone and SHBG.
- Age is inversely associated with total testosterone but positively associated with SHBG.
Nutrient Associations
- Zinc and vitamin D deficiencies have been linked to lower testosterone levels.
- A diet high in processed foods and refined carbohydrates may contribute to insulin resistance and lower SHBG.
Elevated Free Androgen Index (FAI) in Women
Elevated FAI levels in women can signify underlying conditions related to androgen excess or imbalance.
Conditions Associated with Elevated FAI
- Polycystic ovary syndrome (PCOS) is strongly associated with elevated FAI levels. PCOS is characterized by high androgen levels, irregular menstrual cycles, and polycystic ovaries.
- Androgen-secreting tumors of the ovaries or adrenal glands can lead to excessive androgen production and elevated FAI.
- Congenital adrenal hyperplasia and other adrenal disorders that disrupt steroidogenesis can result in high androgen levels and FAI.
Clinical Manifestations of High FAI
- Hirsutism (excessive hair growth in a male pattern)
- Acne
- Irregular or absent menstrual cycles
- Infertility or difficulty conceiving
- Male pattern baldness or hair thinning
Impact on Quality of Life
- Higher FAI levels were associated with poorer quality of life in women with PCOS, particularly in domains related to hirsutism, menstrual irregularity, depression, and weight concerns.
Diagnosis and Evaluation
- FAI is calculated as: (total testosterone / SHBG) x 100%
- FAI levels >5 are considered indicative of PCOS in women.
- Additional tests like prolactin, 17-hydroxyprogesterone, and pelvic ultrasound may be ordered to identify the underlying cause.
In summary, elevated FAI in both men and women often signifies underlying conditions related to androgen imbalance or excess. Proper evaluation and management are crucial to address the underlying cause and associated symptoms.
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Adult men with too little testosterone may lose lean muscle mass, become fatigued, feel weak, and develop depression. Low testosterone can reduce libido and contribute to erectile dysfunction. Gynecomastia—the development of breast tissue in men—is another symptom of low testosterone. Boys with low testosterone may fail to develop secondary sex characteristics such as deepened voice, pubic hair, and facial hair. Low testosterone is less problematic for women, but it can interfere with sexual function.
Some specific causes of low free androgen index are:
- Hypogonadism
- Testicular injury
- Testicular cancer
- Testicular cancer treatment
- Type 2 diabetes mellitus
- Obesity
- Chronic liver disease
- Chronic kidney disease
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As a PRO member and medical practitioner, Healthmatters.io has been an invaluable tool for tracking my clients' data. The layout is intuitive, making it easy to monitor trends and spot patterns over time. The ability to customize reports and charts helps me present information clearly to my clients, improving communication and outcomes. It's streamlined my workflow, saving me time and providing insights at a glance. Highly recommended for any practitioner looking for a comprehensive and user-friendly solution to track patient labs!
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