The free androgen index is inaccurate in women when the SHBG concentration is low
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Summary: Objective/Context: The free androgen index (FAI) is known to give erroneous results in men, but it is still a commonly used test for the investigation of hyperandrogenism in women. This study aimed to compare the results of the FAI with the gold standard equilibrium dialysis method for free testosterone in women. Design/Patients: Free serum testosterone T (ED‐T) and total serum T (T) were measured by equilibrium dialysis and LC‐MS/MS in patients with polycystic ovarian syndrome (n = 130), normal female controls (n = 53) and normal males (n = 120). Calculated free T (cFT) and free androgen index (FAI) were also measured in these patients. In addition, cFT was retrospectively calculated in 4223 female patients with a normal T (<1.6 nmol/L) routinely investigated for hyperandrogenism. Results: The cFT showed good agreement with measured ED‐T, and the ratio cFT/ED‐T was stable across all SHBG concentrations. In contrast, the FAI/ED‐T ratio and the FAI/cFT ratio increased when the concentration of SHBG fell below 30 nmol/L. Conclusions: The FAI is not a reliable indicator of free T when the SHBG concentration is low and would give misleading information in a large number of women being investigated for hyperandrogenism.
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FAI is highly impacted by SHBG concentrations; in subjects with altered SHBG, FAI can increase or decrease dramatically, causing artificial over- or underestimation of free fraction androgens.
“Caution, however, should be exercised, as the FAI is highly impacted by SHBG concentrations. In human subjects, male or female, in whom SHBG concentrations are altered, FAI could increase or decrease dramatically. This results in an artificial over- or underestimation of free fraction androgens [220].”
From Role of sex hormone-binding globulin in the free hormone hypothesis and the relevance of free testosterone in androgen physiology (2022) · cites this paper as [220]
The Results (page not supplied) show that FAI rises sharply as SHBG falls, and the Discussion reports a similar increase in the FAI/free-testosterone ratio in men and women. The paper supports caution about overestimation at low SHBG, but does not establish that altered SHBG generally causes either over- or underestimation. (LLM, conf=0.88)
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Androgens, Endometriosis and Pain
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- Authors
- Keevil, B. G., Adaway, J., Fiers, T., Moghetti, P., & Kaufman, J.
- Affiliations
- Manchester Academic Health Science Centre (GB)
- Ghent University Hospital (BE)
- University of Verona (IT)
- Corresponding author
- Keevil, Brian G.
- Venue
- Clinical Endocrinology
- Publisher
- Wiley
- Published
- 2018-02-26
- Volume
- 88
- Issue
- 5
- Pages
- 706-710
- ISSN
- 0300-0664 (ISSN-L)
- 1365-2265
- OpenAlex
- W2789993335
- Cited by
- 35
- References
- 4
- Citations by year
- 2026: 1 · 2025: 7 · 2024: 4 · 2023: 4 · 2022: 3 · 2021: 6 · 2020: 4 · 2019: 4 · 2018: 2
- FWCI
- 4.27
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Clinical Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion, other-oa)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- free androgen index, sex hormone-binding globulin, free testosterone, hyperandrogenism, polycystic ovary syndrome, equilibrium dialysis, women, diagnostic accuracy
- MeSH terms
- Androgens, Chromatography, Liquid, Female, Humans, Polycystic Ovary Syndrome, Retrospective Studies, Sex Hormone-Binding Globulin, Testosterone, Hyperandrogenism, Tandem Mass Spectrometry
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