Implications of Androgen Assay Accuracy in the Phenotyping of Women With Polycystic Ovary Syndrome
Abstract
Context/objective Hyperandrogenism is a common feature of women with polycystic ovary syndrome (PCOS) and is considered a cardinal element for the diagnosis and phenotyping of this condition. Unfortunately, routinely available methods for measuring serum androgens suffer from major limitations. No data are available on the impact of androgen assay quality on the assignment of PCOS women to the different clinical phenotypes of PCOS, when defined according to the Rotterdam criteria for diagnosis. Patients Two hundred four consecutive Caucasian women with PCOS, diagnosed by the Rotterdam criteria participated in the study. Design Assessment of total T (TT), free T (FT), and androstenedione (A) by both a chemiluminescent assay, routinely available in our hospital, and gold standard methodology, ie, liquid chromatography-mass spectrometry and equilibrium dialysis, was performed. The results were compared and the associations of these data with clinical and metabolic features of PCOS women were analyzed. Results By using gold standard assays, TT was high in 36.3% of women, whereas A only marginally contributed to identifying hyperandrogenemic patients. However, gold standard FT measurement was elevated in 70.6% of the PCOS patients, identifying them as hyperandrogenemic. Routine TT and A assays, and the derived calculated FT, were strikingly inaccurate, with substantial overestimation. These assays erroneously classified 60 patients (29.4%), 32 as false hyperandrogenemic, and 28 as…
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Total T by direct immunoassay misclassifies PCOS in 1 out of 3 subjects.
“As a consequence, total T by direct immunoassay misclassifies PCOS in 1 out of 3 subjects [193].”
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 [193]
In contrast to total T, free T seems to be a better marker to determine hyperandrogenemia in women with PCOS, provided that accurate and high quality methodology is used for measured or calculated free T.
“In contrast to total T, free T seems to be a better marker to determine hyperandrogenemia in women with PCOS [187], provided that accurate and high quality methodology is used for measured or calculated free T [193, 194].”
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 [193]
Notwithstanding more accurate total T results can be achieved with LC-MS/MS, total T may be an insensitive marker for hyperandrogenism in women.
“Notwithstanding more accurate total T results can be achieved with LC–MS/MS, total T may be an insensitive marker for hyperandrogenism in women [193].”
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 [193]
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Self-citation
- Authors
- Tosi, F., Fiers, T., Kaufman, J.-M., Dall'Alda, M., Moretta, R., Giagulli, V. A., Bonora, E., & Moghetti, P.
- Affiliations
- University of Verona (IT)
- Corresponding author
- Moghetti, Paolo
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2016-02
- Volume
- 101
- Issue
- 2
- Pages
- 610-618
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2202442770
- Cited by
- 67
- References
- 6
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 5 · 2023: 9 · 2022: 6 · 2021: 3 · 2020: 4 · 2019: 7 · 2018: 10 · 2017: 9 · 2016: 5 · 2015: 1
- FWCI
- 9.51
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion)
- Funders
- Università degli Studi di Verona
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
- Health Sciences › Medicine › Physiology › Clinical Laboratory Practices and Quality Control
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- polycystic ovary syndrome, hyperandrogenism, free testosterone, total testosterone, androstenedione, Rotterdam criteria, metabolic risk, chemiluminescence assay, equilibrium dialysis
- MeSH terms
- Adult, Algorithms, Androgens, Androstenedione, Dialysis, False Positive Reactions, Female, Humans, Phenotype, Polycystic Ovary Syndrome, Reference Standards, Testosterone, Reproducibility of Results, Hyperandrogenism, Risk Assessment, Young Adult
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