Performance of Total Testosterone Measurement to Predict Free Testosterone for the Biochemical Evaluation of Male Hypogonadism
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PURPOSE: Guidelines recommend serum total testosterone measurement as the initial test to evaluate male hypogonadism, reserving free testosterone assessment for men with suspected sex hormone-binding globulin abnormalities or total testosterone near the lower limit of normal. We determined the performance of total testosterone measurement as a test to identify men with normal vs low free testosterone. MATERIALS AND METHODS: We examined the electronic medical records of all 3,672 men evaluated for hypogonadism by a serum testosterone panel, including total testosterone, sex hormone-binding globulin, albumin and calculated free testosterone, from January 1, 1997 through December 31, 2007 in a network that serves veterans in Washington. RESULTS: The sensitivity and specificity of low total testosterone (less than 280 ng/dl) to rule out and predict low calculated free testosterone was 91.0% and 73.7%, respectively. At thresholds of less than 350 and less than 400 ng/dl the sensitivity of total testosterone for low calculated free testosterone increased to 96.8% and 98.2%, and at thresholds of less than 150 and less than 200 ng/dl specificity increased to 98.9% and 92.6%, respectively. CONCLUSIONS: Total testosterone between 280 and 350 ng/dl is not sensitive enough to reliably exclude hypogonadism. Total testosterone must exceed 350 to 400 ng/dl to reliably predict normal free testosterone. Except when levels are less than 150 ng/dl total testosterone measurement has low specificity for the biochemical diagnosis of hypogonadism.
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In a cohort of 3672 men, total T had an AUC of 0.93 as a predictor of calculated free T, but 61.7% of subjects with decreased total T had normal calculated free T.
“Overall, with an area under the receiver operator curve of 0.93, total T was, in general, found to be a good predictor of calculated free T. In contrast, however, 61.7% of cohort subjects with decreased total T levels had normal calculated free T [249].”
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 [249]
At total T of 280 ng/dL, sensitivity and specificity for predicting low calculated free T were 91.0% and 73.7%; sensitivity ≥95% only at total T 350 ng/dL, specificity ≥98% only at total T 150 ng/dL.
“In this study, at the assays lower limit of normal (total T of 280 ng/dL), sensitivity and specificity of predicting low calculated free T were only 91.0 and 73.7%, respectively. Acceptable levels for sensitivity, 95.0% and up, were only acquired at a total T cut-off of 350 ng/dL, while on the other hand specificity only reached satisfactory levels of 98.0% and more at a total T cut-off of 150 ng”
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 [249]
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- Authors
- Anawalt, B. D., Hotaling, J. M., Walsh, T. J., & Matsumoto, A. M.
- Affiliations
- University of Washington (US)
- Corresponding author
- Anawalt, Bradley D.
- Venue
- Journal of Urology
- Published
- 2012-04
- Volume
- 187
- Issue
- 4
- Pages
- 1369-1373
- ISSN
- 0022-5347 (ISSN-L)
- 1527-3792
- PMC
- PMC10368284
- OpenAlex
- W2031612883
- Cited by
- 55
- References
- 14
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 3 · 2023: 3 · 2022: 8 · 2021: 1 · 2020: 1 · 2019: 4 · 2018: 2 · 2017: 4 · 2016: 6 · 2015: 4 · 2014: 7 · 2013: 4 · 2012: 3
- FWCI
- 4.62
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Journal of Urology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (5u54hd012629-31)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (U54HD042454, U54HD42454, U54-HD-12629, U54HD-012629)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- male hypogonadism, total testosterone, free testosterone, sex hormone-binding globulin, sensitivity and specificity, veterans
- MeSH terms
- Adult, Aged, Aged, 80 and over, Humans, Hypogonadism, Male, Middle Aged, Predictive Value of Tests, Testosterone, Young Adult
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