Age-stratified reference ranges for directly measured serum free testosterone in healthy men

Walravens Joeri; Snaterse Gido; Narinx Nick; Antonio Leen; Reyns Tim; Fiers Tom; Kaufman Jean-Marc; Lapauw Bruno

doi:10.1530/endoabs.106.017

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Endocrine Abstracts (2024) 106 017 | DOI: 10.1530/endoabs.106.017

BES2024 BES 2024 CLINICAL STUDIES (17 abstracts)

Age-stratified reference ranges for directly measured serum free testosterone in healthy men

Walravens Joeri ¹ , Snaterse Gido ¹ , Narinx Nick ² , Antonio Leen ² , Reyns Tim ³ , Fiers Tom ³ , Kaufman Jean-Marc ¹ & Lapauw Bruno ¹

Author affiliations

¹Ghent University Hospital, Department of Endocrinology, Gent, Belgium. ²Leuven University Hospital, Laboratory of Clinical and Experimental Endocrinology, Leuven, Belgium. ³Ghent University Hospital, Department of Clinical Chemistry, Gent, Belgium

Introduction: Determination of serum (calculated) free testosterone (FT) in clinical practice has been suggested by several clinical guidelines for the diagnosis of male hypogonadism in men with borderline total T concentrations and in situations with altered sex hormone-binding globulin, as it correlates better with androgen exposure than total T. The gold-standard for the determination of FT levels is considered to be directly measured free testosterone (mFT) using equilibrium dialysis followed by mass spectrometry (ED LC-MS/MS). However, no widely accepted reference ranges are available for this clinical parameter. We established mFT reference ranges for healthy men aged 18 to 79 years.

Objective: To establish reference ranges for directly measured FT in serum of healthy adult men.

Methods: Reference ranges were determined following Clinical & Laboratory Standards Institute guideline C28A3c per age decade. Serum samples were analyzed from healthy men participating in the SIBLOS/SIBEX and EMAS studies, both population-based cohort studies. Additionally, healthy men between 18 to 24 years were recruited locally at UZ Gent. Exclusion criteria were medications or conditions that affect sex steroid metabolism or a BMI larger than 35 kg/m². mFT levels were measured in 996 men using ED LC- MS/MS as previously reported (1). Subsequently, 95% reference ranges were determined using the non- parametric method.

Results: We present age-stratified 95% mFT reference ranges. These reference ranges show an expected, decreasing trend of mFT with aging. Median mFT decreases at a remarkably stable rate of, on average, 14% per decade up into the 6th decade of life. The lower and upper limits decrease by, on average, 16% and 18% per decade, respectively.

Table 1
Age category (years)	Median mFT (ng/dl)	95% mFT reference range (ng/dl)
18-29 (n = 140)	12,0	6,7 - 25,3
30-39 (n = 252)	9,8	4,9 - 18,5
40-49 (n = 207)	8,1	4,3 - 14,2
50-59 (n = 146)	7,1	3,8 - 12,8
60-69 (n = 126)	6,4	3,4 - 11,7
70-79 (n = 125)	5,6	2,7 - 8,7

Conclusion: We have determined mFT reference ranges in healthy men aged 18 to 79. These reference ranges are a first step to improving the framework for further development and integration of free testosterone measurements and calculations in clinical practice.

References: 1. Fiers et al. (2018). Reassessing Free-Testosterone Calculation by Liquid Chromatography–Tandem Mass Spectrometry Direct Equilibrium Dialysis. J Clin Endocrinol Metab. 2018;103(6). doi:10.1210/jc.2017-02360.