Endocrine Abstracts

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 spectromety (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 69 years.

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

Methods: Reference ranges were determined following Clinical & Laboratory Standards Institute guideline C28-A3c per age decade. Serum samples were analyzed from healthy men participating in the SIBLOS/SIBEX and EMAS studies, both population-based cohort studies. Exclusion criteria were medications or conditions that affect sex steroid metabolism or a BMI larger than 35 kg/m2. mFT levels were measured in 867 men using ED LC-MS/MS as previously reported (1). Subsequently, 95% reference ranges were determined using the non-parametric method.

Results: We present 95% mFT age-stratified reference ranges. These reference ranges show an expected, decreasing trend of mFT with aging. Lower limits and median mFT decrease at a remarkably stable rate of, on average, 12% per decade up into the 6th decade of life. However, in the upper limit, a marked decrease of 25% occurs after 39 years, followed by smaller decreases of 6% per decade in older age categories.

Conclusion: We have determined mFT reference ranges in healthy men aged 25 to 69. 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.

Reference: 1. Fiers T, Wu F, Moghetti P, Vanderschueren D, Lapauw B, Kaufman JM. 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