Directly measured free testosterone may better predict sexual symptoms of hypogonadism than calculated approximations

Joeri Walravens; Nick Narinx; Tim Reyns; Dirk Vanderschueren; Wu Frederick C.; Tom Fiers; Leen Antonio; Jean-Marc Kaufman; Bruno Lapauw

doi:10.1530/endoabs.112.013

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Endocrine Abstracts (2025) 112 013 | DOI: 10.1530/endoabs.112.013

BES2025 BES 2025 CLINICAL STUDIES (21 abstracts)

Directly measured free testosterone may better predict sexual symptoms of hypogonadism than calculated approximations

Joeri Walravens ^1,2 , Nick Narinx ^3,4 , Tim Reyns ¹ , Dirk Vanderschueren ^3,4 , Frederick C. Wu ⁵ , Tom Fiers ¹ , Leen Antonio ^3,4 , Jean-Marc Kaufman ^1,2 & Bruno Lapauw ^1,2

Author affiliations

¹Ghent University Hospital, Gent, Belgium; ²Ghent University, Gent, Belgium; ³KU Leuven, Leuven, Belgium; ⁴University Hospitals Leuven, Leuven, Belgium; ⁵University of Manchester, Altrincham, United Kingdom

Introduction: Several clinical guidelines suggest assessment of serum free testosterone (FT) for diagnosis of hypo - gonadism in men. Mathematical approximations of FT (cFT) are most used. However, direct measurement of FT (mFT) using equilibrium dialysis followed by mass spectrometry (ED LC-MS/MS) is considered the gold-standard. We evaluated whether low mFT or low cFT are differentially associated with sexual symptoms of hypogonadism.

Methods: Serum samples were selected of 525 men aged 55 to 85 years participating in the EMAS study (1). Total T and SHBG levels were measured using LC-MS/MS and immunoassay, respectively. FT levels were calculated using the Vermeulen formula and measured using ED LC-MS/MS. Sexual symptoms of hypogonadism were assessed using the EMAS Sexual Function Questionnaire. The cFT threshold was placed at 220 pmol/l (2). The mFT threshold was placed at 190 nmol/l, based on the lower reference for healthy adult men aged 18-39. Logistic regression was used to determine altered probabilities of symptoms compared to the group with normal FT levels.

Results: Participants were divided in four groups: normal mFT/normal cFT (n = 242), normal mFT/low cFT (n = 13), low mFT/normal cFT (n = 128) and low mFT/low cFT (n = 142). The low mFT/normal cFT and low mFT/low cFT groups had an increased risk of insufficient erections (OR: 2.2 and 2.9), less frequent sexual thoughts (OR: 1.9 and 2.5) and lower sexual desire (OR: 2.2 and 2.2).

Conclusion: The low mFT groups had increased odds of sexual symptoms, even with normal cFT levels. As such, mFT levels may be more accurate to assess androgen exposure than cFT levels.

References: 1. Lee, D. M. et al. The European Male Ageing Study (EMAS): design, methods and recruitment. Int J Androl 32>, 11–24 (2009).2. Corona, G. et al. European Academy of Andrology (EAA) guidelines on investigation, treatment and monitoring of functional hypogonadism in males. Andrology 8, 970–987 (2020).

Keywords: Male hypogonadism, free testosterone, sexual function