SAT-165 Directly Measured Free Testosterone May Better Predict Sexual Symptoms of Androgen Deficiency Than Calculated Free Testosterone Levels

Abstract Disclosure: J. Walravens: None. N. Narinx: None. T. Reyns: None. D.M. Vanderschueren: None. F.C. Wu: None. T. Fiers: None. L. Antonio: None. J. Kaufman: None. B. Lapauw: None. Introduction: Guidelines suggest determination of serum free testosterone (FT) for diagnosis of male hypogonadism, especially in men with borderline low total T or with altered sex hormone-binding globulin. While mathematical approximations of FT (cFT) are most used, direct measurement of FT (mFT) using equilibrium dialysis followed by mass spectrometry (ED LC-MS/MS) is considered the gold standard. It is unclear if mFT can provide additional value over cFT in confirming androgen deficiency. Objective: To evaluate whether low mFT and cFT are differentially associated with sexual symptoms of androgen deficiency. Methods: Total T and SHBG levels were determined using LC-MS/MS and immunoassay, respectively, on serum samples of 525 community-dwelling men aged 55 to 85 years participating in the EMAS study1. FT levels were calculated using the Vermeulen formula and measured directly using ED LC-MS/MS. Sexual symptoms of hypogonadism were assessed using the EMAS Sexual Function Questionnaire. Participants were grouped by low or normal mFT and cFT levels. The cFT threshold was 220 pmol/L2. The mFT threshold was 190 pmol/L, the lower reference limit for mFT in healthy men aged 18-39 years in the SIBLOS study3. Logistic regression was used to determine if men with low FT had increased risk of sexual symptoms compared to those with normal FT. Results: Participants were divided in four groups: normal mFT/normal cFT (n = 258; mean age: 67.4 ± 7.6; mean BMI: 26.8 ± 3.2), normal mFT/low cFT (n = 15; mean age: 63.4 ± 8.6; mean BMI: 27.6 ± 2.5), low mFT/normal cFT (n = 112; mean age: 73.3 ± 8.03; mean BMI 27.2 ± 3.6) and low mFT/low cFT (n = 140; mean age: 74.6 ± 7.8; mean BMI: 28.3 ± 3.2). The low mFT/normal cFT and low mFT/low cFT groups had an increased risk of insufficient spontaneous erections (OR: 2.4 (CI: 1.5-4.0) and 2.8 (1.8-4.6)), less frequent sexual thoughts (OR: 1.9 (1.2-3.1) and 2.5 (1.6-4.0)) and lower sexual desire (OR: 1.8 (1.1-3.0) and 2.0 (1.3-3.1)). The normal mFT/low cFT group had no significantly increased risks of sexual symptoms. Conclusion: Men with low mFT had higher risks of lower sexual function, even with normal cFT. As such, mFT may be more accurate to assess androgen deficiency than cFT. However, given challenges in measuring FT, it is now not easily available for clinicians. Future efforts of academy and industry should focus on harmonizing methods and developing validated diagnostic thresholds for mFT. 1.Lee, D. M. et al. The European Male Ageing Study (EMAS): design, methods and recruitment. Int J Androl32, 11-24 (2009). 2.Wu, F. C. W. et al. Identification of Late-Onset Hypogonadism in Middle-Aged and Elderly Men. New England Journal of Medicine363, 123-135 (2010). 3.Lapauw, B. M. et al. Serum Estradiol Is Associated With Volumetric BMD and Modulates the Impact of Physical Activity on Bone Size at the Age of Peak Bone Mass: A Study in Healthy Male Siblings. Journal of Bone and Mineral Research24, (2009). Presentation: Saturday, July 12, 2025