Leen Antonio1, Frederick C W Wu1, Terence W O'Neill1, Stephen R Pye1, Tomas B Ahern1, Michaël R Laurent1, Ilpo T Huhtaniemi1, Michael E J Lean1, Brian G Keevil1, Giulia Rastrelli1, Gianni Forti1, György Bartfai1, Felipe F Casanueva1, Krzysztof Kula1, Margus Punab1, Aleksander Giwercman1, Frank Claessens1, Brigitte Decallonne1, Dirk Vanderschueren1. 1. Department of Clinical and Experimental Medicine (L.A., B.D., D.V.), KU Leuven, Laboratory of Clinical and Experimental Endocrinology, Leuven, Belgium; Department of Cellular and Molecular Medicine (L.A., M.R.L., F.C.), KU Leuven, Laboratory of Molecular Endocrinology, Leuven, Belgium; Department of Endocrinology (L.A., B.D., D.V.), University Hospitals Leuven, Leuven, Belgium; Andrology Research Unit (F.C.W.W., T.B.A.), Endocrinology and Diabetes Research Group, Institute of Human Development, Faculty of Medical and Human Sciences, The University of Manchester, Manchester, UK; Manchester Royal Infirmary (F.C.W.W.), Central Manchester University Hospitals National Health Services (NHS) Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK; Arthritis Research UK Centre of Epidemiology (T.W.O.N., S.R.P.), The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK; National Institute for Health Research Manchester Musculoskeletal Biomedical Research Unit (T.W.O.N.), Central Manchester NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK; Department of Clinical and Experimental Medicine (M.R.L.), KU Leuven, Laboratory of Gerontology and Geriatrics, Leuven, Belgium; Department of Surgery and Cancer, Imperial College London (I.T.H.), Hammersmith Campus, London, UK; Department of Physiology (I.T.H.), Institute of Biomedicine, University of Turku, Turku, Finland; Department of Human Nutrition (M.E.J.L.), University of Glasgow, Glasgow, UK; Department of Clinical Biochemistry (B.G.K.), University Hospital of South Manchester, Manchester, UK; Sexual Medicine and Andrology Unit (G.R.), Department of Experimental Clinical and Biochemical Sciences, University of Florence, Florence, Italy; Endocrinology Unit (G.F.), Department of Experimental Clinical and Biochemical Sciences, University of Florence, Florence, Italy; Department of Obstetrics, Gynaecology and Andrology (G.B.), Albert Szent-György Medica
Abstract
CONTEXT: During aging, total testosterone (TT) declines and SHBG increases, resulting in a greater decrease in calculated free T (cFT). Currently, guidelines suggest using TT to diagnose androgen deficiency and to reserve cFT only for men with borderline TT. OBJECTIVE: Our objective was to investigate if either low cFT or low TT is more strongly associated with androgen-related clinical endpoints. METHODS: A total of 3334 community-dwelling men, aged 40-79 years, were included in this study. Differences in clinical variables between the referent group of men with both normal TT (≥10.5 nmol/liter) and normal cFT (≥220 pmol/liter) with those who had normal TT/low cFT, low TT/normal cFT, and low TT/low cFT were assessed by regression models adjusted for age, center, body mass index, and comorbidities. RESULTS: A total of 2641 men had normal TT (18.4 ± 5.5 [mean ± SD] nmol/liter)/normal cFT (326 ± 74 pmol/liter), 277 men had normal TT (14.2 ± 3.7)/low cFT (194 ± 23), 96 men had low TT (9.6 ± 0.7)/normal cFT (247 ± 20), and 320 men had low TT (7.8 ± 2.5)/low cFT (160 ± 55). Men with normal TT/low cFT were older and in poorer health. They had higher SHBG and LH and reported more sexual and physical symptoms, whereas hemoglobin and bone ultrasound parameters were lower compared to the referent group. Men with low TT/normal cFT were younger and more obese. They had lower SHBG, but LH was normal, whereas features of androgen deficiency were lacking. CONCLUSIONS: Low cFT, even in the presence of normal TT, is associated with androgen deficiency-related symptoms. Normal cFT, despite low TT, is not associated with cognate symptoms; therefore, cFT levels should be assessed in men with suspected hypogonadal symptoms.
CONTEXT: During aging, total testosterone (TT) declines and SHBG increases, resulting in a greater decrease in calculated free T (cFT). Currently, guidelines suggest using TT to diagnose androgen deficiency and to reserve cFT only for men with borderline TT. OBJECTIVE: Our objective was to investigate if either low cFT or low TT is more strongly associated with androgen-related clinical endpoints. METHODS: A total of 3334 community-dwelling men, aged 40-79 years, were included in this study. Differences in clinical variables between the referent group of men with both normal TT (≥10.5 nmol/liter) and normal cFT (≥220 pmol/liter) with those who had normal TT/low cFT, low TT/normal cFT, and low TT/low cFT were assessed by regression models adjusted for age, center, body mass index, and comorbidities. RESULTS: A total of 2641 men had normal TT (18.4 ± 5.5 [mean ± SD] nmol/liter)/normal cFT (326 ± 74 pmol/liter), 277 men had normal TT (14.2 ± 3.7)/low cFT (194 ± 23), 96 men had low TT (9.6 ± 0.7)/normal cFT (247 ± 20), and 320 men had low TT (7.8 ± 2.5)/low cFT (160 ± 55). Men with normal TT/low cFT were older and in poorer health. They had higher SHBG and LH and reported more sexual and physical symptoms, whereas hemoglobin and bone ultrasound parameters were lower compared to the referent group. Men with low TT/normal cFT were younger and more obese. They had lower SHBG, but LH was normal, whereas features of androgen deficiency were lacking. CONCLUSIONS: Low cFT, even in the presence of normal TT, is associated with androgen deficiency-related symptoms. Normal cFT, despite low TT, is not associated with cognate symptoms; therefore, cFT levels should be assessed in men with suspected hypogonadal symptoms.
Authors: Andrea Salonia; Giulia Rastrelli; Geoffrey Hackett; Stephanie B Seminara; Ilpo T Huhtaniemi; Rodolfo A Rey; Wayne J G Hellstrom; Mark R Palmert; Giovanni Corona; Gert R Dohle; Mohit Khera; Yee-Ming Chan; Mario Maggi Journal: Nat Rev Dis Primers Date: 2019-05-30 Impact factor: 52.329
Authors: L Antonio; D Vanderschueren; N Narinx; K David; J Walravens; P Vermeersch; F Claessens; T Fiers; B Lapauw Journal: Cell Mol Life Sci Date: 2022-10-07 Impact factor: 9.207
Authors: Drew B Day; Brent R Collett; Emily S Barrett; Nicole R Bush; Shanna H Swan; Christina Wang; Sheela Sathyanarayana Journal: Psychoneuroendocrinology Date: 2019-12-24 Impact factor: 4.693
Authors: S Clifton; W Macdowall; A J Copas; C Tanton; B G Keevil; D M Lee; K R Mitchell; N Field; P Sonnenberg; J Bancroft; C H Mercer; A M Wallace; A M Johnson; K Wellings; F C W Wu Journal: J Clin Endocrinol Metab Date: 2016-08-23 Impact factor: 5.958