Giulia Rastrelli1, Terence W O'Neill2, Tomas Ahern3, György Bártfai4, Felipe F Casanueva5,6, Gianni Forti7, Brian Keevil8, Aleksander Giwercman9, Thang S Han10, Jolanta Slowikowska-Hilczer11, Michael E J Lean12, Neil Pendleton13, Margus Punab14, Leen Antonio15, Jos Tournoy16, Dirk Vanderschueren15, Mario Maggi1, Ilpo T Huhtaniemi17, Frederick C W Wu2. 1. Sexual Medicine and Andrology Unit, Department of Experimental Clinical and Biomedical Sciences "Mario Serio", University of Florence, Florence, Italy. 2. Division of Musculoskeletal and Dermatological Sciences, Faculty of Biology, Medicine and Health, Arthritis Research UK Centre for Epidemiology, Manchester Academic Health Science Centre, University of Manchester and NIHR Manchester Musculoskeletal Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester, UK. 3. Andrology Research Unit, Division of Endocrinology, Diabetes & Gastroenterology, Domain of Cardiovascular, Metabolic and Nutritional Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK. 4. Department of Obstetrics, Gynaecology and Andrology, Albert Szent-György Medical University, Szeged, Hungary. 5. Department of Medicine, Santiago de Compostela University, Complejo Hospitalario Universitario de Santiago (CHUS). 6. CIBER de Fisiopatologia Obesidad y Nutricion (CIBERobn), Instituto Salud Carlos III, Santiago de Compostela, Spain. 7. Endocrine Unit, Department of Experimental Clinical and Biomedical Sciences "Mario Serio", University of Florence, Florence, Italy. 8. Department of Clinical Biochemistry, University Hospital of South Manchester, Wythenshawe, Manchester, UK. 9. Reproductive Medicine Centre, Malmö University Hospital, University of Lund, Malmö, Sweden. 10. Institute of Cardiovascular Research, Royal Holloway, University of London, Egham, UK. 11. Department of Andrology and Reproductive Endocrinology, Medical University of Lodz, Lodz, Poland. 12. Department of Human Nutrition, University of Glasgow, Glasgow, UK. 13. Division of Neuroscience and Experimental Psychology, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre Hope Hospital, Salford, UK. 14. Andrology Unit, United Laboratories of Tartu University Clinics, Tartu, Estonia. 15. Laboratory of Clinical and Experimental Endocrinology, Department of Chronic Diseases, Metabolism and Ageing, Katholieke Universiteit Leuven, Leuven, Belgium. 16. Gerontology and Geriatrics, Department of Chronic diseases, Metabolism and Ageing, Katholieke Universiteit Leuven, Leuven, Belgium. 17. Department of Surgery and Cancer, Institute of Reproductive and Developmental Biology, Imperial College London, London, UK.
Abstract
OBJECTIVE: Limited evidence supports the use of free testosterone (FT) for diagnosing hypogonadism when sex hormone-binding globulin (SHBG) is altered. Low total testosterone (TT) is commonly encountered in obesity where SHBG is typically decreased. We aimed to assess the contribution of FT in improving the diagnosis of symptomatic secondary hypogonadism (SH), identified initially by low total testosterone (TT), and then further differentiated by normal FT (LNSH) or low FT (LLSH). DESIGN: Prospective observational study with a median follow-up of 4.3 years. PATIENTS: Three thousand three hundred sixty-nine community-dwelling men aged 40-79 years from eight European centres. MEASUREMENTS: Subjects were categorized according to baseline and follow-up biochemical status into persistent eugonadal (referent group; n = 1880), incident LNSH (eugonadism to LNSH; n = 101) and incident LLSH (eugonadism to LLSH; n = 38). Predictors and clinical features associated with the transition from eugonadism to LNSH or LLSH were assessed. RESULTS: The cumulative incidence of LNSH and LLSH over 4.3 years was 4.9% and 1.9%, respectively. Baseline obesity predicted both LNSH and LLSH, but the former occurred more frequently in younger men. LLSH, but not LNSH, was associated with new/worsened sexual symptoms, including low desire [OR = 2.67 (1.27-5.60)], erectile dysfunction [OR = 4.53 (2.05-10.01)] and infrequent morning erections [OR = 3.40 (1.48-7.84)]. CONCLUSIONS: These longitudinal data demonstrate the importance of FT in the diagnosis of hypogonadism in obese men with low TT and SHBG. The concurrent fall in TT and FT identifies the minority (27.3%) of men with hypogonadal symptoms, which were not present in the majority developing low TT with normal FT.
OBJECTIVE: Limited evidence supports the use of freetestosterone (FT) for diagnosing hypogonadism when sex hormone-binding globulin (SHBG) is altered. Low total testosterone (TT) is commonly encountered in obesity where SHBG is typically decreased. We aimed to assess the contribution of FT in improving the diagnosis of symptomatic secondary hypogonadism (SH), identified initially by low total testosterone (TT), and then further differentiated by normal FT (LNSH) or low FT (LLSH). DESIGN: Prospective observational study with a median follow-up of 4.3 years. PATIENTS: Three thousand three hundred sixty-nine community-dwelling men aged 40-79 years from eight European centres. MEASUREMENTS: Subjects were categorized according to baseline and follow-up biochemical status into persistent eugonadal (referent group; n = 1880), incident LNSH (eugonadism to LNSH; n = 101) and incident LLSH (eugonadism to LLSH; n = 38). Predictors and clinical features associated with the transition from eugonadism to LNSH or LLSH were assessed. RESULTS: The cumulative incidence of LNSH and LLSH over 4.3 years was 4.9% and 1.9%, respectively. Baseline obesity predicted both LNSH and LLSH, but the former occurred more frequently in younger men. LLSH, but not LNSH, was associated with new/worsened sexual symptoms, including low desire [OR = 2.67 (1.27-5.60)], erectile dysfunction [OR = 4.53 (2.05-10.01)] and infrequent morning erections [OR = 3.40 (1.48-7.84)]. CONCLUSIONS: These longitudinal data demonstrate the importance of FT in the diagnosis of hypogonadism in obesemen with low TT and SHBG. The concurrent fall in TT and FT identifies the minority (27.3%) of men with hypogonadal symptoms, which were not present in the majority developing low TT with normal FT.
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