Symptomatic Androgen Deficiency Develops only When Both Total and Free Testosterone Decline in Obese Men Who may have Incident Biochemical Secondary Hypogonadism: Prospective Results from the EMAS

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).

Prospective observational study with a median follow-up of 4.3 years.

3369 community-dwelling men aged 40-79 years from eight European centres.

Subjects were categorised 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.

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)].

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. This article is protected by copyright. All rights reserved.

Clinical endocrinology. 2018 Jun 01 [Epub ahead of print]

Giulia Rastrelli, Robert J A H Eendebak, Terence W O'Neill, Tomas Ahern, Bartfai Gyorgy, Felipe F Casanueva, Gianni Forti, Brian Keevil, Aleksander Giwercman, Thang S Han, Jolanta Slowikowska-Hilczer, Michael E J Lean, Neil Pendleton, Margus Punab, Leen Antonio, Jos Tournoy, Dirk Vanderschueren, Mario Maggi, Ilpo T Huhtaniemi, Frederick C W Wu, EMAS study group

Sexual Medicine and Andrology Unit, Department of Experimental Clinical and Biomedical Sciences "Mario Serio", University of Florence, Viale Pieraccini, 6 - I-50139, Florence, Italy., 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, Old St Mary's Building, The University of Manchester, Hathersage Road, Manchester, M13 9WL, UK., Arthritis Research UK Centre for Epidemiology, Division of Musculoskeletal and Dermatological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester and NIHR Manchester Musculoskeletal Biomedical Research Centre, Manchester University NHS Foundation Trust, Oxford Road Manchester, M13 9PL, UK., Department of Obstetrics, Gynaecology and Andrology, Albert Szent-György Medical University, Semmelweis u.1 - H-6725, Szeged, Hungary., Department of Medicine, Santiago de Compostela University, Complejo Hospitalario Universitario de Santiago (CHUS), CIBER de Fisiopatología Obesidad y Nutricion (CB06/03), Instituto Salud Carlos III - University Hospital of Santiago de Compostela, Choupana Street sn - 15706, Santiago de Compostela, Spain., Endocrine Unit, Department of Experimental Clinical and Biomedical Sciences "Mario Serio", University of Florence, Viale Pieraccini, 6 - I-50139, Florence, Italy., Department of Clinical Biochemistry, University Hospital of South Manchester, Southmoor Road, , M23 9LT, Wythenshawe Manchester, UK., Reproductive Medicine Centre, Malmö University Hospital, University of Lund, Jan Waldenströms 47, Malmö, Sweden., Institute of Cardiovascular Research, Royal Holloway, University of London, Egham, Surrey, TW20 0EX, UK., Department of Andrology and Reproductive Endocrinology, Medical University of Lodz, 91-425, Lodz, Sterlinga str. 5, Poland., Department of Human Nutrition, University of Glasgow, 10-16 Alexandra Parade, Glasgow, G31 2ER, UK., Division of Neuroscience and Experimental Psychology, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre Hope Hospital, Stott Lane, Salford, M6 8HD, UK., Andrology Unit, United Laboratories of Tartu University Clinics, Ludvig Puusepa, 1a - 50406, Tartu, Estonia., Laboratory of Clinical and Experimental Endocrinology, Department of Chronic Diseases, Metabolism and Ageing, Katholieke Universiteit Leuven, Herestraat 49, BE-3000, Leuven, Belgium., Gerontology and Geriatrics, Department of Chronic diseases, Metabolism and Ageing, Katholieke Universiteit Leuven, Herestraat 49, BE-3000, Leuven, Belgium., Department of Surgery and Cancer, Institute of Reproductive and Developmental Biology, Imperial College London, Hammersmith Campus, Du Cane Road, London, W12 0NN, UK.