ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2015) 37 OC2.4 | DOI: 10.1530/endoabs.37.OC2.4

Low free testosterone is associated with hypogonadal symptoms in men with normal total testosterone levels: results from the European Male Ageing Study

Leen Antonio1,3, Frederic Wu4, Terrence O’Neill5, Stephen Pye6, Emma Carter4, Joseph Finn4, Michaël Laurent2,6, Ilpo Huhtaniemi7, Martin Rutter4,8, Giulia Rastrelli9, Gianni Forti9, Gyorgy Bartfai10, Felipe Casanueva11, Krzysztof Kula12, Margus Punab13, Aleksander Giwercman14, Frank Claessens2, Brigitte Decallonne13 & Dirk Vanderschueren1,3


1Department of Clinical and Experimental Medicine, Laboratory of Clinical and Experimental Endocrinology, KULeuven, Leuven, Belgium; 2Department of Cellular and Molecular Medicine, Laboratory of Molecular Endocrinology, KULeuven, Leuven, Belgium; 3Department of Endocrinology, University Hospitals Leuven, Leuven, Belgium; 4Andrology Research Unit, Centre for Endocrinology & Diabetes, Institute of Human Development, The University of Manchester, Manchester, UK; 5Arthritis Research UK Epidemiology Unit, The University of Manchester, Manchester, UK; 6Department of Clinical and Experimental Medicine, Division of Gerontology and Geriatrics, KULeuven, Leuven, Belgium; 7Institute of Reproductive and Developmental Biology, Department of Surgery and Cancer, Imperial College London, London, UK; 8Manchester Diabetes Centre, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK; 9Andrology Unit, Department of Clinical Physiopathology, University of Florence, Florence, Italy; 10Department of Obstetrics, Gynaecology and Andrology, Albert Szent-Gyorgy Medical University, Szeged, Hungary; 11Department of Medicine, Santiago de Compostela University, Complejo Hospitalario Universitario de Santiago (CHUS); CIBER de Fisiopatología Obesidad y Nutricion, Santiago de Compostela, Spain; 12Department of Andrology and Reproductive Endocrinology, Medical University of LodZ, Lodz, Poland; 13Andrology Unit, United Laboratories of Tartu University Clinics, Tartu, Finland; 14Reproductive Medicine Centre, Malmö University Hospital, University of Lund, Lund, Sweden.


Background: During ageing, total testosterone (TT) declines and SHBG increases, resulting in a greater decline of free testosterone (FT) compared to TT. However, guidelines suggest using TT to diagnose androgen deficiency and to reserve FT only for men with borderline TT. We investigated if isolated low FT or isolated low TT was associated with androgen-related endpoints in healthy men.

Methods: 3369 community-dwelling men, aged 40–79, were included. We assessed differences between men with both normal TT (≧10.5 nmol/l) and calculated FT (≧220 pmol/l) (referent), men with normal TT/low FT (group 1) and men with low TT/normal FT (group 2) by descriptive statistics and ordinal logistic regression adjusted for age, centre, BMI and comorbidities.

Results: 2540 men had normal TT (18.4±5.5 (mean±S.D.) nmol/l) and FT (326±75 pmol/l). There were 261 men in group 1 (normal TT (14.2±3.7 nmol/l), low FT (195±22 pmol/l)) and 92 men in group 2 (low TT (9.6±0.7 nmol/l), normal FT (247±20 pmol/l)).

Compared to referent, men in group 1 were older and had higher SHBG, whereas group 2 was younger and had lower SHBG. BMI was higher in both groups. Men in group 1, but not group 2, were in poorer health and had lower haemoglobin. Regression analysis showed that men in group 1 had less frequent morning erections (P=0.012), more erectile dysfunction (P<0.001) and more physical symptoms (limited vigorous activity (P=0.011), walking 1 km (P=0.026) and bending (P=0.005)). Compared to referent, sexual and physical symptoms did not differ in group 2.

Conclusions: Independent of age, BMI and comorbidities, men with isolated low FT, but normal TT, have more androgen deficiency-related symptoms than men with normal TT and FT levels; whereas symptoms do not differ in men with isolated low TT. Not only total, but also FT levels should therefore be assessed in men with hypogonadal symptoms.

Disclosure: The European Male Ageing Study is funded by the Commission of the European Communities Fifth Framework Programme ‘Quality of Life and Management of Living Resources’ Grant QLK6-CT-2001-00258.

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