Volume 73 Supplement 1

Methods in Epidemiology Symposium

Open Access

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

  • Leen Antonio1,
  • Frederick Wu2,
  • Terrence O'Neill3,
  • Stephen Pye3,
  • Emma Carter4,
  • Joseph Finn5,
  • Michaël Laurent6,
  • Ilpo Huhtaniemi7,
  • Martin Rutter5,
  • Giulia Rastrelli8,
  • Gianni Forti8,
  • Gyorgy Bartfai9,
  • Felipe Casanueva10,
  • Krzysztof Kula11,
  • Margus Punab12,
  • Aleksander Giwercman13,
  • Frank Claessens6,
  • Brigitte Decallonne14 and
  • Dirk Vanderschueren14
Archives of Public HealthThe official journal of the Belgian Public Health Association201573(Suppl 1):P10


Published: 17 September 2015


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.


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.


2540 men had normal TT (18.4-5.5 [mean-SD] 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. Men in group 1, but not group 2, were in poorer health, had lower haemoglobin and a decrease in bone ultrasound measurements. Regression analysis showed that men in group 1 had less frequent morning erections, more erectile dysfunction, fewer sexual thoughts and more physical symptoms (limitations in doing vigorous activity, walking 1 km and bending). Compared to referent, sexual and physical symptoms did not differ in group 2.


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.

Authors’ Affiliations

KU Leuven
Andrology Research Unit, University of Manchester
Arthritis Research UK Epidemiology Unit, The University of Manchester
Andrology research Unit, The University of Manchester
Andrology Research Unit, The University of Manchester
Laboratory of Molecular Endocrinology, KU Leuven
Institute of Reproductive and Developmental Biology, Imperial College London
Andrology Unit, University of Florence
Department of Andrology, Albert Szent-Gyorgy Medical University
Department of Medicine, Santiago de Compostela University
Department of Andrology, Medical University of Lodz
Andrology Unit, United Laboratories of Tartu University Clinics
Reproductive Medicine Centre, Malmö University Hospital
Laboratory of Clinical and Experimental Endocrinology, KULeuven


© Antonio et al. 2015

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.