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

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 WuEMAS Study Group

Research output: Contribution to journalArticlepeer-review

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

MEASUREMENTS: 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.

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

Original languageEnglish
JournalClinical Endocrinology
Early online date1 Jun 2018
DOIs
Publication statusPublished - 2018

Keywords

  • Journal Article

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