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

• Published in: Clinical Endocrinology Vol. 89; no. 4; pp. 459 - 469
• Main Authors: Giulia, Rastrelli, Terence W, O'Neill, Tomas, Ahern, György, Bártfai, 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, Min, Jiang
• Format: Journal Article
• Language: English
• Published: England Wiley 01.10.2018; Wiley Subscription Services, Inc
• Subjects: Adult; Aged; androgen deficiency; androgen deficiency; free testosterone; obesity; secondary hypogonadism; sex hormone-binding globulin; sexual symptoms; total testosterone; Clinical Medicine; Diagnosis; Erectile dysfunction; Free testosterone; Globulins; Gynaecology, Obstetrics and Reproductive Medicine; Gynekologi, obstetrik och reproduktionsmedicin; Health Sciences; Hormone replacement therapy; Humans; Hypogonadism; Hypothyroidism; Hälsovetenskap; Klinisk medicin; Logistic Models; Male; Medical and Health Sciences; Medicin och hälsovetenskap; Middle Aged; Obesity; Observational Studies as Topic; Prospective Studies; secondary hypogonadism; sex hormone binding globulin; sexual symptoms; Testosterone; total testosterone; secondary hypogonadism; sex hormone-binding globulin; sexual symptoms; total testosterone; androgen deficiency; free testosterone; obesity
• ISSN: 0300-0664; 1365-2265; 1365-2265
• DOI: 10.1111/cen.13756

Summary 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.