Clinical predictors and consequences of increasing shbg levels over time: results from the european male ageing study

Objectives Testosterone (T) circulates bound to sex hormone-binding globulin (SHBG). Although it is commonly deemed that only the amount of T not linked to proteins (free T) is biologically active, evidence supporting this hypothesis is lacking. To investigate the predictors and clinical consequences of developing or maintaining increased SHBG levels in ageing men from European general population. Methods 3369 men from the general population of eight European countries were recruited in the longitudinal population-based study “European Male Ageing Study”. Subjects completed questionnaires, underwent physical examination, physical and cognitive functional tests and blood sampling during two visits (one baseline and one after a median of 4.3 years of follow-up). Results Among a series of putative candidate predictors for new occurred-stable high SHBG, older men, reporting physical inactivity, with liver diseases and with higher T and LH at baseline were more predisposed to maintain or develop high SHBG; conversely, obesity, higher LDL and IGF1 were protective towards the occurrence of SHBG. Concerning the clinical consequences, men who develop or maintain high SHBG levels reported the new occurrence or worsening of erectile dysfunction, impaired morning erections and low sexual desire. Moreover, they had new or worsened feelings of sadness, worse physical functioning, vitality, mental and social well-being. This was confirmed by worse scoring in physical performance and memory tests, as well as by higher scores on the Beck Depression Inventory. Conclusions The development or maintenance of high SHBG levels is associated with symptoms of hypogonadism, independently of total T levels. Besides sexual symptoms, also physical and depressive symptoms are present. The cognitive and physical performance is also compromised. This study demonstrates that increased SHBG favor the development or worsening of hypogonadism-related symptoms. This provides evidence for the role of SHBG in limiting the biological activity of T, thus supporting the free hormone hypothesis. Conflicts of Interest None