INTRODUCTIONThe first‐line assessment for the evaluation of gonadal status in men with features of androgen deficiency is total testosterone (TT), as indicated by all current guidelines and recommendations. However, they all report that TT could provide misleading information in conditions known to alter sex hormone‐binding globulin (SHBG) levels. In fact, according to the free hormone hypothesis, only the fraction of T that circulates unbound to albumin or SHBG, that is free T (FT), is able to play a biological role. Hence, increased SHBG could remarkably affect androgen status, possibly leading to features of androgen deficiency, despite apparently normal or borderline TT. Although largely assumed, the free hormone hypothesis is not supported by robust experimental evidence, and the impact of changes in SHBG on T bioactivity is still speculative. Recently, in a transgenic mouse model overexpressing human SHBG, higher TT than wild‐type controls but similar FT was demonstrated. Despite higher TT, transgenic mice had hypogonadal features, including a weight reduction in seminal vesicles and of androgen‐dependent pelvic floor muscles. These findings indicate that TT per se is not sufficient to describe the androgen status, when SHBG is increased, thus providing experimental evidence for the free hormone hypothesis.In humans, the role
Clinical Endocrinology – Wiley
Published: Jan 1, 2018
Keywords: ; ; ; ; ; ;
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