Abstract
BackgroundAdult onset male hypogonadism (AOH) is a common clinical condition whose diagnosis and management are controversial, and is often characterized by a low level of SHBG, but our understanding of why testosterone levels are low when SHBG is low is incomplete.MethodsThis retrospective chart review was performed to compare the relationship between SHBG and testosterone in the plasma of men presenting for evaluation of AOH with a cohort of men treated chronically with transdermal testosterone.ResultsThe level of SHBG was < 30 nmol/L in 73% of men who presented for evaluation of AOH, and was inversely proportional to BMI in both the untreated and the testosterone-treated men. As in previous populations, the level of SHBG was highly positively correlated (r = 0.71, p < 0.01) with the total testosterone level in untreated men presenting for evaluation of AOH, but no relationship was found between the level of SHBG and total testosterone among men who were being treated with a transdermal testosterone preparation.ConclusionsThese findings further support the idea that SHBG regulates testicular negative feedback either directly or by modulating the entry of testosterone or estradiol into cells in the hypothalamus and/or pituitary to control gonadotropin synthesis and secretion which explains in part the low testosterone levels in men with AOH.Trial registrationNot applicable
Highlights
Adult onset male hypogonadism (AOH) is a common clinical condition whose diagnosis and management are controversial, and is often characterized by a low level of sex hormone-binding globulin (SHBG), but our understanding of why testosterone levels are low when SHBG is low is incomplete
Adult onset male hypogonadism (AOH) is a clinical condition characterized by symptoms consistent with androgen deficiency together with a consistently low total testosterone level that is not explained by classical disorders of the hypothalamus-pituitary or the testis [1]
Of the 33 men seeking an evaluation for hypogonadism, 7 men had a total testosterone level below the assay reference range (< 250 ng/dL, 8.68 nmol/L) and 14 were below 300 ng/dL (10.4 nmol/L), a level which is often selected as the threshold to diagnose testosterone deficiency [26]
Summary
Adult onset male hypogonadism (AOH) is a common clinical condition whose diagnosis and management are controversial, and is often characterized by a low level of SHBG, but our understanding of why testosterone levels are low when SHBG is low is incomplete. Adult onset male hypogonadism (AOH) is a clinical condition characterized by symptoms consistent with androgen deficiency together with a consistently low total testosterone level that is not explained by classical disorders of the hypothalamus-pituitary or the testis [1]. The binding affinity of SHBG for testosterone is high, and has been reported to vary across total testosterone levels [6], and to demonstrate allosteric interaction between the two binding sites [7]. It follows that the level of SHBG, which binds testosterone with high affinity and transports testosterone in the circulation, is strongly positively correlated with the level of testosterone in plasma [8, 9]
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