In conclusion, testosterone deficiency promotes obesity, especially visceral obesity, IR, MetS and T2-DM, which in turn contribute to a further reduction of testosterone levels, determined by (1) IR-mediated and pro-inflammatory cytokine-mediated decrease of SHBG levels, ultimately resulting in negative feedback on the HPT axis; (2) direct inhibitory effect of increased leptin levels on Leydig cells; and (3) indirect inhibition due to HPT axis suppression induced not only by estradiol excess but also by inflammatory mediators, leptin resistance and IR. Here, SHBG is linked to obesity disorder.