Approximately half of the estradiol in the blood is bound to SHBG, the remainder bound to albumin or freely circulating [42] A common consequence of obesity-related hyperinsulinemia is a reduction in SHBG, resulting in an increase in bioavailable estrogen allowing more free or albumin-bound estradiol to bind with estrogen receptors [41]. The gene discussed is SHBG; the disease is obesity due to melanocortin 4 receptor deficiency.