-Protective effect on excess adiposity of E2 replacement in post-menopausal women (n=40) (249).-In postmenopausal women, E2 is inversely correlated with adiponectin and insulin sensitivity (n=101) (174, 250).-Associated with BMI and adiposity in postmenopausal women (171, 174, 251).-Declines with aging in both men (252, 253) and women.-Lifestyle-mediated weight loss decreases E2 in older women (230).-Inversely related to cognitive decline (254). The gene discussed is INS; the disease is Mental deterioration.