-Inversely associated with obesity in premenopausal women (241–244).-Associated with insulin sensitivity in premenopausal women (245, 246).-Hyperestrogenemia is associated with insulin resistance (247, 248).-In twin men discordant for obesity (n=18 pairs), E2 levels are higher in the heavier twin (172). Here, INS is linked to obesity due to melanocortin 4 receptor deficiency.