Study 1 : 15 lean subjects received placebo or physiologic replacement-dose recombinant human leptin ( metreleptin ) following short term complete caloric deprivation to induce severe hypoleptinemia ; Study 2 : 7 women with relative leptin deficiency due to strenuous exercise or low weight received 3 months of metreleptin ; Study 3 : 17 women with relative leptin deficiency were randomized to receive metreleptin or placebo over 9 months .