Context. States of acute and chronic energy deficit are characterized by increased GH secretion and decreased IGF-I levels.

Objective. To determine whether changes in levels of leptin, a key mediator of the adaptation to starvation, regulate the GH-IGF system during energy deficit.

Design, Setting, Patients, and Intervention. We studied 14 healthy normal-weight men and women during 3 conditions: baseline fed and 72-h fasting (to induce hypoleptinemia) with administration of placebo or recombinant methionyl human leptin (r-metHuLeptin) (to reverse the fasting-associated hypoleptinemia). We also studied 8 normal-weight women with exercise induced chronic energy deficit and hypothalamic amenorrhea at baseline and during 2 to 3 months of r-metHuLeptin treatment.

Main Outcome Measures. GH pulsatility, IGF levels, IGF and GH binding protein levels.

Results. During short-term energy deficit, measures of GH pulsatility and disorderliness and levels of IGFBP-1 increased whereas leptin, insulin, IGF-I (total and free), IGFBP-4, IGFBP-6, and GHBP decreased; r-metHuLeptin administration blunted the starvation associated decrease of IGF-1. In chronic energy deficit, total and free IGF-I, IGFBP-6 and GHBP levels were lower compared to euleptinemic controls; r-metHuLeptin administration had no major effect on GH pulsatility after two weeks but increased total IGF-I levels and tended to increase free IGF-1 and IGF-BP3 after one month.

Conclusions. The GH/IGF system changes associated with energy deficit are largely independent of leptin deficiency. During acute energy deficit r-metHuleptin administration in replacement doses blunts the starvation induced decrease of IGF-1 but during chronic energy deficit r-metHuleptin administration increases IGF-1 and tends to increase free IGF-1 and IGF-BP3.