Limited evidence supports the short-term efficacy of medications and lifestyle interventions. The long-term efficacy and safety of pediatric obesity treatments remain unclear.

Pediatric obesity prevention programs caused small changes in target behaviors and no significant effect on BMI compared with control. Trials evaluating promising interventions applied over a long period, using responsive outcomes, with longer measurement timeframes are urgently needed.

The present outcomes suggest a tetrapartite model of GH regulation in men, in which systemic concentrations of Te, DHT, and E(2) along with abdominal visceral fat determine the selective actions of GH secretagogues and SS.

Context: Sex-steroid hormones amplify pulsatile GH secretion by unknown mechanisms. Ghrelin is the most potent natural GH secretagogue discovered to date. A plausible unifying postulate is that estradiol (E 2 ) enhances hypothalamo-pituitary sensitivity to ghrelin (a physiological effect). The hypothesis is relevant to understanding the basis of hyposomatotropism in aging and other relatively hypogonadal states. Objective:Our objective was to test the hypothesis that E 2 supplementation potentiates ghrelin's stimulation of pulsatile GH secretion. Setting:The study was conducted at an academic medical center. Subjects:Healthy postmenopausal women (n ϭ 20) were included in the study.Interventions: Separate-day iv infusions of saline vs. five graded doses of ghrelin were performed in volunteers prospectively randomly assigned to receive (n ϭ 8) or not receive (n ϭ 12) transdermal E 2 for 21 d were performed.Measures: GH secretion was estimated by deconvolution analysis and abdominal visceral fat mass determined by computerized axial tomography were calculated.Results: E 2 supplementation augmented ghrelin's stimulation of basal (nonpulsatile) GH secretion by 3.6-fold (P ϭ 0.022), increased GH responses to low-dose ghrelin by 2.9-fold (P ϭ 0.035), did not alter ghrelin efficacy, and elicited more regular patterns of acylated ghrelin concentrations during saline infusion (P ϭ 0.033). Abdominal visceral fat negatively determined responses to ghrelin (R ϭ Ϫ0.346; P Ͻ 0.005). Conclusions:Transdermal E 2 supplementation potentiates GH secretion stimulated by physiological but not pharmacological concentrations of acylated ghrelin, and concomitantly regularizes patterns of bioactive ghrelin secretion in postmenopausal women. Accordingly, the estrogen milieu appears to control sensitivity of the hypothalamopituitary unit to acylated ghrelin. A ging is associated with a progressive decline in GH and IGF-I availability (1-3). Healthy older individuals with relative hyposomatotropism and patients with pathological GH deficiency share a similar physical phenotype marked by osteopenia, sarcopenia, visceral adiposity, insulin resistance, hyperlipidemia, increased risk of cardiovascular disease, and di-

Acylated ghrelin has a multifold larger distribution volume and MCR than total ghrelin. An estrogenic milieu augments synthesis and/or acylation of ghrelin peptide without altering its MCR.