The study shows that in healthy women, getting older sharply cuts down how much growth hormone (GH) is released in bursts, even when estrogen levels are kept constant. Both single shots and continuous infusions of GHRP‑2 (a GH‑releasing peptide) produce much smaller GH spikes in post‑menopausal women compared to younger women.

Because estrogen production and age are strong covariates, distinguishing their individual impact on hypothalamo-pituitary regulation of growth hormone (GH) output is difficult. In addition, at fixed elimination kinetics, systemic GH concentration patterns are controlled by three major signal types [GH-releasing hormone (GHRH), GH-releasing peptide (GHRP, ghrelin), and somatostatin (SS)] and by four dynamic mechanisms [the number, mass (size), and shape (waveform) of secretory bursts and basal (time invariant) GH secretion]. The present study introduces an investigative strategy comprising 1) imposition of an experimental estradiol clamp in pre- (PRE) and postmenopausal (POST) women; 2) stimulation of fasting GH secretion by each of GHRH, GHRP-2 (a ghrelin analog), and l-arginine (to putatively limit SSergic restraint); and 3) implementation of a flexible-waveform deconvolution model to estimate basal GH secretion simultaneously with the size and shape of secretory bursts, conditional on pulse number. The combined approach unveiled the following salient percent POST/PRE contrasts: 1) only 27% as much GH secreted in bursts during fasting (P < 0.001); 2) markedly attenuated burstlike GH secretion in response to bolus GHRP-2 (29%), bolus GHRH (30%), l-arginine (37%), constant GHRP-2 (38%), and constant GHRH (42%) (age contrasts, 0.0016 </= P </= 0.027); and 3) a 160% prolongation and 32% abbreviation of the time required to achieve maximal GH secretion after injection of l-arginine and bolus GHRP-2, respectively (both, P < 0.001). Accordingly, age selectively determines both the size (amount) and shape (waveform) of GH secretory bursts in healthy women independently of the short-term estrogen milieu.