Because estrogen production and age are strong covariates, distinguishing their individual impact on hypothalamo-pituitary regulation of GH output is difficult. In addition, at fixed elimination kinetics systemic GH concentration patterns are controlled by 3 major signal types: GH-releasing hormone (GHRH), GH-releasing peptide (GHRP, ghrelin) and somatostatin (SS), and by 4 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 (i) imposition of an experimental estradiol (E₂) clamp in pre- (PRE) and postmenopausal (POST) women; (ii) stimulation of fasting GH secretion by each of GHRH, GHRP-2 (a ghrelin analog) and L-arginine (to putatively limit SSergic restraint); and (iii) 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 percentage POST/PRE contrasts: (a) only 27% as much GH secreted in bursts during fasting [P < 0.001]; (b) markedly attenuated burst-like 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 (c) 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.