Somatostatin (SS) released by hypothalamic neurons inhibits GH exocytosis noncompetitively. Therefore, we postulated that attenuation of GH feedback-induced SS outflow would help to unmask covariates of endogenous secretagogue drive. To this end, 42 healthy pre- and postmenopausal women (PRE, POST) were randomly assigned to receive leuprolide plus estradiol (E₂) or leuprolide plus placebo (Pl). A putatively low-SS milieu was imposed by L-arginine infusion. Deconvolution and regularity analyses were applied to 6-h GH concentration-time profiles. By 2-way ANOVA, age negatively (P < 0.001) and E₂ positively (P = 0.001) determined pulsatile GH secretion in the presumptively SS-deficient milieu (P < 0.001). Comparable effects were exerted on the mass of GH secreted per burst per unit distribution volume (age P = 0.001, E₂ P < 0.001, overall P < 0.001). E₂ alone predicted basal (nonpulsatile) GH secretion (P = 0.004). Stepwise forward-selection multivariate regression demonstrated that age (P = 0.0017) and E₂ (P = 0.0002) together explained 46% of intersubject variability in pulsatile GH secretion (P < 0.001), and fully replaced the negative univariate effect of abdominal visceral fat (R² = 0.32, P < 0.001). Moreover, age and E₂ (but not AVF) interacted to supervise GH regularity (P = 0.007). We conclude that age and E₂ availability individually and together constitute primary predictors of basal, pulsatile and patterned GH secretion in an inferentially feedback-silenced context in healthy women. Therefore, both factors must be considered in framing hypotheses of endogenous GH drive.