In healthy women, both age and estrogen levels shape how strongly the body releases growth hormone when stimulated with GHRP‑2. Older, post‑menopausal women produce less GH than younger women, but giving extra estrogen boosts the response. GHRP‑2 works better than the classic hormone GHRH, especially when estrogen is low, and belly fat mainly dampens the GHRH effect, not the GHRP‑2 effect.

Growth hormone (GH) secretion is subject to complex regulation. How pre- and postmenopausal age (PRE, POST), estradiol (E(2)) availability, and abdominal visceral fat (AVF) jointly affect peptidyl-secretagogue drive of GH secretion is not known. To this end, healthy PRE (n = 20) and POST (n = 22) women underwent a low- vs. high-E(2) clamp before receiving a continuous intravenous infusion of GH-releasing hormone (GHRH) or GH-releasing peptide (GHRP-2). According to analysis of covariance, PRE and POST women achieved age-independent hypo- and euestrogenemia under respective low- and high-E(2) clamps. All four of age (P < 0.001), E(2) status (P = 0.006), secretagogue type (P < 0.001), and an age x peptide interaction (P = 0.014) controlled pulsatile GH secretion. Independently of E(2) status, POST women had lower GH responses to both GHRH (P = 0.028) and GHRP-2 (P < 0.001) than PRE women. Independently of age, GHRP-2 was more stimulatory than GHRH during low E(2) (P = 0.011) and high E(2) (P < 0.001). Stepwise forward-selection multivariate analysis revealed that computerized tomographic estimates of AVF explained 22% of the variability in GHRH action (P = 0.002), whereas age and E(2) together explained 60% of the variability in GHRP-2 drive (P < 0.001). These data establish that age, estrogen status, and AVF are triple covariates of continuous peptide-secretagogue drive of pulsatile GH secretion in women. Each factor must be controlled for to allow valid comparisons of GH-axis activity.