Growth hormone secretagogues like hexarelin can reliably raise GH levels in people, but the boost gets smaller as you age and is stronger when estrogen levels are high (e.g., during puberty). They also slightly raise prolactin and can trigger ACTH/cortisol spikes in certain conditions, and they affect sleep, appetite, and heart function.

Growth hormone secretagogues (GHSs) are synthetic peptidyl and nonpeptidyl molecules with strong, dose-dependent, and reproducible growth hormone (GH)-releasing activity even after oral administration. GHSs release GH via actions on specific receptors (GHS-R) at the pituitary and, mainly, at the hypothalamic levels. GHSs likely act as functional somatostatin antagonists and meantime enhance the activity of GH-releasing hormone (GHRH)-secreting neurons. The GH-releasing effect of GHSs is independent of gender but undergoes marked age-related variations. Estrogens play a major role in enhancing the GH response to GHSs at puberty, which GHRH hypoactivity, somatostatinergic hyperactivity and impaired activity of the putative GHS-like ligand and receptors probably explain the reduced GH-releasing effect of GHSs in aging. The activity of GHSs is not fully specific for GH. Their slight prolactin-releasing activity probably comes from direct pituitary action. In physiological conditions, the ACTH-releasing activity of GHSs is dependent on central actions; a direct action on GHS-R in pituitary ACTH-secreting tumors likely explains the peculiar ACTH and cortisol hyperresponsiveness to GHSs in Cushing disease. GHSs have specific receptor subtypes in other central and peripheral endocrine and nonendocrine tissues mediating GH-independent biologic activities. GHSs influence sleep pattern, stimulate food intake, and have cardiovascular activities. GHs have specific binding in normal and neoplastic follicular derived human thyroid tissue and inhibit the proliferation of follicular-derived neoplastic cell lines. The discovery of ghrelin, a 28 amino acid peptide synthesized in the stomach but also in other tissues, has opened new fascinating perspectives of research in this field.