Long-acting growth hormone therapy in paediatric growth hormone deficiency: reduced treatment burden and unproven motivation-related neuroendocrine effects

Long-acting growth hormone (LAGH) formulations represent an important therapeutic advance in the management of growth hormone deficiency (GHD) because they reduce injection frequency and treatment burden and may improve adherence and patient-reported experience. Beyond these established advantages, we propose a hypothesis-generating framework in which motivation- and reward-related neuroendocrine pathways may interact with hypothalamic regulation of the growth hormone (GH) axis. This review summarises current knowledge on the neurobiological interplay among motivation, reward, stress, and GH secretion, with specific relevance to paediatric GHD and LAGH therapy. We discuss the roles of dopaminergic signalling, endogenous opioid systems, hypothalamic control of GH secretion, and the bidirectional interactions between GH and central neural circuits. Because direct clinical evidence in paediatric LAGH-treated populations remains limited, the proposed relationships should be interpreted as biologically plausible but not yet established causal mechanisms. Finally, we outline future translational and clinical studies needed to determine whether motivational state is associated with endocrine responses, treatment experience, or clinical outcomes beyond the well-documented benefit of improved adherence.