Growth hormone is not a direct muscle builder in the way testosterone is. Training intensity, protein intake, sleep quality, and insulin signaling all modulate IGF-1 levels. Growth hormone does not directly stimulate muscle protein synthesis the way testosterone does. If you're curious about the head-to-head between ipamorelin and sermorelin specifically, we have a detailed breakdown in our Ipamorelin vs Sermorelin comparison. For body recomposition, a second injection in the morning (fasted) or post-workout adds additional GH stimulus without compounding side effects. GH itself has sleep-promoting properties — GH receptors are present in sleep-regulatory brain regions, and GH administration in clinical settings consistently improves sleep architecture. The improved sleep quality many users report isn't a side effect or placebo. We recommend following these patients with regular examinations for changes in body composition and IGF-1 levels during GHS treatment, as well as with blood glucose and Hb A1c monitoring. In a 2-month trial of ibutamoren in 24 obese males, fasting glucose and insulin levels were unchanged, whereas an oral glucose tolerance test showed impairment of glucose homeostasis at 2 and 8 weeks(56). A large trial in Alzheimer’s patients found a more patients with increased blood glucose levels in the ibutamoren group (15.4%) than the placebo group (4.6%), with similar differences in HbA1c levels between the groups(65). In 32 healthy elderly patients, Chapman et al. observed that 25 mg of daily ibutamoren increased glucose concentrations by 25.3% and 26.9% above baseline at 2 and 4 weeks, respectively. Within the limits of current literature, growth hormone secretagogues appear safe, with few of the studies cited in this review observing serious adverse events (AEs) with the use of GHRPs. After one year, open label treatment for an additional 2 years demonstrated that the positive effects on body composition were maintained(57). Gelander et al. evaluated the short-term effects of 1 mg sermorelin and GHRH 1–40 injections on GH, IGF-1, prolactin, follicle-stimulating hormone (FSH), and LH levels in short children with pulsatile GH secretion (25). As a result of these controversies and limitations, a new class of drugs known as growth hormone secretagogues (GHS) (Table 1) has emerged as a potential alternative to GH therapy. In a recent meta-analysis of 16 trials of hypogonadal men receiving TTh, Guo et al. found that although TTh led to increased lean body mass and a reduction in total cholesterol levels, the observed decrease in fat mass was not significant. Partially in response to this, growth hormone secretagogues (GHS) have emerged as a potential novel adjunctive therapy for some of the symptoms of hypogonadism, although current data on their clinical efficacy largely remain lacking. Fewer than 30% of researchers achieve meaningful growth hormone amplification with ipamorelin monotherapy. While the above studies observed numerous AEs, another randomized, double-blind, placebo-controlled trial evaluating the effects of 4 weeks of ibutamoren administration in 32 healthy elderly patients observed no AEs(63). This difference impacts the GH release pattern (pulsatile vs flat), long-term pituitary function, cost, side effect profile, and how the body utilizes the growth hormone. At 12 months, a 0.14 mmol/L decrease in LDL cholesterol was observed with ibutamoren treatment, although no changes in total testosterone levels were observed. Following this, GH, IGF-1, skeletal muscle function, body composition, and endocrine-metabolic functions were measured as outcomes. Consistent with this, patients’ waist-hip ratio and GH peak following sermorelin actually showed an age-independent inverse correlation. All 10 elderly men were given 14 days of twice daily injections of either low (0.5 mg) or high dose (1 mg) sermorelin which was then held for 14 days before being restarted for another 14-day period. It was noted that both peptides increased GH by a similar magnitude; however, sermorelin also produced small acute rises in prolactin, FSH, and LH. Sermorelin has been employed in both the diagnosis and treatment of GH deficiency although there is limited research on its use in the setting of hypogonadism (23). GHRH receptor activation leads to cAMP production via the Gs protein/adenylate cyclase and mitogen-activated protein kinase pathways (24). The GHS consist of a variety of synthetic peptide or non-peptide agents that stimulate endogenous GH release.
