Realizing the reported misuse of human growth hormone (GH), investigation of a safe alternative mechanism for increasing endogenous GH is needed. Several GH secretagogues are available, including GH-releasing peptides (GHRPs) GHRP-2 and GHRP-6, and the GH-releasing hormone analog, sermorelin (SERM). Insulin-like growth factor 1 (IGF-1) serves as a surrogate marker for GH. Here, the effect of GHRP/SERM therapy on IGF-1 levels is evaluated. A retrospective review of medical records was performed for 105 men on testosterone (T) therapy seeking increases in lean body mass and fat loss who were prescribed 100 mcg of GHRP-6, GHRP-2, and SERM three times daily. Compliance with therapy was assessed, and 14 men met strict inclusion criteria. Serum hormone levels of IGF-1, T, free T (FT), estradiol (E), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were evaluated. Mean (SD) age of the cohort was 33.2 (2.9) years, and baseline IGF-1 level was 159.5 (26.7) ng/mL. Mean (SD) duration of continuous GHRP/SERM treatment was 134 (88) days. Mean posttreatment IGF-1 level was 239.0 (54.6) ng/mL ( p < .0001). Three of the 14 men were on an aromatase inhibitor and/or tamoxifen prior to treatment and another 4 men were coadministered an aromatase inhibitor and/or tamoxifen during treatment. Inhibition of E production or estrogen receptor blockade resulted in smaller increases in IGF-1 levels. GHRP/SERM therapy increases serum IGF-1 levels with strict compliance to thrice-daily dosing. The results suggest that combination therapy may be beneficial in men with wasting conditions that can improve with increased GH secretion.
Fourteen hypogonadal men on T therapy with baseline IGF-1 levels <200 ng/mL were treated with GHRP-6, GHRP-2, and SERM three times daily at a dose of 100 mcg of each compound delivered via subcutaneous injection ([Table 1]). Mean (SD) age within the cohort was 33.2 (2.9; range 29–39) years. Baseline mean (SD) hormone levels were IGF-1 159.5 (26.7; range 97–195) ng/mL, T 586.9 (550.5; range 76–1640) ng/dL, FT 12.9 (11.8; range 2.2–36.7) ng/dL, FSH 1.1 (1.9; range 0.02–7) mIU/mL, LH 1.1 (1.4; range 0.02–4) mIU/mL, and E 5.5 (9.0; range 2–38) ng/dL. Mean (SD) duration of GHRP-6/GHRP-2/SERM treatment was 134 (88) days. Significant increases in IGF-1 levels were observed at all follow-up intervals ([Table 2] and [Figure 1]). Significant increases in T and FT levels were also observed starting at 90 days of follow-up. No significant changes in LH, FSH, or E levels were observed at any point during follow-up. Anthropomorphic data were not available for the majority of men on follow-up.
GHSs can potentially provide similar benefits to those seen with the use of GH while avoiding the safety concerns associated with GH use, in part because GHSs can reproduce the physiologic pulsatility of GH secretion and limit GH and IGF-1 production to the normal physiologic range (Bowers, 2008; [Smith, 2005]). Due to the relatively recent clinical use of GHSs for changes in lean body mass and anti-catabolic effects, longer-term safety data paralleling those from GH studies are lacking. Safety studies performed using MK-0677 established an excellent safety profile en route to clinical development ([Smith, 2005]). MK-0677 had relatively few and mild adverse events such as dizziness, stomachache, and transient increases in aspartate transaminase (AST)/alanine transaminase (ALT) in trials in healthy young men, obese men, elderly men and women, and osteoporotic women ([Chapman et al., 1996]). Safety concerns relating to an increased incidence of congestive heart failure (CHF; 4 in the treatment group vs. 1 in the placebo group) was seen in one trial of MK-0677 in patients above 60 years of age with hip fracture ([Adunsky et al., 2011]). Another trial with 25% more participants and a comparable subject pool and study design did not identify adverse drug effects related to CHF, and treatment was well tolerated ). The relatively small sample sizes of these studies may limit our understanding of the adverse effects of MK-0677.
Combination therapy with the GHSs GHRP-6, GHRP-2, and SERM increases serum IGF-1 levels with strict compliance to thrice-daily dosing. Increases in serum IGF-1 while on treatment approached the upper limits of the laboratory reference range (250 ng/mL), but were inhibited by blocking estrogen action. Taken together, the results suggest that combination therapy with GHRP-6, GHRP-2, and SERM may be beneficial in wasting conditions in which increases in fat-free mass are desirable.