There has been an increasing awareness that male hypogonadism clinically evidenced by the signs and symptoms of low testosterone is a common clinical condition that affects the person’s quality of life and long term health. Hypogonadism is associated with obesity and metabolic syndrome. Testosterone remains the standard treatment for those who test low on blood tests, however the benefits of treatment may be diminished by other factors. One of these is an insufficient level of growth hormone, measured as IGF. This would particularly interfere when a person’s goal would be to lower body fat and correspondingly improve muscle mass to benefit their overall health. To address this need growth hormone secretagogues (GHS) such as sermorelin have emerged as a potential new therapy to reverse some of the the signs and symptoms of hypogonadism and generalized aging in aging men. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7108996/
Growth Hormone and IGF-1 stimulators that can significantly improve body composition while ameliorating specific hypogonadal symptoms including fat gain and muscular atrophy.
Testosterone is an essential hormone for male sexual, physical and mental health.
Hypogonadism is a clinical syndrome that is characterized by low serum testosterone levels that are found in conjunction with clinical symptoms such as decreased libido, reduced bone mass, increased fat mass, and other metabolic disturbances (1,2). Obesity is linked to male hypogonadism. In Obese men testosterone converts to the estrogenic hormone estradiol because fat (adipose tissue) contains the enzyme called aromatase which promotes that conversion metabolically. This inhibits luteinizing hormone secretion, and reduces natural testosterone production (3).
There have been many studies that have documented an increase in hypogonadism in men with obesity, metabolic syndrome, diabetes, and hypertension. Particularly, obese men have been found to be more than twice as likely to manifest hypogonadism compared to the nonobese (4,5). Also those with low total and free testosterone levels are found to have a greater incidence of metabolic syndrome and diabetes. (6,7). The term “subclinical hypogonadism” refers to a person whose physiologic abnormalities such as the development of hormonal deficiency precede the onset of the clinical signs and symptoms that will become manifest at some point when their hormonal deficiency worsens 8. Treatment before the abnormal clinical picture is fully developed may reverse early physiologic changes and avoid the development of a full blown clinical syndrome.
Growth Hormone therapy has been shown to improve lean body mass, decrease body fat , and improve serum lipid profiles (16,17). One published meta analysis which included 54 scientific studies was published in 2012. It found that patients receiving who received Growth Hormone therapy had a significant reduction in body fat measurements accompanied by increased muscle mass(18). Despite theoretical concerns regarding the possibility of the promotion of malignancy this has never been demonstrated throughout the analysis of these many studies. Because of the controversy that arose with increasing off label use of growth Hormone promoted as a general anti-aging strategy and treatment, in 1988 and 1990 amendments made to the Food, Drug and Cosmetic Act made it illegal to use Growth Hormone for off-label conditions in an attempt to counter this use of Growth Hormone that had developed, and some of the advertising claims that were made for it. The widespread use of administering Growth Hormone as a performance-enhancing agent by high athletes drew negative attention to this use, and precipitated the political impetus to stop this usage of growth hormone 19. Holt RIG, Erotokritou-Mulligan I, Sönksen PH. The history of doping and growth hormone abuse in sport. Growth Horm IGF Res 2009;19:320-6. 10.1016/j.ghir.2009.04.009 [PubMed] [CrossRef] [Google Scholar]
As a result of the practical limitations to the use of growth hormone, GH secretagogues emerged as an alternative. These agents appeared to impart many of the same beneficial effects as seen with Growth hormone therapy itself, while demonstrating safety and avoiding regulatory concerns. Growth hormone secretagogues are made of amino acid chains classified as peptides which can enhance a person’s natural hormone production, and thus mimic the benefits of growth hormone therapy without the use of growth hormone itself. Comparable health benefits such as increased muscle mass and decreased body fat have been well demonstrated. The natural physiological pulsatile secretion of growth hormone has been clearly measured and described (21,22). Thus, an increasing number of physicians have been administering growth hormone secretagogues to their patients to get many of the same benefits of GH therapy with substantially less risk https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5632578/
Two of the rigorously studied and tested compounds are Sermorelin and Tesamoreiln.
Sermorelin [GHRH-(1-29)], is a GHRH (growth hormone releasing hormone) analog derived from the first 29 amino acids of the GHRH protein (23). Its physiological impact on the hypothalamic-pituitary-axis has been extensively studied and described (24).
Researcher E Corpas and his team published an evaluation of sermorelin’s effects on GH and IGF-1 levels in 9 young men 22 to 33 years old and 10 elderly men 60 to 78 years old (27). https://pubmed.ncbi.nlm.nih.gov/1379256/ It appeared in the Journal of clinical Endocrinology and Metabolism in 1992.
All of the ten elderly men were given 14 days of injections . The older men had lower baseline IGF-1 levels when compared to the younger men but sermorelin treatment resulted in elevations in IGF-1 related to the dose administered, achieving levels approaching those of the younger men. It was also seen that the measured elevations of IGF-1 (Growth hormone) remained above baseline levels in the elderly men even 2 weeks after stopping sermorelin, suggesting that sermorelin can produce longer lasting effects.
Compared to baseline, the mean peak GH secretory responses were significantly increased in elderly men at both low and high doses. The authors also observed that the areas under GH peaks at night were significantly higher than those during the day for both young and elderly men, confirming that the majority of GH release occurs at night irrespective of age. These findings highlight that sermorelin is an effective stimulator of GH and IGF-1 levels in elderly men with reduced IGF-1 levels.
Another small study conducted enrolled 11 healthy older men between the ages of 64 and 76 years old. They received nightly injections for 6 weeks (28). Assessments were done at the end of the six week study period and included metabolic testing, body composition, GH, and IGF-1 levels, and also assessment of muscle strength and function. The Sermorelin therapy was shown to nearly double the 12-h mean amount of GH released by the pituitary, but blood testing showed that the levels did not go above physiological norms. Sermorelin treatment successfully lead to significant improvements in muscle strength tests, muscle endurance and the abdominal crunch test. The treatment did not result in any change in testosterone levels measured. It was also noted that a decrease in mean systolic blood pressure was observed. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2699646/
Semorelin has a very good safety profile. Infrequent side effects include redness at the injection site, and facial flushing, nausea rarely.
