SERMORELIN
Sermorelin (brand name Geref) was first patented in 1990 by manufacturer EMD Serono. The first product Geref injection 0.05 mg base/amp was approved by FDA on December 1990, followed by Geref injection, 0.5 mg base/vial and 1.0 mg base/vial which was approved by FDA in September 1997. Later in December 2008, the manufacturer EMD Serono notified FDA that Geref injection was being discontinued. Thereafter, the FDA moved this product to the “Discontinued Drug Product List.” The only possible reason why Geref was discontinued was because it had become increasingly difficult to procure and manufacture the active ingredient required to produce the commercially sold Sermorelin drug(6). There were no safety reasons that led to the discontinuation. That being said, FDA has also confirmed that other companies may continue applying for similar Sermorelin formulations (i.e. generic versions of brand product Geref) and file for FDA approval under ‘New Drug Applications (NDA)’. FDA will continue to review and approve these formulations for market distribution, provided all legal and regulatory requirements are met (14). Even though Geref brand was discontinued, there are numerous generic formulations of Sermorelin peptide available. Sermorelin, otherwise also known as GRF 1-29 amide, is a synthetic peptide composed of 29 amino acids. This is the shortest peptide inducing biological activities similar to those induced by naturally occurring growth hormones. Many clinical studies have shown Sermorelin is a highly effective medication and can be a promising candidate to treat other diseases besides growth deficiency and obesity, including male hypogonadism and certain types of cancer. In 2008, the brand drug Geref was discontinued, solely due to difficulties in the manufacturing process of the active ingredient used to manufacture the peptide. However, since there are no safety and efficacy concerns pertaining to Sermorelin, FDA has since approved several generic versions of Sermorelin which are still sold in the market. Lastly, there are various other similar growth hormone secretagogues that are being explored for their potential use and candidacy in the therapeutic world. Some of the main benefits of Sermorelin shown in various studies include: Growth hormone releasing hormones (GHRH) start appearing in the human body during weeks 18 and 29 of the gestation period, which thereby leads to production of growth hormones and body development (1). GHRH are an integral part of the human body for all bodily activities – whether it is metabolic rate, muscle development or building energy levels. As people tend to age, growth hormone levels begin to decline naturally. It is said that post the age of 30 years, GHRH hormone levels decline by an average of 15% every ten years (1). Besides, growth deficiency (or dwarfism) is a naturally occurring phenomenon which may be due to GHRH deficiency. Peptides, such as Sermorelin, which are also called ‘growth hormone secretagogue’, are useful in fighting such growth hormone deficiency. Sermorelin is a 29 amino acid peptide, the shortest man-made peptide that can induce biological activity in the human body. Sermorelin is an exact match to the human growth hormone releasing hormone (GHRH) (2). Sermorelin polypeptide is an analog of the GHRH factor consisting of GHRH (1-29 acid)-amide, which is found in several mammals including humans. Owing to the presence of this structure, Sermorelin is used in the diagnosis and treatment of growth hormone deficiency (3). It was in the early 1980s that the effects of growth hormone fragment GHRF (1-29) amide was discovered. Several research studies were conducted on rats where exogenous GHRF (1-29) amide (i.e. Sermorelin) was administered in conscious and anaesthetized rats. It was observed that this treatment stimulated the pituitary gland and promoted growth. Post this discovery, growth hormone secretagogues (such as Sermorelin) became promising candidates in treating growth deficiency in humans (4). By 1987, Sermorelin was approved by the US Food and Drug Administration for human administration through medical prescription (5). Sermorelin, otherwise also known as GRF 1-29 amide (commercial name Geref) was first patented in 1990 by the manufacturer EMD Serono (6). In 2008, Sermorelin brand drug Geref was discontinued – not due to safety reasons, but due to difficulties in manufacturing the active ingredient used for Sermorelin production (6). As there have been no safety or efficacy concerns reported, FDA has since approved various generic versions of Sermorelin, provided all legal and regulatory requirements are met, which are still available in the market till date (14). More details are described below in the article. As mentioned before, Sermorelin is a growth hormone analogue and is an exact match of the human growth hormone, constituting first 29 amino acids out of the usual 44 amino acids found in human growth hormone. Sermorelin binds with the growth hormone receptors found on the pituitary gland and stimulates secretion of the growth hormones. The main positive advantage of the peptide is that it does not induce any significant change in the levels of prolactin, insulin, cortisol, glucose, and thyroid hormones – which is further described in the research studies below. This added advantage makes Sermorelin a promising candidate in the diagnosis and treatment of growth hormone deficiency in humans (6). Below are the main advantages of the peptide: Being a growth hormone analogue, most of the effects and uses of the peptide are similar to that of the naturally occurring growth hormone. Due to increased growth hormone secretion, Sermorelin improved collagen production and improved skin tone – thereby reducing aging and wrinkles. Recent studies have shown that patients with recurrent glioma were most sensitive to Sermorelin – thereby making Sermorelin the next potential effective medication in glioma treatment. More details regarding glioma study to follow. In the 1980s, researchers R.G Clark and I.C Robinson administered multiple intravenous injections of 1 microgram of fragment GRF 1-29 amide to fully understand the scope and use of this fragment in mammals. After 3 to 5 minutes of administration, high peak levels of growth hormones were observed. Frequency of administration was increased in both female and male rats from 180 minutes to 90 minutes and then to every 40 minutes. Interestingly, female rats showed consistent elevated levels for growth hormones each time the fragment GRF 1-29 amide was administered. However, the male rats showed elevated levels of growth hormones intermittently, responding to two injections at a time (4). This study proved that exogenous administration of GRF 1-29 amide was fully responsive and could be potentially used in growth retardation problems in humans. Based on studies conducted in the 1990s, it was concluded that Sermorelin can be used as a diagnostic tool to identify growth hormone deficiency where Sermorelin can be administered intravenously at a dose of 1 microgram/kg body weight and the hormone responses will be monitored (7). When children are administered with Sermorelin, there would be increased growth hormone responses in children suffering from growth deficiency. However, Sermorelin alone cannot detect growth deficiency induced by hypothalamus deficit – in this case, other provocative tests also need to be conducted to ensure an accurate diagnosis. When Sermorelin was administered in children subcutaneously at the dose of 30 microg/kg body weight, it showed positive results in children (pre-puberty age) with idiopathic GH deficiency. Increased rate of growth and height velocity was observed within 12 months of consistent, continuous treatment. These elevated effects were sustained for an average of 36 months after continuous use (7). HIV patients suffering from lipodystrophy have reduced levels of growth hormones in the body. Because of this, scientists carried out a controlled trial study with 31 HIV infected patients, aged 18 to 60 years, suffering from lipodystrophy, to investigate the effects of Sermorelin on them (8). All 31 patients were divided into two groups, where one was administered with 1 mg dose of Sermorelin subcutaneously, and the other group was administered with placebo for 12 weeks. Post the treatment, it was noticed that growth hormone levels had significantly increased in Sermorelin treated patients as compared to the ones treated with placebo. Levels of insulin-like growth factor (IGF-1) had increased – resulting in increased lean body mass in the peptide treated patients. Interestingly, abdominal visceral fat and ratio of trunk to lower extremity fat has significantly reduced. There was no other change in the glucose or insulin levels. This study suggested that Sermorelin was well tolerated and can be a beneficial, useful candidate in the treatment of lipodystrophy for this population (8). In the early 2000s, research studies were conducted with 89 healthy older patients between 68 and 69 years of age, to understand the correlation between growth hormone decrease and impaired cognition. With increasing age, levels of growth hormone decline, which result in reduced physiological functions, including cognition (i.e. ability to collect, process and recollect information). Post treatment with Sermorelin, it was observed that there was improved performance in the Wechsler Adult Intelligence scale (WAIS) – i.e. improved IQ levels, picture arrangement tests and verbal tests. These results were regardless of the patient’s gender and estrogen levels. This study suggested GHRH compounds such as Sermorelin can also potentially be used to improve cognitive capacity for other individuals suffering from mild cognitive impairment and Alzheimer’s disease (9). The main cause of glioma is treatment insensitivity. The purpose of this study was to determine which drugs would be most effective in patients suffering from recurrent glioma. The study was designed where 1018 glioma patients were treated with over 4000 drugs each, and after the treatment, a drug resistant score (DRS) was determined for all drugs, for each patient. After the treatment and rigorous screening, it was discovered that patients were most sensitive to Sermorelin. Upon analysis, it was discovered that Sermorelin blocks the tumor cell cycles and thereby prevents the tumor cell proliferation. This enhances the immune response towards the tumor cells. This study proved that Sermorelin can potentially be used in cancer treatment, and this data analysis could be further extended to pancreatic and lung cancer. More studies would determine further use of Sermorelin in cancer treatment (10). Male hypogonadism is characterized by decreased levels of testosterone along with clinical symptoms such as high fat mass to bone mass ratio and low libido. Main cause of male hypogonadism is obesity. Obese men are at a higher risk of hypogonadism as compared to their leaner counterparts. Sermorelin had initially proved to be effective in increasing lean mass, due to which it was selected as a candidate for this study. All participants were divided into two groups where one group was treated with Sermorelin followed by GHRH 1-40, with a one week interval between the two treatments, whereas the other group was given the same treatment in reverse order. Post treatment, it was noticed for both the groups that Sermorelin stimulated the release of FSH and LH in the body which would in turn stimulate testosterone production in vivo. Thus, Sermorelin could be a potential candidate in the treatment of hypogonadism. Studies were carried out on 19 men, 9 of whom were aged between 22 and 33 years of age and 10 were aged between 60 and 78 years. Elderly men were treated with either 0.5 mg or 1.0 mg dose of Sermorelin for a period of 28 days, with an interval of 14 days in between the two treatments. Testosterone levels in old men increased after the administration of Sermorelin; however, it should be noted that the levels were not statistically significant. Furthermore, researchers also discovered that elevated levels of growth hormones, induced by Sermorelin treatment, were at peak during the night time, for both young and old men, as compared during the day. This study suggested the possible use of Sermorelin, and similar growth hormone secretagogues, in the treatment of male hypogonadism (11). Below listed are the side effects reported with Sermorelin administration. While not all of the side effects may occur simultaneously or at the same intensity, it is recommended to seek medical advice immediately if these are persistent. Everyone is different and has a different medical profile. Depending on the individual profile (such as allergies, simultaneous consumption of other medicines, patient age and medical history), the side effects may differ. As always, one must consult a healthcare professional immediately upon continued adverse reactions after use (12). Multiple research and clinical studies have been conducted for Sermorelin via intravenous or subcutaneous route of administration. For injection, 2mg of Sermorelin was administered with peak concentrations reaching within 20 minutes. However, it should be noted that Sermorelin is a short acting drug with the mean half-life of 11 to 12 minutes after administration (6). While studies are still on going for the growth hormone secretagogues, studies have suggested that a low dose (1-2 micrograms / kg body weight) administered subcutaneously every 3 hours have been effective (13). Based on clinical studies, peak growth hormone levels were seen during the night time rather than day time – suggesting that taking the medication during bed time is recommended for the best results (11). It should always be noted that these are only recommended statistics based on clinical studies; however, each individual profile is different. Seeking medical advice is highly recommended to obtain the best results. Products must be stored in cool temperatures and refrigerated. Do not freeze the product and must keep it out of reach of children (12). It is suspected that Sermorelin is used as a doping agent by athletes as means to build their energy levels, increase recovery rate, and improve the overall endurance. This is why Sermorelin has been banned by the World Anti-Doping Agency (WADA) and is captured in their 2021 Prohibited List (15), (16). Since the mean half-life of Sermorelin is only 11 to 12 minutes (6), it is recommended to administer the medication in combination with another growth hormone secretagogue, Ipamorelin. Being another synthetic growth hormone peptide, Ipamorlin is comparatively faster acting medication with the average half-life of 2 hours. Since both medications have different mechanisms of action, where Ipamorelin peptide acts on the pituitary gland while the Sermorelin peptide acts solely on the growth hormone secreting receptors, an individual administering the Sermorelin Ipamorlin or combination gets a higher “kick” and immediate, longer lasting results rather than only administering one medication.What is the Current Status of Sermorelin?
FDA conducted an investigation where all records pertaining to the withdrawal of Geref drug products were reviewed and all relevant literature and analytical data were evaluated. FDA concluded that Geref injections were not withdrawn from sale for safety or efficacy reasons .Summary
Sermorelin for sale
What You Need to Know About Sermorelin
Introduction
Peptide History
Mechanism of action
Sermorelin Benefits
Research and Clinical Studies
Early Research and Discovery
Sermorelin Use in Growth Hormone Deficiency in Children
Its Use in HIV-infected Patients with Lipodystrophy
Its Use in GH deficiency induced impaired cognition
Its Use in Recurrent Glioma
Its Use in Male Hypogonadism
Sermorelin Peptide Side Effects
Sermorelin Dosage, Mode of Administration
Sermorelin Peptide Storage
Is Sermorelin Banned in Sports?
Common Sermorelin Peptide Combinations / Blends