Sermorelin: how it works, what studies show and regulatory status

Does sermorelin help with building muscle, losing fat, recovery or healthy aging? The drug stimulates the release of growth hormone. What is missing, though, are controlled studies showing such benefits in healthy adults. Results that are often cited come from research on other drugs or other routes of administration. They cannot simply be carried over to sermorelin.

What is sermorelin?

Sermorelin is the shortest fragment of human growth hormone-releasing hormone (GHRH) that retains the hormone’s full biological activity. GHRH is made in the hypothalamus, a region of the brain. It signals the pituitary gland to release growth hormone.

Sermorelin was once an approved drug. Under the name Geref, it was used to test growth hormone release and to treat growth disorders in children. The manufacturer later discontinued the product. Today sermorelin is offered mainly as a compounded medication, prepared individually by a pharmacy. Its marketing also targets adults who hope it will have anti-aging effects or change their body composition.

How does sermorelin work?

Sermorelin binds to the same receptor in the pituitary gland as the body’s own GHRH and activates it. That is why it is called a GHRH receptor agonist. The pituitary then releases growth hormone (GH) in pulses. This in turn raises levels of insulin-like growth factor 1, or IGF-1.

Sermorelin acts for a shorter time than CJC-1295, but uses the same signaling pathway. The wellness claims aimed at adults rest on this effect on hormone levels. That alone does not show that it improves health or well-being.

Is sermorelin FDA approved?

According to the information this article is based on, there is currently no FDA-approved sermorelin product on the market. That is a separate question from whether earlier approvals still legally exist. The FDA is the US drug regulator; for sport, the prohibited list of the World Anti-Doping Agency (WADA) also applies.

Area	Status
FDA approval	Approved by the FDA as Geref and later discontinued, reportedly for business reasons and not because of safety concerns. According to the information used here, there is currently no FDA-approved sermorelin product on the market.
Individual compounding	Offered as a compounded medication prepared for individual patients. Its earlier approval partly sets its regulatory position apart from that of peptides that were never approved. Whether, and under what conditions, compounding it is currently permitted remains to be clarified.
Anti-aging and performance enhancement	Not approved for either purpose.
Sport	According to the WADA list, GHRH analogs including sermorelin are prohibited at all times.

What does the research show?

The historical human studies looked at sermorelin for its medical uses at the time: diagnosing whether the pituitary can release enough growth hormone, and treating growth hormone deficiency in children. These uses were established. Physiological studies also show that activating the GHRH pathway increases growth hormone release during the night (1). No benefit for wellness use in adults can be inferred from this.

There are no controlled studies showing that sermorelin gives healthy adults more muscle, less body fat, better recovery or a favorable effect on aging. The expectations along these lines rest on its effect on hormone levels.

Frequently asked questions

What is sermorelin, and how does it differ from human growth hormone?

Sermorelin is a synthetic GHRH analog made of 29 amino acids, in other words a drug that corresponds to the body’s own GHRH. It binds to GHRH receptors in the anterior lobe of the pituitary gland, where it triggers a pulsed release of the body’s own growth hormone. Treatment with human growth hormone (HGH), by contrast, supplies the hormone directly.

The hypothalamus can still dampen sermorelin’s signal through somatostatin when enough hormone is present (2). This feedback mechanism is thought to limit GH excess. Whether that makes sermorelin safer than directly administered HGH cannot be said, however: there are no head-to-head studies comparing their safety.

HGH given from outside bypasses the pituitary entirely. Sermorelin, by contrast, can only trigger GH release if the pituitary is intact and able to respond to the stimulus.

What does research on the GHRH drug class show about visceral fat loss?

Controlled studies of tesamorelin show a reduction in visceral fat, the fat tissue around the internal abdominal organs. Tesamorelin binds to the same receptor as sermorelin and likewise stimulates pulsed GH release. Even so, these results do not show that sermorelin has the same effect.

In a randomized controlled trial of 412 patients, visceral adipose tissue fell by 15.2% after 26 weeks on tesamorelin. Participants received 2 mg daily subcutaneously, meaning as an injection under the skin. In the placebo group, visceral adipose tissue increased by 5.0% (p < 0.001; 3).

A pooled analysis of two phase 3 trials with 806 participants in total found a reduction in visceral adipose tissue (VAT) of about 15.4% versus placebo after 26 weeks. The effect persisted through week 52. No clinically meaningful changes in glucose levels were found (4).

In a 12-month randomized controlled trial of 60 adults with abdominal obesity (marked excess weight with a lot of belly fat) and reduced GH secretion, visceral adipose tissue fell by a net 19% compared with placebo. Triglycerides, a measure of certain blood fats, dropped by a net 37 mg/dL (5).

These findings apply to tesamorelin and to the groups studied in each case. For sermorelin, there are no controlled studies showing a favorable effect on body fat in healthy adults.

How does the GHRH pathway affect IGF-1 levels?

When the GHRH receptor is activated, the pituitary releases GH in pulses. GH then stimulates the liver to release IGF-1. The IGF-1 level serves as the main downstream measure of how well this hormone system, the growth hormone axis, is working.

In seven healthy men aged 65 to 78, the GH response to a GHRH test was weaker than in young men. Over 12 days they received 100 mcg of GHRH-40 intravenously (into a vein) every 2 days. Afterward their GH response recovered to a statistically significant degree (6). What was studied here was the response to GHRH-40; the study provides no direct evidence of an effect of sermorelin on IGF-1 levels.

A retrospective study looked back at data from 14 men on testosterone therapy. They had received sermorelin together with GHRP-2 and GHRP-6 for an average of 134 days. Their IGF-1 levels rose from 159.5 to 239.0 ng/mL, an increase of about 50% (p < 0.0001; 7). Because several drugs were given together, it is impossible to tell how much of this rise was due to sermorelin.

Does sermorelin affect sleep quality?

There are no direct randomized controlled trials on sleep for subcutaneously administered sermorelin. What has been studied is how GHRH affects deep sleep, also called slow-wave sleep. These results cannot simply be carried over to sermorelin.

In controlled experiments with seven healthy men, GHRH increased the share of deep sleep in total sleep time from 14.0% to 20.2%. Relative to the baseline, that is a 44% increase (8). Another study in healthy young men found an almost tenfold increase in deep sleep when GHRH was given during the late phase of sleep (9). That figure refers to deep sleep, not to total sleep time.

In older adults with an average age of 69.3 years, GHRH reduced the number of times they woke during the night. The effects were much smaller than in younger adults, however. The researchers took this as a sign that GHRH works less well with age (10).

In these studies GHRH was given intravenously. They therefore do not answer whether sermorelin injected under the skin improves sleep quality.

Is sermorelin FDA approved, and what is its regulatory status?

According to the information used here, there is currently no FDA-approved sermorelin product on the market. Historically, the FDA granted approval in 1990 as a diagnostic agent and in 1997 for treating idiopathic growth hormone deficiency in children. “Idiopathic” means that no cause can be identified. The manufacturer discontinued the product in 2008.

The FDA later determined that the discontinued GEREF products had not been withdrawn from sale for reasons of safety or effectiveness (11). That determination alone does not settle the current approval status.

Sermorelin is offered as a compounded medication prepared for individual patients. The fact that such a compounded preparation is available does not mean the product currently has FDA approval. The conditions that currently apply to this kind of compounding still need to be clarified.

What does research show about sermorelin and lean muscle mass?

For healthy adults, there are no controlled studies showing more or better muscle from sermorelin. The results often cited come from studies of tesamorelin. Those studies measured different things: muscle mass, muscle cross-sectional area, muscle density and lean body mass are not the same. Lean body mass in particular cannot be equated with muscle mass.

A secondary analysis looked at data from 341 adults with HIV. It compared people who responded to tesamorelin over 26 weeks with the placebo group. Compared with placebo, muscle density in four trunk muscle groups rose by 1.56 to 4.86 Hounsfield units (all p < 0.005). Computed tomography uses this unit to describe tissue density. Lean muscle cross-sectional area increased by 0.64 to 1.08 cm² in four trunk muscle groups (12). The analysis was limited to people who responded to tesamorelin, so the result does not describe the effect in everyone treated.

A meta-analysis of five randomized controlled trials compared tesamorelin with placebo in adults with HIV. Lean body mass increased by an average of 1.42 kg (95% confidence interval: 1.13 to 1.71 kg; p < 0.001; 13). The confidence interval describes the statistical uncertainty around the estimated average effect.

No corresponding muscle gain from sermorelin can be inferred from these tesamorelin studies.

What is the somatopause, and why does GH decline with age?

Growth hormone secretion starts to decline gradually from early adulthood. This process is called the somatopause (14). Studies suggest that several processes are involved.

One study found evidence in older men that the hypothalamus released less GHRH and that this contributed to their lower GH levels. When GHRH was injected, by contrast, young and older men responded with comparable GH release (15).

In another study, the pituitary of men aged 65 to 78 responded more weakly to a GHRH test than that of young men. After repeated doses of GHRH, this response recovered. The reduced sensitivity therefore appears to be at least partly reversible (6).

The effect of GHRH on sleep and cortisol was also weaker in older adults. The researchers interpreted this as a sign of reduced GHRH effectiveness with age (10).

So the studies do not paint a consistent picture of how the pituitary responds. Taken together, they suggest that both weaker signals from the hypothalamus and lower sensitivity of the pituitary may contribute to the decline in GH secretion.

Sources

• Sources: a GHRH physiology study (Jessup et al., European Journal of Endocrinology, 2004, DOI: 10.1530/eje.0.1510561 1 ), indexed on PubMed; FDA records on the discontinued Geref product; and the WADA Prohibited List. This document is educational, is not medical advice or a health claim, and is not an offer to sell any product. Original reference