Sermorelin Therapy: Benefits, Side Effects, and Clinical Evidence

Sermorelin is a synthetic peptide (group of amino acids) that mimics the action of growth hormone-releasing hormone (GHRH), a natural substance produced in the
brain. By stimulating the front of the pituitary gland, sermorelin increases the body’s own production of growth hormone (GH), which in turn raises levels of insulin-like
growth factor 1 (IGF-1). These hormones play a crucial role in regulating metabolism, body composition, and overall health.

Subcutaneous sermorelin is used off-label (without FDA approval) in adults for several purposes. The most common off-label uses include anti-aging and general wellness,
athletic performance enhancement, and, less frequently, the management of adult growth hormone deficiency.

For you, there is reason to believe it can improve vitality, increase lean body mass, reduce body fat, enhance sleep quality, and boost energy. The rationale for these uses is
based on the natural decline in growth hormone secretion with age, known as “somatopause,” and the hypothesis that restoring GH levels may counteract some of the
metabolic and physical changes associated with aging.

The New England Journal of Medicine emphasizes that there is no compelling evidence from controlled studies that growth hormone therapy, including GHRH analogues like
sermorelin, provides meaningful benefits in healthy adults without a confirmed diagnosis of GHD.

What does that mean?

It is important to realize that high-quality randomized controlled trials are hard to come by. They are easy to do for a new medication, where they give one group a placebo and
compare blood glucose numbers with the group that got the novel medication. It is much more difficult to quantify sleep quality and energy levels. People don’t like filling
out surveys, so scientists often end up with fewer data points and unreliable results.

I want you to know that we recommend omega-3 fatty acids for mood, cognition, and inflammation, without robust data. We are almost certain that something like curcumin helps with arthritis and inflammatory bowel disease, but there are no high-quality trials to prove this. Most doctors, including me, agree that CoQ10 helps long-term for patients with heart failure or family history of dementia, but there are no meta-analyses to prove this either.

The strongest clinical evidence for the health benefits of GHRH analogues in adults comes from studies of tesamorelin, a peptide closely related to sermorelin. In a
randomized, double-blind, placebo-controlled trial published in The Journal of Clinical Endocrinology and Metabolism, daily subcutaneous administration of tesamorelin (2
mg once daily) in abdominally obese adults with reduced GH secretion resulted in a statistically significant reduction in visceral adipose tissue (VAT), improvement in
carotid intima-media thickness (cIMT), reduction in serum triglycerides, and lower C-reactive protein (CRP) levels compared to placebo over 12 months.

If you’re a nerd like me, this deep dive into the above study is for you. VAT decreased by 35 cm² (95% CI: -58, -12; P = 0.003), cIMT improved by 0.04 mm (95% CI: -0.07,
-0.01; P = 0.02), CRP decreased by 0.15 mg/L (95% CI: -0.30, -0.01; P = 0.04), and triglycerides dropped by 37 mg/dL (95% CI: -67, -7; P = 0.02). IGF-1 levels increased by
92 μg/L (95% CI: +52, +132; P < 0.0001).

While tesamorelin is not identical to sermorelin, both are GHRH analogues with similar mechanisms of action. These findings suggest that subcutaneous administration of a
GHRH analogue in adults can reduce visceral fat and improve certain cardiovascular risk factors, without adversely affecting glucose metabolism.

In a smaller, single-blind, randomized, placebo-controlled trial of nightly subcutaneous sermorelin in older adults (ages 55–71), administration of 10 micrograms per kilogram
body weight for 16 weeks resulted in significant increases in nocturnal GH and IGF-1 levels, increased skin thickness in both men and women, and increased lean body mass
and insulin sensitivity in men. Quality of life parameters showed improvement in general well-being and libido in men, but not in women, and sleep quality was unaffected. The only adverse event noted was transient hyperlipidemia, which resolved by the end of the study.

Subcutaneous administration is preferred, with injections given at bedtime to optimize physiological response. The injection site should be rotated to minimize local reactions.

The main absolute contraindication for sermorelin therapy in adults is the presence of an active cancer. Increased GH and IGF-1 levels may theoretically promote tumor
growth or recurrence, and adults with any active cancer—including solid tumors, hematologic cancers, or pituitary neoplasms—should not receive sermorelin. Soft
contraindications include diabetes, untreated thyroid or adrenal issues, benign intracranial hypertension, and diseases of the retina. We can’t approve it for
professional athletes, as it is on WADA’s list of performance-enhancing drugs.

Subcutaneous sermorelin is generally well tolerated in adults, with the most common side effects being mild and transient. Local reactions at the injection site, such as pain,
erythema, and transient facial flushing, are frequently observed and usually resolve without intervention. Systemic side effects are infrequent but may include mild
symptoms such as headache, nausea, and dizziness. In the adult trial by Khorram et al, the only adverse event noted was transient hyperlipidemia (basically cholesterol), which resolved by the end of the study. There were no serious or persistent local reactions, and no cases of impaired glucose tolerance or diabetes were reported.

Unlike recombinant GH, sermorelin has not been associated with significant fluid retention, peripheral edema, arthralgia, myalgia, carpal tunnel syndrome, or sleep
apnea in the available adult studies. The safety profile of sermorelin may be more favorable than that of rhGH, particularly with respect to fluid retention and metabolic
complications, but direct comparative data are not available.

Long-term safety data for sermorelin in adults are lacking. Large cohort studies of rhGH replacement in adults, such as the KIMS study, have shown that appropriate GH
therapy does not increase the risk of cancer, cardiovascular events, or diabetes when used in selected patients and dosed to maintain IGF-1 within the normal range.

I often recommend sermorelin to my patients who do not meet criteria for GLP-1 agonist medications, in order to improve the muscle-to-fat ratio. As long as you don’t
have cancer and are not a professional athlete, it is a generally well-tolerated and safe option.

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