I’ve been inundated over the past few years with patients interested in peptides, in particular the growth hormone secretagogue peptides. The peptide “craze” has largely been fueled by social media and health influencers who have no legitimate medical training. Chiropractors, body builders, personal trainers, “scientists”, flunky doctors with horrendous credentials, the list goes on.

Many of my patients have used “research grade” or “lab use only” peptide “stacks” according to these snake oil salesmen with absolutely NO discussion of risks and ZERO medical supervision. In some cases, I’ve had to clean up the unfortunate health consequences of their peptide use. Meanwhile, the social media quacks who sell peptides cash checks at the bank with no legal repercussions. In any case, I’ve had to discuss these peptides countless times with patients so I decided to write a blog with some medical honesty to help men navigate this health space. 

As a urologist, board certified by the American Board of Urology, I actually have legitimate expertise in andrology, or the study of male hormones. There are two medical specialties with expertise in andrology. Urology and endocrinology, that’s it. Anyone else claiming to be an expert on testosterone or male hormones is quite frankly a liar and a fraud. Just because someone is a physician who prescribes testosterone or hormone activating peptides, does NOT make them an expert in any way, shape or form. An MD with an interest in a particular area of medicine does not equate to years of legitimate training in a medical speciality like urology or endocrinology. 

At our practice, we have two urologists and an endocrinologist on staff. Endocrinology is the ONLY medical specialty with expertise in human growth hormone (HGH). While urologists who specialize in andrology also have expertise in other male hormones, endocrinologists are bar none the experts when it comes to HGH. We do not sell peptides. We do not sell supplements. We do not advocate the use of drugs without legitimate human data. And yes, make no mistake about it, peptides are drugs. So here’s the scoop. 


What are Peptides?

Peptides are nothing new. Many drugs are peptides. Insulin is a peptide. Growth hormone is a peptide, discovered in the 1950’s. It has sparked scientific interest for decades on multiple fronts. Its ONLY legitimate use in medicine is for the treatment of growth hormone deficiency. Growth hormone deficiency is a clinical diagnosis that requires provocative testing by an endocrinologist. It is NOT the same as the age related decline in growth hormone production discussed in longevity medicine circles. And for the record, longevity medicine is not a legitimate medical specialty. 

There is NO viable scientific evidence that growth hormone or any other peptide is a longevity hormone. NONE. Taking growth hormone will NOT make you live longer. In fact, it may have the opposite impact on your longevity. Human growth hormone is often abused by professional athletes and body builders due to its effects on body composition. Recombinant HGH (rHGH) is tightly regulated due to this potential for abuse. 


Growth Hormone Physiology

So what is growth hormone and what is its physiologic function? Growth hormone is a polypeptide hormone secreted by the anterior pituitary gland at the base of the brain. It regulates post-natal growth, metabolism and body composition. It is secreted in a pulsatile fashion with most production occurring at night. Adequate deep sleep is essential for normal growth hormone production. 

Growth hormone secretion is regulated by hypothalamic peptides, in particular growth hormone releasing hormone (GHRH). The hypothalamus is a part of the brain adjacent to the pituitary gland. It regulates pituitary gland function and the release of multiple hormones in addition to HGH. 

Growth hormone releasing hormone stimulates the biochemical synthesis and release of HGH from the anterior pituitary gland. Somatostatin, a hormone produced by the GI tract, inhibits the release of HGH by the pituitary. Ghrelin, a GI peptide also known as the “hunger” hormone, facilitates HGH release by modulating GHRH and somatostatin. Insulin-like growth factor-1 (IGF-1) provides negative feedback at both the hypothalamus and pituitary creating the classic negative feedback loop seen in many hormone systems. Other factors modulate HGH production including fasting, exercise and adiposity. For example, with each unit increase in body mass index (BMI), HGH production falls by about 5%. 

Growth hormone exerts its effects directly on tissues and indirectly through IGF-1, a peptide produced by the liver. Growth hormone serves as an anabolic signal during fasting and stress. It stimulates lipolysis (fat breakdown) and inhibits insulin sensitivity which raises blood sugar. During feeding periods, HGH works with IGF-1 and insulin to exert anabolic effects on muscle and energy storage. 

Growth hormone deficiency is a clinical diagnosis made by an endocrinologist using multiple criteria including provocative testing. Most patients interested in using growth hormone do NOT have bonafide growth hormone deficiency.


Age-Related Decline in Growth Hormone

Growth hormone production declines with aging with the most prominent decline occurring between the ages of 25-35. This decline is often referred to as “somatopause” and appears to be due to a decrease in GHRH production by the hypothalamus, not pituitary failure or hepatic GH resistance. As men age beyond 35, growth hormone levels fall further and more production starts to occur during the daytime. As mentioned earlier, body composition has a profound effect on growth hormone production with aging. As men accumulate abdominal fat (an unfortunate consequence of aging), growth hormone production falls. This can create a vicious cycle of worsening body composition.

The clinical significance of this decline in growth hormone with aging remains controversial. While the reduction in growth hormone with aging is associated with increased adiposity, reduced muscle mass and metabolic changes consistent with those seen in HGH deficient adults, animal studies suggest that reduced HGH-IGF-1 signaling is associated with increased longevity. Human longevity studies support the protective effects of lower HGH levels. Mutations that confer a resistance to growth hormone appear to increase longevity by a decade. 

Currently, HGH administration in healthy older adults without pituitary pathology is NOT recommended. While there may be small benefits in terms of body composition with HGH usage, side effects can be profound and functional outcomes have been questionable. To be clear, there is NO legitimate scientific data to support the use of HGH in healthy adults to promote health or longevity. 


Growth Hormone Secretagogues

Growth hormone secretagogues (GHS) are peptides that stimulate the release of human growth hormone by the pituitary gland. These drugs have been around for decades and for the most part, have been used in the diagnosis and treatment of human growth hormone deficiency. They have been studied for other conditions including the treatment of certain metabolic disorders and lipodystrophy but remain investigational in this regard. There are a multitude of GHS including but not limited to hexarelin, ipamorelin/CJC-1295, sermorelin, growth hormone releasing peptides 2 and 6, ibutamoren and tesamorelin. I won’t get into the details and differences of each GHS in this article but for the most part, they all have the potential to increase the production of growth hormone by the pituitary. Unlike recombinant human growth hormone, these drugs maintain the normal pulsatile physiology and negative feedback with IGF-1. In other words, they do NOT suppress endogenous growth hormone production or lead to supraphysiologic growth hormone levels seen with rHGH usage.

The internet has been long proposing that using these peptides to increase growth hormone production has health benefits. They claim that they can improve sleep, mood, sexual performance, energy and body composition. They also claim that they can improve recovery from work-outs and heal soft tissue injuries. There is simply NO good human data to support any of this. That may be an unfortunate medical fact but it is the honest truth.


Testosterone Deficiency and the Role of Growth Hormone

Testosterone deficiency is a condition in men where low testosterone levels lead to a constellation of symptoms including low libido, fatigue, poor sleep, cognitive impairment, loss of muscle mass and increased adiposity. The gold standard for treating low testosterone is testosterone replacement therapy, a treatment well known to andrologists like me. Testosterone therapy improves sexual performance, mood, sleep, cognitive function and body composition. 

Although the benefits of testosterone therapy are well known, there is evidence that the significance of these improvements vary widely among patients. Some studies have failed to show improvements in body composition in men taking testosterone therapy. This has sparked some interest from urologists who treat low testosterone regarding the use of growth hormone to improve body composition in men who have not responded well to standard testosterone replacement. 

Growth hormone therapy has demonstrated improvements in lean mass and decreased adiposity along with improved lipid profiles in some studies. While growth hormone therapy offers some promise to men who fail to see improvements in body composition on testosterone, growth hormone therapy remains controversial and is tightly regulated. It is also associated with side effects including joint pain, intracranial hypertension, diabetes, edema and a theoretical risk of promoting cancer. Law makers made it illegal to use GH for off label conditions due to false advertising that it can reverse the effects of aging. Abuse by athletes and body builders led to even more scrutiny. 


Low Testosterone and Growth Hormone Secretagogues

Due to these limitations and concerns, growth hormone secretagogues became an area of interest as an alternative to rHGH therapy. These compounds appear to have some of the same benefits compared to growth hormone without the high incidence of side effects. Growth hormone secretagogues consist of peptide and non-peptide drugs that stimulate GH release. They work by either directly mimicking GHRH or through interactions with the ghrelin receptor. Growth hormone secretagogues have been shown to increase GH and IGF-1 levels comparably to recombinant HGH therapy without causing supraphysiologic levels. Several of these compounds have been studied in men using testosterone concomitantly. The studies are small and of relative short duration. 

Testosterone deficiency is a prevalent condition that can cause bothersome symptoms and predispose men to adiposity and loss of muscle mass. While most men respond well to testosterone, there is a subset of patients who continue to struggle with body composition and other symptoms of low testosterone including poor sleep and fatigue. Growth hormone secretagogues offer these men a possible solution however the data is far from robust. Small studies have shown benefits in body composition and anecdotally some men see other improvements in low T symptoms. However, until we have better human data patients should be wary of their use. Growth hormone secretagogues carry some of the same risks as exogenous growth hormone use and patients using these peptides must be warned accordingly. Medical supervision is also required to monitor men for side effects, lab abnormalities and malignancy. 

Conclusions

Reputable compounding pharmacies that are regulated at the federal or state level do produce some of these GHS. Currently, they are the only reputable source for obtaining these drugs. They will only be dispensed with a prescription from a licensed physician. Patients must understand that the data for using these drugs is extremely limited and the results from small human trials are anything but impressive. Men planning to use these peptides should seek out a physician with legitimate expertise in andrology and growth hormone. Social media fame and medical interest in hormones do not equate to medical expertise.