Human Growth Hormone, ‘the Sweet Syringe of Youth’: Myths, Evidence and Controversy

If you read magazines, watch television or use the Internet, chances are you have probably seen advertisements touting the miraculous age-reversing and bodybuilding properties of synthetic human growth hormone (HGH) treatment. One website advertises that its customers can be young forever with HGH, an injectable drug that has been dubbed “the sweet syringe of youth.”[1] “Anti-aging” clinics across the country draw in new customers by promising to “balance” their hormones; increase their strength, energy and sex drive; and help them build muscle, lose weight and sleep better — all under the supervision of a licensed physician.[2]

The generic name for synthetic HGH is somatropin. It is sold under a number of brand names in the U.S., including GENOTROPIN, HUMATROPE, NORDITROPIN FLEXPRO, NORDITROPIN NORDIFLEX, NUTROPIN, NUTROP-IN AQ, OMNITROPE, SAIZEN, SEROSTIM, TEV-TROPIN, VALTROPIN and ZORBTIVE.

While somatropin is approved for limited uses in the U.S., it is illegal to promote the drug for any use in healthy individuals, such as to build muscle or reverse aging. Yet laws have been poorly enforced and have not prevented the widespread sale of HGH as an anti-aging elixir. Use of the drug for this purpose has skyrocketed over the past two decades, with the approximate number of users growing from fewer than 2,000 in the mid-1990s to tens of thousands or more today, fueling a multibillion-dollar industry.[3],[4]

Evidence on the anti-aging properties of HGH always has been tenuous at best, and the drug is linked to numerous side effects and a possible increased risk of diabetes. More recently, several studies have suggested that the secret to long life may lie in part in low levels of HGH.

Arm yourself against the misinformation on HGH by understanding the science behind this increasingly popular drug.

Growth hormone and the Rudman study

In the early 1980s, scientists discovered that levels of naturally occurring growth hormone and a second growth-stimulating hormone, insulin-like growth factor 1 (IGF-1), decrease with age in humans and other animals, suggesting a possible link between these hormones and aging.[5] In humans, growth hormone secretion rates peak during puberty, then decline sharply to approximately 15 percent of peak levels by age 55.[6] These decreases also appear to correlate with decreases in muscle mass, declines in immune function and other aspects of aging.[7]

Scientists soon dubbed the natural decline in growth hormone that occurs with aging “somatopause,” evoking a comparison to menopause in women.[8] Some researchers were intrigued by the idea that keeping growth hormone levels high could counter the effects of aging.

Results from some studies indicated that injections of HGH or synthetic IGF-1 could bring about helpful changes in adults and children with extremely low natural growth hormone levels, a condition known as growth hormone deficiency, which, in adults, is almost entirely limited to individuals who have experienced damage to the pituitary gland from cancer, traumatic brain injury, childhood disease or other causes.[9]

In 1990, a group of researchers led by Dr. Daniel Rudman published in The New England Journal of Medicine (NEJM) the results of the first test of synthetic HGH therapy in healthy older adults: a small clinical trial reporting data on 21 healthy men over 60 who had low IGF-1 levels, placing them in the bottom third for their age group.[10] Twelve men who received HGH therapy for six months experienced modest improvements: a 9 percent increase in “lean body mass” (fluid and muscle tissue),a 2 percent increase in vertebral (spinal) bone mineral density and a 14 percent decrease in fat tissue, compared with the nine men who received no treatment.

The Rudman study generated much excitement, and purveyors of HGH continue to promote this small, early trial as “one of the best examples of medical literature” on the effectiveness of this treatment.[11] In fact, there were numerous problems with the study. While Rudman’s NEJM paper described no major adverse events after six months of treatment, the HGH-treated group experienced a striking number of dropouts due to side effects: The original Rudman study reported data on 12 men who had completed the first six months of treatment, but actually 50 subjects had received HGH treatment, with 27 dropping out before the study was completed (and data from an additional 11 men were not reported, for reasons that are unexplained).[12] Men who dropped out experienced carpal tunnel syndrome, breast enlargement and raised blood sugar, including one case of diabetes.

Later researchers attempting to reproduce the results seen in the Rudman study observed severe side effects using the same doses of HGH, forcing them to reduce the doses by half or more.[13] Furthermore, while these studies largely confirmed the physiological effects observed in the Rudman study, the effects did not translate into improved functioning on measures such as sleep, mood, strength or aerobic capacity.

Finally, the Rudman study was not blinded: Both subjects and researchers knew who received HGH and who did not. This meant that there was a high potential that the changes observed were due to placebo effect (participants responding positively to the knowledge that they had received treatment, rather than the treatment itself) or to biased measurements (researchers changing the way they observed and interpreted results based on knowledge that a subject had been treated).

Poor evidence of benefit, many side effects

Although much research has been done on HGH treatment in the decades after the Rudman study was published, no large, long-term, high-quality trial has ever been conducted to test its benefits and risks as an anti-aging treatment. All of the randomized, controlled trials conducted to date have involved small groups of subjects. The largest controlled trial enrolled only 68 people. (By contrast, trials for FDA-approved drugs typically enroll hundreds to thousands of subjects.)

In 2007, a group of researchers at Stanford University combined the results of these trials in an attempt to better assess the overall risks and benefits of HGH for aging. The results of that review, reported in the July 2007 issue of Worst Pills, Best Pills News,[14] were not encouraging. HGH injections did decrease fat mass and increase lean body mass (although it is not clear whether the increase was due to new muscle or water bloating).[15] HGH-treated patients also experienced slightly lower cholesterol levels. However, the researchers found no evidence of beneficial effects on bone density, oxygen consumption, blood sugar levels or other outcomes relevant to health.

Most importantly, side effects from treatment were frequent: HGH-treated subjects experienced higher rates of fluid retention, carpal tunnel syndrome, joint pain, breast enlargement in males and new cases of diabetes relative to subjects in the control groups.

Do growth hormones promote longevity or shorten lives?

It remains unclear what role natural growth hormone and IGF-1 actually play in the aging process. Randomized, controlled studies of synthetic HGH treatment have generally not been designed to detect important clinical outcomes, such as risk of cancer, risk of cardiovascular disease or long-term survival.

Other evidence on growth hormones and mortality has led to puzzling questions. Mice with several different mutations that cause growth hormone deficiency or resistance to the action of growth hormone live longer than their genetically normal siblings.[16] However, studies in humans have been inconsistent, with some showing shorter life spans for individuals with growth hormone deficiency and others showing that those individuals are protected against cancer.[17]

More recently, two studies by one group of researchers have explored how growth-stimulating hormones may play a role in the lives of exceptionally long-lived individuals. The first, published in 2008, showed that female children of people who lived to be over 100 were more likely to have a mutation that prevented their bodies from fully processing IGF-1, giving them shorter stature.[18] In 2014, the same research group published a second study of very long-lived individuals (median age 97), which showed that both women and individuals with a history of cancer with low IGF-1 levels had significantly longer survival times than women with higher levels.[19]

Ultimately, the key to long life may be in avoiding extremes: A recent analysis looking at mortality and natural IGF-1 hormone levels in 12 studies with 14,906 participants demonstrated that individuals with either especially low or especially high IGF-1 levels are at increased mortality risk compared with those with IGF-1 levels in the middle of the normal range.[20]

Selling the ‘anti-aging’ cure

While it is illegal for manufacturers or distributors of HGH to promote the drug for anti-aging, a number of health care providers across the country still offer HGH treatments to healthy older adults. Many of these anti-aging clinics have been able to avoid prosecution by representing their services as the legitimate practice of medicine, testing and treating older adults for growth hormone “deficiency.” However, some recommend HGH replacement therapy based solely on IGF-1 blood levels, without the confirmatory growth hormone stimulation test recommended in the labels of approved HGH drugs and by more established guidelines.[21]

What You Can Do

Currently, there is little evidence that boosting growth hormone levels in otherwise healthy adults provides important health benefits, and there is evidence that it can cause harm. The only adults who should consider HGH treatment are those with certain rare conditions that cause severe deficiency in natural growth hormone. Growth hormone stimulation blood tests may be unreliable, and chances of a false-positive diagnosis with a single test are significant.[22] For this reason, we do not recommend such testing in healthy older adults who have not already been diagnosed with a condition that is linked to growth hormone deficiency.

References

[1] Langreth R, Sweet Syringe of Youth. Forbes. Dec. 12, 2000. http://www.forbes.com/forbes/2000/1211/6615218a.html. Accessed June 19, 2014.

[2] The Anti-Aging Group. www.antiaginggroup.com. Accessed June 11, 2014.

[3] Langreth R, Sweet Syringe of Youth. Forbes. December 12, 2000. http://www.forbes.com/forbes/2000/1211/6615218a.html. Accessed June 19, 2014.

[4] Wang S. Scientists warn of risks from growth hormone. Wall Street Journal. March 24, 2014.

[5] Sonntag WE, Csiszar A, deCabo R, et al. Diverse roles of growth hormone and insulin-like growth factor-1 in mammalian aging: progress and controversies. J of Gerontology. 2012;67A(6):587-598.

[6] Hersch E, Merriam G, Growth hormone (GH)—releasing hormone and GH secretagogues in normal aging: Fountain of youth or pool of Tantalus? Clinical Interventions in Aging. 2008;3(1):121-129.

[7] Sonntag WE, Csiszar A, deCabo R, et al. Diverse roles of growth hormone and insulin-like growth factor-1 in mammalian aging: progress and controversies. J of Gerontology. 2012;67A(6):587-598.

[8] Ibid.

[9] Molitch ME, Clemmons DR, Malozowski S, et al. Evaluation and treatment of adult growth hormone deficiency: An endocrine society clinical practice guideline. J Endocrinol Metab. 2011;96(6):1587-1609.

[10] Rudman D, Feller AG, Nagraj HS, et al. 1990. Effects of human growth hormone in men over 60 years old. N Engl J Med. 323:1–6.

[11] The Anti-Aging Group. www.antiaginggroup.com. Accessed June 11, 2014.

[12] Cohn L, Feller AG, Draper MW. Carpal tunnel syndrome and gynaecomastia during growth hormone treatment of elderly men with low circulating IGF-I concentrations. Clin Endocrin. 1993;39:417-425.

[13] Hersch E, Merriam G, Growth hormone (GH)—releasing hormone and GH secretagogues in normal aging: Fountain of youth or pool of Tantalus? Clinical Interventions in Aging. 2008;3(1):121-129.

[14] Human Growth Hormone not recommended as antiaging treatment. Worst Pills, Best Pills News. July 2007. /newsletters/view/540. Accessed July 1, 2014.

[15] Liu H, Bravata DM, Olkin I, et al. Systematic review: The safety and efficacy of growth hormone in the healthy elderly. Ann Intern Med. 2007;146:104-115.

[16] Bartke A, Growth hormone and aging: A challenging controversy. Clin Interventions in Aging. 2008;3(4):659-665.

[17] Ibid.

[18] Suh Y, Atzmon G, Cho MO, Hwang D, Liu B, Leahy DJ, Barzilai N, Cohen P. Functionally significant insulin-like growth factor I receptor mutations in centenarians. Proc. Natl Acad. Sci. 2008;105:3438–3442.

[19] Milman S, Atzmon G, Huffman D, et al. Low insulin-like growth factor-1 level predicts survival in humans with exceptional longevity. Aging Cell. March 12, 2014. doi: 10.1111/acel.12213.

[20] Burgers AM, Biermasz NR, Schoones JW, Meta-analysis and dose-response metaregression: circulating insulin-like growth factor (IGF-I) and mortality. J Clin Endocrinol Metab. 2011; 96(9):2912-20.

[21] Molitch ME, Clemmons DR, Malozowski S, et al. Evaluation and treatment of adult growth hormone deficiency: An endocrine society clinical practice guideline. J Endocrinol Metab. 2011;96(6):1587-1609.

[22] Ibid.