In search for ‘fountain of youth,’ growth hormone offers risks, not benefits

The off-label use of recombinant human growth hormone as an anti-aging “wonder drug” — despite evidence suggesting serious associated risks — continues to rise in the United States and worldwide, an issue that is confounding endocrinologists who note that lower levels of GH could actually be protective in aging.

In people with true GH deficiency, GH therapy can improve many of the associated metabolic and psychological abnormalities. Treatment is associated with reduced visceral and trunk fat mass, and increased lean body mass, skeletal muscle mass and aerobic capacity, often resulting in an improved quality of life. Such improvements make GH therapy an attractive agent for older adults seeking a rejuvenation drug; however, endocrinologists caution that any observed benefits in people without GH deficiency come with serious risks.

“Growth hormone definitely is lipolytic and causes fat weight loss, and so that is very enticing to an internist managing a 70-year-old individual who has the resources to pay for growth hormone,” Shlomo Melmed, MB, ChB, MACP, dean, executive vice president and professor of medicine at Cedars-Sinai Medical Center in Los Angeles, told Endocrine Today. “What they don’t know is the literature. ... A lack of growth hormone is advantageous to aging and is advantageous to protection against cancer and diabetes. These clinicians ... may in fact be negating any potential benefits of the physiologic drop of growth hormone level that occurs during aging.”

Several features of GH deficiency, including weight gain, increased fat mass, changes in lipid levels, difficulty concentrating and memory impairment, mirror the typical manifestations of aging, Maria Fleseriu, MD, FACE, professor of neurological surgery and professor of medicine in the division of endocrinology, diabetes and clinical nutrition in the School of Medicine at Oregon Health & Science University and director of the OHSU Northwest Pituitary Center, told Endocrine Today.

Shlomo Melmed

“Because of this, many are attempting using GH as a ‘fountain of youth,’” Fleseriu said. “Most studies do not actually support the concept that GH administration for elderly individuals, who are secreting relatively low GH, can actually improve functional performance, and furthermore, the potential for toxicity is higher among the elderly population. However, an increase in the illegal use of GH for aging has been exponential in the U.S.”

Troublesome side effects

In a review published in January in the World Journal of Men’s Health,Andrzej Bartke, PhD, professor of internal medicine and physiology at Southern Illinois University School of Medicine in Springfield, wrote that mouse models have demonstrated that an absence of GH signals, due to mutations affecting anterior pituitary development, GH secretion or GH receptors, produces an “impressive extension of longevity.” The extension of health span observed in these mice, as well as an analysis of survival curves, suggest that in the absence of GH, aging is slowed down or delayed.

“The corresponding endocrine syndromes in the human have no consistent impact on longevity, but are associated with remarkable protection from age-related disease,” Bartke wrote in the review. “Moreover, survival to extremely old age has been associated with reduced somatotropic (GH and insulin-like growth factor I) signaling in women and men.”

In both humans and mice, he added, the elevation of GH levels into the supranormal range is associated with increased disease risks and reduced life expectancy, likely representing acceleration of aging.

“The widely advertised potential of GH as an anti-aging agent attracted much interest,” Bartke wrote. “However, results obtained thus far have been disappointing with few documented benefits and many troublesome side effects.”

Melmed called that data observed in mouse models compelling.

Maria Fleseriu

“There is no prospective study showing that any of the frailty of aging is reversed by growth hormone,” Melmed said. “There are no prospective data to show that there is any added longevity by giving growth hormone, and there is a robust body of clinical evidence now that low growth hormone is in fact beneficial for many of the diseases of aging, especially cancer.”

Giving GH to adults who are not GH deficient can also induce mild acromegaly, Fleseriu said, which has known complications, including cardiovascular disease, cancer and increased mortality.

“Of course, due to the use of GH for unapproved etiology being illegal, there are no prospective studies regarding all adverse effects,” Fleseriu said. “However, fluid retention and discomfort in the joints have been reported. GH treatment can also increase blood sugar levels, headaches and cause blurred vision.”

Whom to test, treat

Melmed said he is often asked by clinicians whether older adults with a low IGF-I level should be tested for GH deficiency. In most cases, he said, the answer is no.

Endocrine Society guidelines on hormonal replacement in hypopituitarism in adults, published in 2016, advise against administering GH to older adults with age-adjusted low IGF-I levels and no history of pituitary or hypothalamic disease. The guidelines similarly advise against administering GH to enhance athletic performance, as the practice is illegal in the U.S. and has poor scientific or ethical justification.

There are several dynamic tests available to diagnose GH deficiency, Fleseriu said, including the gold-standard insulin tolerance test, glucagon stimulation test and, more recently, a macimorelin stimulation test. Cutoffs are different for each test, and results could vary based on sex and patient BMI, Fleseriu said.

“Even more important is who should be tested for GH deficiency,” Fleseriu said. “Testing for GH deficiency should be limited to patients that have evidence of pituitary destruction, including a history of surgery or radiation for a pituitary or sellar lesion, pituitary hypoplasia, hypothalamic mass or infiltration, history of traumatic brain injury, contact-sports injury or stroke.”

Going further, Melmed said the general use of GH therapy by internists should be discouraged to reduce further misuse of the drug.

“If a patient is suspected of growth hormone deficiency, they should be seen by a qualified endocrinologist who understands the pitfalls and the caveats of growth hormone reserve testing in the adult,” Melmed said. – by Regina Schaffer

Disclosures: Fleseriu reports she has received consultant fees and her institution has received research support from Novo Nordisk and Pfizer. Melmed reports he has received an investigator-initiated research grant from Pfizer.

The off-label use of recombinant human growth hormone as an anti-aging “wonder drug” — despite evidence suggesting serious associated risks — continues to rise in the United States and worldwide, an issue that is confounding endocrinologists who note that lower levels of GH could actually be protective in aging.

In people with true GH deficiency, GH therapy can improve many of the associated metabolic and psychological abnormalities. Treatment is associated with reduced visceral and trunk fat mass, and increased lean body mass, skeletal muscle mass and aerobic capacity, often resulting in an improved quality of life. Such improvements make GH therapy an attractive agent for older adults seeking a rejuvenation drug; however, endocrinologists caution that any observed benefits in people without GH deficiency come with serious risks.

“Growth hormone definitely is lipolytic and causes fat weight loss, and so that is very enticing to an internist managing a 70-year-old individual who has the resources to pay for growth hormone,” Shlomo Melmed, MB, ChB, MACP, dean, executive vice president and professor of medicine at Cedars-Sinai Medical Center in Los Angeles, told Endocrine Today. “What they don’t know is the literature. ... A lack of growth hormone is advantageous to aging and is advantageous to protection against cancer and diabetes. These clinicians ... may in fact be negating any potential benefits of the physiologic drop of growth hormone level that occurs during aging.”

Several features of GH deficiency, including weight gain, increased fat mass, changes in lipid levels, difficulty concentrating and memory impairment, mirror the typical manifestations of aging, Maria Fleseriu, MD, FACE, professor of neurological surgery and professor of medicine in the division of endocrinology, diabetes and clinical nutrition in the School of Medicine at Oregon Health & Science University and director of the OHSU Northwest Pituitary Center, told Endocrine Today.

Shlomo Melmed

“Because of this, many are attempting using GH as a ‘fountain of youth,’” Fleseriu said. “Most studies do not actually support the concept that GH administration for elderly individuals, who are secreting relatively low GH, can actually improve functional performance, and furthermore, the potential for toxicity is higher among the elderly population. However, an increase in the illegal use of GH for aging has been exponential in the U.S.”

Troublesome side effects

In a review published in January in the World Journal of Men’s Health,Andrzej Bartke, PhD, professor of internal medicine and physiology at Southern Illinois University School of Medicine in Springfield, wrote that mouse models have demonstrated that an absence of GH signals, due to mutations affecting anterior pituitary development, GH secretion or GH receptors, produces an “impressive extension of longevity.” The extension of health span observed in these mice, as well as an analysis of survival curves, suggest that in the absence of GH, aging is slowed down or delayed.

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“The corresponding endocrine syndromes in the human have no consistent impact on longevity, but are associated with remarkable protection from age-related disease,” Bartke wrote in the review. “Moreover, survival to extremely old age has been associated with reduced somatotropic (GH and insulin-like growth factor I) signaling in women and men.”

In both humans and mice, he added, the elevation of GH levels into the supranormal range is associated with increased disease risks and reduced life expectancy, likely representing acceleration of aging.

“The widely advertised potential of GH as an anti-aging agent attracted much interest,” Bartke wrote. “However, results obtained thus far have been disappointing with few documented benefits and many troublesome side effects.”

Melmed called that data observed in mouse models compelling.

Maria Fleseriu

“There is no prospective study showing that any of the frailty of aging is reversed by growth hormone,” Melmed said. “There are no prospective data to show that there is any added longevity by giving growth hormone, and there is a robust body of clinical evidence now that low growth hormone is in fact beneficial for many of the diseases of aging, especially cancer.”

Giving GH to adults who are not GH deficient can also induce mild acromegaly, Fleseriu said, which has known complications, including cardiovascular disease, cancer and increased mortality.

“Of course, due to the use of GH for unapproved etiology being illegal, there are no prospective studies regarding all adverse effects,” Fleseriu said. “However, fluid retention and discomfort in the joints have been reported. GH treatment can also increase blood sugar levels, headaches and cause blurred vision.”

Whom to test, treat

Melmed said he is often asked by clinicians whether older adults with a low IGF-I level should be tested for GH deficiency. In most cases, he said, the answer is no.

Endocrine Society guidelines on hormonal replacement in hypopituitarism in adults, published in 2016, advise against administering GH to older adults with age-adjusted low IGF-I levels and no history of pituitary or hypothalamic disease. The guidelines similarly advise against administering GH to enhance athletic performance, as the practice is illegal in the U.S. and has poor scientific or ethical justification.

There are several dynamic tests available to diagnose GH deficiency, Fleseriu said, including the gold-standard insulin tolerance test, glucagon stimulation test and, more recently, a macimorelin stimulation test. Cutoffs are different for each test, and results could vary based on sex and patient BMI, Fleseriu said.

“Even more important is who should be tested for GH deficiency,” Fleseriu said. “Testing for GH deficiency should be limited to patients that have evidence of pituitary destruction, including a history of surgery or radiation for a pituitary or sellar lesion, pituitary hypoplasia, hypothalamic mass or infiltration, history of traumatic brain injury, contact-sports injury or stroke.”

PAGE BREAK

Going further, Melmed said the general use of GH therapy by internists should be discouraged to reduce further misuse of the drug.

“If a patient is suspected of growth hormone deficiency, they should be seen by a qualified endocrinologist who understands the pitfalls and the caveats of growth hormone reserve testing in the adult,” Melmed said. – by Regina Schaffer

Disclosures: Fleseriu reports she has received consultant fees and her institution has received research support from Novo Nordisk and Pfizer. Melmed reports he has received an investigator-initiated research grant from Pfizer.