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Saturday, April 14th 2007

Growth Hormone Replacement

Should the relatively healthy elderly, who do not meet the clinical definition for growth hormone deficiency, be taking HGH?

“Growth hormone levels drop with age, and I’m just bringing them up to a normal physiologic level,” explains Dr. Mark Gordon, a Los Angeles, California, physician who says he aims to give patients the hormone levels of a young adult. “In the course of that return, we see improvement in a whole array of medical conditions.” He says he started practicing what he calls “interventional endocrinology” after seeing HGH injections speed recovery from orthopedic injuries.

The CNN article is full of anecdotes and personal stories, which shouldn’t inform anyone’s opinion on this use for human growth hormone.

The 1990 study which the CNN article cites as starting the HGH anti-aging “craze” is available in full, for free (even without registration). The article is available without registration because the NEJM appears to have a campaign to battle misinformation and propaganda promoting HGH as a fountain of youth drug.

Other articles, reviews, and editorials on the subject of HGH in non-deficient adults are also available for free and without registration. Included amongst these are Dr. Vance’s piece “Can Growth Hormone Prevent Aging?

She goes over what the original 1990 study found,

[I]t is necessary to recall exactly what the study by Rudman et al. demonstrated. Twelve healthy men, 61 to 81 years of age, who had serum concentrations of insulin-like growth factor I below those found in normal young men received growth hormone for six months. (Insulin-like growth factor I mediates the action of growth hormone, and its concentration reflects the circulating concentration of growth hormone.) The weekly dose of growth hormone was approximately twice as high as the dose used in adult men with a growth hormone deficiency.

The administration of growth hormone in older men resulted in a 4.7-kg increase in lean body mass, a 3.5-kg decrease in adipose mass, and an increase of 0.02 g per square centimeter in lumbar-spine density; systolic blood pressure and the fasting glucose concentration increased significantly.

Dr. Vance goes on to touch on the main problem with these claims of the anti-aging properties of growth hormone. There simply is not enough research documenting the long term effects of HGH use. And there is ample reason to speculate that those long term effects might have some non-benign consequences amongst them.

As the CNN article brings up,

“Growth hormone is secreted in our body to promote cell growth, and cancer is unbridled cell growth,” says gerontologist Dr. Thomas Perls, who campaigns vehemently against the use of HGH. “It’s basically throwing gasoline on the fire.”

A link to cancer, however, has not been proven in humans, only in mice. Research has shown that mice with high levels of growth hormone actually live shorter lives than those with low levels. But the doses in those studies were much higher for body weight than those typically given by anti-aging doctors.

There is of course more evidence, beyond supraphysiological GH administration in mice, that GH and IGF (which GH stimulates the liver to produce) are at least permissive for neoplasm development. For instance people with acromegaly appear more prone to certain types of cancer and appear to have a higher mortality associated with those cancers. Acromegaly is the over production of GH in adults. Of course the argument is, as in the mouse studies, that the levels in these patients are far above any dosing given for “anti-aging” purposes.

Excessive GH & IGF Can Cause Acromegaly

Tangential evidence for an increased cancer risk also exists in studies of childhood cancer survivors. Hypopituitarism and growth hormone deficiency are apparently common consequences of radiation treatment for childhood leukemias, and the like. Of course, radiation, chemo, and indeed an initial childhood cancer all predispose children to developing a second neoplasm. However, controlling for these, it appears clear that those children who receive growth hormone replacement further increase their risk for a second neoplasm. So says data from the Childhood Cancer Survive Study (follow up article here). Both the papers require a subscription.

The lack of direct long term studies on the use of HGH for non-deficient adults as an anti-aging tool, means we must play around with circumstantial evidence for the consequences of HGH use. As with the cancer risk, studies on the overall mortality of patients taking HGH often deal with varying patient populations, which makes extrapolating their findings out to HGH anti-aging users dangerous. As well, the findings are confusing and sometimes contradictory. They find an increased mortality for patients given GH or they find no increased mortality. I will say, from a casual glance, that so far it does appear that increased mortality is largely associated only with very high GH doses. Far beyond the dosing given for anti-aging purposes. But that is a) merely my observation from a very scant Ovid search and b) muddled by the lack of research on the long term effects of HGH specifically for anti-aging.

The most detailed look at the efficacy and safety of HGH as an anti-aging compound, that I could find, was published this year in January. In the Annals of Internal Medicine it is titled “Systematic Review: The Safety and Efficacy of Growth Hormone in the Healthy Elderly,” and is currently available without a subscription.

It is a meta-analysis of 18 studies of HGH use in the non-growth hormone deficient elderly. To demonstrate the point I’ve been trying to hit home about the lack of research on the subject – all these studies combined included only 202 legitimate subjects. As well, a good portion of the publication is dedicated to critiquing the value and quality of the studies which the authors were evaluating.

They could find no studies on the subject that met all eight of their initial criteria:

  • Had at least 10 participants
  • Participants underwent therapy for at least 2 weeks
  • Participants were all community dwelling (as opposed to hospital inpatients or long term care facility residents)
  • Had participants with a mean age of at least 50
  • Provided data on at least one clinical outcome
  • Did not focus solely on GH-releasing factor or IGF-1 (as opposed to GH itself)
  • Did not explicitly include those with diabetes, heart disease, thyroid disease, osteoporosis or cancer
  • Did not evaluate GH as a treatment (for example in HIV patients)

None of the studies they evaluated lasted longer than a year.

At the least we should get a sense of the lack of evidence and quality research on the issue of HGH as an anti-aging treatment. Which should prompt anyone considering taking it to enter into such with a sense of caution.

Beyond the increase in lean body mass, decrease in fat, and decrease in total cholesterol the meta-analysis found that GH was associated with edema (swelling) and joint pain. There was also an association with blood sugar problems and even frank diabetes but those didn’t rise to the level of clinical significance.

This line in the conclusion states it best,

No evidence that we reviewed suggested that GH prolongs life.

It is a further step than might be imagined to go from increased lean body mass and potential improvements in one’s lipid profile to a longer, healthier life.

What I’ve taken away from this little review is that we simply do not know enough about HGH’s use as an anti-aging treatment. At current I certainly wouldn’t be recommending my grandmother take it.