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Life Extension Magazine

LEF Magazine May 1998

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Growth Hormone
IGF-1 & Prostate Cancer


A new study shows a link between IGF-1 and prostate cancer. Here, a Harvard-trained medical doctor responds.

The January 23 issue of the prestigious journal Science contained an important article with the title "Plasma Insulin-Like Growth Factor-1 and Prostate Cancer Risk: A Prospective Study." This well-done statistical study by June Chan and her co-authors at the Harvard School of Public Health shows that men who happen to have high levels of IGF-1 have up to a four-fold increased risk of developing prostate cancer.

The implication is that, until more is known, men with a high PSA blood level or a strong family history of prostate cancer should think twice before starting on GH or GH-releasing agents.

My first reactions to the study were shock, disappointment and disbelief. I am 50 years old and for five years, I have been taking 3 grams of arginine per day in the form of Powermaker II from the Life Extension Foundation in order to release extra growth hormone (GH) from my pituitary gland to retard the aging process. I am well aware of the studies in mice showing that direct injections of growth hormone extend life up to three-fold, and that there is anecdotal evidence regarding improved physiology in people taking supplemental GH.

In addition to Powermaker II, I'd like to take GH, but can't afford it. Besides, I hope that the GH-releasing amino acids in the product will release other pituitary hormones that decline with age.

If IGF-1 goes down with normal aging and high IGF-1 is associated with prostate cancer, wouldn't you predict that the risk of prostate cancer would decline with age rather than increase?

However, I continue to have questions about the link between IGF-1 and prostate cancer, for a number of reasons, and I'd like to gather more data as a follow-up to the Chan study.

The Chan study used blood samples collected from male physicians who took part in the Physicians' Health Study, an analysis of 14,916 male doctors age 40 to 82 that began in 1982. Subjects filled out biographical questionnaires, had physical exams, and provided blood samples that were stored away for future study. The subjects were followed for 10 years, and their physical condition and subsequent health problems were logged. During the 10 years, 520 of the subjects developed clinically proven prostate cancer. Of that number, 152 had stored blood samples adequate to test for IGF-1 and other hormones.

The authors of the paper divided the 152 subjects into four quartiles, based on their IGF-1 level. Using sophisticated statistical techniques, they analyzed the association between IGF-1 levels and prostate cancer, after adjusting for all other possible risk factors for prostate cancer, including prostate specific antigen (PSA) levels, height, weight, body mass index, polymorphisms (different forms) of the androgen receptor gene, and plasma levels of other hormones.

After all this work, they found that the 38 subjects in the highest quartile of IGF-1 (293.76 to 499.6 ng/ml) developed prostate cancer 4.32 times as often as the subjects in the lowest quartile of IGF-1 (99.4-184.8 ng/ml).

Since nearly all men taking supplemental GH hope to raise their IGF-1 into the 300 to 500 range in order to obtain age-retarding effects, the increased risk of prostate cancer demonstrated by Chan and co-workers demands attention.

The effect of IGF-1 on prostate cancer was independent of the PSA level. Although at present IGF-1 is not routinely measured by physicians the PSA level is often measured because elevations in PSA are an early warning sign of prostate cancer. Chan found that subjects with both high PSA and high IGF-1 levels were 17 times more likely to develop prostate cancer. The authors concluded that measurement of IGF-1 and PSA should be used in tandem to predict the risk of prostate cancer.

But that is where I get stuck. If IGF-1 goes down with normal aging and high IGF-1 is associated with prostate cancer, wouldn't you predict that the risk of prostate cancer would decline with age rather than increase?

Growth Hormone: An Odyssey

Growth hormone is a small protein released into the blood from the pituitary gland near the brain. GH circulates for only a few minutes before being absorbed by the tissues of the body. GH then causes tissues to release local hormones called IGFs, or insulin-like growth factors, that stimulate cells to increase in size, function and number. IGFs have obvious importance in growing children, but the pituitary gland continues to make GH throughout life. A current theory is that the steady, significant decline in GH production in aging mammals is the preeminent cause of aging.

Although GH is released in nocturnal, pulsatile (in a rhythmic pulsation) fashion, the level of IGF-1 is relatively constant over time. In the Chan study, only a single measurement was taken, and the assumption was made that this measurement was a good indicator of the individual's natural production of GH over a lifetime. This assumption seems incredible, but it may actually be valid. There is a good correlation between IGF-1 level and height, even in advanced age. Since height is dependent on total GH secretion during childhood, the fact that the correlation persists in adulthood suggests that a single measurement of IGF-1 can serve as a barometer of lifetime GH function.
Prostate cancer is an "old man's tumor," but the part of the population with the highest levels of IGF-1 is young men. Something doesn't add up.

One possibility is that prostate cancer takes many decades to develop. In this case the high IGF-1 levels in young men would not result in prostate cancer until older age. This might be true, but it would be a departure from the behavior of other cancers and it is difficult to prove. Studies show that men who eventually develop prostate cancer have a gradual rise in PSA for one to five years before clinical cancer is diagnosed.

As noted, the rise in PSA is the first indicator of incubating cancer, but it is non-specific to solely prostate cancer. Prostatitis or pelvic trauma also can raise the PSA enough to confuse the picture. In addition, autopsy studies of men 60 and older who died of causes other than cancer frequently show nests of tumor cells in their prostates. Such evidence of early cancer is very rarely seen in men younger than 50.

Many authorities have worried that supplemental GH might increase the risk of cancer, but the proponents of GH replacement therapy have countered with the following arguments: first, that patients with acromegaly or giantism-deformities resulting from abnormal enlargement of parts of the skeleton-who have high levels of GH are not notably known for an increased cancer risk; and second, that there is evidence that GH improves the function of the immune system.

GH-directed enhancement of the immune system should serve to decrease the likelihood of clinical cancer, since a major function of the immune system is to detect and destroy cells that have been transformed to grow in a cancerous fashion. This prediction has been borne out in animal studies. The Chan study, on the other hand, is the first to suggest that the GH-directed enhancement of cell division in humans may overwhelm the improved immune function, leading to clinical cancer, at least in the prostate.

If it is true, the prostate-cancer promoting potential of GH might be blunted by having patients simultaneously take saw palmetto extract, since this extract has anti-testosterone effects.

As a result of the recent explosion of publications regarding anti-aging, large numbers of older people in this country are taking growth hormone or GH-releasing agents. It is important that this ready-made population be organized so that data on the prevalence of prostate cancer in GH users can be obtained. I am not aware that the National Institute on Aging is making any attempt to do this.

I invite anyone taking GH or a GH-releasing agent for more than a year, and who has developed prostate cancer, to write to me, Dr. Michael Anchors, 16220 Frederick Rd., Suite 210, Gaithersburg, Md., 20877, or to e-mail me at manchors@aol.com, so I can begin the collection of data and pass it on to the proper scientific channels.

In the meantime, I would encourage everyone over 50 who is on GH or a GH-releasing agent to get their PSA checked every six months, or at least once a year. No one should be satisfied with a PSA in the 2 to 4 range if the trend shows that the PSA is going up. A PSA measurement lower than 2 is safe. Digital rectal exams are only marginally useful.

People taking GH or GH-releasing agents should, of course, have their IGF-1 checked, if for no other reason than to ensure that the agent they are taking is working. Ideally, the IGF-1 should be measured during the time an individual is both on and off the medicine. Not all GH-releasing agents work or continue to work in any given individual, and not all GH preparations are effective. These medicines are too expensive to be taken continuously without the assurance that the medicine is working.

Everyone should continue to read Life Extension magazine for updates on this story and other research news regarding anti-aging.

Michael Anchors is a physician in Rockville, Md., with a Ph.D. in biochemistry from Harvard Medical School, as well as an M.D. degree. The author of Safer Than Phen-Fen (Prima Publishing, 240 pages), Dr. Anchors has a long-standing interest in gerontology.

Further Reading
  • Chan JM, Stampfer MJ, Giovannucci E, Gann PH, Ma J, Wilkinson P, Hennekens CH, Pollak M, "Plasma Insulin-Like Growth Factor-I and Prostate Cancer Risk: A Prospective Study" Science 1998;279:563-566.
  • Khansari DN, Gustad T, "Effects of long-term, low-dose growth hormone therapy on immune function and life expectancy of mice." Mech. of Aging and Develop. 1991;57:87-100.
  • Klatz R, Kahn C, Grow Young with HGH, Harper Collins Publishers, 1997
  • Marcus R, Butterfield G, Hooloway L, Gilliland L, Baylink DJ, Hintz RL, Sherman, BM "Effects of Short term Administration of Recombinant Human Growth Hormone to Elderly people." J. Clin. Endocrinol. Metab. 1990;70;519-527.
  • Gann PH, Hennekens Ch, Stampfer MJ, "A prospective evaluation of plasma prostate-specific antigen for detection of prostatic cancer [see comments]" JAMA 1995;273:289.