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Growth hormone, sex steroid combination ‘not ready for prime time'

November 12, 2002

NIA Press Office | 301-496-1752 | nianews3@mail.nih.gov

In the first study of the separate and combined effects of growth hormone and sex steroids in healthy older men and women, investigators found that growth hormone replacement substantially increased lean body mass and decreased fat mass in both sexes. In combination with testosterone, growth hormone significantly improved cardiovascular endurance in older men. But the researchers also reported a number of side effects, including an increased incidence of glucose intolerance and diabetes among men, which raise important questions about the safety of using growth hormone alone or in combination with other treatments that are often touted as so-called "anti-aging" therapies.

"Although this study suggests that growth hormone or related substances, particularly given in combination with testosterone in older men, may one day be a promising therapeutic agent in the treatment of certain age-related conditions, it is not ready for prime time," said Marc R. Blackman, M.D., the study's lead investigator. "There is much that we still don't know about its efficacy and, more importantly, there are too many known and potential adverse consequences associated with it. It is a fascinating and promising area of research, but at this time we can't recommend it for use outside of a carefully controlled and monitored clinical trial."

The study*, published in the November 13, 2002 issue of the Journal of the American Medical Association (JAMA) , was conducted jointly by investigators from the National Institute on Aging (NIA) Intramural Research Program and investigators from the Johns Hopkins University School of Medicine in Baltimore, supported by grants from the NIA and the National Center Research Resources.

Human growth hormone (hGH) is made by the pituitary gland, a pea-sized structure located at the base of the brain, and is important for normal development and maintenance of tissues and organs. Testosterone and estrogen, two important sex steroids, work in combination with hGH to spark puberty and maturation during adolescence. Dr. Blackman, who is now Clinical Director and Director of Intramural Research at the National Center for Complementary and Alternative Medicine, hypothesizes that similar interactions are involved in the natural declines of hGH and sex steroids in later decades, contributing to the onset of age-related changes such as decreased muscle mass and increased body fat. So in theory, replenishing these hormones could slow or reverse some age-related effects.

To test this, Dr. Blackman and his colleagues studied 57 healthy men and 74 healthy women, ages 65 to 88, divided into eight groups**. These volunteers were given recombinant human growth hormone (hGH) alone, a sex steroid alone, a combination of hGH and sex steroids, or placebos for both hGH and sex steroids. After 26 weeks of treatment, the volunteers were assessed for changes, compared to baseline measures, in lean body mass, total fat mass, muscle strength, cardiovascular endurance and adverse effects. (Cardiac endurance, measured during a treadmill exercise test by the amount of oxygen consumed, is an important gauge of the body's capacity for work).

Overall, both men and women exhibited significant increases in lean body mass and decreases in fat mass after treatment with hGH, and men treated with both hGH and testosterone had greater improvements in these measures than did those who were treated with either hormone alone. Older men who received hGH plus testosterone also had improved cardiovascular endurance. However, this effect was not evident among men treated with hGH or testosterone alone, or among older women treated with hGH, estrogen and progestin, or a combination of growth and sex hormones. The study detected no clear effect of treatment on muscle strength.

Adverse effects of treatment were reported in up to 40 percent of the volunteers, with the greatest percentages occurring among men and women who were treated with hGH, with or without concomitant sex steroid. Common side effects in both sexes included joint pain, swelling, and carpal tunnel syndrome. In general, men experienced more frequent and severe side effects than did women. Eighteen men treated with hGH developed either transient glucose intolerance, a precursor to diabetes, or diabetes, compared with seven men not receiving the hormone. No women developed glucose intolerance or diabetes, but they were more prone than men to develop swelling (edema). All side effects, including diabetes, abated two to six weeks after treatment was discontinued.

The differences in both beneficial and adverse effects of hGH between men and women could have been partly due to dosage, Dr. Blackman said. In the study, both sexes were treated based on body weight. But subsequent studies have found that women need higher doses of hGH to elicit a physiological response similar to that of men.

"This study makes the important point that because adverse effects were common in response to growth hormone administration, individuals, particularly those who are elderly, should not use hGH outside of controlled investigational studies. Growth hormone has not yet been demonstrated to be of clinical utility as an anti-aging intervention," said Stanley Slater, M.D., deputy director of the NIA's Geriatrics and Clinical Gerontology Program. "Nonetheless, there were significant changes in body composition and cardiovascular endurance, which were augmented by the addition of testosterone in men. This remains an interesting area for further research."

The adverse effects found in this study follow a recent report suggesting that long-term treatment of young and middle-aged adults with human pituitary growth hormone increased the risk of subsequent cancer. Whether older persons treated with hGH for extended periods will demonstrate an increased risk of cancer is unknown.

Although there is no conclusive evidence that hGH administration can prevent aging, some people spend a great deal of money on supplements. These supplements are claimed, by some, to increase muscle, decrease fat, and to boost an individual's stamina and sense of well-being. Shots of hGH can cost more than $15,000 a year. They are available only by prescription and should be given by a doctor. But individuals should be wary of this controversial treatment because so little is known about its long-term risks and benefits, Dr. Slater said.

* M.R. Blackman, J.D. Sorkin, T. Munzer, M.F. Bellantoni, J. Busby-Whitehead, T.E. Stevens, J. Jayme, K.G. O'Connor, C. Christmas, J.D. Tobin, K.J. Stewart, E. Cottrell, C. St. Clair, K. M. Pabst, S.M. Harman, "Effects of Growth Hormone and Se/x Steroid Administration in Healthy Aged Men and Women," JAMA , 2002; 288: 2282-2292.

** The study volunteers were divided into the following groups: Men either received recombinant human growth hormone (hGH) plus placebo testosterone (T); T plus placebo hGH; hGH plus T; or placebos for both hGH and T. Women either received hGH plus placebo estrogen and progestin (HRT); HRT plus placebo hGH; hGH plus HRT; or placebos for both hGH and HRT.

The National Institute on Aging and the National Center for Research Resources are two of 27 Institutes and Centers that constitute the National Institutes of Health. The NIA leads Federal efforts to support and conduct basic, clinical, epidemiological, and social research on aging and the special needs of older people. For more information about the NIA, visit the website at www.nia.nih.gov.

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