Hormones and (Anti-)Aging

In the late 1980s, at veterans administration hospitals in Milwaukee and Chicago, 12 men age 60 and older began receiving injections three times a week that dramatically reversed some signs of aging. The injections increased their lean body (and presumably muscle) mass, reduced excess fat, and thickened skin. When the injections stopped, these changes reversed, and the signs of aging returned. What the men were taking was recombinant human growth hormone (HGH), a synthetic version of the hormone that is produced in the pituitary gland and plays a critical part in normal childhood growth and development.

At the same time, evidence was accumulating that menopausal hormone therapy with estrogen (alone or in combination with a progestin in women with a uterus) could benefit postmenopausal women by reducing cardiovascular disease, colon cancer, and other diseases of aging. Further studies have indicated that, although estrogen remains an effective way to control hot flashes, long-term use of these hormones may increase risk for several major age-related diseases in some women, especially when treatment is started years after menopause. The finding that levels of testosterone in men decreased with aging raised the question of whether they too might benefit from sex hormone treatment.

As a result of these preliminary observational findings, the National Institute on Aging (NIA) launched a series of research initiatives to clarify what influence hormone replacement therapy might have on the aging process. So far, most of these studies have been inconclusive, but have led many investigators to question whether the risks of hormone replacement may outweigh any benefit. Supplements of HGH, for instance, can promote diabetes, joint pain, carpal tunnel syndrome, and pooling of fluid in the skin and other tissues, which may lead to high blood pressure and heart failure. Studies in mice have raised other concerns about the hormone. Investigators have found that mice deficient in growth hormone production live substantially longer than normal mice, while mice overproducing growth hormone live shorter than average lives. This finding suggests that even if hGH replacement therapy is initially beneficial, ultimately it may be harmful and actually might curtail longevity.

Similarly, there is scant evidence that testosterone supplementation has any positive impact in healthy older men. In fact, some studies suggest supplementation might trigger excessive red blood cell production in some men. This side effect can increase a man's risk of stroke.

Estrogen is perhaps the most well studied of all hormones. Yet results from the Women's Health Initiative, the first major placebo-controlled, randomized clinical trial of estrogen therapy with or without progestin to prevent some chronic diseases of aging, surprised the medical community. There were more cases of stroke, blood clots, heart disease, and breast cancer in postmenopausal women using estrogen and progestin in the study, and more cases of possible dementia in women older than age 65, than in those using the placebo. But, there were also fewer bone fractures and cases of colon cancer. In postmenopausal women using estrogen alone, there were more cases of stroke and fewer bone fractures than in those women on placebo. Other studies indicate that menopausal hormone therapy is effective in controlling moderate-to-severe menopausal symptoms, so research is ongoing to evaluate benefits and risks in menopausal and younger postmenopausal women.

As research continues, the pros and cons of hormone replacement may become more precisely defined. These hormonal supplements appear to increase risk and provide few clear-cut benefits for healthy individuals and do not seem to slow the aging process.

In fact, normal physiological aging is quite variable, according to investigators involved in the Baltimore Longitudinal Study of Aging, a long-term NIA study begun in 1958 that has tracked the lives of more than 1,000 people from age 20 to 90 and beyond. Not only do individuals age overall at vastly different rates, it is quite likely that age-related changes in various cells, tissues, and organs differ as well. For instance, kidney function may decline more rapidly in some individuals. In others, bone strength may diminish faster. The organs that age fastest in one person may not age as rapidly in another. This suggests that genes, lifestyle, and disease can all affect the rate of aging and that several distinct processes are involved.

Reprinted from: National Institute on Aging. Available at: www.nia.nih.gov/HealthInformation/Publications/AgingUndertheMicroscope/chapter03.htm. Accessed Aug. 21, 2006.