Testosterone: "Older men . . . go to their physicians and say, 'I don't have energy, I don't have sex interest, I can't get around,' " said Dr. Thomas Gill, professor of geriatric medicine and director of the Center on Disability and Disabling Disorders at the Yale University School of Medicine. Increasingly, what they get is testosterone.
Low testosterone levels do become more common in men as they age: Levels start falling at around age 30 and decrease by 1% to 2% per year, with ranges generally falling between 300 and 1,000 nanograms of testosterone per deciliter of blood depending on age. The decline may increase past 65.
But it is unclear whether the issues associated with aging in men -- decreased sex drive, less energy, cognitive impairment and reduced muscle mass -- are due to a decrease in testosterone or to other changes that come with aging, Gill says. Long-term studies on effectiveness of the therapy are lacking, and the few small, shorter-term trials that exist have produced mixed results.
A 2008 study published in the Journal of the American Medical Assn. looked at mobility, cognition, bone mineral density, quality of life and other issues in 237 men in the Netherlands. The participants, ages 60 to 80, were given either a placebo or testosterone over a six-month period.
Lean body mass increased and fat decreased in the testosterone group, but mobility and muscle strength did not change. There was improvement in insulin sensitivity (in which cells become less sensitive to insulin, forcing the body to overproduce it). But more of the testosterone group had metabolic syndrome, a cluster of health risk factors that include obesity, high blood pressure, inflammation and high cholesterol.
No difference in quality-of-life measures (such as vitality, mood improvements and social functioning) was detected between the two groups.
A New England Journal of Medicine article from October 2006 reported similar results in a two-year study of 87 elderly men. The Mayo Clinic authors found that increasing testosterone in men with low levels did not increase muscle strength, physical performance or quality of life.
Doctors are concerned about side effects associated with testosterone. Potential problems include the worsening of sleep apnea, enlargement of the prostate and overproduction of red blood cells, which can cause a stroke if the levels climb too high. And because the treatment can raise blood levels of prostate-specific antigen (PSA), the marker screened for in prostate cancer tests, it may lead to detection of very slow-growing cancers that would never have presented problems to the patient. This can lead to unnecessary treatments with potential for side effects such as incontinence or impotence.
According to the National Institute on Aging, men who have extreme testosterone deficiencies related to damage of the testes or pituitary glands from trauma, infections or tumors may benefit from testosterone supplementation. But the institute says more research is needed to see if replacement therapy will help those without such extreme issues -- and to fully understand the potential long-term side effects.
To try and fill in some of the unknowns, Gill and others are working on one of the largest testosterone trials to date, to take place at 12 medical centers across the country.
Eight hundred men with low testosterone will receive either testosterone or a placebo for a year and be monitored for changes in vitality, sexual and cognitive function, anemia, bone density and cardiovascular health. Potential participants are currently being screened; more information can be found at www.ttrial.org.
Human growth hormone: Human growth hormone is produced by the pituitary gland, located at the base of the brain. The hormone helps fuel growth and maintains tissues and organs; after age 25, the amount of hormone released begins to decrease, dropping by about 50% every seven years, according to some estimates.
Supplementation was initially used just for children with HGH deficiency, which made them unable to attain a "normal" height. It has also been used for adolescents and adults who have had their pituitary gland removed because of a tumor or other issue.
The hormone is administered by injection. Though it has not been approved by the Food and Drug Administration for treating elderly individuals experiencing physical decline, it is being used "off label" for this purpose.
Again, research on the safety and benefits of HGH is mixed, and the National Institute on Aging says there is no conclusive evidence that the hormone can reduce the physical decline that comes with age.
A 2007 Annals of Internal Medicine review of HGH did find some benefits. The article, which analyzed 31 research studies on a total of 220 elderly male participants, observed that those who were treated with HGH had reduced fat mass and increased lean body mass.
The review also found that participants' weight, bone density and serum lipid levels did not change. But the men who got the hormone were more likely to have carpal tunnel syndrome, fluid buildup in the soft tissues or to develop diabetes.
The National Institute on Aging cautions against using growth hormone therapy for anti-aging purposes, citing only short-term studies on its effectiveness as well as potential risks such as diabetes, joint pain, heart failure and cancer.
By time people are 80, HGH levels are virtually undetectable, but that may be a protective mechanism, according to Dr. Shlomo Melmed, senior vice president and dean of faculty at Cedars Sinai Medical Center.
"It is part of the normal aging process and may be protective against cancers related to aging," he said. "The science is against this -- it is a dangerous medicine and has a lot of side effects."
HGH therapy is also controversial because of its cost, which can run upward of $15,000 a year, says Dr. Ronald Swerdloff, professor of medicine at the David Geffen School of Medicine.
"We need more data on effectiveness and adverse effects," Swerdloff says. "An industry has developed . . . where special clinics or groups are promoting testosterone and HGH rather indiscriminately for people. . . . But nothing we do will prevent people from getting older."