Men with low levels of testosterone are more likely to be depressed, Australian researchers have found, and they recommend that those with abnormally low levels be treated with injections of the sex hormone. A study of men over the age of 70 revealed that those with the lowest testosterone levels are three times more likely to suffer depression than those with the highest levels.
The results held regardless of overall physical health; the link between poor health and depression is well established. "There is good rationale for considering using testosterone replacement to improve mood" for patients with low levels of testosterone, said the author of the study, published in Archives of General Psychiatry. "This is the most compelling case for the link yet."
Lead author Dr. Osvaldo P. Almeida, MD, PhD, director of research at the Western Australian Centre for Health and Ageing, and professor and chair of Geriatric Psychiatry, School of Psychiatry and Clinical Neurosciences, at the University of Western Australia, in Perth, notes that. "Older men with depression should be assessed for hypogonadism, and older hypogonadal men who fail to respond to standard antidepressant therapy may benefit from testosterone replacement."
The study looked at 3,987 men aged 71 to 89 years who live in Perth, Australia. The men were screened for cognitive impairment and depression, and 203 (5.1%) had a score within the depression range (scores of 7 or more). Compared with men in the highest 20%, the odds of having depression in men in the lowest 20% for total testosterone were almost doubled. This change could be accounted for by other health problems, but when they looked at the more reliable "free testosterone" blood test , the researchers found that even after eliminating the effects of other health issues, the low testosterone itself was associated with a 270% higher risk of depression.
According to Dr. Almeida, "The findings of this study are compelling in suggesting a causal relationship between low free testosterone and depression in older men… The association is biologically plausible; there is evidence from lab work that testosterone may increase the bioavailability of serotonin and noradrenaline in the brain and this could explain its antidepressogenic effect."
It is free testosterone, or testosterone that is not bound to the proteins albumin and sex-hormone-binding globulin, that is biologically active (also called "bioavailable" testosterone). "In other words, if we wish to clarify what testosterone does, we need to look at free testosterone," said Dr. Almeida.
He noted, too, that while depression is more prevalent among women, the gap between the sexes "all but disappears" later in life. "Our findings may partly explain why that is so," he said.
"There's definitely a connection," claims Dr. William McDonnell, director of the Fuqua Center for Late-Life Depression at Emory University. "For years, we've known that depression can be related to low thyroid levels and to B-12 deficiency. But the effect of low testosterone levels has been little known. It's really an undiscovered field."
Although it's often hard to pinpoint the cause of depression, or even to say exactly what it is, there's little denying that testosterone levels drop with age and that many older men experience depression.
The numbers, in fact, are dramatic. As if youth doesn't confer enough blessings, only 1 percent of men ages 20 to 40 have low testosterone. But rates rise to 7 percent between ages 40 and 60, and to 20 percent between 60 and 80, according to a study on WebMD.com. Roughly 35 percent of men older than 80 show low levels.
As many as 5 million American men have low testosterone levels, known medically as hypogonadism.
"Somewhere between age 60 and 80, at least half of all men will experience a significant decline in testosterone levels," said Dr. Martha Louise Elks, associate dean of the Morehouse School of Medicine.
Symptoms of low testosterone
As men get older, the ability to produce testosterone declines. This decrease in testosterone production is sometimes referred to as andropause or “male menopause.” If testosterone levels fall below the normal range some typical symptoms may include:
· Low sex drive
· Erectile dysfunction (ED)
· Fatigue
· Reduced muscle mass and strength
· Inability to concentrate
· Decreased bone density; osteoporosis
In addition to age-related low testosterone, there are certain medical conditions that can cause low testosterone. These medical conditions can begin in youth or in adulthood, and can affect testosterone levels throughout a man’s life. Some of these conditions are associated with the testicles, primary gland and hypothalamus (a part of the brain that controls many of the body’s glands). Occasionally, the problem can be genetic.
In younger men, low testosterone production may reduce the development of body and facial hair. Muscle mass and genitals may not develop normally, and younger men’s voices may fail to deepen.
Check levels
"Either doctors don't think to check or patients are embarrassed to ask about it," Elks said. "I don't know if a blood test needs to be routinely given for it, but physicians at least need to routinely ask about changes in libido as a man ages."
Elks is a hormone specialist. The relationship between depression and low testosterone "has been common knowledge in the medical literature for years, but it just hasn't been taught much in medical school," she said. "Sexual dysfunction obviously is a topic that male teachers have a hard time talking about."
Another reason it escapes detection is the steady -- rather than dramatic -- nature of testosterone decline.
Emory is embarking on a study of testosterone levels in patients with depression. One study group is composed of patients with Parkinson's disease, half of whom also experience depression.
"Some Parkinson's patients who don't respond very well to antidepressants like Prozac or Paxil have very low testosterone levels," said McDonald, a geriatric psychiatrist.
Also to be studied are prostate cancer patients, as well as depressed men without Parkinson's who fail to respond to medication. Testosterone worsens prostate cancer, and patients are treated with drugs and even castrated in severe cases. Researchers will assess depression rates in this group as well.
Treatment for low testosterone takes various forms -- shots, patches and a gel called AndroGel produced by Unimed Pharmaceuticals Inc., a subsidiary of Solvay Pharmaceuticals Inc., whose U.S. headquarters is in Marietta.
"If you like the mood shifts of adolescence, you'll love the mood shifts of testosterone shots," Elks said.
Supplements can have a quick effect, boosting stamina and dramatically increasing a man's sense of well-being.
"Someone with low testosterone is generally sluggish, has problems sleeping, doesn't concentrate well and is losing weight," McDonald said. "It's a general malaise. Give him testosterone and he'll start putting on weight, sleep better and get his energy back."
Side Effects
Taking testosterone supplements is not without danger. Besides spurring the growth of prostate cancer, supplements can "affect the liver and raise overall cholesterol," wrote Dr. Ken Goldberg for WebMD. Men receiving them should have "an annual PSA blood test, digital rectal exams every six months and annual liver and blood counts."
AndroGel has been on the market since mid-2000. It is applied to the shoulder, upper arm or abdomen once a day, and quickly restores testosterone levels.
AndroGel has been a popular product, with sales topping $100 million last year, said Unimed CEO Jean-Louis Anspach. A market that had been growing at a rate of 9 percent to 12 percent in the three years before the gel's launch has grown by more than 60 percent since.
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