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Testosterone: dangerous or age-fighting?
06:31 - Source: CNN

Story highlights

Testosterone treatment improves bone density, anemia in older men with low testosterone levels

It is associated with a lower risk of cardiovascular events in men who are 40 or older and have low levels

CNN  — 

Testosterone therapy, when used by men over age 65 who have low testosterone levels, offers some health benefits but also poses potential risks, suggests a roundup of five new studies in the Journal of American Medicine and JAMA Internal Medicine.

Testosterone treatment improves bone density and anemia in those men, the results indicated. But on the downside, it increases the amount of plaque buildup in coronary arteries while doing nothing to improve cognitive function, the researchers found.

A separate study separate study, published in JAMA Internal Medicine, also showed that testosterone therapy is associated with a lower risk of cardiovascular events in men 40 or older over a period of about three years.

The Testosterone Trials

Testosterone therapy is recommended for men whose blood levels of this masculine hormone fall below the normal range. Symptoms of low blood levels include low sex drive, fatigue, body and facial hair loss, and decreased muscle mass. Supplemental testosterone is usually taken as a gel, by injection or via a skin or mouth patch.

Researchers at the Perelman School of Medicine at the University of Pennsylvania designed and coordinated the Testosterone Trials, a series of studies at 12 academic medical centers across the United States. The studies were a response to the Institute of Medicine’s call in 2003 for more rigorous study of the positive and negative health effects of testosterone replacement therapy in older men.

The studies received support from the National Institutes of Health and from AbbVie (formerly Solvay and Abbott Laboratories), which makes a testosterone product.

The Testosterone Trials included 788 men who were 65 years or older and had low blood levels of testosterone. The researchers randomly assigned half the participants to use a daily testosterone gel and the other half a placebo gel for one year. Then, the researchers measured specific health outcomes in each participant at three months, six months, nine months and one year, with an additional year of followup in some of the studies.

According to Susan S. Ellenberg, lead biostatistician on the study and a professor at the University of Pennsylvania, the Testosterone Trials are really a “single trial” and “a single randomization.”

“People could be in only one trial, or they could be in multiple trials, but it was all sub-studies under one big umbrella trial,” she explained. She added that all of the sub-studies did not include the total 788 participants.

The Cognition Trial, which looked at memory and general cognitive function, did include all participants. The results showed no improvements in memory or any other measure of cognitive function for the men using the testosterone gel.

The Bone Trial found that testosterone treatment improved bone density and bone strength in the men. However, the Cardiovascular Trial showed more plaque buildup in the coronary arteries of men treated with testosterone. Yet the number of cardiovascular events, such as heart attacks, was similar for the men treated with testosterone and those using placebo. The Bone and Cardiovascular Trials, made use of high-tech CT scan measurements and compared both groups.

Finally, in the Anemia Trial, testosterone treatment helped correct anemia with no identifiable cause and helped correct anemia caused by iron deficiencies.

“There had been suggestions previously that testosterone might be efficacious in (these four) areas. Turns out it was efficacious in some but not in others,” said Dr. Peter Snyder, senior author and a professor of medicine at the University of Pennsylvania.

In February 2016, Snyder and his colleagues published in the New England Journal of Medicine the very first results from the Testosterone Trials, which he explained were designed to study efficacy of the treatment but not risk. “Risk would require the study of many, many more men followed for a much longer period of time,” said Snyder, who said that last year’s published research indicated testosterone improved sexual function and mood.

Ellenberg said the results of these four studies do not produce some “overwhelming single answer” to the question of whether testosterone therapy has positive health effects.

“I think this will help men and their physicians decide whether this is a reasonable treatment for them,” she said. “The importance of the studies will depend on the individual needs of patients because they all address different issues.”

She noted a definitive finding was that “for men who are mildly anemic, testosterone treatment might move them into normal hemoglobin level.”

However, the studies do not address the long-term effects of testosterone. There were not enough people and not enough follow-up time “to be able to really assess those, and that’s a really important piece within the spectrum of making treatment decisions,” Ellenberg said.

Looking ahead, she said, “we have additional data from these studies that we will be analyzing, and some we are in the process of analyzing, and we will be publishing more papers from this study.”

Lower risk of cardiovascular events

A wholly separate study, led by T. Craig Cheetham of the Southern California Permanente Medical Group in Pasadena, examined the association between testosterone therapy and cardiovascular events in men 40 or older with a verified diagnosis of low testosterone. Participants, all members of the Kaiser Permanente California health care plan, included 8,808 men prescribed testosterone therapy, whether as an injection, orally or topically.

This study, which was funded by the National Institutes of Health, examined their pharmacy and medical records for heart attacks, unstable angina, stroke or sudden cardiac death over a period of three years and four months on average.

Cheetham said he and his colleagues conducted this study “because of concerns regarding the cardiovascular safety of testosterone replacement therapy.” He explained that the previous studies selected patients who were elderly, frail or with cardiovascular risk factors. “It was our observation that there were many men using testosterone replacement therapy that did not fall into these categories,” he said.

Among men with low testosterone, Cheetham’s study found, testosterone prescriptions are associated with a lower risk of cardiovascular events over a median follow-up of about three years.

This finding is consistent with a couple of Department of Veterans Affairs studies that “suggest testosterone replacement therapy is associated with lower risk of all-cause mortality,” said Cheetham, and the normalization of testosterone levels after therapy is associated with “a reduced risk of myocardial infarction and stroke.”

Despite his own results, Cheetham is not suggesting men ignore studies that found an increased risk.

“Caution is probably warranted when using testosterone replacement therapy in frail elderly males and those with a high degree of cardiovascular risk,” he said.

Not an elixir of youth

Dr. Bradley Anawalt, a member of the Endocrine Society Leadership Council, said the Testosterone Trials in particular “were necessary and important. There is too little known about the effects of testosterone on men’s health in general and in older men in particular.”

Meanwhile, older men have a general interest in the “possible ‘rejuvenating’ effects of testosterone,” said Anawalt, who was not involved in the studies. “The methodology of the studies was excellent. There are no major flaws, just the caveat that the studies were not designed to determine” the long-term effects, he said. He added that they also were not designed to determine whether testosterone might prevent heart attacks or dementia in men.

“It is still essential to perform studies that are five or 10 years, or longer,” Anawalt said.

As a whole, the testosterone trials suggest that older men with low testosterone levels “may benefit from testosterone therapy with improved sexual function and bone mass and strength,” he said. “Testosterone therapy is not a rejuvenating therapy, though.”

Unfortunately, many men believe just the opposite and want a prescription for testosterone therapy despite having adequate levels.

Dr. Caroline Messer, an endocrinologist at Lenox Hill Hospital in New York City, said she is visited “all the time” by patients of all ages who are shopping for a prescription.

“People have already Googled the typical signs of (low testosterone levels), so they come in saying they’re having difficulty growing body mass, that they can’t grow facial hair, and they’ll say that they feel weak and exhausted,” said Messer, who was not involved in the studies. “They know the catchwords to say.”

“It’s very typical; we have to sort of always be on our toes,” she said.

Young men want it for “higher libido and to build muscles,” she said. Sometimes, they have body dysmorphic disorder; other times, they’re bodybuilders.

Older men “think of it sort of as an elixir of youth,” Messer said. “Most recently, I had a patient complaining of brain fog, and another endocrinologist put him on testosterone for brain fog despite having normal levels.”

In fact, most testosterone prescribers in the US and Canada are primary care providers – up to 73% – while only 18% of men had the Endocrine Society’s recommended two blood tests before starting treatment, according to recent research. This same study finds a fourfold increase in the use of testosterone therapy in the US between 2000 and 2011.

“I think a lot of younger men are getting it online,” Messer said. “It’s really not that hard to get it, but it’s expensive.”

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    Although she hasn’t personally seen any extreme medical harms in those who take testosterone, she has heard complaints, including testicular shrinkage.

    “And I see men who have been put on it by other doctors and don’t realize that it’s a medical castration,” Messer said. “And they’re like, ‘I’m not sure why I haven’t been able to conceive for the past year,’ and I explain to them that they’re really not making any sperm.”

    That said, she’s mainly seen positive effects in the men taking testosterone.

    “I mostly see improved energy and improved sexual drive and maybe a little bit of weight loss, a little more muscle, a little less fat,” Messer said. Still, worries about the unknown health risks and says longer-term studies are needed.

    “Men are not asking for this for their bone density or the slight anemia,” she said, adding that there are better medicines to treat bone density anyway. “It’s nothing to do with that. It’s really all about libido. That’s what I see in my practice.”