Testosterone therapy does not increase heart risk in a group of men

The largest study ever to assess the safety of hormone replacements in men has reassuring news for a limited group of patients whose bodies are not producing enough testosterone, finding that the hormone does not increase heart attacks, strokes and cardiac deaths.

The new results, which come from a large clinical trial of its kind considered the gold standard in medicine, do not dispel all concerns. But they appear to resolve decades of conflicting findings about the cardiac safety of testosterone therapy for men with a condition called androgen deficiency, or hypogonadism.

The authors pointed out that the results did not apply to the many middle-aged and older men who take testosterone offered at anti-aging centers in hopes of building muscle or increasing their energy and libido, often without being properly assessed. Instead, it only affects the small percentage of the country’s male population, thought to be in the low single digits, with a true medical diagnosis of hypogonadismor with persistently low testosterone levels and symptoms that may include osteoporosis and anemia as well as low libido.

“We’ve never had a study of more than 5,000 men followed for up to four years, with their heart attacks and strokes carefully tracked,” said Dr. Bradley Anawalt, endocrinologist and professor of medicine at the Washington University School of Medicine. not involved in the trial.

“The important caveat is that this should not be taken to mean that testosterone does not cause heart attacks and strokes in men without hypogonadism,” he said. “It’s not a sign that testosterone is safe to take in large amounts, for normal men.”

While testosterone levels tend to decline with age, as well as with weight gain, true hypogonadism is much less common, the study authors say, and experts say the prevalence and incidence have not been well studied.

The study recruited 5,246 men across the United States between the ages of 45 and 80 with the diagnosis and randomly assigned them to receive a patch with a standard dose of testosterone or a placebo with no active ingredient. All of the men had heart disease or were at high risk. But after an average of two years of follow-up, researchers found that testosterone did not increase their risk of heart attacksstrokes or other deaths from heart disease.

Some 7% of men in each group experienced some cardiac event during the follow-up period, whether or not they took testosterone.

But the study identified other potentially serious complications that occurred at low rates in patients who received the treatment, including a higher risk of acute kidney disease, blood clots in the vessels that send blood to lungs and a heart arrhythmia called atrial fibrillation.

“We have solved an important question: can we give testosterone to men with androgen deficiency to try to help them without harming them?” said Dr. Steven Nissen, the study’s lead author and cardiologist at the Cleveland Clinic. “And the answer is yes.'”

True hypogonadism involves low testosterone levels along with symptoms and often has a clear cause, such as a genetic syndrome, chemotherapy, head trauma or pituitary tumor, Dr. Anawalt said.

The study results were presented Friday at the Endocrine Society’s annual meeting in Chicago and published in the New England Journal of Medicine. Although the trial was conducted by the Cleveland Clinic Coordinating Center for Clinical Research and a contract research organization, it was funded by pharmaceutical companies that manufacture testosterone, at the request of the Food and Drug Administration.

However, the study does not resolve all of the safety questions that have obsessed testosterone for decades. The clinical trial did not include the kind of older men who flocked to anti-aging centers. Many of these centers prescribe testosterone, often without testing hormone levelsaccording to the FDA Only patients with a clear diagnosis of testosterone deficiency based on repeated testing and showing symptoms of deficiency were included.

Long-term data are still lacking and the trial’s retention rate was low, with 60% of patients in each group stopping using the patch before the end of the trial.

The researchers took steps to address these limitations, but said gaps remained.

“It wasn’t a perfect trial, and it doesn’t definitively answer the question forever — and certainly not for patients who are different from those in the study,” Dr. Nissen said, in a pointed reference to the men taking testosterone without a diagnosis of hypogonadism.

But the trial results provide important information for doctors and patients with hypogonadism, as many doctors and patients may have been reluctant to treat the condition due to concerns about heart disease.

“This allows practitioners who were treating patients with hypogonadism to worry less about whether there is a cardiovascular risk that will outweigh any benefit, and to focus more on patients who may benefit from replacement. testosterone,” said Dr. Michael Lincoff. , the study’s lead author, also at the Cleveland Clinic.

Other researchers are analyzing the data to determine the effectiveness of testosterone treatment in relieving the symptoms of hypogonadism, which include depression, osteoporosis, anemia, loss of muscle mass, and a troublesome condition called hypertrophy. benign prostate, which blocks the flow of urine, in addition to sexual symptoms.

The Food and Drug Administration has approved testosterone products only for men whose low testosterone levels are caused by a medical condition like hypogonadism, but doctors are allowed to use drugs for other purposes “outside MA”.

The agency reviewed testosterone replacement therapy in 2010 after a clinical trial of the hormone stopped when patients taking it began having heart attacks, and in 2015 the FDA asked testosterone manufacturers to conduct a clinical trial to assess the risk.

The agency also added a so-called black box label to testosterone products, warning of a possible increased risk of heart attacks and strokes.

Dr. Shalender Bhasin, an endocrinologist at Brigham and Women’s Hospital in Boston, who is the study’s co-principal investigator, is analyzing the trial results to see if testosterone therapy actually improves sexual function and resolves other symptoms of hypogonadism.

“Folklore holds that testosterone improves sexual function, but even in this area there are only three or four randomized trials, and most only lasted three to six months,” he said. , noting that there was a “substantial placebo effect on sexual symptoms.

Dr. Bhasin’s studies, which are yet to be published, will look at the effects of testosterone on the prostate, bone fractures and the progression of diabetes, among others.