Testosterone therapy does not increase heart risk in a group of men
The largest study ever conducted to evaluate the safety of hormone replacement for men has some reassuring news for a limited group of patients whose bodies don’t make enough testosterone, as they find the hormone does not exacerbate heart attacks, strokes and cardiac death.
The new results, which come from a large clinical trial of the sort considered the gold standard in medicine, don’t allay concerns. But they seem to resolve decades of conflicting findings about the heart safety of testosterone treatment for men with a medical condition called androgen deficiency, or hypogonadism.
The authors emphasized that the results did not apply to the many middle-aged and older men who use testosterone offered at anti-aging centers in hopes of building muscle or boosting their energy and sex drive, often without being properly evaluated . Instead, it only refers to the small percentage of the country’s male population, presumably in the low single digits, with a real medical diagnosis of hypogonadismor with consistently low testosterone levels and symptoms that can include osteoporosis and anemia, as well as low libido.
“We’ve never had a study of more than 5,000 men followed for four years where their heart attacks and strokes were carefully monitored,” says Dr. Bradley Anawalt, an endocrinologist and professor of medicine at the University of Washington School of Medicine, who was not involved in the trial.
“The important caveat is that this should not be interpreted as saying that testosterone does not cause heart attacks and strokes in men without hypogonadism,” he said. “It’s not a signal that it’s safe to take large amounts of testosterone for normal men.”
While testosterone levels tend to decline with age, as well as weight gain, true hypogonadism is believed to be much less common, according to the study authors, and experts say its prevalence and incidence have not been well studied.
The study included 5,246 men in the United States aged 45 to 80 with the diagnosis, and randomly assigned them to receive a patch containing a standard dose of testosterone or a placebo with no active ingredient. All men had heart disease or were at high risk for it. But after an average of two years of follow-up, researchers found that testosterone had not increased their risk of heart attacksstrokes or other deaths from heart disease.
About 7 percent of the men in each group experienced some kind of cardiac event during the follow-up period — whether or not they took testosterone.
But the study identified other potentially serious complications that occurred in low rates in patients receiving the treatment, including a higher risk of acute kidney disease, blood clots in blood vessels that supply blood to the lungs, and a heart rhythm disorder called atrial fibrillation.
“We 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 senior author and a cardiologist at Cleveland Clinic. “And the answer is ‘yes’.”
True hypogonadism includes low testosterone levels as well as symptoms and often has a clear cause, such as a genetic syndrome, chemotherapy, head trauma or a pituitary tumor, said Dr. Anawalt.
The study findings were presented Friday at the annual meeting of the Endocrine Society 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 drug companies that make testosterone, on behalf of the Food and Drug Administration.
However, the study doesn’t resolve all the safety questions that have dogged testosterone for decades. The clinical trial did not include the kind of older men who have flocked to anti-aging centers. Many of those 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 with symptoms of deficiency, were included.
Long-term data are also still lacking, and the study’s retention rate was low, with 60 percent of patients in each group stopping using the patch before the end of the study.
Researchers took steps to account for these limitations, but said there were still shortcomings.
“This was not a perfect study and it doesn’t definitively answer the question forever — and certainly not for patients who are different from those in the study,” said Dr. Nissen, in a pointed reference to men taking testosterone without a diagnosis of hypogonadism.
But the study’s results provide important information for doctors and patients with hypogonadism, as many doctors and patients may have been reluctant to treat the condition because of concerns about heart disease.
“This allows practitioners who have treated patients with hypogonadism to be less concerned about whether there is cardiovascular risk outweighing any benefit, and more focused on which patients are likely to benefit from testosterone replacement,” said Dr. Michael Lincoff, the study’s lead author, who is also at the Cleveland Clinic.
Other researchers are analyzing the data to determine how effective testosterone treatment is in alleviating the symptoms of hypogonadism, including depression, osteoporosis, anemia, loss of muscle mass and a nasty condition called benign prostatic hypertrophy that blocks urine flow. to sexual symptoms.
The Food and Drug Administration has only approved testosterone products for men whose low testosterone levels are caused by a medical condition such as hypogonadism, but doctors are allowed to use drugs for other “off-label” purposes.
The agency reviewed testosterone replacement therapy in 2010 after a clinical trial of the hormone was halted when patients taking it experienced heart attacks, and in 2015 the FDA required the makers of testosterone to conduct a clinical trial to evaluate 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 a co-principal investigator on the study, is analyzing the results of the study to see if testosterone therapy really improves sexual function and resolves other symptoms of hypogonadism.
“The folklore is that testosterone improves sexual function, but even in that area there are only three or four randomized trials, and most of them were only three to six months long,” he said, noting that there was a “substantial placebo effect on sexual symptoms.”
The studies of dr. Bhasin, which have not yet been published, will look at, among other things, the effects of testosterone on the prostate, bone fractures and the progression of diabetes.