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Published in CenterView on February 27, 2012
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Women's health researchers probe cardiovascular risks of enhanced testosterone

By Jack Mazurak

With weight gain, testosterone levels drop in many men, leading doctors to prescribe supplements of the sex hormone.

Testosterone supplements improve feelings of wellbeing, turn up libido and help prevent osteoporosis. They also help the body gain muscle mass.

But the lack of safety data on those supplements, particularly about cardiovascular effects after chronic exposure, prompted researchers at the UMMC Women's Health Research Center to organize an experiment with rats.

Their study found testosterone helped unlace several detrimental knots of obesity. Leptin, glucose and cholesterol levels all fell in the testosterone treated group of obese rats, as did insulin resistance. But blood pressures shot up.

That came as a surprise, given all the other positive numbers.

"What it suggests is that obese men who have less testosterone would benefit from testosterone supplements but that their blood pressures should be monitored carefully," said Dr. Jane Reckelhoff, distinguished professor of physiology and biophysics and the center's director.

The journal Hypertension published the study online in January and is scheduled to print it in an issue this spring. A grant from the National Institutes of Health funded the research.

The alarming increase in Americans' waistlines the past decade means millions of people are in or headed for a condition known as metabolic syndrome.

Characterized by fat in the midsection, poor insulin sensitivity, elevated blood pressure and constant low-level inflammation, metabolic syndrome essentially edges a person toward more serious chronic diseases including diabetes, hypertension and heart disease.

Since men's bodies reduce testosterone output with obesity, which accompanies metabolic syndrome, the researchers wondered if adding supplements would protect against hypertension and cardiovascular disease or speed their progression.

The scientists dosed seven obese male rats and seven lean male rats with testosterone for 10 weeks, time enough to be considered chronic exposure. Two control groups - obese and normal-weight male rats - received no testosterone.

The treated obese rats' weight decreased by 21 percent, insulin resistance improved by 40 percent and their fasted blood-glucose levels were down compared to the untreated obese group. Proteinuria and albuminuria - signs of kidney injury measured in the urine - fell in the treated obese group but increased in the lean test group.

However, blood pressures in the treated obese rats rose on average 10 mm Hg. Meanwhile, blood pressures in the lean rats treated with testosterone didn't change.

In humans, 10 mm Hg can represent enough change to push a person from normal categorization into hypertension.

"If men respond to testosterone supplements like rats, they will see positive results like body-fat reductions, increases in lean muscle mass and they'll feel better overall," said Reckelhoff, senior investigator on the study. "But their blood pressures will likely go up and will need to be monitored."

Beyond the obvious liability comparing rats to humans, Reckelhoff said the recent study needs another caveat.

"We increased testosterone levels by tenfold in our rats. That's well past the level you'd see in a normal-weight, middle-aged rat," she said, indicating doctors wouldn't prescribe patients such a high dose of supplements.

Reckelhoff founded the Women's Health Research Center in 2009 to study how gender-based differences - such as sex hormones like testosterone and estrogen - play roles in health and disease.

"Because androgens are illegal in athletics, there are very few studies done in humans on their chronic effects," she said. "The NIH needs to do more safety studies on the long-term effect of testosterone particularly on obese men with regard to their cardiovascular status."