Judging by the booming demand for testosterone gels and creams, low testosterone is an epidemic in middle-aged men. But a study has found that male hormones are more complex than a diagnosis of Low T may suggest: A drop in estrogen also plays a role in declining libido and erectile dysfunction.
In fact, some of the symptoms routinely associated with low testosterone are almost exclusively due to insufficient estrogen, according to research published this week in The New England Journal of Medicine.
"Estrogen deficiency in men is bad," said lead author Dr. Joel Finkelstein, a physician at Massachusetts General Hospital. "It leads to bone loss, it leads to fat accumulation, it leads to sexual dysfunction and loss of sex drive."
Finkelstein and his colleagues found a link between low testosterone levels and decreases in lean body mass, muscle size and strength, whereas increases in body fat were associated with a drop in estrogen. Both testosterone and estrogen were important for maintaining normal libido and erectile function.
The findings are significant because a typical diagnosis of low testosterone, based on blood levels of the hormone, does not take into account symptoms such as osteoporosis and body-fat composition, he said. "What this study tries to provide is a framework for interpreting a testosterone level more objectively."
A level-headed approach to testosterone replacement therapy – and the condition known as Low T – may be long overdue.
Prescriptions for testosterone gels are surging, despite side effects that may include prostate disorders and cardiovascular problems. In the United States alone, sales of AndroGel, the industry bestseller, increased to $1.4-billion in 2012 from $544-million (U.S.) in 2008.
"I think people have gotten ahead of themselves," Finkelstein said, adding that studies have not established that the benefits of taking testosterone outweigh the risks.
Future studies require a clearer understanding of how hormones work in men, he said.
A small amount of the testosterone produced in healthy men is converted into estrogen. Since low testosterone results in low estrogen, Finkelstein and colleagues set out to isolate the specific role of estrogen in supporting physical functions.
The researchers gave men aged 20 to 50 a drug that suppressed the production of all reproductive hormones. One group of about 200 men used testosterone gel at various dosage levels for 16 weeks, or a placebo. In a second group of the same size, men received the same testosterone doses along with an enzyme that blocked the conversion of testosterone into estrogen.
In men whose estrogen production was not blocked, leg muscle size and strength did not decrease until testosterone blood levels became quite low. The men reported decreases in sexual desire with each drop in testosterone levels, but erectile function remained until testosterone levels were extremely low.
When estrogen production was blocked, increases in body fat were seen at all testosterone dosage levels, but suppressing estrogen production had no effect on lean mass, muscle size or leg strength. Moreover, declines in sexual function were much more obvious when estrogen production was suppressed, regardless of the men's testosterone levels.
As newer testosterone drugs enter the market, the role of estrogen should not be overlooked, Finkelstein said. Most testosterone preparations in North America include the enzyme for estrogen production, however some products in development, particularly in Europe, may prevent estrogen production. "You want to have estrogen in the right proportion," he pointed out.
Finkelstein and colleagues are working on a follow-up study in men over age 50 to confirm their findings. In older men, however, it is unclear whether low testosterone is an actual medical problem requiring treatment. As Stephen Colbert has quipped on his TV show, Low T may be nothing more than "a pharmaceutical-company-recognized condition affecting millions of men with low testosterone – previously known as getting older."
Researchers including Finkelstein are calling for a Men's Health Initiative similar to the Women's Health Initiative, which uncovered dangerous side effects associated with estrogen replacement therapy. Large-scale testosterone replacement cannot be recommended until the cause-and-effect relationship between hormone levels in men and physical symptoms such as fat accumulation are better established, Finkelstein said.
"Right now, we're not ready to start using [testosterone] in men just because they're older and have testosterone levels that are slightly below the reference range," he said.