A decline in testosterone is often blamed for men's loss of muscle, energy and sex drive as they get older, but the culprit for some age-related changes may be a drop in men's levels of the female hormone estrogen, a new study suggests.
Researchers found that declining levels of estrogen in men may play a role in the accumulation of body fat. Before this study, low levels of testosterone were thought to be responsible for both men's loss of muscle mass, and gain of body fat with aging.
"The function of estrogen in men has largely been ignored," said study researcher Dr. Joel Finkelstein, an endocrinologist at Massachusetts General Hospital in Boston. Until now, the study of the hormone in men has mainly been limited to the role of estrogen deficiency in bone loss, he said.
"Men make estrogen from testosterone, and women do, too," Finkelstein said. So when men age and testosterone levels naturally decline, men also experience a drop in levels of estrogen circulating in their blood.
The new results suggest that when estrogen levels drop, men experience some of the same consequences that women do after menopause: They have more bone loss, their libido declines, and they gain more fat around their midsection. [Macho Man: 10 Wild Facts About the Male Body]
The study is published online today (Sept. 11) in The New England Journal of Medicine. The researchers received some funding from Abbott Labs, a pharmaceutical company that makes the testosterone gel used in the study.
Estrogen important for men
In the study, researchers looked at 400 healthy men ages 20 to 50 who had normal testosterone levels. First, they gave all the participants injections of a drug that reduced the men's normal production of sex hormones to levels typical of males before puberty.
Next, the researchers gave 198 men one of four dosage levels of testosterone gel, which the men applied to their skin daily for 16 weeks, or a placebo gel. The other 202 men used similar doses of the testosterone gel every day for 16 weeks, and also took a drug designed to block the conversion of testosterone into estrogen.
The researchers wanted to tease out which symptoms -- changes in men's body fat, muscle mass, strength and sexual function -- were due to reductions in testosterone, estrogen or both hormones. They also wanted to determine the testosterone levels at which these physiological effects occur.
The results showed that many of the undesired effects of testosterone deficiency in men are actually due to the accompanying decrease in estrogen, Finkelstein said.
Changes in men's muscle mass and size, and strength were largely linked with low levels of testosterone, but it was declining levels of both testosterone and estrogen that were associated with a reduced sex drive and erectile function, the researchers said.
"We were surprised at the dramatic effects that low levels of estrogen had on fat accumulation and sexual function in men," Finkelstein said. "We knew that these effects were seen in studies on mice, and these results very accurately predicted what occurred in humans."
Interpreting testosterone levels
"This is a beautifully done study that allows physicians to get a little better handle on interpreting testosterone levels," said Dr. Bradley Anawalt, an endocrinologist and professor of medicine at the University of Washington Medical School in Seattle, who was not involved in the research.
"But the real mind-blower of this study is the idea that estrogen has an important role in male physiology," Anawalt said.
The study has very important implications for medical practice, he said. The results clearly show that testosterone has a differential effect on body organs, such as fat, muscle, the penis and the mind, he said.
And the findings help doctors understand the threshold levels of testosterone in the blood associated with age-related complaints, and at what levels testosterone therapy may benefit some men.
Normal testosterone levels in men are considered from 300 to 900 nanograms per deciliter.
The study showed that men with small drops in testosterone at the lower end of the normal range -- between 300 and 500 ng/dl -- are likely to have decreases in erections and a reduced sex drive, Anawalt said.
If levels fall below 300 ng/dl, men may start to accumulate fat, and when testosterone dips below 200 ng/dl, men may experience a decline in muscle mass and strength, he said.
Anawalt said that one limitation of the study is the researchers used averages to measure treatment outcomes in the participants, so physicians need to be careful about applying these results to individual men.
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