Estrogen, the "female" hormone, is a lot more important to men than even many doctors think, according to a surprising new study published Wednesday in the New England Journal of Medicine.
Researchers at Massachusetts General Hospital in Boston found that it's actually a lack of estrogen that's most responsible for the accumulation of body fat plaguing men with low testosterone levels, raising their risks of cardiovascular disease and diabetes. Low estrogen is also a big contributor to the sexual dysfunction and low libido usually blamed solely on low testosterone.
The research could change the way doctors prescribe hormones for men, experts suggest.
"It's a blockbuster, a mind bender for the general public and many scientists," Brad Anawalt, an endocrinologist and vice chair of the Department of Medicine at the University of Washington, who was not involved with the study, told NBC News.
Men make about 80 percent of their estrogen through the conversion of testosterone into an estrogen by an enzyme called aromatase. So when testosterone drops, so does estrogen. Low testosterone itself is linked to declines in lean muscle mass, muscle size, and strength, the study found.
That low estrogen weakens male bones, as it does in post-menopausal women, has long been known. But most effects of "low T," more properly called hypogonadism, have been blamed on low testosterone itself, helping fuel a more than 500 percent spike in prescriptions from 1993 to 2000. Despite concerns of possible harmful side effects, the percentage of American men over 40 receiving testosterone approximately tripled to nearly 3 percent of the population from 2001 to 2011, according to a study published this year in JAMA Internal Medicine.
A normal range for testosterone -- between 300 and 1,000 nanograms per deciliter of blood -- is based on the mean levels found in the general population. But the study revealed that a healthy range should really depend upon the individual body tissue or system. It's not one-size-fits-all.
As testosterone drops -- beginning about age 35 -- the first thing affected is sexual function, due to both low testosterone and estrogen, Anawalt explained. Further drops begin to affect fat metabolism due to low estrogen. Finally, with very low testosterone, muscle mass and strength fall.
Currently, a man with a measure of 300, and complaining of lower muscle mass and strength, might be given a testosterone prescription. Thanks to advertising "we think of testosterone like sprinkling on table salt," Anawalt said.
But now, "if he has a T level of 300, this study suggests that his loss of strength is not related to testosterone level, he's just [age] 50," Anawalt said.
Conversely, a man with a level at 300 but who has a different problem, might need more testosterone, endocrinologist Joel Finkelstein, who led the study, explained.
"If you come in and I say, ‘Oh, God, fat's accumulating on this guy,' it's not enough. That fat is accumulating because of a drop in estrogen."
Then, a doctor may wish to prescribe extra testosterone as a way to boost estrogen, Finkelstein said.
The study used 400 healthy men between 20 and 50 years old. All the men were given a drug to stop their production of testosterone and estrogen and divided into two groups. Some men in one group were then given a placebo testosterone replacement product, while others were given increasing doses of the real thing.
The men in the other group were given the same replacement dosages, but also a drug to inhibit aromatase, so their bodies would make almost no estrogen.
Finkelstein's team then tracked the way the subjects' bodies reacted over a period of 16 weeks by using scans, surveys, and strength tests.
The men who received replacement doses of testosterone, but whose estrogen production was blocked, showed significant increases in three key body fat measures as well as erectile dysfunction and low sexual desire.
"When you lose estrogen, it's all bad," Finkelstein said. "With estrogen loss you get fat accumulation, loss of libido, bone loss."
Because those effects are related to osteoporosis, diabetes, cardiovascular disease, the "billion dollar question" is whether older men should be routinely given testosterone replacement to increase both their T levels and estrogen levels as part of preventive medicine, Finkelstein said.
"What do we do about men as they age into their 60s, 70s, 80s? Is it helpful or harmful? Both? Neither? We don't know," Finkelstein added.
The Mass General researchers plan to repeat the study using groups of older men to find out.
Both Finkelstein and Anawalt cited the Women's Health Initiative, a huge study that found unexpected risks with hormone replacement therapy for post-menopausal women, as a cautionary tale.
However, Anawalt suggested doctors would be "hard-pressed" to prove prescribing testosterone for most older men at a dosage enough to raise it above normal is risky.
"If we cannot prove harm, and the potential benefit is sex function, perhaps lower fat accumulation, a number of doctors and patients are going to glom onto that and say it sounds like a good plan," he said.
Still, Anawalt added, "I predict a number of us would be leery about it."
Brian Alexander is a frequent contributor to NBC News and a co-author of "The Chemistry Between Us: Love, Sex, and the Science of Attraction."