麻豆传媒

Some symptoms traditionally attributed to low testosterone may actually be due to estrogen deficiency, researchers found.

In a small study of men whose hormone levels were altered to mimic low testosterone -- and in some cases, to completely inhibit estrogen production -- it appeared that androgen deficiency accounted for decreases in lean mass, muscle size, and strength, while a lack of estrogen was responsible for increases in body fat, according to , of Massachusetts General Hospital, and colleagues.

Both hormones appeared to contribute to declines in sexual desire and erectile function, they .

"Some of the symptoms routinely attributed to testosterone deficiency are actually partially or almost exclusively caused by the decline in estrogens that is an inseparable result of lower testosterone levels," Finkelstein said in a statement.

Testosterone therapy in deficient men has been shown to improve fat mass, muscle, sexual desire, and other common symptoms, leading to the conclusion that androgen deficiency is behind them. But estrogen is metabolized from testosterone with the help of the enzyme aromatase.

So men with low testosterone also have low estrogen, making it unclear which hormone supports which function, the researchers wrote.

To tackle the issue, Finkelstein and colleagues gave healthy men ages 20 to 50 goserelin to suppress their own testosterone production, and then randomly assigned them to one of two groups for a 16-week study.

The first group of 198 men took either placebo or normal testosterone replacement with one of five doses: 1.25 g, 2 g, 2.5 g, 5 g, or 10 g.

The other 202 men were randomized to those same groups, except they were also given the aromatase inhibitor anastrozole (Arimidex) to block estrogen production.

Overall, they found that changes in lean mass, thigh muscle, and leg strength were attributable to changes in testosterone levels, while changes in fat measures were primarily related to changes in estrogen, they wrote. Both sex hormones contributed to sexual desire and erectile function.

Specifically, in the cohort that continued to produce estrogen, increases in body fat were seen at a mild level of testosterone deficiency -- i.e., those on placebo and lower doses of testosterone. The percentage of body fat fell significantly for those on 10 g/day of the hormone.

Decreases in lean body mass and muscle area and strength didn't develop until testosterone levels became quite low, at either 1.25 g or on placebo, they wrote.

Sexual desire fell with declining testosterone levels, while erectile function was preserved until testosterone levels were very low.

Among men who were blocked from producing estrogen, the researchers saw increases in body fat at all levels of testosterone supplementation -- but there was no effect on lean muscle mass, muscle size, or leg strength, the researchers reported.

They also noted that the adverse effects on sexual function became more obvious when estrogen was suppressed.

Finkelstein and colleagues concluded that the results imply testosterone levels regulate lean body mass, muscle size and strength, while estrogen levels regulate fat accumulation -- and that sexual function appears to be regulated by both hormones.

They said their findings "support changes in the approach to evaluation and managment of hypogonadism in men."

"Our findings ... indicate that estrogen deficiency is largely responsible for some of the key consequences of male hypogonadism," they concluded, "and suggest measuring estradiol might be helpful in assessing the risk of sexual dysfunction, bone loss, or fat accumulation in men with hypogonadism."

In an accompanying editorial, , said the study raises new questions that flow from its "understandable limitations in duration, participant profile, and range of androgen-sensitive endpoints."

"Longer studies are required to partition the effects of testosterone on bone density and fractures or on prostate growth and diseases," Handelsman wrote, adding that researchers should also investigate its effects on metabolism, cardiovascular function, and cerebral function.

"Nevertheless," he concluded, "this excellent study contributes to our expanding appreciation of the complex mechanisms of action of testosterone."

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