September 11, 2013, 6:06 p.m.
Testosterone is powerful--in the male human body and in the American pharmacological marketplace. From 1993 to 2000, prescriptions for testosterone replacements increased fivefold, boosted by advertising campaigns that invited aging men to "talk to their doctor about low T" if they were experiencing decreased energy, sex drive or muscle tone. 
Until now, however, physicians haven't really known just how low testosterone levels might produce these symptoms, and just how low testosterone would need to drop to cause changes in a man's energy level, his body composition or his sexual function. In fact, while men were lining up in droves to get tested for "low T," physicians and researchers really weren't sure whether the problem was testosterone at all.
In a curious twist, it turns out that some of men's "low T" symptoms are, in fact, attributable to a deficiency of "the female hormone," estrogen.
That's right. Low E, not low T, may be responsible for the decline in many men's sexual function and their accumulation of body fat.
The study was published in the New England Journal of Medicine on Thursday.
The new research explored what mix of hormone levels in healthy younger men might bring on the hallmark symptoms of male hypogonadism: loss of energy and strength, sexual dysfunction and depressed libido and changes in body composition that add flab and sap muscle tone.
Because a portion of a male's testosterone is converted to the hormone estradiol--a form of estrogen--researchers knew there was more to the hormonal mix than just testosterone. So they recruited more than 300 healthy men between 20 and 50 and tinkered with their hormonal balance to see what the effects would be.
All the men had their testosterone hormone production suppressed by four monthly injections of the drug goserelin (marketed as Zoladex) and either a placebo testosterone replacement or actual testosterone replacement that ranged across four levels, from very little replacement to complete replacement. These men were further divided into two groups: half getting a medication that blocks the conversion of testosterone to estradiol, the other half not.
The results help tease apart which of men's mid- or late-life symptoms may stem from testosterone loss and which from a failure to convert enough of that testosterone to estradiol. The results also flesh out the levels of testosterone loss that are typically necessary to induce symptoms such as low sex drive, body composition changes and flagging energy.
The accumulation of body fat was seen in most of the men whose testosterone was less than fully replaced, but such increases were particularly widespread in those whose estrogen levels were low. Sexual function suffered among the men whose testosterone was was less than fully replaced as well. But again, the effect was much more pronounced in men whose estrogen levels were also low.
Reduced testosterone levels alone were enough to degrade a man's lean body mass, the size of his thigh muscle or his leg strength. Those weren't further degraded when a man's ability to convert testosterone to estrogen was blocked, suggesting that these problems are largely caused by low testosterone alone.
The result may be the first step to a more precise diagnosis of those "non-specific symptoms" that men complain to their doctors about, and which lead to them with ever greater frequency taking home a prescription for hormone replacement.
It may also be a reminder to men that testosterone alone is not the source of their vitality: estrogen too, plays a role.