Middle-Aged Men, Too, Can Blame Estrogen for That Waistline It is the scourge of many a middle-aged man: he starts getting a pot belly, using lighter weights at the gym and somehow just doesn't have the sexual desire of his younger years. Nathan Weber for The New York Times Ben Iverson took part in a study of men aged 20 to 50 who agreed to have their testosterone production turned off for 16 weeks. The study is being repeated to measure vitality in older men. The obvious culprit is testosterone, since men gradually make less of the male sex hormone as years go by. But a surprising new answer is emerging, one that doctors say could reinvigorate the study of how men's bodies age. Estrogen, the female sex hormone, turns out to play a much bigger role in men's bodies than previously thought, and falling levels contribute to their expanding waistlines just as they do in women's. The discovery of the role of estrogen in men is "a major advance," said Dr. Peter J. Snyder, a professor of medicine at the University of Pennsylvania, who is leading a big new research project on hormone therapy for men 65 and over. Until recently, testosterone deficiency was considered nearly the sole reason that men undergo the familiar physical complaints of midlife. The new frontier of research involves figuring out which hormone does what in men, and how body functions are affected at different hormone levels. While dwindling testosterone levels are to blame for middle-aged men's smaller muscles, falling levels of estrogen regulate fat accumulation, according to a study published Wednesday in The New England Journal of Medicine, which provided the most conclusive evidence to date that estrogen is a major factor in male midlife woes. And both hormones are needed for libido. "Some of the symptoms routinely attributed to testosterone deficiency are actually partially or almost exclusively caused by the decline in estrogens," said Dr. Joel Finkelstein, an endocrinologist at Harvard Medical School and the study's lead author, in a news release on Wednesday. His study is only the start of what many hope will be a new understanding of testosterone and estrogen in men. Dr. Snyder is leading another study, the Testosterone Trial, which measures levels of both hormones and asks whether testosterone treatment can make older men with low testosterone levels more youthful - by letting them walk more quickly, feel more vigorous, improve their sexual functioning and their memories, and strengthen their bones. Smaller studies have been promising but unreliable, and estrogen has not been factored in. "We had ignored this hormone in men, but we are studying it now," said Dr. Alvin M. Matsumoto, a testosterone and geriatrics researcher at the University of Washington School of Medicine and the V.A. Puget Sound Health Care System, who is a Testosterone Trial researcher. We are just starting out on this road. Both men and women make estrogen out of testosterone, and men make so much that they end up with at least twice as much estrogen as postmenopausal women. As levels of both hormones decline with age, the body changes. But until now, researchers have focused almost exclusively on how estrogen affects women and how testosterone affects men. Dr. Finkelstein's study provides a new road map of the function of each hormone and its behavior at various levels. It suggests that different symptoms kick in at different levels of testosterone deficiency. Testosterone, he found, is the chief regulator of muscle tone and lean body mass, but it takes less than was thought to maintain muscle. For a young man, 550 nanograms of testosterone per deciliter of blood serum is the average level, and doctors have generally considered levels below 300 nanograms so low they might require treatment, typically with testosterone gels. But Dr. Finkelstein's study found that muscle strength and size turn out to be unaffected until testosterone levels drop very low, below 200 nanograms. Fat accumulation, however, kicks in at higher testosterone levels: at 300 to 350 nanograms of testosterone, estrogen levels sink low enough that middle-aged spread begins. As for sexual desire and performance, both require estrogen and testosterone, and they increase steadily as those hormone levels rise. Researchers say it is too early to make many specific recommendations, but no one is suggesting that men take estrogen, because high doses cause feminine features like enlarged breasts. Although doctors prescribe testosterone gels for men whose levels fall below 300 nanograms per deciliter, that cutoff point is arbitrary, and there is no clinical rationale for it, Dr. Finkelstein said. Often men take the hormone to treat complaints like fatigue, depression or loss of sexual desire, which may or may not be from low levels of testosterone. The data suggest that men with levels around 300 nanograms who complain of sexual problems may want to try testosterone, but those who complain of flagging muscle strength should not blame testosterone deficiency, Dr. Finkelstein said. But, he added, "symptoms of low testosterone tend to be quite vague." Today, millions of men are using testosterone gels, fueling a nearly $2 billion market.