THE first surge of testosterone happens in the uterus, a few weeks into development, causing an embryo with the XY combination of chromosomes to develop male sex organs.
A second and poorly understood surge happens during infancy. About its only noticeable effect is when a baby boy's spontaneous erection shocks his parents.
Then comes puberty, the third and final testosterone surge. Voices deepen. Chins and chests sprout hair. Muscles develop and limbs grow long.
By the late 20s, testosterone surges are history.
And so, many men fear, are the glory days of manhood. During their youth, testosterone helped build muscles, strength and bone. It coursed through their brains, sent signals to their genitals, awakened their sexual desires. It sharpened their visual memory so they could keep track of a puck or a ball and bring cheers from the crowds. It gave them the energy to work all night, the confidence to stare down a competitor -- maybe even the foolhardiness to jump out of an airplane or scale a peak.
Researchers are learning more about this hormone that first makes an embryo a boy, and then turns boys into men -- increasingly with an eye on the hormone's role in the aging body. They're finding that testosterone replacement therapy can boost muscle mass, decrease fat deposits, improve sex drive, enhance energy level and increase bone density. It may also lift depression in some men.
They are also finding that the improvements can come at a cost.
As men age, slowly but relentlessly testosterone levels start to fall, beginning at about the age of 30 and at a rate of 1% to 2% a year. The brain becomes less predictable in regulating testosterone, and production within the testes drops off. Worse, the testosterone still produced is less able to enter the cells of muscles, bones and organs to do its work.
It is no coincidence that bad things begin to happen to a man's body, at the same relentless pace. Lean muscle mass is replaced by potbellies. Bones weaken. Memory fades. Fatigue and depression can set in.
Sex drive, which once disrupted high school classes and ruled fraternities, calms down. Sexual performance wanes. "Even Viagra cannot overcome very low testosterone," says Dr. John Morley, chairman of the division of geriatrics at St. Louis University School of Medicine.
Meanwhile, the threat of major illness increases with each passing decade: heart disease, cancer, diabetes, dementia and arthritis.
It would be wonderful if a fountain of youth hormone could help men regain the sexual stamina, physique, strength and mental agility of the surge years while reducing -- or at least not increasing -- the risk of disease.
There are some known side effects. Taking testosterone can cause acne, enlargement of male breasts and temporary infertility. It can worsen sleep apnea, a serious disorder that causes a person to stop breathing during sleep -- sometimes hundreds of times a night.
There are also many unknowns. For instance, it isn't yet clear whether testosterone raises the risk of heart disease, reduces it or acts neutrally. Although some studies show that testosterone therapy lowers cholesterol, it appears to lower not only the bad cholesterol, or LDL, that clogs arteries, but also the good cholesterol, or HDL, that protects against heart disease.
Testosterone therapy also increases the production of red blood cells, thickening the blood -- good for men with anemia, but potentially increasing the risk of heart attack and stroke, especially among current and former smokers who already have increased red blood cells.
Weighing risks, benefits
By far the most troublesome unknown is whether testosterone replacement therapy increases the risk of prostate cancer.
"That's the 800-pound gorilla sitting on the living room couch," says Dr. S. Mitchell Harman, president of the Kronos Longevity Research Institute in Phoenix, a private research center focusing on the biological underpinnings of aging. "We can't really tell men what the risk-benefit ratio is."
The big problem with testosterone studies so far is that they involve small numbers of patients and usually run six months or less -- leaving unanswered the risks of long-term use.
Even without solid evidence, many men are betting on the benefits of testosterone replacement anyway. In 2004, American pharmacists dispensed 1.86 million prescriptions for testosterone supplements, according to pharmaceutical consulting firm IMS Health, the vast majority of them for men. In 2000, they dispensed 590,000 prescriptions.
In earlier years, most treated men went to their physicians for injections. Today, nearly three-fourths of prescriptions are for Androgel, a topical treatment first approved in 2000. Rubbed daily onto any fatty area of the body, the gel has greatly reduced the inconvenience of treatment.