Hot, hot hormones.
Reviewed by Craig H. Kliger, MD
Testosterone has been the subject of controversy recently, fueled partly by an April cover story in The New York Times Magazine. Author Andrew Sullivan extolled the effects of the hormone as treatment for his HIV-induced deficiency. Citing bursts in libido, confidence, and energy as a result, he refers to his testosterone injections as "a biweekly encounter with a syringe full of manhood."
Interest rose even higher when, shortly after Sullivan's piece appeared, AndroGel was introduced on the market. The injections used in Sullivan's treatment are painful (he describes the three-inch needle and the resulting trickle of blood) and produce wildly erratic hormone levels (huge burst shortly after the injections, insufficient levels a few days later). But AndroGel, a user-friendly cream containing androgens (the class of steroid hormones to which testosterone belongs), can be absorbed through the skin. AndroGel boasts no-muss, no-fuss easy daily applications that produce far more consistent blood levels of the drug. A cover story in Time Magazine on this development aroused further lively media coverage.
All this buzz about testosterone supplementation evoked a burning question, especially among men of a certain age: Where can guys who are no longer teenagers sign up for this stuff?
The Story Behind the Story
Unfortunately, the optimistic reports about testosterone have omitted some important information, such as the need for painful injections. And they failed to consider the very basic question: Do most men need extra testosterone to reverse some of the typical declines in sexuality as they age?
Interestingly, the answer is no.
Extra testosterone can definitely improve the lives of men with extremely low levels of testosterone due to disease -- say, 5% of normal, due to conditions such as the removal of a pituitary tumor, removal of the testes (in the case of testicular cancer, for example), or in Sullivan's case, HIV. In these cases, the lowered level would likely affect libido. If you were to boost such a man's testosterone levels by giving him supplemental doses of the hormone, you would expect his behavior to return to normal. That was Sullivan's experience, with some healthy placebo effects tossed in on top -- a possibility he barely raises in his piece.
But most men simply don't need AndroGel. Here's why.
Testosterone levels tend to decline gradually in men, starting in early middle age. The popular perception, and one trumpeted throughout Sullivan's piece, is that this decline is a cause of the typical decrease in energy, edge, and sex drive that often accompanies aging.
But there is simply no scientific data to support a cause-and-effect relationship between the (slow) decline in testosterone experienced during normal aging and a negative impact on libido, sexual performance, or level of energy. Furthermore, even the temporary declines in testosterone experienced by many men during periods of stress (traffic jams, a poor evaluation by a superior) typically do not appear to make any long-term difference in their libido and performance, either.
All this buzz about testosterone supplementation evoked a burning question, especially among men of a certain age: Where can guys who are no longer teenagers sign up for this stuff?
Behavior Drives Hormones, Not Vice Versa
For argument's sake, let's suppose that for every smidgen of a decline in testosterone, there was a proportional decline in sexual drive, energy, and libido, while for every smidgen of a rise, there was an increase. If that were the case, researchers should be able to select a group of normal, healthy guys for a study, measure their testosterone levels, and show that the men with the higher testosterone levels are more libidinous, sexually active, or more aggressive.
Indeed, some studies have suggested such a correlation. But there turns out to be a confounding factor: Acting aggressively and having sex both raise testosterone levels, so the correlation seems due to behavior driving the hormones, rather than the other way around. This phenomenon has been discussed in many leading texts on the subject.
When experiments control for those factors -- acting aggressively and having sex -- the vast majority of studies, whether of humans or animals, show that individual differences in testosterone levels across the normal range don't particularly predict individual differences in aggressiveness or sexual activity. My own study, "Testicular function, social rank, and personality among wild baboons," published in the journalPsychoneuroendocrinology (Vol. 16, No. 4, 1991), is among the many to have found this.
A Mere 15% of Normal Is Enough
Here is the critical point: Give Sullivan replacement testosterone so that his circulating levels return to 15% of normal, 100% of normal, or 150% of normal, and you will have roughly the same effect in all cases. The best single review on this subject is "Behavioral effects on androgens in humans," published in the August 1996 issue of the American Journal of Psychiatry. Over a very wide range, testosterone has pretty much the same effect on behavior. Push levels below that range (due to castration or any of a number of diseases), and physiology and behavior change. Push levels above that range, by abusing anabolic steroids, and you'll typically boost aggression, perhaps libido as well. But within that broad range -- from 15% to 150% of normal -- behavior and libido remain roughly the same.
Increases Body Mass, Not Sex Drive
So what CAN extra testosterone do? A few studies, including one in the October 1992 issue of the Journal of Clinical Endocrinological Metabolism, have shown that boosting testosterone levels in aged males increases body mass and decreases cholesterol levels. Sullivan, who experienced a 20-pound weight gain, can now squat more than 400 pounds and feels a surge of energy "less edgy than a double espresso but just as powerful."
However, there have been no double-blind studies showing that supplemental testosterone reinstates "youthful" sexual performance or libido, alertness, or energy.
And the testosterone experts agree. Consider the following summary from a recent review published in the July 2000 issue of the journal Geriatrics: "Hormones such as DHEA, human growth hormone, and testosterone tend to decline with aging, but the therapeutic value of [restoring] them to 'normal' physiologic levels has not been substantiated by controlled clinical trials." Furthermore, Williams' Textbook of Endocrinology (1998, 9th edition), essentially the "bible" of the field, states that "The decline in male sexual function with age does not appear to be endocrine-mediated."
So a 50% decline in some guy's testosterone level as he ages from a 20-something to a 50-something is unlikely to have much impact on his physiology and behavior. And therefore using something like AndroGel to boost his levels from 50% to 100% won't likely have much of an impact, either.
Stress Inhibits Testosterone, But Does It Matter?Similarly, low testosterone secretion induced by stress is no reason to take supplemental testosterone, either. All sorts of stressors, whether physical or psychological, can inhibit the secretion of all the hormones involved in the complex release of testosterone. Anesthetize someone for surgery, slice into his belly with a scalpel, and testosterone levels begin to decline. The same thing will happen for a male primate who has just been toppled from a high rank in the group hierarchy. Ditto for a man going through a stressful cognitive task like a final exam. Or -- an example that I get an odd pleasure out of citing -- a study in the May 1972 Archives of General Psychiatryfound that men in the early, highly stressful period of officer's training in the military have suppressed testosterone levels, too.
So this decline under stress appears to be a well-established phenomenon. But the bottom line is, what are the consequences of this decline in testosterone levels during stress? A loss of sexual drive or performance? Decreased aggressiveness? Decreased muscle metabolism?
None of the above, almost certainly. The declines in testosterone levels during stress, even with severe, chronic stress, just aren't dramatic enough to produce such adverse consequences.
So, men shouldn't worry much about the consequences of yet another traffic jam or deadline on their testosterone. The problem isn't that testosterone levels go down during stress. It's that erect penises do. But that's another subject . . . for another story.
Robert Sapolsky is professor of biological sciences at Stanford University, and of neurology at Stanford University School of Medicine. He is the author of Why Zebras Don't Get Ulcers: A Guide to Stress, Stress-Related Diseases.
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