WASHINGTON (Jun 20, 1995 - 08:54 EDT) -- Tired of hormone as cultural myth, as shorthand for swagger and machismo, ferocity and obnoxiousness, the bearskin beneath the three-piece suit?

Do the ubiquitous references to “testosterone poisoning” and “testosterone shock,” to “testosterone-fueled heavy metal” and ‘testosterone-crazed oppressors” make you feel a bit, well, testy?

Do you think it unfair to blame one lousy little chemical for war, dictatorships, crime, Genghis Khan, Gunga Din, Sly Stallone, the NRA, the NFL, Stormin’ Norman Schwarzkopf and the tendency to interrupt in the middle of a sentence?

Ready to give the so-called male hormone a break and retire all testosterone cliches with a single pound of Iron John’s drum?

Retire away. As it turns out, testosterone may not be the dread “hormone of aggression” that researchers and the popular imagination have long had it. It may not be the substance that drives men to behave with quintessential guyness, to posture, push, yelp, belch, punch and play air-guitar.

If anything, this most freighted of hormones may be a source of very different sensations: calmness, happiness and friendliness, for example.

Friendliness???

Reporting in Washington last week at the annual meeting of the Endocrine Society, researchers said that it was a deficiency of testosterone, rather than its excess, that could lead to all the negative behaviors normally associated with the androgen.

Studying a group of 54 so-called hypogonadal men, who for a variety of reasons were low in testosterone, Dr. Christina Wang of the University of California in Los Angeles and her colleagues, found that before treatment, the men expressed a surprising suite of negative emotions.

They did not feel passive or depressed or timid, as standard ideas of testosterone deficiency might predict. Instead, they described feelings of edginess, anger, irritability. Aggression.

When the men were given testosterone replacement therapy, and were asked to complete questionnaires about their moods several times over the course of two months of treatment, their general sense of well-being improved markedly. Their anger and agitation decreased, their sense of optimism and friendliness heightened.

“Every parameter we looked at went in the same direction,” Dr. Wang said. “The positive mood increased, the negative mood decreased.”

Dr. Willis K. Samson, a professor and chairman of physiology at the University of North Dakota School of Medicine, said, “Testosterone has been given such a negative knock. Work like this helps show the up side of this very important male hormone.”

The commonly held belief that testosterone produces antisocial behavior “may be a misconception,” he added.

Dr. Wang’s work is in keeping with similar findings from other laboratories that question how relevant testosterone is to human aggression.

Some studies even indicate another, improbable source of aggression: estrogen. Yes, the gal hormone.

Other work presented at the meeting showed that when male mice were genetically deprived of their ability to respond to estrogen, they lost a lot of their natural aggressiveness, becoming much less likely to fight with other males or to display the general paranoia exhibited by ordinary male rodents.

Considered together, the new work underscores how primitive is scientists’ understanding of the effects of hormones on human and even animal behavior.

Testosterone was first isolated nearly half a century ago, yet its influence on the brain and behavior remains largely a matter of creative speculation.

“It’s more an art form than a science form,” particularly when it comes to human research, said Dr. William J. Bremner, an endocrinologist at the Seattle Veterans Affairs Medical Center and the University of Washington.

What is not open to debate is that to call testosterone or any of the related androgens “male” hormones, or to call estrogens “female” hormones is a misnomer: both sexes possess some amounts of each other’s hormones.

But they differ considerably in the relative amount circulating through the blood.

In the case of testosterone, women on average have about 40 nanograms of the hormone per deciliter of blood, and a score of 120 would rank as extremely high (and very likely result in hirsutism, acne and other problems of excess androgens).

Men, by contrast, normally have anywhere from 300 to 1,000 nanograms of testosterone per deciliter, or 10 times a woman’s concentration.

This discrepancy explains in part why testosterone has been tagged as the hormone of aggression. Men have so much more of it than women—more of it than women have of estrogen relative to males. Men also commit the vast majority of violent crimes and get into many more accidents than do women.

There has been other evidence implicating testosterone as the bearer of brutality. When scientists inject laboratory animals with testosterone, male and female animals alike respond with more aggressive behavior, becoming more likely to attack intruders or to begin mounting anything that moves.

Moreover, some studies of prison populations, wife beaters or other groups considered hostile and foul-tempered, suggest that aggressive men have comparatively high testosterone levels.

And then there are those football players or weight-lifters who take super-high doses of anabolic steroids—synthetic androgens—in an attempt to build strength and muscle mass. Often, such men report feeling prepared to go out and puree their opponents.

But scientists are beginning to question the relevance of animal behavioral studies to human emotions, and even to wonder what subsidiary effects the testosterone injections could be having on laboratory animals to explain their increased aggression.

As for the human studies, they are contradictory and open to various interpretations. For example, stress can affect hormone levels in ways that are only now being mapped out; and prisoners are likely to be under extremes of stress.

Dr. Wang notes that while competitive athletes may report feeling pugilistic on anabolic steroids, “this is a highly select group of subjects with a particular psychological makeup.” And the drugs they take are not native testosterone, but usually a synthesized mix of androgens, with who knows what effect coming from each.

So far, there have been no good, controlled studies seeking to evaluate the effect of giving excess testosterone to androgenically normal men. In lieu of such studies are recent experiments comparing the mood states of hypogonadal men before and after treatment, like Dr. Wang’s work.

One missing element of this report, however, is a conventional control group—seeing what happens to men with low testosterone if they are given a dummy medication rather than real testosterone. Do they, too, feel happier and friendlier?

Such an experiment would be unethical, said Dr. Wang, because hypogonadal men who visit the clinic are ill and need treatment to restore muscle and bone mass and healthy cholesterol levels. Denying them testosterone would be like denying a diabetic insulin.

Offering a partial explanation, Bremner and his colleagues reported in the June 1994 issue of The Journal of Clinical and Endocrinological Metabolism their results of seeing what happens to healthy men when they are artificially and temporarily brought to a state of low testosterone.

Some of the subjects were immediately given testosterone replacement, while others received dummy medication.

The study was mainly intended to look at the effects of testosterone on libido, but the researchers noted that the men with a drug-induced state of hypogonadism reported increased levels of aggression.

“Perhaps it made them uncomfortable or unhappy in a variety of ways, and that unhappiness registered itself as a high score on the aggression scale,” Bremner said.

What Bremner’s study and other reports found that does conform to stereotypical notions of the male hormone is that testosterone is profoundly important to a man’s sex drive, though not to his mechanical abilities in bed.

Hypogonadal men report a sharp drop in sexual interest, which testosterone replacement quickly restores. The androgen may also play a role in female sexuality, and a growing number of menopausal women are asking that testosterone be added to their hormone replacement regimen to restore a lackluster libido. But the data linking sex drive and testosterone in women are fiercely debated.

Testosterone therapy also appears to give men and women more energy, vim, the desire to leap out of bed in the morning and embrace the demands of the day with can-do concentration. That zestiness is not the same as aggression, which if anything is often accompanied by poor concentration and underlying malaise, researchers said.

If testosterone qua testosterone is not the demonic potion of legend, its yangian counterpart, estrogen, may not be so innocent.

Reporting last month at the annual meeting of the American Pediatric Society, Dr. Jordan W. Finkelstein, Dr. Howard Kulin and their colleagues at Penn State University said that they compared the effects of giving estrogen therapy to girls who suffered from delayed onset of puberty with that of giving testosterone to boys who likewise were late in sexually maturing.

The girls showed earlier and larger increases in aggression than did the boys, until the boys received the last and highest dose of testosterone.

The researchers propose that for both sexes, the cause of the teen-age spike in aggressive and very likely insolent behavior is estrogen.

As scientists only lately are beginning to appreciate, most of the effect of testosterone on the brain is paradoxically estrogenic in nature.

That is because the brain is rich in the enzyme aromatase, which converts testosterone into estrogen. The newly transformed hormone then acts on the nerve cells of the brain through estrogen receptors, proteins designed specifically to link up with it.

A male’s brain also has some receptors for testosterone, but they are far fewer in number or distribution, and the converting enzyme aromatase does not leave much testosterone around to hook up with these androgen receptors anyway.

Thus, in both boys and girls, as they reach adolescence and their respective sex hormones surge, the influence of either hormone on the brain and behavior probably works its dark art as estrogen.

In the Pennsylvania study, the girls may have had a jump on aggressive behavior over the boys because they were given direct injections of estrogen and therefore their brains did not need to go through the work of converting testosterone to estrogen.

The centrality of the brain’s estrogen receptors to aggressive behavior was highlighted by a new study of receptor-deficient mice, presented at the endocrine meeting.

Dr. Donald W. Pfaff of Rockefeller University in New York, his student, Sonoko Ogawa, and Dr. Kenneth S. Korach of the National Institutes of Health, have analyzed male mice genetically altered so that they lack nearly all estrogen receptors.

Testing the male mice in a variety of circumstances, the researchers determined that they were unusual in many ways. Normal male mice do not tend to wander across open fields as females do, but prefer to skulk along borders; males without estrogen receptors generally took the female attitude, and freely walked where they pleased.

Ordinary males respond to intruders in their territory with violent attacks, chasing, biting and generally seeking to harm the interloper. These males react to newcomers tepidly if at all, perhaps nipping if the animal comes too close, but never attacking the stranger outright.

Significantly, the altered males still have all their androgen receptors intact. It is only the ability of their brain to respond to estrogen that is defective.

The researchers have yet to report on the behavior of female mice lacking estrogen receptors. Those results will probably break a few paradigms of their own.

Until then, perhaps it is time for a new hormonal cliche to explain aggression. How about this: The estrogen was so thick you couldn’t beat it down with a rolling pin. 
 
 
 
 

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