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Two on One: AndroGel

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Two on One    

Hormones and He-Men

by Deborah Blum and Anne Fausto-Sterling

 

THE SETUP: This month, an artificial hormone treatment called AndroGel hits the market. A gel that delivers a steady dosage of testosterone into the body, developed for men who cannot naturally produce enough of the hormone on their own, AndroGel has sparked considerable public debate regarding the potential effects — and ethical implications — of such treatments and whether or not it might actually influence the behavior of the men who take it. Some have wondered whether, by simply taking AndroGel, a man can boost his masculinity, including his sex drive and virility. But, as Deborah Blum and Anne Faust-Sterling explain, the science of the male sex drive isn’t quite so simple: what makes a man is actually surprisingly variable.


THE PLAYERS: Deborah Blum is a Pulitzer Prize-winning science journalist and author of, most recently, Sex on the Brain: The Biological Differences Between Men and Women. Anne Fausto-Sterling is Professor of Biology and Women’s Studies at Brown University. Her book Sexing the Body: Gender Politics and the Construction of Sexuality was published in February.



FAUSTO-STERLING: Ever since the big T made the cover of Time, I’ve been thinking about how nice it would be if more people knew a little history. The fact is that drug companies have been trying to market hormone preparations since 1889, when a French physiologist named Charles-Edouard Brown Sequard injected himself with some ground-up guinea pig and dog testicles and told the Biology Society of Paris that he felt younger and more virile. A few years later, and only after the market had been glutted with glandular potions of uncertain provenance, he admitted that it was probably just the excitement of the moment that had made him feel better. The ensuing skepticism set back serious hormone research for three decades.


     

In the 1930s, when crystalline steroid hormones became available and scientists unravelled their chemical structures, pharmaceutical companies flooded the market with dozens of potions–ovary extracts for the girls and testicular gumbos for the boys. My favorite account of this craze is The Male Hormone, by science writer Paul de Kruif (on whose classic Microbe Hunters I sharpened my proto-scientist teeth). He announced to the world that he was taking testosterone to restore his manliness — why, he had even cried in his boss’s office! But he was sure testosterone would prevent any more such indiscretions. After all, he said, “it’s borrowed manhood,” but “it’s what makes bulls bulls.” So you can imagine my general skepticism about AndroGel. Most likely it will be an important medicine for men with very low hormone levels, but an antidote for the loss of manliness in an age of liberated women? Hardly!



BLUM: I always liked the 1920s version of boosting hormone power, an experiment in which they grafted monkey testes onto aging men. The raw male power of the jungle! The scientists reported that they had to turn away volunteers. I spent some serious time wondering about those who were accepted. What did those sewn-on monkey testes look like, or, for that matter, smell like after a week or so?


     

But this was before the actual isolation of testosterone, as were the French experiment and the assorted glandular stews of the 1930s you cite. It took awhile to actually isolate and identify testosterone (which won Adolf Butenandt and Leopold Ruzicka the 1939 Nobel Prize) and although, as I recall, medical journals of the time were pretty excited by this discovery of “sexual dynamite,” it’s taken an equally lengthy period to have medically valid versions of testosterone out there.


     

The goofiness of such scientific history and the theatrical efforts of pharmaceutical companies aside, I’m not sure we can just dismiss AndroGel as a matter of over-promotion. It’s an experiment in the making. After all, in recent decades, there’s been some very interesting — and sometimes very good — science linking testosterone to muscle growth, energy, sex drive and a range of behaviors like competiveness.



FAUSTO-STERLING: I don’t want to dismiss AndroGel as just over-promotion, but there is a great deal of hype going on here — to say nothing of a reshaping of contemporary ideas about masculinity. I agree, testosterone is a very potent growth hormone, and its availability in the gel form is a genuine medical advance, since it can now be administered painlessly (though wouldn’t “real” men get off on braving the needles?) and without the fluctuating dosage of repeated injections. Medically, AndroGel is appropriate for men whose testosterone levels fall below the very broad range of normal levels. For these men, testosterone certainly does improve energy, sex drive and muscle development (I think the data on competitiveness is far less clear).


     

But what about men who want to use AndroGel who already have enough T? Or maybe there can never be enough? My trainer is always pointing out to me the guys in the gym who “help” their muscles along with extra chemicals. How long will it be before their livers start to crumble? If any of the men want to have children, I’d suggest they start monitoring their declining sperm counts. It used to be that paternity was the mark of virility. Now, apparently, bulging muscles mark the man. Is this because women can — to a great extent — control baby production?



BLUM: You mean, instead of producing large crops of children, men are now growing large crops of muscles to signal their studliness? It’s a fascinating idea.


     

Your comments remind me of that long-time biologist’s description of high-testosterone males — the “live fast and die” model. This wasn’t meant to describe humans but hormone-loaded young males in other species who tended to hurtle off into battles with other males at the first whisper of a spring mating season. If they survived the injuries, they often didn’t live that long anyway because — as you point out — testosterone turns out to be great for building muscles but not so great for general health. It’s a notable immune suppressant. We may actually agree here that, except for those who are clinically lacking, testosterone therapy is a risky business.


     

However, I don’t see that our recent fascination with testosterone is merely about men grasping onto a remaining shred of masculine territory. It’s also part of a larger backlash against decades of insistence that biology had nothing to do with behavior. Though biology doesn’t completely determine one’s behavior, it does influence it. There’s validity to Andrew Sullivan’s point in The New York Times Magazine (much as I have infuriated my friends by saying it) that if men have ten times more testosterone circulating than women, on the average, then you really would expect to see some differences in behavior. There are reasons why the brain has receptors for testosterone and other hormones and neurotransmitters.



FAUSTO-STERLING: But that is too static a picture. Receptors turn over: old ones are lost; new ones are made. This happen in response to behavior. Consider the following: male mice that have no contact with pups will not display paternal behavior toward them. But a few hours a day spent in the presence of pups induces a paternal protective response. Their improved fathering correlates with an increase in estrogen receptors in one part of the brain and a decrease in another one. (Most of the time, testosterone does not directly change cells; whether naturally produced or introduced through artifical means like AndroGel, it is first converted into estrogen by a special set of enzymes, taking effect when it becomes attached to receptors in muscle, bone, brain and other tissues throughout the body. What differs between men and women, in addition to the circulating levels of hormones, are the number, types and tissue locations of estrogen and testosterone receptors.) It seems plausible that parenting experience induced receptor changes in the brain, and that these in turn fed into the improved parenting response. There are lots of examples like this in the animal literature. My point is that organisms are not separable from their environments. A good theory of human development and behavior must always account for both biology and environment at once.


     

Also, any good theory must acknowledge individual variability. An article in the February 2000 issue of the Archives of General Psychiatry reported on a study on the effects of testosterone on mood and aggression in normal men, which found that a 600mg weekly dosage increased manic symptoms in these men — on average. But there was little uniformity in the response. Some men had very strong responses to the additional T while “most” showed little psychological change. Clearly, individual variability is more important than a statistical effect on a large group.



BLUM: No argument there — when I first started researching biology of behavior, I went to the wonderful Institute for Behavioral Genetics in Boulder, Colorado, and they basically sat me down in a chair and declared that “individual variability” came before all other factors.


     

Furthermore, I’m as irritated as you are by biological determinism, and recent research on testosterone illuminates your other point about the interaction between genetics and environment, between the primordial soup and the squishy, flexible, adaptable creatures swimming around in it.


     

Granted, the human studies don’t always look consistent, but an early 1970s study at Emory University on the alpha male monkey — the biggest, toughest bully atop the hierarchical hill — illustrated this point.


     

Scientists had long known that the alpha male was the highest in testosterone, and assumed a causal effect — that it was his high-T levels that pushed him to the top, made him the most aggressive and competitive. But when they started manipulating Mr. Alpha’s life, they realized they were wrong. The alpha primate’s testosterone stayed high as long as he was in dominant position, but when he was removed and put in a group of unfriendly females (and monkey females can be very tough), his testosterone levels plummeted. He had the hormone profile of a submissive monkey.


     

That’s a remarkably consistent pattern, across other species and across the whole accumulation of human data — that the hormone responds to the event. In other words, biology responds to who and where and what we are on a daily, an hourly, a split-second basis. Yes, men have a higher baseline of testosterone and, yes, that may influence behavior in ways that we are still determining. But, to me, that’s not nearly as fascinating or important as the other lesson we’ve learned: that we are never nailed in place by biology, and that we may even have some conscious control, if we sort it out, over some of those neurotransmitters and hormones. And that’s why, as I say in Sex on the Brain, I’m a member of the testosterone fan club.



FAUSTO-STERLING: Now we really are agreeing, not about the testosterone hoopla, but about what one really learns by studying testosterone, or any other hormone for that matter. The studies showing the susceptibility of T levels to social situations, as you point out, are not new and they are are certainly well-known among hormone biologists. They support my contention that understanding the body can best be done by studying the body-in-social-context. But as a scientist who deeply loves biology and who revels in the subtleties of organismal function, the abysmal science behind hormonal determinism — as in articles like Andrew Sullivan’s, which purport to present the scientific truth (writ large) about our bodies — is what truly drives me crazy.



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©2000

Deborah Blum and