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Testosterone Dreams

Pharmacology and Our Human Future

Testosterone Dreams is an investigation of modern attitudes toward enhancing the mental, physical, and sexual powers of human beings. The chapters that follow explore the theory and practice of human enhancement by focusing on the complex, and sometimes bizarre, history of the synthetic hormone testosterone and the careers it has made, both inside and outside the medical world, over the past sixty years. Testosterone is the hormone of choice for this purpose because it has played all the major roles in which a charismatic hormone can function: it has been regarded as a rejuvenating drug, as a sexually stimulating drug, and as a doping drug that builds muscle and boosts athletic performance. The first chapter of this book presents a history of testosterone therapy and the primitive "organotherapy" that preceded it. Of particular interest here is the medical and social status of synthetic testosterone and its derivatives, the anabolic-androgenic steroids. Why has testosterone acquired a special, even fashionable, cachet as a particularly dynamic hormone? When have testosterone drugs been viewed as harmful or benign? Why is testosterone finally prevailing despite the law that regulates its use? What has the pharmaceutical industry done to create a market for testosterone products? The second chapter describes early testosterone therapies for "frigid" women and homosexuals and explains why the drug companies failed to create a mass market for testosterone products after the Second World War. Chapter 3 and 4 show how the commercial promotion of testosterone drugs has overcome these obstacles and is now mainstreaming testosterone therapy as a socially acceptable enhancement. Chapters 5 through 7 examine the role of testosterone drugs in the world of Olympic sport and the doping epidemic they have unleashed over the past forty years. We shall examine the world of high-performance athletics as a kind of parallel universe in which pharmacological performance enhancement has become a way of life for entire groups of athletes. In this subculture of drug-taking athletes we find the doctor-patient relationships that have long served as models for the hormone entrepreneurs who now offer to enhance the mental, physical, and sexual athleticism of their patients.

Testosterone dreams are the fantasies of hormonal rejuvenation, sexual excitement, and supernormal human performance that have been inspired by testosterone since it was first synthesized in 1935. This scientific achievement was driven by a competition among three teams of researchers sponsored by rival pharmaceutical companies, all dreaming of a male hormone market that would produce profits like those of the already-established market for female hormones.1 During the years that followed, a steady stream of medical observations pointed to exciting prospects for the "androgenic" drugs derived from testosterone. An association between testosterone treatment and muscular enlargement in male mammals was proposed in 1938.2 "Androgens exert a tonic and stimulating action, associated perhaps with their metabolic effects," the Journal of the American Medical Association stated in 1942.3 Scientists were already distinguishing between testosterone's effects on "sexual function" and "mental and physical vigor," between its capacities to produce "sexual stimulation" and "constitutional rehabilitation."4 Over the next several decades, the growing use of testosterone and its derivatives, the anabolic-androgenic steroids, would demonstrate that many people were interested in using testosterone products for a variety of purposes.

The first public advocate of testosterone therapy for aging men was the popular science journalist Paul de Kruif, whose manifesto The Male Hormone was published with some fanfare in 1945. Excerpted in Reader's Digest and promoted by a full-page review in Newsweek ("Hormones for He Men"), The Male Hormone was in some respects a prophetic book.5 "The male hormone," de Kruif declared, "is now ready for the trial of its possible power to extend the prime life of men."6 Commending his "courageous honesty," one reviewer declared that de Kruif had brought out into the open "the questions raised by the laboratory synthesis and the now unlimited production of testosterone, the male hormone."7

The excitement about testosterone's medical and commercial prospects was shared by some of the major pharmaceutical companies of this era. "Of all the sex hormones," Business Week reported in December 1945, "testosterone is said to have the greatest market potentialities." Two companies, Schering and Glidden, had been fighting it out in court for the right to manufacture synthetic sex hormones.8 By 1937 testosterone propionate was being produced in sufficient quantities for use in clinical trials.9 By 1938 the production of testosterone had already resulted in antitrust proceedings and controversy in the pharmaceutical industry.10 The manufacture of testosterone, de Kruif predicted in 1945, "will make its producers wealthy."11

De Kruif declared that a growing demand for testosterone would "soon bring it within reach of everybody." The availability of methyl testosterone in pill form convinced him that a practical way to administer the drug had finally been found. The potential clientele seemed to be enormous: "How many millions of American males, not the men they used to be, would flock to the physicians and the druggist, a bit shame-faced and surreptitious, maybe, but hopeful, murmuring: 'Doc, how about some of this new male hormone? Physicians, too, seemed to be ready for a breakthrough in treatments. Despite the warnings issued by the American Medical Association, "many physicians, and more of them all the time, were trying out testosterone on this, that, and almost every disease of the middle and later years of the lives of men."12 So it appeared that an inexpensive supply, a healthy demand, and favorable medical opinion would soon add up to a viable market for androgen drugs.

Testosterone became a charismatic drug because it promised sexual stimulation and renewed energy for individuals and greater productivity for modern society. Physicians described the optimal effect of testosterone as a feeling of "well-being," a term that has been used many times over the past half century to characterize its positive effect on mood.13 In the early 1940s testosterone was hailed as a mood-altering drug whose primary purpose was the sexual restoration and reenergizing of aging males. The sheer numbers of these potential patients suggested that they would eventually constitute a lucrative market. This idea was still in the air a decade after The Male Hormone was published. "The present results with steroid therapy in geriatrics are astonishing," one gerontologist wrote in 1954. "Their future possibilities stagger the imagination."14 Interest in testosterone was strong enough to prompt the American Medical Association to advise that "these substances ought to be kept out of vitamin pills."15

The idea that testosterone was a performance-enhancing drug that could boost the productivity of socially significant people appeared in 1939, along with the idea of the male menopause. Testosterone replacement therapy would help older men in important positions fulfill their "social and economic responsibilities."16 Paul de Kruif offered his readers a similar vision of drug-induced productivity that made a prophetic connection between elite athletes and their civilian counterparts. "We know how both the St. Louis Cardinals and St. Louis Browns have won championships, super-charged by vitamins," he observes. "It would be interesting to watch the productive power of an industry or a professional group that would try a systematic supercharge with testosterone[.]"17 Within a generation, sports audiences around the world were enjoying record-breaking performances achieved by athletes whose "productive power" was boosted by testosterone-based anabolic steroids. The "doping" of athletes with androgens and other hormones can thus be understood as one of the human enhancements that will precipitate an unprecedented crisis of human identity during the twenty-first century.

As more drugs are finding new and often unexpected uses, the distinction between illegitimate doping and socially acceptable forms of drug-assisted productivity is gradually disappearing. One consequence of this vanishing boundary is that the de facto legitimizing of a drug can also create an implicit or even explicit obligation to use it for purposes society or certain subcultures define as desirable. Compulsory doping of this kind has been observed in certain athletic subcultures for many years. Shot-putters, weightlifters, and professional cyclists are among the most obvious examples of athletes whose communities have legitimated (and effectively mandated) the consumption of illicit drugs for the purpose of staging more "productive" competitions. The former East German elite sports program practiced compulsory dopingñand Olympic medal productionñon a unique scale. My point is that modern societies have embarked on various kinds of pharmacological practices that exemplify what we may call compulsory or obligatory doping.

People can feel obligated to dope themselves for military, professional, or sexual purposes. The amphetamine drugs once known as "pep pills," for example, found widespread military use during the Second World War. In March 1944, the air surgeon of the United States Air Force explained to the American public that despite the "disgrace" into which Benzedrine had fallen on account of its widespread abuse by civilians, it played an essential wartime role in keeping military pilots alert while they were in action.18 Amphetamines were subsequently provided to pilots in the Vietnam and Gulf wars. After two U.S. Air Force pilots killed four Canadian soldiers in a "friendly-fire" incident in Afghanistan in April 2002, their lawyers argued that these men had felt compelled to take Dexedrine pills that could have affected their behavior on that fateful night.19 Although air force officials deny that they require pilots to take these drugs, the consent form presented to their aviators suggests otherwise.20

It is not surprising that military officials are unwilling to endorse the doping of their personnel openly and unambiguously. "The aviation community and the air force community certainly don't like to talk about so-called 'performance enhancing' drugs," one defense policy expert pointed out during the Afghanistan inquiry.21 The blanket stigmatizing of drugs by governmental authorities forces those responsible for producing even legitimate drug-dependent performances to cover up or apologize for their pharmacological policies. In this sense, the U.S. Air Force policy that issues amphetamines to pilots and authorizes them to "self-regulate" their drug use bears a striking resemblance to the tacit drug policy followed for many years by the professional cyclists who ride in the Tour de France.22

The same predicament has confronted Australian authorities, who in 1998 discovered that large numbers of soldiers in one of their elite units were using doping drugs. They responded by legitimizing these drugs and issuing guidelines for their use, on the grounds that any technique that promoted the survival of their fighting men was acceptable.23 In 2002 the Australian Defence Force's director of personnel operations expressed concern about an "apparent increase in illegal drug use, particularly steroid abuse" among soldiers. The Sydney Morning Herald reported that these military personnel were "using steroids to bulk up, boost stamina and self-esteem and to recover more quickly from injuries they have sustained." This ostensibly rational use of steroids could lead to a compulsory doping subculture if left unchecked. The director of personnel operations thus felt obliged to declare that steroid doping would subvert rather than enhance a soldier's fitness: "Drug involvement leads to reduced performance, health impairment, presents a security risk and has the potential to endanger the safety of our soldiers."24 As in the case of amphetamine-consuming pilots, a military establishment found itself caught between the potential utility of performance-enhancing drugs and a social stigma that threatened to become a public relations problem. The solution was to declare that any performance enhancement from these drugs came at too high a price in undesirable side effects. The problem with this argument, as we shall see, is that it offers no justification against performance-enhancing drugs that do not have side effects.

Compulsory doping in the workplace is a real possibility in a culture that promotes productivity and accepts pharmacological solutions to human problems. "How might a substance like Prozac enter into the competitive world of American business?" Peter D. Kramer asked in Listening to Prozac.25 As in the world of high-performance sport, it can be a short step from posing such questions to implementing performance-enhancing solutions that exert pressure on every performer. Some years later another psychiatrist answered Kramer's question by pointing out that SSRI (selective serotonin reuptake inhibitor) antidepressants like Prozac had become "all-purpose psychoanalgesics" for competitive situations. "People think they've got to keep up with the Joneses, pharmacologicallyñif everyone at your office is taking Zoloft to stay alert and work long hours, you've got to have it, too."26 This is the predicament Kramer had already anticipated in his best-selling book. The same dynamic has promoted the use of antidepressants and other psychiatric medications among American studentsña trend that some find troubling. "We work against having medication used in the Olympics," says the director of psychological services at one American college, so why should drug-taking be allowed to "increase performance in school?"27 This flagrant discrepancy between the treatment of athletic and academic performances amounts to an unresolved cultural crisis to which we shall return later in this book.

Such scenarios show how hard it can be to determine where therapy ends and performance enhancement begins. This uncertainty about the boundary between healing and enhancement changes our sense of what is "normal" and what is not. If I become fatigued while my drug-taking coworkers stay alert, their "supernormal" stamina may well recalibrate the very idea of normal functioning. Their greater productivity might eventually legitimize their doping habit and make it compulsory for everyone. In this work environment, it is the drug-free worker who is in a state of deficiency. The ultimate drug of this kind, currently being marketed as Provigil, can apparently keep people awake and alert for days. Small wonder it "is showing signs of becoming a lifestyle drug for a sleep-deprived 24/7 society" that demands round-the-clock performance from employees.28 "Even as sleep disorders increase," Jerome Groopman notes, "firms are pushing their employees to disrupt their normal sleep patterns in order to provide services around the clock."29 In the meantime, the company that manufactures Provigil is asking the Food and Drug Administration for permission to expand its uses to make it a billion-dollar drug.

The logic of obligatory self-medication has shaped the use of female hormone replacement therapy (HRT) for decades. The declared purposes of estrogen replacement were to enhance both the labor productivity and the sexual appeal of aging women. More than half a century ago the American Medical Association recommended estrogen replacement for all menopausal female workers during the Second World War to promote efficiency: "The employee may because of her emotional instability become irritable and thus lessen production," one concerned commentator warned.30 After the war, as we shall see, many physicians promoted estrogen replacement therapy (ERT) with great success as an anti-aging therapy that could provide husbands with more satisfying sexual partners and thereby save endangered marriages. The biochemistry of sexual pleasure could thus enhance social stability.

Today's version of hormone-enhanced well-being for older women is based on demands for productivity, disease prevention, and sexual fulfillment. It is important to recognize that these calls can come from institutions as well as from individuals. For example, the demand for emotionally stable female production-line workers in the 1940s eventually became a demand for emotionally stable female executives. In the 1960s the estrogen-promoting physician Robert Wilson warned: "With more and more women entrusted with decision-making posts in business, government, and in various institutions, the effects of menopause present a new type of management problem that has yet to be fully understood by the experts of corporate administration." According to Sonia McKinlay, an expert on menopause, "letting it be known that you're on HRT may become a requirement for women in upper levels of management and government to prove that they're 'in control' of possible symptoms and not declining. Margaret Thatcher made it known that she was a user" to legitimize her power in the eyes of her male colleagues.31

Hormone replacement can also be presented as a cost-saving public health program:

Hormonal replacement therapy . . . is now promoted on a large scale for preventing osteoporosis and cardiovascular diseases. If a consensus is reached in biomedical science that menopause is a deficiency disease, this will have important implications for physicians and women alike. If the physician wants to act according to good medical practice, the prescription of hormonal replacement therapy is not only legitimated, but will be imperative. On the other hand, it is conceivable that the woman suffering from one of the aforementioned diseases, and who declines to take hormonal therapy, will be held responsible for her condition. . . .

Presenting hormonal replacement therapy in economic terms is likely to turn it into a political issue. In the worst of all scenarios, one can imagine that social security will penalize women for diseases or invalidity allegedly due to hormone deprivation.32

Hormone therapy to promote sexual desire in older women can include the administration of testosterone as well as estrogen. This procedure is increasingly popular, in part because of the greater sexual demands of older men who are now taking Viagra. "Patients come in and they look you straight in the eye and say, 'I have no libido, something's wrong, fix it, says Dr. Mary Lake Polan, head of the department of obstetrics and gynecology at Stanford University School of Medicine. "Five years ago, nobody ever came in and said that. And I can't believe there has been a change in the way people relate to each other in that period of time."33 This surge in demand for aphrodisia is symptomatic of a growing medicalization of modern life that appears to create opportunities for deepening human experience. Yet a medical technique that restores sexual activity can also be experienced as a mandate to be sexually active even in the absence of desire. Constant exposure to modern society's sexual propaganda means that "many people will feel 'inadequate' when faced with evidence about extremes of sexual performance."34 Drug-induced sexual fitness and the concept of "performance" can turn sexual relations into an intimate competitive sport judged by quantitative norms. Thus "lifestyle" medicine appears to offer a choice as to "whether to grow old or not" as a professionally or sexually active person.35 In either case, whether the decision is to become more productive or to become more erotic, the availability of the hormone can create a social pressure to use it.

Why testosterone did not become a mass-market drug in the 1940s is a major theme of this book. The most important factor was the sexual conservatism of most physicians and the society they served. The belief that testosterone was a sexually stimulating drug made it a potential threat to sexual morality as well as a promising therapy. Sensational coverage had given the male hormone a quasi-pornographic image that its female counterpart had never acquired.36 Commenting on testosterone's unsavory reputation in 1946, Science Digest reported that "the uninformed continue to believe that the sole use of this innocent chemical is to turn sexual weaklings into wolves, and octogenarians into sexual athletes."37

The pharmaceutical companies that sought to shape medical opinion by placing advertisements in professional journals were not yet allowed to go directly to the public and solicit customers for prescription drugs over the heads of their physicians. What is more, the aging men of the 1940s directed their requests for testosterone to male physicians who often had little interest in salvaging the sex lives of middle-aged or older people. The campaign to sexually rejuvenate senior citizens was not possible until a momentous social transformation of attitudes toward erotic experience had taken place. During the second half of the twentieth century the Kinsey Reports on human sexuality, together with the sexual freedom made possible by the birth control pill, dismantled the old cultural restraints that had prevented sexual expression from becoming an entitlement for the adult population.

This book tells the story of testosterone's gradual liberation from the restraints that have limited its use over the past sixty-five years. The transformation of testosterone's roles inside and outside of medicine has taken place both in the larger social sphere, where ideas about health and sexual mores shape human desires and behaviors, and within the smaller world of clinical medicine that evaluates and promotes therapeutic drugs. In the larger world the use of testosterone was once inhibited by a social conservatism that kept most doctors uninterested in the sexual problems of older people. In addition, the idea that testosterone might serve as a "tonic" for the general population has for many years made little headway against the belief that people with normal hormone levels cannot benefit from supraphysiologic doses of the drug.38 "The prevailing experience," the American Medical Association reported in 1941, "is that endocrine preparations almost invariably fail when they are given to otherwise normal individuals" for the purpose of stimulating sexual desire.39 The same principle applied when testosterone was administered to stimulate premature babies or estrogen was given to women to increase the size of their breasts.40 The marketing of testosterone and estrogen thus required the concept of a hormone deficiency that could be normalized by means of synthetic hormone products.41 Only such a deficiency legitimized hormone therapy.

Today it is the aging process that provides the deficiency that justifies hormone therapies that can include testosterone, human growth hormone, or both.42 The dramatic increase in the use of testosterone products is now a matter of record, even if medical authors are unable to determine how much of this trade outside doctors' control, occurs on the black market.43 The medical publications that once decried hormone quackery now serve as a forum for a cautious but unmistakable legitimizing of hormone therapy to treat the process that has become known as the male menopause or andropause. "Improvement of clinical symptoms of andropause via androgen substitution therapy has long been recognized," one team of medical researchers noted in 2002. The list of symptomsñdiminished energy, virility, fertility and a decrease in bone and muscle massñshows how easy it is to conflate declining hormone levels and the aging process itself.44 Clinical guidelines for the diagnosing of low male testosterone levels (hypogonadism), published with pharmaceutical industry support in 1996, point to "symptoms that are often denied by the patient and ignored by the physician. . . . In aging men, these symptoms and signs may be difficult to appreciate because they are often attributed to 'getting older.45 This intriguing observation suggests that hormone therapy can make getting older a symptom-free experience, and it is this illusion that does much to sustain the "anti-aging" hormone market. The frequent use of terms such as quality of life and psychological well-being to describe the effects of hormone therapies employing testosterone, the adrenal hormone DHEA (dehydroepiandrosterone), or the "prohormone" androstenedione makes it clear that their purpose is life enhancement as well as therapy in the traditional sense.

Testosterone therapy is also being presented as less hazardous that it was once assumed to be. Even as "designer androgens," which would have minimal effects on the prostate and on cholesterol levels, are being developed,46 the long-standing medical concern that exogenous testosterone stimulates the growth of existing prostate cancers has been called into question.47 A 1996 study that administered supraphysiologic doses of testosterone to normal men for ten weeks detected no unhealthy side effects. The report concludes, however, with the standard warning about the possible consequences of extended use that has appeared in many such reports over the past decade.48

This ongoing conflict between cautionary statements and cautious optimism about hormone therapy has created an opening for medical practices that inhabit the gray zone between scientifically based medicine and quackery. The medical literature on the promises and hazards of testosterone and human growth hormone therapy has created a disorienting situation that is easily exploited by entrepreneurial physicians who have chosen not to wait for long-term clinical trials of these hormone therapies. The stunning discovery in 2002 that the overall risks of ERT outweighed its benefits demonstrated that even decades of studies endorsing the value of a hormone treatment can be wrong. As the principal investigator of the dissenting federal study notes: "They linked up a very beneficial product for treating menopausal symptoms to the answer for treating all of a woman's aging problems," and it was the powerful appeal of a way to solve these problems that prevailed over scientific caution.49 According to the same study, hormone therapy for menopause did not even improve "quality of life" measures such as sexual enjoyment.50 Here massive anecdotal evidence of lifestyle benefits collided with the best available clinical data, leaving doctors wondering where the HRT boom had come from in the first place. Testosterone, too, has benefited from a massive anecdotal endorsement of its effects and may well prove to be vulnerable to the same kind of scrutiny that has undone the reputation of HRT for women.

Finally, access to testosterone is facilitated by the various tricks and maneuvers that patients and doctors can use to circumvent the Anabolic Steroids Control Act of 1990, which places limits on a physician's ability to prescribe anabolic steroids for patients who might need them.51 Testosterone magazine offers advice on how to find and manipulate "open-minded" doctors by inventing symptoms or producing them by means of dieting and sleep deprivation.52 A far more significant work-around is the legal prescription of these drugs for "off-label" uses, defined as "treatment indications with little or no proven efficacy" that also lack package insert information approved by the FDA.53 Even though this federal agency's approval of a drug is limited to the treatment of a specific disease, doctors are free to prescribe drugs for other usesñincluding anti-aging therapies.54 This is how every blockbuster drug, from Prozac to Provigil, becomes a marketing phenomenon. This is why "the vast majority of psychotropic medications prescribed for preschoolers are being used off-label."55 The use of human growth hormone (HGH) has spread in a similar fashion, since "estimates suggest that one third of prescriptions for growth hormone in the United States are for indications for which it is not approved by the Food and Drug Administration."56 Prescribing these drugs to patients who have off-label disorders amounts to conducting large-scale experiments on human subjects under the rubric of therapy. The male hormone, too, has inspired many such experiments. Testosterone Dreams can thus be read as the story of how synthetic testosterone is becoming a major off-label drug.