Early synthetic testosterone products were also applied to a variety of female complaints, such as menorrhagia, painful breast conditions, dysmenorrhea and estrogen-driven breast cancers, on the grounds that testosterone neutralized estrogen. For about a century, physicians have recognized that altering the hormonal balance in certain women can cause their metastatic breast tumors to regress. Today it is accepted that about a third of all women with breast cancer have "hormone-dependent" tumors; androgen therapy serves as a second- or third-choice treatment for postmenopausal women with advanced breast cancers. In contrast, the androgen treatments of the 1940s were administered to women of various ages at a time when the mechanism of their antitumor effect was even less well understood than it is now. A clinically valid observation from this period, however, was that androgens could relieve pain, increase appetite and weight and promote a sense of well-being even if they failed to arrest tumor growth.
A consequence of treating women with testosterone was the discovery that androgens could renew or intensify female libido in most patients. One investigator reported in 1939 that the daily application of a testosterone ointment had enlarged the clitoris of a married woman who was then able to achieve orgasm. More commonly, subfascial pellets and injections were used to achieve similar effects, and the massive doses given to some breast cancer patients rarely failed to intensify their sex drive.
The use of testosterone to enhance female sexual response did not, however, become standard therapy. Currently it appears that only a small number of physicians in the U.S., and a greater proportion in Britain and Australia, use androgens for this purpose. As mentioned, testosterone therapy did not catch on in part because of certain side effects. Then, as now, some patients experienced reawakened sexual urges as emotionally disruptive and unwelcome. The most important impediment to a general testosterone therapy, though, was that clinicians wanted an anabolic steroid that would not virilize their female patients, giving them a deeper, husky voice, hair on the face and body, and an enlarged clitoris. Although not all physicians were alarmed by these symptoms, different assessments of them, including whether they might be irreversible, led to heated exchanges in professional journals.
The idea that testosterone could counteract the effects of estrogen led to its use as a therapy for male homosexuals (a goal the transplant surgeons had embraced in the early 1920s). "It is clearly evident that the estrogenic values are higher among the homosexuals," wrote one research team in "Endocrinology" in 1940, concluding that "the constitutional homosexual has different sex hormone chemistry [from] the normal male." In 1944 another group described "a series of clinical trials of organotherapy" involving 11 "overt homosexuals who applied for treatment for various reasons." In one Orwellian turn of phrase, they revealed that four subjects had "accepted organotherapy by compulsion"--a court order in one case and parental injunctions in the other three.
The organotherapy, which was uncontrolled by a placebo group, was a failure. Indeed, given that five subjects complained of increases in their sexual drive, the researchers conceded the likelihood that "the administration of androgen to the active (or aggressive) homosexual would rather regularly intensify his sex drive" instead of reducing it. Yet even this obstacle did not entirely extinguish their furor therapeuticus. "The results in appropriate cases," they wrote, "are too good to permit undue pessimism as to the value of this treatment."
Also during the 1940s, scientists discovered that testosterone could facilitate the growth of muscle tissue. Charles D. Kochakian, a pioneer in synthetic hormone research, reported as early as 1935 that androgens stimulated the protein anabolic processes, offering the possibility that androgen therapy might restore protein tissue and stimulate growth in patients suffering from a spectrum of disorders. The clinical literature of the early 1940s often discussed the correlation between androgens and heightened muscularity, including speculations about the use of these drugs to boost athletic performance. One group of researchers decided in 1941 "to investigate whether the endurance in man for muscular work could be increased by testosterone" and obtained positive results. In 1944 another scientist wondered whether "the reduction of working capacity with age might proceed differently if the sex-hormone concentration could be artificially maintained at a higher level."
The writer Paul de Kruif popularized many of these findings in "The Male Hormone," published in 1945. This widely read book may have helped promote testosterone use among athletes. According to anecdotal reports, West Coast bodybuilders began experimenting with testosterone preparations in the late 1940s and early 1950s. News of the efficacy of these drugs apparently spread during the early 1960s to other strength-intensive sports, from the throwing events of track and field to football.
Over the past 30 years anabolic steroid use has entered other Olympic sports, including hockey, swimming, cycling, skiing, volleyball, wrestling, handball, bobsledding and soccer. Steroid use is well documented among male athletes in college and high school. Of the estimated one million steroid abusers in the U.S., many take these drugs for noncompetitive bodybuilding. Drug-testing programs, designed to suppress steroid use in sports, have been seriously flawed since they were first implemented in the 1970s. These procedures often lack the sensitivity needed to catch drug users, and many elite athletes and corrupt sports officials have learned to avoid detection.
Clinical Uses of Testosterone
Some of the clinical uses of testosterone products date from the earliest period of androgen therapy. The most frequent and accepted application of anabolic steroids has been as a replacement therapy for men with hypogonadism. They have also been administered to treat impotence in patients with normal and below normal serum testosterone levels. Testosterone esters are frequently employed to stimulate growth and to initiate puberty in boys experiencing a significant developmental delay. Since the 1940s androgens have been used to treat wasting conditions associated with chronic debilitating illnesses (such as those suffered by victims of Nazi concentration camps) and trauma (including battle injuries), burns, surgery and radiation therapy.
Because anabolic steroids increase red blood cell production (erythropoiesis), they were the first-choice therapy for a variety of anemias before bone marrow transplantations and synthetic erythropoietin treatments became common. And from the late 1930s to the mid-1980s psychiatrists prescribed anabolic steroids for the treatment of depression, melancholia and involutional psychoses. Testosterone esters are now routinely used as an adjunct to human growth hormone (hGH) therapy for children who are hGH deficient. Most recently some physicians have begun testing anabolic steroids as a treatment for the weakness and muscle wasting that occurs during the progression of HIV infection and AIDS. Clinical case studies are promising and indicate that these patients experience an improved sense of well-being and an increase in strength, lean mass and appetite.
In addition, since the late 1970s testosterone esters have been evaluated as a possible method to regulate male fertility via the endocrine feedback loop. The hypothalamus reacts to high levels of testosterone in the blood by reducing the release of yet another hormone, luteinizing hormone-releasing hormone, which via the pituitary gland affects not only the body's production of testosterone but also of sperm. In 1990 the World Health Organization reported results from a 10-center, global trial that established the efficacy of anabolic steroids as a male contraceptive that produces minimal short-term physical side effects. It is interesting to note that the doses prescribed for these subjects exceeded those taken by the banned Olympic sprinter Ben Johnson. This comparison suggests that legitimizing anabolic steroids as male contraceptives would weaken the medical argument against their routine use by athletes.
During the late 1980s, researchers again began evaluating the effects of testosterone on "successful" aging, motivated in part by a graying society and favorable preliminary results of hGH supplementation in healthy older men. During the early 1990s, several scientists conducted pilot studies of the effects of testosterone supplementation in men over 54 years old who had either low or normal testosterone levels. The results were generally positive, including a gain in lean body mass and strength, a possible decline in bone resorption (with the potential to reverse or improve frailty), an increase in reported sexual desire and activity, and better spatial cognition and word memory.
Because most physicians intuitively accept the efficacy of hormonal replacement therapy in women, they may readily adopt a comparable hormone therapy for men. Implicit cultural acceptance of mass male hormone therapy seems evident in the fact that over the past several years the lay press has broadcast and printed numerous reports on the potential benefits of both testosterone and estrogen therapy for the aging population. The Hormonal Healthcare Center in London administers testosterone injections to hundreds of men irrespective of age, and a gynecologist at Chelsea and Westminster Hospital in London currently prescribes testosterone pellets for about 25 percent of his postmenopausal patients. This trend is likely to continue, meaning that mass testosterone therapy could become standard medical practice within a decade.
This prediction is based on the fact that popular expectations and commercial motives can help define new medical "disorders." In 1992, for example, the National Institutes of Health requested proposals for research on whether testosterone therapy can prevent physical ailments and depression in older males, thereby raising the question of whether the aging process itself is about to be officially recognized as a treatable deficiency disease. John B. McKinlay, director of the New England Research Institute in Watertown, Mass., and a specialist on aging, has offered the following prognosis: "I don't believe in the male midlife crisis. But even though in my perspective there is no epidemiological, physiological or clinical evidence for such a syndrome, I think by the year 2000 the syndrome will exist. There is a very strong interest in treating aging men for profit, just as there is for menopausal women."
Commercial interest in response to the public's demand for androgens could cause physicians to overlook possible deleterious side effects and overestimate their clinical value. For example, in the January 1994 issue of the "Journal of Urology," McKinlay and his colleagues stated that there was no correlation between any form of testosterone and impotence, a "major health concern" affecting a potential market of 18 million men for whom testosterone has long been prescribed on a much smaller scale. But failing to confirm the value of testosterone for one disorder is unlikely to deter its use to strengthen aging bodies or restore a waning interest in sex. Indeed, aging is increasingly being viewed as a medical problem, and this shift is leading to the recognition of a "male menopause" as treatable as its female counterpart. The official status of such a syndrome will signify new societal definitions of physiological normality and further legitimize ambitions to boost the human organism to higher levels of mental and physical performance.
BOX: Anabolic-Androgenic Steroids
The anabolic-androgenic steroids are all synthetic derivatives of testosterone, the natural male hormone produced primarily by the testes. Women also produce testosterone, but in lower amounts than do men. The hormone is responsible for the androgenic, or masculinizing, and anabolic, or tissue-building, effects noted during male adolescence and adulthood. The main androgenic effects in males include the growth of the reproductive tract and the development of secondary sexual characteristics. In the pubertal male the latter is charted by increases in the length and diameter of the penis, development of the prostate and scrotum, and the appearance of the pubic, axillary and facial hair.
The anabolic effects are those that take place in the somatic and nonreproductive tract tissue, including thickening of the vocal cords, an acceleration of linear growth appearing before bony epiphyseal closure, enlargement of the larynx and development of libido and sexual potentia. An increase in muscle bulk and strength as well as a decrease in body fat also occurs.
JOHN M. HOBERMAN and CHARLES E. YESALIS share an interest in the history of performance-enhancing drugs. Hoberman, a professor of Germanic languages at the University of Texas at Austin, has written often about the history of sports medicine and high-performance athletics. Yesalis is professor of health policy and administration and exercise and sports science at Pennsylvania State University. He studies the nonmedical uses of anabolic-androgenic steroids and other muscle-building drugs