History of the Development of Anabolic Androgenic Steroids

  

Few people know of the current state of anabolic androgenic steroids (AAS); it may be rarer still to find someone with knowledge of the history of anabolic steroids. Sadly, the best texts on the subject directly from the pioneers are difficult to locate as they have been out of print for decades, such as Charles Kochakian’s Anabolic Actions of Steroids and Remembrances.¹ One exception is the recent text Testosterone Dreams: Rejuvenation, Aphrodisia, Doping by John Hoberman, which is excellent.² However, policymakers and their clinical gatekeepers (physicians) do not generally take time to read much outside of their specialties, do not refer to popular media, and rely heavily on reviews and research in academic texts.

Considering the conflict that arises between recreational anabolic steroid users and the regulatory agents of medical professionals and legislative policymakers, it should be of interest to learn the history of the development of AAS as it is presented to health care providers and elected officials. A recent review was published in Pediatric Clinics of North America.³ Each issue of Pediatric Clinics of North America is devoted to a single topic, magnifying the impact of each article. This review is interesting in that it focuses on the relatively primitive techniques used to identify a ‘male factor’ and then isolate the responsible molecule.

The review also touches on the pioneering efforts (some misguided, others seemingly barbaric) in applying the male factor and later testosterone to provide restorative therapy to men. It should be of no surprise to anyone that the desired endpoint for many patients was to restore or enhance male sexual prowess. Despite any measurable advance in civilized endeavors over the last 6,000 years, enhancing male sexual prowess remains a driving influence, as demonstrated by the sales of Viagra and related drugs, as well as the comments made on the effect of certain other drugs, such as Melanotan II.^4,5

Recreational and competitive sports did not hold the position in society that they do now, and the display of one’s body was considered vulgar and vain until the relatively puritanical era of the early- to mid-20th century passed. Thus, there was relatively little mention of sports performance enhancement until the 1950s. Of course, physique development and performance enhancement are now considered to be the dominant purposes for the use of testosterone and related anabolic steroids (AAS). However, when questioned in a large survey, most users admitted that attracting potential sexual partners remains the primary reason for steroid use (by improving one’s physique or social status through athletic performance).⁶ The more things change, the more they stay the same.

Myriad Effects of Androgens

The review, authored by Drs. Dotson and Brown, of Columbus Children’s Hospital and The Ohio State University respectively, begins by discussing [some of] the myriad effects of endogenous (natural) androgens— anabolic (tissue-building) and androgenic (masculinizing).³ It is interesting that they label vocal cord-thickening and laryngeal (voice box) enlargement as anabolic, when many consider those to be masculinizing effects.

The history of the pursuit of AAS is acknowledged to have begun over 6,000 years ago as farmers and herders castrated animals to make them easier to domesticate.³ Many married men might jokingly identify with this in a figurative sense, as demonstrated in the comedy routine of the late Sam Kinison: “You’re married now, I guess you won’t be needing this.”

The earliest surviving recorded curatives for impotence or libido problems date back to the Yellow Emperor’s (Huang Ti) Dynasty of China from approximately 2600 B.C. Later, but still ancient cures from the eighth century B.C. are described in writings from India and the Middle East, the ‘cradle of civilization.’ Moving along the timeline, it is revealed that the Egyptians (1600 B.C.), India (eighth century B.C.) and Romans would prepare elixirs and potions, consuming testicles and animal penises to obtain mystical ‘powers.’⁷ Those with a liberal arts education might immediately wonder what psychoanalyst Sigmund Freud would think of such behavior. Interestingly, Freud appears later in the history of AAS.

It was the Greeks who introduced the idea of using the sexual organs of animals or phallus-shaped plants for performance enhancement in sports, at least in Western cultures. Of course, prior to the era of Greek culture, sports took place in gladiatorial arenas where enhancement usually involved heavier armor or more lethal weapons. It is amazing how the Greeks and Romans are revered for their architectural and philosophical advances, but no mention is ever made of their forage into performance enhancement.

The review leaps forward to the late 1700s, a revolutionary time in more ways than one. Scottish surgeon John Hunter was the Royal Surgeon to King George III and a distinguished scholar. He was a strong advocate of observation and experimentation. Some of his rumored behavior is indisputably odd by today’s standards— self-inoculating himself with venereal disease to study the progress of the disease, and displaying the skeleton of a man who suffered from gigantism against his deathbed wishes, after acquiring the remains through bribery.⁸

Hunter is believed by many to be the Scottish equivalent to da Vinci, and one of the United Kingdom’s esteemed professional societies bears his name. Hunter performed the first documented testicular transplant (from a rooster to a hen), resulting in androgenic features in the hen.⁹ Several decades later, German physiologist Arnold Berthold proved that a substance in the bloodstream produced the male features in roosters, but his findings went largely unnoticed.^3,9,10

Pissing Contests and Testicular Transplants

One of the preeminent names in endocrinology is Charles-Édouard Brown-Séquard, who lived from 1817 to 1894. Many tales of his work during his tenure as a Harvard professor abound, including stories of experimenting upon himself with self-injections of testicular extracts from guinea pigs and dogs. Brown-Séquard published a famous report of his [subjective] increased strength, mental abilities, and appetite, relief from constipation and an increased arc in his urine stream.¹¹ On the face of things, it appears that Brown-Séquard was interested in combating aging-related symptoms of androgen deficiency. A close friend whose career is in academics suggests that he might have been involved in performance enhancement, since half of a professor’s time is spent in departmental pissing contests. This comment was made in jest, but it reflects the underlying tension and competition that pervades all levels of modern society— even the hallowed halls of academia.

According to the review, the first people to propose injecting athletes with hormonal substances were Austrian physiologist Oskar Zoth and his physician partner, Fritz Pregl in 1896.³ They self-injected testosterone extracts from bulls and plotted the strength of their middle fingers on ‘fatigue curves.’ Pregl went on to win the Nobel Prize in chemistry in 1923 for unrelated work. Why they chose to use the middle finger is a matter of speculation, though again, Sigmund Freud might offer some insight.

The late 1800s and early 1900s were years of frenetic study in the signaling of the body. Two prominent English physiologists, Bayliss and Starling, coined the term ‘hormone’ from the Greek for ‘to impulse or arouse.’¹²

In 1911, the first suggestion of a dose-response curve was published when André Pézard observed that a rooster developed a more prominent comb with greater doses of extract.^3,10 At this point, physicians began to use rudimentary operations that by today’s standards are bizarre and replete with risks of infection and tissue rejection. The ‘Steinach operation’— basically a vasectomy— was provided to ‘middle-aged and listless’ men. The claimed benefits of the Steinbach operation included hair regrowth, better erections, reduced complaints of premature ejaculation, and improved libido. Critics believed Steinbach’s claims were due to placebo effect, but his list of patients included prominent intellectuals, including Sigmund Freud and William Butler Yeats.³ Again, my esoteric and overeducated friend commented that Steinbach probably whispered, “Your mother loves you” into Freud’s ear during the procedure to ensure his sexual arousal.

The more alarming trend that was being practiced during this time was testicular transplantation from ‘donors’ into patients. Many of the donors were recently-executed prisoners and the early patients were often fellow prisoners.³ Of course, that sort of treatment is no longer tolerated in the U.S. penal system. One affluent surgeon developed a technique wherein he would slice the donor testicle(s) lengthwise prior to implanting the tissue slices between muscle layers in the abdomen or pelvis. His patients apparently included the well-connected and wealthy, as the case of one patient was reported in The New York Times— Harry F. McCormick, husband of Edith Rockefeller.³ Within years, the supply of testes donors could not meet demand, and certain entrepreneurial surgeons substituted the testicles of rams, boars, chimpanzees, and other mammals. Animal rights activists campaigned against this practice and editorial cartoonists (the early predecessors to Jay Leno) were quick to publish their parodies.

Testes Extracts to Boost Performance?

For modern-day AAS users, the history of AAS begins in the late 1920s when scientists were scrambling to discover the chemical containing the androgenic properties of these testes extracts responsible for providing the improvements in vitality and sexuality. The first related success occurred in 1929 when German chemist Adolf Butenandt isolated the female sex hormone estrone from the urine of pregnant females. Just two years later, Butenandt isolated androsterone.^3,13 As overjoyed as current AAS users may be at hearing of the discovery, Butenandt was likely more ecstatic, as the 15 mg of androsterone was filtered from 15,000 liters of urine from local policemen.^3,9 Androsterone is a metabolite of testosterone, a waste product excreted after testosterone has been enzymatically degraded, removing most of the androgenic and anabolic properties.

The race commenced among pharmaceutical companies, recognizing the unmet demand from men for a treatment for decreased vitality, as well as depressed libido and sexual function. Within months of each other, several chemists published papers on various methods of synthesizing testosterone from chemical precursors, such as cholesterol. Butenandt, one of the primary chemists, received the Nobel Prize in chemistry for his work with sex hormones in 1939.¹³ As material became available, clinical experiments with men suffering from hypogonadism were undertaken, focusing on impotence and sexual desire. It is worthy to note that topical preparations were also formulated to promote sexual desire in women by 1939.³ Remember, this was as the United States was exiting the Great Depression, the only financial crisis worse than today’s economic calamity (so far).

  It was the discovery by Charles Kochakian that the male sex hormone has properties that are anabolic as well as androgenic.^1,3,14 The anabolic function of androgenic steroids captured as much attention as the sexual functions. In 1945, Paul de Kruif published a book titled The Male Hormone, which reported the increased libido and enhanced athletic performance provided by testosterone and related drugs.¹⁵ The world was just recovering from World War II.

Sports and Bodybuilding

From the late 1940s to today, the history of AAS diverts into the realm of sports and bodybuilding. Many of the clinical uses were replaced by more specific treatments; reports of masculinizing side effects in women and liver tumors with chronic use of oral agents caused the class of drugs to fall into disfavor. By the late 1960s, it was suspected that much of the profit from AAS came from black-market distribution. Nonetheless, clinical experimentation on aging men suffering from signs of hypogonadism continued. Paul Niehans, author of the 1960 text Introduction to Cellular Therapy, provided testicle cell injections to prestigious patients such as Pope Pius XII and Aristotle Onassis.^3,16

Despite the unmet demand and growing knowledge base, pharmaceutical companies discontinued AAS production as regulatory and social pressures were applied. This reduction in resource allocation to AAS research coincided with the first Anabolic Steroid Control Act, making the distribution, use and possession of AAS without a physician’s prescription a felony. While the pharmaceutical companies have developed a number of novel (patentable) delivery mechanisms for testosterone, (patches, gels, non-alkylated oral Andriol, long-acting Nebido, and intranasal), the main crux in development has been toward non-steroidal selective androgen receptor modulators (SARMs).¹⁷ This leaves the United States demand for testosterone and other AAS unmet by legitimate, licensed and regulated manufacturers.

This void was quickly filled by the black market. Initially, finished products from Mexican, Pacific Rim, or European pharmaceutical companies were shipped or smuggled into the United States.¹⁸ As the delivery of these compounds became more uncertain due to actions of the Drug Enforcement Administration, U.S. Customs, U.S. Postal Inspectors, Homeland Security, etc., underground labs began meeting demand by purchasing AAS precursors from China, Mexico, India and other countries.¹⁹ These compounds were not monitored as closely and could be imported more easily, particularly if they were mislabeled from the point of origin. Unfortunately, the purity and potency of the precursors and finished products were often well below pharmaceutical standards. Cases of intentional adulteration or frank fraud have been reported, at times resulting in injury to the end user.

Dotson and Brown ended the review discussing the uncertain role testosterone and AAS have in clinical medicine, reported side effects, and the incidence and impact of adolescent drug abuse.³ Though these are all important topics to consider and address, their discussion diverts the reader’s attention away from the original intent of the article, the history of AAS.

The review was interesting and valuable, but it does no service to the readers of this article merely to reiterate the points presented. Instead, it is interesting to look at some of the highlights and consider them in light of the current position of AAS in the clinical, social and economic times.

Ethics, Risks and Gym Rats

AAS are considered by the public, policymakers, and professionals solely as illicit performance-enhancing drugs used by athletes and adolescents without regard of ethics or risks. Legislators, the media, and prosecutors have labeled anyone involved or interested in the field of AAS as unscrupulous pharmacies, rogue physicians, criminals, and scorned athletes. Yet, the history of AAS identification and development includes some of the most notable names in the fields of physiology, chemistry, medicine, surgery and endocrinology. The Nobel Prize has been granted to some who have experimented with and studied the potential of using AAS or related compounds to restore or enhance health and performance. Those who have sought the restorative powers of the humoral or glandular male factor, primarily for decreased libido, impotency, and signs of aging-related decline in androgen status, include notable figures in religion, science, psychology and industry. The demand for a better quality of life prevailed through some of the greatest global and national challenges in history, including the Great Depression and World War II.

It is not only the athletes and ‘gym rats’ buying AAS through the black market for sports titles and larger muscles who are placed in harm’s way by the antithetical turn from the 6,000 year-pursuit of the male factor. It is every man seeking to delay or reverse the deterioration in vitality, independence and esteem that occur almost inevitably with aging. It is every healthy man seeking to improve his social status or sexual attractiveness by improving his appearance and performance, both physical and sexual. These goals may seem vain, but they are an innate driving force, embedded within the nature of mankind, as evidenced by the presence of such demand since recorded time.

The rush to innovate drives America’s competitive place in the international market. Yet, it is the country that is trying to quash, and thus create a black market for, research and development in life-enhancing therapies. The history of AAS should establish that the field has been part of mankind’s recorded history, been nurtured by and advanced through the efforts of some of the greatest minds in medicine, science, religion and industry. Perhaps a better understanding of the history of AAS could alleviate many of the concerns of policymakers and professionals, redirecting development, supporting research and relaxing indications for clinical use.

References:
1. Kochakian C. Anabolic Actions of Steroids and Remembrances. University of Alabama Press, Birmingham, AL;1984. ISBN-13: 9789994291205.
2. Hoberman J. Testosterone Dreams: Rejuvenation, Aphrodisia, Doping. University of California Press, Berkeley, CA;2005. ISBN-13: 9780520221512.
3. Dotson JL, Brown RT. The history of the development of anabolic-androgenic steroids. Pediatr Clin North Am, 2007 Aug;54(4):761-9.
4. Lexchin J. Bigger and better: how Pfizer redefined erectile dysfunction. PLoS Med, 2006 Apr;3(4):e132.
5. Evans-Brown M, Dawson RT, et al. Use of melanotan I and II in the general population. BMJ, 2009 Feb 17;338:b566.
6. Cohen J, Collins R, et al. A league of their own: demographics, motivations and patterns of use of 1,955 male adult non-medical anabolic steroid users in the United States. J Int Soc Sports Nutr, 2007 Oct 11;4:12.
7. Shah J. Erectile dysfunction through the ages. BJU Int, 2002 Sep;90(4):433-41.
8. Kobler J. The Reluctant Surgeon. The Akadine Press, Pleasantville, NY;1999. ISBN-13: 978-1888173963.
9. Freeman ER, Bloom DA, et al. A brief history of testosterone. J Urol, 2001;165:371-3.
10. Medvei VC. The History of Clinical Endocrinology. Parthenon Publishing Group, Pearl River NY;1993. ISBN-10: 1850704279.
11. Brown-Séquard CE: Note on the effects produced on man by subcutaneous injections of a liquid obtained from the testicles of animals. Lancet, 2:105-107:1889.
12. Henderson J. Ernest Starling and 'Hormones': an historical commentary. J Endocrinol, 2005 Jan;184(1):5-10.
13. Karlson P. Adolf Butenandt (1903-1995). Nature, 1995 Feb 23;373(6516):660.
14. Hoberman JM, Yesalis CE. The history of synthetic testosterone. Sci Am, 1995 Feb;272(2):76-81.
15. de Kruif P. The Male Hormone. Permabooks, New York;1948. ASIN: B000KD7ECO.
16. Lambert G. Conquest of Age. The extraordinary story of Dr. Paul Niehans. Rinehart & Company Inc., New York; Clarke, Irwin & Company Limited,Toronto;1959. ASIN: B001UC6GDM.
17. Gao W, Dalton JT. Expanding the therapeutic use of androgens via selective androgen receptor modulators (SARMs). Drug Discov Today, 2007 Mar;12(5-6):241-8.
18. Ryan J. DEA Announces Charges in Largest Ever Steroid Probe. ABC News 2005 December 15. Available at: http://abcnews.go.com/US/LegalCenter/story?id=1411333, accessed April 9, 2009.
19. Schmidt MS. U.S. Arrests 124 in Raids on Global Steroid Ring. The New York Times, 2007 September 24. Available at: http://www.nytimes.com/2007/09/24/sports/24cnd-steroid.html?ref=sports, accessed April 9, 2009.