THG: Most Controversial Steroid Ever

Its existence was suspected, known only through whispers generated along the rumor stream that tries to monitor who is gaining an edge in the world of competitive athletics. One of perhaps dozens of designer drugs used by some of the world's top athlete-celebrities, it's made and distributed by the shadowy figures hovering on the edges of the playing fields and in the corners of the training centers. Yet, in the few weeks that have transpired since its discovery, nearly every sports broadcaster and reporter has posted a headline or cover story about the greatest controversy yet exposed to the public regarding the use of illicit drugs by athletes.

A History of Controversy

Three major controversies involving steroids have occurred during modern sports history. The first happened in 1988 when Olympic gold medalist Ben Johnson of Canada was stripped of his medal after testing positive for stanazolol (Winstrol).¹ Olympic officials believed Johnson and others were being guided by physicians who could provide the drug on a schedule that would clear the drug from the system prior to any competition's urine drug testing.

 The second transpired in the summer of 2002, when the U.S. Anti-Doping Agency (USADA) determined that Tammy Thomas, a female cyclist who won a silver medal in the 2001 World Championships, was using norbolethone.² Norbolethone is an anabolic steroid developed decades ago, but never marketed for commercial use. The USADA announced concern that the discovery indicated clandestine labs were making and providing performance-enhancing drugs for athletes, specifically structured so as to be undetectable by current drug-testing methods.³ As norbolethone had never before been available, there was no drug "fingerprint" to compare. Until the USADA has a specific "fingerprint" in its files, it is unable to identify drugs, which is required to declare a test positive. The identification of norbolethone by the USADA prevents other athletes from obtaining the same drug, and the same advantage, that Thomas had used to acquire her high ranking in the competitive sport of cycling.

The latest controversy poses the greatest challenge to the USADA and other drug-testing centers. It involves the creation of a new molecule, one never before documented, designed as much for its ability to remain undetected as for its performance-enhancing properties. One such drug, THG, is the center of a media blitz, as dozens of athlete-celebrities are being subpoenaed before a federal grand jury, while many others are threatened with suspension from competition.^3-8 Beyond ending the professional career of these athletes, the taint of a positive drug test is also likely to cancel many lucrative endorsement contracts and lessen fan support of the teams and players involved.

            What Exactly is THG?

The media has focused on the people implicated in this scandal, including Victor Conte of BALCO Labs, inventor of the ZMA mineral supplement.^3-8 One politician is using this connection to suggest THG was marketed as a supplement, but this was never the case.⁹ While all the intrigue and celebrity gossip is suitable fodder for headlines, what most scientists, athletes and bodybuilders would like to know is: What exactly is THG?

THG. These three letters form the abbreviation for tetrahydrogestrinone, a previously undocumented androgenic steroid. In the media, THG has been compared to two steroids, primarily because of its chemical structure; these steroids are gestrinone and trenbolone.¹⁰ This alone may make many bodybuilders begin to quiver with excitement, as trenbolone is one of the most highly regarded anabolic steroids for promoting quality mass gains. Further, the gains achieved with trenbolone are thought to have greater permanence than the more fleeting gains of testosterone esters. Before grouping THG with trenbolone, it is important to understand why this comparison is made and decide if it is accurate. Much of this discussion deals with the molecular structure of anabolic steroids, as THG has never been studied clinically.

Anabolic steroids have four rings connected side by side. The rings are formed by individual carbon atoms that are linked together by chemical bonds. Any carbon atom may have functional groups attached to it, forming a "tag" that defines the function of the steroid. It's the different types of bonds and functional groups that determine what effect a steroid has in the body. Not all steroids are androgens; some act as estrogens, others are catabolic, acting like cortisol, and still others have different functions, such as vitamin D, cholesterol, etc. It is this chemical complexity that accounts for the different drug profiles of the various anabolic steroids. This explains why some are effective for mass gains but cause water retention, while others promote lean gains but do not develop strength, as well.

THG and related steroids (trenbolone and gestrinone) have three double bonds along three rings of the molecule, an unusual pattern that is different from naturally produced hormones. One effect of this double-bond pattern is to protect the steroid from aromatization, meaning THG is unlikely to have any significant conversion to an estrogen.¹¹ This is obviously important to athletes, as estrogen excess leads to water retention, fat accumulation and causes gynecomastia in males. By preventing aromatization (and thus, estrogen formation), the athletes are likely to become harder, more defined and leaner. This would be particularly important for the track and field athletes. Not surprisingly, then, most of the positive THG drug tests are being discovered among track and field athletes.

The lack of estrogenic effect would limit some of the mass/weight gain seen with many anabolic steroids. However, it's being suggested that many of the athletes who were using THG may have been combining it with hGH (human growth hormone) to augment the size and strength gains of the drug use, as hGH cannot be detected using current testing methods.³

            Undesirable Side Effects

It is difficult to estimate what degree of anabolism would be experienced from THG use, as gestrinone and trenbolone have very different effects in the body. Gestrinone is an anti-estrogenic, anti-progestin steroid used to treat female conditions such as endometriosis, contraception, cyclical breast pain and fibrocystic disease of the breast.^12-15 The use of gestrinone is associated with some weight gain, but there are no clinical trials reporting its use in males. Androgenic side effects are noted in some women treated with gestrinone.¹⁶ One interesting side effect of gestrinone is the marked reduction of sex-hormone binding globulin in the blood, which would increase testosterone bioavailability, though it would decrease the half-life.¹⁷ Gestrinone is odd in that it has a triple bond side chain attached to the 17-carbon. THG has this bond fully hydrolyzed, resulting in a C-17a ethyl alkylation of the base steroid, meaning that it is an alkylated steroid, just like most oral steroids. C-17a alkylation is associated with greatly increased liver toxicity.

In fact, the one steroid that THG most closely resembles is a drug called metribolone.¹⁸ Metribolone was referred to as oral trenbolone. Oral trenbolone sounds like a drug that should have been very popular, but it is reported to be extremely toxic to the liver. One comment about metribolone was that it made Anadrol and Halotestin seem mild in comparison. It would be quite interesting to read the lab reports of the athletes testing positive for THG to see if they suffer from elevated liver enzymes. The drug also affects behavior, suppressing mating behavior in rats and increasing aggression and fighting, as would be expected of an androgen.^19,20

Another side effect likely to occur with THG use, common to most androgens, is suppression of natural testosterone production.^16,21,22 This might cause many users to stay on the drug throughout a competitive season, as they would otherwise suffer from physical withdrawal unless they were able to use hCG or another drug without risking detection. The competitive seasons last longer than one would wisely use a drug closely resembling metribolone, increasing the risk of liver damage.

THG is a new drug, never before described in literature. It is a synthetic anabolic steroid designed primarily to allow athletes participating in drug-tested sports to have a competitive edge over their competition in a manner that violates the rules of their sport. THG would seemingly be effective, as it is essentially an oral form of trenbolone, an anabolic steroid known for its potent androgenic and anabolic effects. However, the unknown nature of THG's effects and the high likelihood of it having significant liver toxicity make it an unwise steroid choice for long-term use. Given that it suppresses natural testosterone production, it's likely that many of the athletes continue to use the drug throughout a competitive season. Absent of its ability to be used undetected (prior to its discovery by the USADA), there is little to recommend THG's use over other steroid choices, particularly trenbolone.

Great Damage Done

It's highly likely that THG is very effective at enhancing athletic performance, as elite caliber athletes would not risk using a drug (placing high-dollar endorsement and sponsorship on the line) without proof of its potency. Given the level of the athletes who have tested positive for THG and the many others who are implicated in this scandal, it's reasonable to assume THG helped win medals and set records. However, despite the benefits that a few individuals gained from using THG, it has done great damage. As yet another steroid scandal involving athlete-celebrities, it focuses negative media attention on steroid use once again, demonizing the practice. Also, as it may involve a highly visible manufacturer of a dietary supplement, it increases the pressure to regulate all supplements, which are facing the threat of greater government restrictions.

Steroid use may have many benefits and its use may one day have a place in American society. However, as long as individuals use anabolic steroids in a forbidden manner, such as violating fair sports play, it's certain the government and society will never view steroid use positively. If an athlete wants to compete in a drug-tested sport or organization, but uses drugs, that athlete should be stripped of any fame or fortune gained. Unfortunately, what will happen is that restrictions will be placed on all future steroid research, making it impossible to ever evaluate any benefits of anabolic steroids.

References 

1. Benjamin D. Shame of the games Ben Johnson is stripped of his gold in the Olympic's worst drug scandal. Time, Oct. 10, 1988.
2. Wanninger R. USADA: U.S. cyclist Tammy Thomas receives lifetime suspension from U.S. Anti-Doping Agency for positive drug test. U.S. Anti-Doping Agency Press Release (719-785-2009). Aug. 30, 2002.
3. Longman J, Drape J. Decoding a steroid: hunches, sweat, vindication. The New York Times, Nov. 2, 2003.
4. Keating P, Assael S. Blood money. ESPN Magazine, Oct. 24, 2003.
5. Dohrmann G. Mineral Man. Sports Illustrated, 2003.
6. Hack D. N.F.L. to impose old penalties for new steroid. The New York Times, Oct. 30, 2003.
7. Jeansonne J. Steroid jury to meet. Big-time athletes could make appearance. Newsday, Oct. 30, 2003.
8. Patrick D. Thwarting performance enhancing drug daunting. USA Today, Oct. 30, 2003.
9. Associated Press. Illegal steroid THG could pose health risks. Government to act on drug sales. Lexington Herald-Leader, Oct. 29, 2003.
10. From Wire Services. FDA bans steroid. Illegal drug THG poses health risks. Boston Globe, Oct. 29, 2003.
11. Llewellyn W. Trenbolone acetate. Anabolics 2002. Molecular Nutrition Press, Patchogue, NY;2002:169-71.
12. Spellacy WN, Mahan CS, et al. Blood glucose, insulin, cholesterol and triglyceride levels in women treated for six months with the weekly oral contraceptive R2323. Contraception, 1978 Aug;18(2):121-6.
13. Coutinho EM. Treatment of endometriosis with gestrinone (R2323), a synthetic antiestrogen, antiprogesterone. Am J Obstet Gynecol, 1982 Dec 15;144(8):895-8.
14. Coutinho EM, Azadian-Boulanger G. Treatment of fibrocystic disease of the breast with gestrinone, a new trienic synthetic steroid with anti-estrogen, anti-progesterone properties. Int J Gynaecol Obstet, 1984 Oct;22(5):363-6.
15. Peters F. Multicentre study of gestrinone in cyclical breast pain. Lancet, 1992 Jan 25;339(8787):205-8.
16. David SS, Huggins GR, et al. A synthetic steroid (R2323) as a once-a-week oral contraceptive. Fertil Steril, 1979 Mar;31(3):278-81.
17. Dowsett M, Forbes KL, et al. A comparison of the effects of danazol and gestrinone on testosterone binding to sex hormone binding globulin in vitro and in vivo. Clin Endocrinol (Oxf), 1986 May;24(5):555-63.
18. Van Mol P. Metribolone. Available through http://www.bodybuilding.com/fun/catmetri.htm accessed Nov. 10, 2003.
19. Sodersten P, Gustafsson JA. Activation of sexual behaviour in castrated rats with the synthetic androgen 17 beta-hydroxy-17 alpha-methyl-estra-4,9,11-triene-3-one (R1881). J Endocrinol, 1980 Nov;87(2):279-83.
20. Van de Poll NE, Taminiau MS, et al. Gonadal steroid influence upon sexual and aggressive behavior of female rats. Int J Neurosci, 1988 Aug;41(3-4):271-86.
21. Fanjul LF, Estevez F, et al. R1881 regulation of steroidogenesis in cultured testicular cells. Biochem Int, 1989 Aug;19(2):301-12.
22. Jia XC, Kessel B, et al. Androgen inhibition of follicle-stimulating hormone-stimulated lutenizing hormone receptor formation in cultured rat granulose cells. Endocrinology, 1985;117(1):13-22.