As the world gets ready to descend on Beijing for the 2008 Olympic Games, new concerns have arisen about the reliability of the urinary testosterone/epitestosterone doping test. These concerns, quite ironically coming in a year when the Olympics are hosted by an Asian nation, focus on racial differences in the reliability of this test that may favor Asian competitors. The paper appears in the Journal of Clinical Endocrinology and Metabolism (ePub March 11, 2008) and comes from an investigation at the Karolinska University Hospital in Stockholm, Sweden.

     To give you a little background, testosterone can be a difficult steroid to detect in athletes because our bodies naturally make this hormone already. This is opposed to say, dianabol, which any finding of in the urine would be indicative of a doping violation. To test for testosterone in this day and age sports agencies rely on a two-step approach. First, the urine is examined for the ratio of testosterone to epitestosterone. Normally the body makes these two hormones in a close ratio. Injection of testosterone usually does not entail also injecting the clinically inert hormone epitestosterone, so an imbalance is looked at to indicate a potential doping issue. If the ratio is above 4:1, step two comes into play. This concerns a very detailed examination of the testosterone molecule itself. This procedure looks at the weight and composition of different carbon isotopes on the testosterone backbone and can determine if the hormone was actually made by the body or not. Because it is so complex, this test is not used as a first line of defense. Passing the testosterone/epitestosterone ratio test is, therefore, the only real hurdle to evading the testosterone screening process.

     As it turns out, there are genetic differences in the way we humans excrete testosterone that can affect the reliability of the testosterone-doping test. And as the scientists in Stockholm have made note, these differences can be huge. What they have honed in on in particular is a gene known as UGT2B17. This gene is important in the glucuronidation and excretion of testosterone. The study looks at a group of people known to have a certain genetic variation where no allele of the UGT2B17 gene is present (referred to as del/del). This genotype is actually very common in Asians, and appears in 66.7 percent of the population. It appears in 9.3 percent of Caucasians.

     The researchers in Sweden wanted to see what would happen if you gave a whopping 500mg dose of testosterone enanthate to subjects with or without this genetic mutation. The subjects (55 healthy male volunteers) were monitored two, six and 11 days after the drug was given to see how common a break in the 4:1 threshold (a step one potential doping violation) would be across groups. As it turned out, subjects with two normal alleles (ins/ins) noticed a 20 times greater average maximum increase in the testostereone/epitestosterone ratio compared to the del/del group. Forty-one percent of the del/del group was actually able to maintain a ratio below 4:1 for the entire 15-day window. None would have been flagged for a violation, even after a 500mg injection. On top of that, over 70 percent of these subjects were testing clear 11 days after the injection. As for the control (ins/ins) subjects, none of them were able to maintain a ratio that was below 4:1 at any time during the investigation. All of them had failed two, six and 11 days post-injection. Given the obviously high dose applied, the potential for clearing the T/E ratio and improving performance with synthetic testosterone is obviously high for this genetic group. With the Olympics still three months away, it also makes one wonder if self-testing for this UGT2B17 gene variant is going to be (or already is) an exploited loophole.

The Latest Steroid Horror Stories

     Regular readers will know that I am not one to perpetuate common myths and misconceptions about the dangers of anabolic steroids. Steroids, at least in an acute (short term) sense, are remarkably safe drugs. At the same time, however, I am very realistic about the potential for harm when these drugs are abused, especially when carried over to the long term. I do fear at times that a growing “steroids are harmless” attitude will have unfortunate consequences for the community in the long run. If bodybuilders do not respect the benefits and risks of these agents equally, the sensational media may actually wind up getting the horror stories they so desperately grasp for. Therefore, when I see reports like the following three, which appeared in accredited journals this past month, I believe it is important to pass them along. Mind you, these reports are not meant to serve as case studies of abuse, or “proof” that steroids will cause a certain result in you. Little detail is known of the background of these cases, so they are here to serve only as reminders of what has happened to other people using these drugs, and that care and respect should always be taken with their use.

Report #1: Stroke in a 26-Year-Old

     The first report appears in the Clinical Neuropharmacology journal (2008 Map-Apr; 31(2):80-5). It comes from the neurology department in the Hospital Privado, located in Mar del Plata, Argentina. The man in the report was a 26-year-old amateur athlete. The paper describes the event as a posterior territory ischemic stroke. This is just a fancy way of explaining that an artery was blocked in the back area of the brain. Ischemic stoke is by far the most common kind of stroke (over 85 percent) and is usually what is being referred to when something is simply described as a “stroke.” Clearly, this is a very serious and potentially life-threatening situation. This occurrence in a 26-year-old man, of course, is alarming.

     The report explains that an examination of the patient was conducted to look for underlying risk factors. This included not only blood work, but an angiograph and echocardiograph as well. The doctors noted that no abnormalities were found in his blood profile, nor the angiograph or echocardiograph. They concluded that the only significant risk factor present in the young man appeared to be his nonmedical use of stanozolol (Winstrol). The drug was being used in performance-enhancing doses measurably in excess of the normal clinical threshold, which usually extends only to 6mg per day. The doctors speculated that the event was a result of the drug use, particularly because of the their “known effects on vascular tone, arterial tension, and platelet aggregation.” Obviously, no conclusions can be drawn from an isolated case study, but the report is worth noting nonetheless.

Report #2: Heart Attack in a 31-year-old

     This next report comes from the medical journal Angiology (2008 Apr 2, Epub). It comes as a brief online abstract, with notes that it is appearing ahead of official publication. As a result, there are going to be little details found on this case until it actually appears in full in the published written journal. Still, the brief report is of concern. It explains, very simply, that myocardial infarction (heart attack) was reported in a 31-year-old male steroid-using bodybuilder. No mention concerning the use of other drugs was made. Admittedly, cases of heart attack in a young man like this are not impossible to find where there are no links to anabolic steroids. But the fact that this was a young steroid-using bodybuilder is difficult to ignore and certainly gives cause for concern. Again, even with details, no conclusions can be drawn from isolated case studies. Still, the report is definitely worth noting (and remembering) given the known negative cardiovascular implications of steroid abuse.

Report #3: Embolism in 56-Year-Old Male

     The last case concerns a pulmonary embolism in a 56-year-old male (European Journal of Internal Medicine, 2008 May;19(3) 214-5). This incident is quite different from the two above, however, in that it concerns the medical use of anabolic/androgenic steroids. In particular, this patient had been given injections of both testosterone and nandrolone. The drugs were being given to aid the healing of a muscle injury. This was only the third time the man had been given these injections, and again, they were administered under the care of a physician. The drugs were administered in this case in the leg muscle. After the medical event, doctors examined the man and noticed with ultrasound that a blood clot had formed in a vein of the leg. Detailed chest imaging confirmed pulmonary embolism. Pulmonary embolism occurs when fat globules block blood vessels in the lungs. This sometimes occurs with the incorrect or high-volume injection of oil-based drugs intended for deep intramuscular use. In such cases, the oil may make its way to circulation rapidly via a blood vessel, causing the problem. Symptoms of pulmonary oil embolism may include chest pain, labored breathing and fits of coughing. In severe cases it can lead to death. This report was included because it reminds us that injections can be tricky, and care should always be taken. High-volume injections are never advisable, and can result in the same event. It is also included because it furthers the focus of this month’s article (recent adverse event reports).

Editor’s Note: William Llewellyn’s critically acclaimed steroid reference guide ANABOLICS 6^th Edition (2007) can be ordered by calling 888-828-8008, or visiting www.anabolicsbook.com.