Retrospectacle: A Neuroscience Blog

One only has to turn on a TV, or browse through any news site, to read the story of disgraced Tour de France winner Flloyd Landis. Landis, an American, was reported to have an abnormally high testosterone to epitestosterone ratio in one of his urine samples given right before the end of of the race. Landis has vehemently denied the allegations, and a secondary “backup” test is being conducted; those results will be released this Saturday. If the test again comes up positive, Landis must relinquish his winner’s jersey and title (he would be the second to do so). But, what is testosterone doping, and how is it detected? (Details below the fold!)

During the Tour de France, Landis was considered a major contender and a favorite to win. Although his performance initially was quite good, he burned out during the climb of La Toussuire and lost ten minutes. The next day (Stage 17) was practically his last chance to make up the time, and miraculously (it seemed) he stunned the world by finishing in third place, just 30 seconds behind the leader. In the final stage, Landis lead the pack to win the race by almost a full minute.

However, on July 27, it was announced that a urine sample he gave before that fateful Stage 17 came back positive for high levels of testosterone, pointing to doping with artificial testosterone. The ratio refers to the levels of epitestosterone to testosterone in the blood. The normal levels for most men are 1:1 or 2:1, and the highest allowable levels for the test are 4:1. Landis’ doctor revealed that his test found a ratio of 11:1. Testosterone can be administered by injection, pill, skin creme or time-released patch. It is not uncommon for cyclists to attempt to dope with this hormone, shown for example, in Spanish doping scandal that implicated nearly 60 cyclists and others in the sport before this year’s Tour. Elevated testosterone, which is a male sex hormone made in the testes, confers a multitude of benefits to an athlete: elevated energy and muscle mass, faster recovery after intense workouts, increased assertiveness and aggression, etc.

The quickest way that labs can test for testosterone doping (and the way mentioned above) is by comparing levels of epitestosterone and testosterone in an athlete’s blood. Epitestosterone is naturally produced in similar levels in the body to testosterone. When the ratio is significantly off (and skewed to the testosterone side) this is strong evidence of doping with an artificial form.

i-262d6c881fa39c4424bf67439fc3d8d5-testost.bmp
Structure of testosterone

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Structure of epitestosterone

A more accurate test which is used to screen for the hormone is a carbon isotope test, which has only been in use for six years, and compares the molecular makeup of compounds found in the urine. Carbon atoms are made up of 6 protons and 6 neutrons, making their atomic weight 12 (carbon 12). But sometimes these atoms have 7 neutrons, raising their atomic weight to 13 (carbon 13).

First, the testosterone is isolated from the sample, then it is compared to the chemical structure of natural testosterone through ratio mass spectrometry. Soy plants, strangely enough, are the most common source of artificial testosterone. This source, which is what drug companies make testosterone from, has less carbon 13 than many other types of plants in the human diet. The test is meant to detect small differences between the collected testosterone in the urine sample and another naturally-occurring hormone in the sample (that wouldn’t be doped). The hormones should have the same ratio of carbon isotopes if they both originated naturally. A positive result means that the carbon isotope ratio (carbon 13 compared to carbon 12) is three or more units higher in the testosterone than in the comparison hormone. This is very strong evidence that the testosterone was not made by the body. Landis had four units (3.99) of difference, significantly more than should be allowed naturally by chance.

And even Nature has reported! From an article today:

Are other naturally occurring substances used for doping?

“The only other substance that is widely used is creatine,” says Michael Rennie, a clinical physiologist at the University of Nottingham, UK. “But that’s not illegal – it’s in meat.” Taking creatine supplements increases an athlete’s ability to produce power through ATP, the body’s energy currency, so they can train harder. Rennie has occasionally come across athletes taking growth hormone to increase muscle mass, but there is little evidence that it has any positive effect on sporting results. It can also cause diabetes if taken long term.

What can be done about it?

Cowan [director of the Drug Control Centre at King's College London] would like to see all athletes individually profiled, creating an athlete’s ‘passport’ system for monitoring them as a matter of course. If their normal levels are disturbed, one explanation would be that they are doping. Cowan hopes to see this system in place for the London Olympics. “It’s a theme that I’m very keen on for London 2012, one that I keep pushing,” he says.

Comments

  1. #1 Abel Pharmboy
    August 2, 2006

    Wait a second…a neuroscientist’s blog? Chemical structures beyond phenylethylamines? Discussion of NMR?

    You MUST come postdoc with us…if I’m still funded!

  2. #2 natural cynic
    August 2, 2006

    A couple of clarifications: Landis won Stage 17, putting him behind the overall leader by 30 sec. Then, on Stage 19, an individual time trial, he finished in third, making up 90 seconds on the then overall leader, to take the overall lead – which was unchanged on the last stage into Paris. And the fateful urine sample was taken after Stage 17. All high finishers and random riders are given tests after each stage.

    Several questions arise:
    Any evidence of tampering? [accusations about tampering have been made about Lance Armstrong's samples]

    If he did it, why did he do it when he knew he would be tested for winning the stage? And to such an extent that it would be so obvious.

    A report claimed that Landis said that he has naturally high testosterone as a result of hypothyriodism – this is next to impossible for an endurance athlete.

    What were his values for the other stages where he had high finishes?

    If he knew he was doping, why didn’t he take epitestosterone too in order to partially mask the testosterone?

  3. #3 Shelley Batts
    August 2, 2006

    Thanks for the info, cynic. All great questions. Its hard to say why any athlete would take banned substances when they know it could result in scandal and sanctions. One possibility is that he was taking high levels of epi as well, and the high test level was a result of an error in his doping regiment (forgot to take it?). I’ve also heard the high test claim as well, but it wouldn’t explain why he didn’t have high epi levels or why the carbon isotope test showed skewed results. So, its looking like it would be pretty hard to claim ‘natural causes’ but perhaps the backup “b” sample (results released on Sat) will shed more light on it. My guess is that after his poor performance in Stage 16 etc., he got drunk like he said, and then just doped on test out of desperation and poor judgement.

  4. #4 Kristjan Wager
    August 4, 2006

    [accusations about tampering have been made about Lance Armstrong's samples]

    Nobody who is into cycling really believes this for a second, nor do they believe that Armstrong wasn’t doped (likewise with all other winners of Tour de France the last two decades). Doping is so widespread in cycling, that it’s impossible to win one of the big races without artificial help.

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