Pure Pedantry

Floyd Landis, most recent winner of the Tour de France, has tested positive for testosterone use:

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Landis denied cheating and said he has no idea what may have caused his positive test for high testosterone following the Tour’s 17th stage, where he made his comeback charge last week. But he aims to find out.

“All I’m asking for,” he said Thursday via teleconference, “is that I be given a chance to prove I’m innocent. Cycling has a traditional way of trying people in the court of public opinion before they get a chance to do anything else.”

Now the cycling world will wait for results from a backup sample which, if negative, will clear Landis. If ultimately proven guilty, Landis could be stripped of the Tour title and fired from the team.

The Switzerland-based Phonak team will ask that the backup sample be tested in the next few days, manager John Lelangue said. The team suspended Landis after the International Cycling Union notified it Wednesday that he had an unusual level of testosterone/epitestosterone” when his test was taken last Thursday, the day he staked his comeback in the Alps.

I thought I would do some research and clarify some of the medicine behind this because the science of how we detect anabolic steroid use is often a litte obscure.

First of all, you should know that testing for anabolic steroids can sometimes be difficult because many of the steroids and hormones that athletes use are naturally occuring in the body. One of these hormones that is regularly abused is testosterone, the primary androgenizing hormone in humans. Testosterone abuse causes increases in muscle mass with or without exercise. How would we test athletes for use of testosterone? Well the straightforward solution would be to just measure their testosterone levels in blood or urine, but that actually doesn’t work because there is a relatively large variability between individuals in basal levels of testosterone.

Instead what anti-doping authorities use is the testosterone to epitestosterone ratio. Epitestosterone is a breakdown product of other hormones. It has never been really associated with a particular biological activity (although some research suggests that it is has an antiandrogenic effect). Until recently it wasn’t even known what enzyme produced epitestosterone, but recent research suggests that it is made from DHEA using an enzyme called 17 alpha hydroxy-steroid dehydrogenase, mostly in the liver.

Here is a diagram of the hypothesized mechanism of production:

i-17bbb4c787c117cdd5232ab8dc3c6d52-1471-2091-6-12-5.jpg

What epitestosterone does and why it is there doesn’t really matter though. What does matter is that the ratio in an individual between testosterone and epitestosterone is relatively constant over time and does not show large variability between individuals. Therefore when testosterone is added artificially, the ratio between the two would go up and this can be detected. For Caucasians the ratio is 2 or less with Asian people having a slightly lower ratio. The arbitrary limit that anti-doping agencies set for what would constitute an unacceptable ratio is 6 4 (Ed: This was corrected after several commenters observed that the UCI protocol lists 4.) . This works only because it is assumed that there is little interconversion between the two compounds and that their rates of excretion are relatively similar. Under normal conditions this is the case:

Detection of exogenous substances means identifying the parent compound or at least one metabolite. Nevertheless, with substances that are produced endogenously, such as testosterone, the presence of the substance alone cannot be considered to be an offence by itself. Moreover, a cut-off value for testosterone concentration cannot be used because of large observed interindividual and intraindividual urinary concentrations of the steroid. However, intake of testosterone causes characteristic changes in the pattern of steroids excreted in the urine. Based on studies of athlete populations, the IOC adopted in 1983 a ratio of testosterone to epitestosterone glucuronides (T/E) with an authorised upper limit of 6.0 as a criterion for the administration of testosterone. Since epitestosterone is only a minor product of the metabolism of testosterone and does not increase after testosterone administration, the resulting effect is an increase in the T/E ratio. In several studies, the distribution of results in Caucasian athlete populations shows generally a mean T/E ratio less than 2.0 whereas in Asian populations the mean T/E ratio is significantly lower. The IOC rules clearly indicate that a T/E ratio greater than 6.0 constituted an offence unless there was evidence that this ratio is due to a physiological or pathological condition–for example, low epitestosterone excretion, androgen producing tumour, and enzyme deficiencies. In addition, it has been observed that hepatic metabolism of steroid hormones may be altered by administration of substances as ethanol with the resulting effect of modifying significantly the T/E ratio. (Citations were removed.)

Floyd Landis has failed one test of T/E ratio. This presumably means that his ratio was above 6 4.

OK so what now? What is going to happen about to Floyd Landis? Well, the authorities have indicated that he has other samples that will be retested. This could be to confirm the other result was not contaminated with something. The authorities may also want to take more samples to see if this result reflects a normal baseline ratio for him — the ratio should be consistent over time and in some cases a pathological state could result in a high ratio.

Another test that they could use — and that I have read some news stories that they may — is isotope measurement. The testosterone in your body is made from cholesterol. Cholesterol comes in part from the food that you eat. The food that you eat was created using energy originally derived from the Sun. It turns out that the process of photosynthesis is selective for certain isotopes of carbon over others. Therefore, it is possible to look at the ratios of these isotopes to see whether testosterone is naturally or synthetically derived. Synthetically derived testosterone should not have the same ratios of carbon isotopes.

There is a test where you take the testosterone from someone’s body and measure its isotope ratio to see if it is synthetic or all-natural. In all likelihood they will do this test as well. Here’s more on that test:

Even if longitudinal study gives good quality information on the potential steroid profile manipulation, there is a lack of definitive proof for the exogenous application of natural steroids. One possible way of solving this problem is the ratio of the two stable carbon isotopes 13C/12C, which can allow the differentiation of natural and synthetic steroids. As exogenous testosterone or precursors contain less 13C than their endogenous homologues, it is expected that urinary steroids with a low 13C/12C ratio originate from pharmaceutical sources. Endogenous steroids are produced from cholesterol in the body. Cholesterol is derived from an average of a wide variety of feed vegetal and animal precursors or synthesised from precursors of feed origin.

In plant tissue, the main source of variation in 13C/12C isotopic ratio is derived from the different photosynthetic pathways for carbon dioxide fixation. Plants incorporate carbon dioxide via photosynthesis by three different mechanisms: the Calvin cycle (C3) pathway, the Hatch-Slack (C4) pathway and the crassulacean acid metabolism (CAM) pathway. The C3 pathway results in a large change in the carbon isotope proportions relative to atmospheric carbon dioxide and hence discriminates more strongly against the heavier isotope 13C compared with the C4 pathway. Main representatives of C3 group are wheat, rice, potato, barley, grape, oats, and sugar beet, whereas maize, sugar cane, millet, and pineapple are the important species of the C4 group. The difference in the 13C enrichment of food products in the diet and even in the food chain is caused by different contribution of naturally 13C-enriched constituents. Because maize, millet, and sugar cane (C4 plants) are the common food ingredients in some areas of Africa, it is expected that the basic 13C enrichment of the body store will be high for local populations.34 It is known that urine samples collected from a country such as Kenya have a higher content of 13C in steroids than western or oceanian countries.

The method for determining the isotopic composition of the relevant analyte includes gas chromatography, a subsequent combustion to CO2, and finally, mass spectrometric analysis of this gas in a special multi-collector mass spectrometer (gas chromatography/combustion/isotope ratio mass spectrometry, GC/C/IRMS). The 13C/12C value of testosterone or that of its metabolites will be measured and compared with that of urinary reference steroids within the sample to take into account variation in an athlete’s diet. In addition, it should be emphasised that the 13C/12C value of these endogenous reference compounds should not be affected by steroid administration. The result will be reported as consistent with the administration of a steroid if a significant difference is observed between the 13C/12C values of testosterone metabolites and the endogenous reference compound. (Citations were removed.)

There is a very legitimate question related to the timing of the positive test. Floyd Landis tested positive on day 17 of the Tour de France — right before he made a miraculous comeback to retake the lead. Some people may speculate that testosterone may have helped him do this. This is unlikely to be the case. Testosterone is used during training periods to gain muscle mass. It is not a stimulant like amphetamines. It is not likely that testosterone would improve performance on such a short time scale, nor has it ever been shown to have that effect.

Finally, there is this issue of Floyd Landis’s existing medical condition, osteonecrosis of the hip. Osteonecrosis of the hip is when there is a loss of blood supply to the head of the femur as it sits in the hip joint. This can be caused by injury — actually it is a very common injury in elderly women with osteoporosis. It is also a side-effect of steroid abuse in some cases. Some doctors have speculated that his hip problem might be indicative of steroid abuse:

He suffers from osteonecrosis, or avascular necrosis, in his right hip. The condition occurs when a bone or joint loses its blood supply, causing the bone to wear down. Landis said that in his case, the condition was brought about by a previous cycling crash.

That’s not unusual. Bone fractures are the biggest risk factor in developing osteonecrosis. However, what is unusual is the positive drug test, which adds a new twist to his story because osteonecrosis is also linked to steroid use, according to the National Osteonecrosis Foundation and other sources.

For reasons still unclear, people who take steroids — including anabolic steroids — appear to have a greater chance of coming down with the condition. Landis has admitted to taking corticosteroids, which, since they are used to treat inflammation and aren’t related to performance, are not banned and wouldn’t throw off tests for other steroids, doctors say.

All steroid use leading to or exacerbating osteonecrosis is a “well proven cause and effect,” said Dr. Mark D. Miller, an orthopedic surgery professor at the University of Virginia, who said that it’s possible Landis’ condition may have been caused or worsened by anabolic steroid use. Dr. Lewis Maharam, a New York sports medicine specialist, echoed that sentiment, but emphasized that osteonecrosis is just as likely to be caused by an injury.

It is really too early to tell whether these allegations are true or not. Frankly, I would believe either way. The science of detecting doping is improving but it still isn’t perfect. I just thought I would summarize the medical aspects so that when you read more about it you willl know the background.

UPDATE: I just heard Landis’s doctor on NPR claiming that Landis had a stiff shot of whiskey on day 16 and maybe that altered his test. It is true that ethanol can alter T/E ratio, but I would speculate the mechanism of that to be that ethanol use alters the levels of the enzymes in the liver that metabolize DHEA into epitestosterone. These enzymes do not change their levels rapidly. A comparable change is the risk that alcoholics get from using Tylenol. Acetaminophen is metabolized into something toxic in high doses in individuals who abuse alcohol becaue they have higher levels of a particular enzyme used to metabolize alcohol (this enzyme also metabolizes acetaminophen). Raising the enzymes levels requires regular alcohol use.

I find it highly unlikely that one shot of whiskey the night before the failed test would be sufficient to raise the enzymes in the liver sufficiently to produce a higher T/E ratio. It just does not happen that fast.

UPDATE: OK scratch that. The mechanism may be due to changes in excretion. However, in a paper related to this, I found the amount that you would have to drink to raise your T/E ratio 40% on average: about 2 g per kilogram body weight. Here is that scoop:

It was shown in a pilot experiment that ingestion of ethanol in amounts lower than 1 g per kilogram body weight had only small or negligible effect on the urinary testosterone/epitestosterone ratio. In this experiment, for seven subjects the ratio between testosterone and epitestosterone in urine was 1.00 +/- 0.07 before the ingestion of 0.5 to 1.0 g of ethanol per kilogram body weight. For urine samples collected 12 h after the ingestion, it was 1.13 +/- 0.07 (P >0.05, Student’s unpaired t-test). Ingestion of ethanol in amounts exceeding 1 g per kilogram body weight, however, always resulted in a significant increase in the ratio between testosterone and epitestosterone. Figure 1 shows the results of a carefully controlled experiment in which four subjects ingested 2 g of ethanol per kilogram body weight. After 14 h, the mean ratio had increased to 38% and after 22 h to 41%. The increase ranged from 30% to 90% in the different subjects we studied. The increase after 14 and 22 h
was statistically significant (P <0.05, Student's unpaired ttest).

Say he weights 70 kg (about 150 lbs). That would be 140 g of alcohol. Say a shot contains 20 grams of alcohol (I am being generous). Then he would have to have a hell of a lot more than a double to change his T/E ratio. He would have had to have more like 7 or 10.

So the question is: Did Landis get soused in the middle of the Tour de France?

UPDATE: Commenter Jeff asks:

John Eustice of ESPN is reporting that Landis’s high ratio was caused by a low epitestosterone (the denominator) level, not a high level of testosterone (the numerator). In other words, he doesn’t have a high testosterone level, just a high ratio because of a low denominator. How is it possible to get a low epitestosterone level and why? Would that help performance? What is going on?

The question is not so much whether he has a low epitestosterone overall, but rather why he would have a low urine epitestosterone. This issue is addressed in the review I cited about epitestosterone, but they draw few firm conclusions.

For example, older men with benign prostatic hypertrophy can have low excretion of epitestosterone:

In a group of men with benign hypertrophy of prostate in the age of 61-70 years a subnormal excretion of epitestosterone 24.5 +/- 12.8 μg per day compared with that of age-matched healthy men 42.8 +/- 14.3 μg per day was observed.

With respect to individuals who naturally have low levels of epitestosterone total or excreted there are some cases — and in some cases this may have to do with race:

The testing is, however, valid only under the assumption that the clearance of both epimers is similar, that testosterone administered exogenously is really not metabolised to epitestosterone, and that the ratio of both epimers is not influenced by racial or individual variations. Some exceptions have recently been observed [16, 50 and 52] in individuals with very low epitestosterone excretion, as have racial differences, e.g. between Japanese (T:E 1.99) and Ainu (T:E 2.77). The testosterone:epitestosterone ratio is also influenced by intake of various external compounds, e.g. by high doses of alcohol, more in females than in males. Andostenedione administration increases epitestosterone excretion while decreasing that of its putative precursor. Dehydroepiandrosterone supplementation can increase the testosterone:epitestosterone ratio. (Citations have been removed.)

I tried to look up the case studies of the individuals who had low epitestosterone excretion. Only one was available because they are relatively old (by Internet standards). That one is a case study, but they don’t explain why the person had low epistestosterone, only that he had it and did not have evidence of a tumor.

It appears that there have been cases of individuals with low epistestosterone excretion naturally. Whether Floyd Landis is one of these is unclear. I can’t off the top of my head think of any other reason why his epitestosterone would be naturally low.

UPDATE: I would add too that within physiological ranges testosterone levels do not correlate with performance. Only when testosterone is abused does it tend to improve performance. Actually, I found this article that suggests that they have even tested this assertion for both cortisol and testosterone in cyclists and found that the two are not correlated.

In the literature the use of plasma levels of cortisol and the testosterone and testosterone: cortisol ratio for training management is encouraged. Decreased levels of testosterone and increased levels of cortisol are suggested to be indicative for a disturbance in the anabolic-catabolic balance, which may express itself in decreased performance. The purpose of the study was to examine if the acute hormonal response to a bout of exercise and the resting levels of testosterone, luteinizing hormone (LH) and cortisol are correlated to performance in cyclists. In addition, the effect of training on this correlation was studied. Ten professional cyclists participated and measurements took place before and after a defined period of training. Maximum workload (Pmax), determined on a cycle-ergometer with a slowly increasing protocol, increased by 30 watt (p < 0.001). Workload at a lactate level of 4 mmol/l (P4) increased by 18 watt (p < 0.05). Post training, resting testosterone levels decreased from 28.8 +/- 74 nmol/l to 24.6 +/- 90 nmol/l (p < 0.05). Resting cortisol levels increased from 272 +/- 110 nmol/l pre training to 379 +/- 242 nmol/l post training (p < 0.05). These results indicate an increased catabolic state. The acute hormonal response and the resting levels of LH were not changed post training. The resting levels of testosterone and cortisol and the acute response to exercise showed no correlation with performance pre and post training. In spite of an increased catabolic state post training there was an increase in performance. These results suggest that in endurance trained cyclists, decreased testosterone levels, increased cortisol levels and a decreased testosterone: cortisol ratio does not automatically lead to a decrease in performance or a state of overtraining. (Emphasis mine.)

With respect to epitestosterone, no physiological action for it has ever been shown in humans, so I doubt that naturally low levels of it would affect performance.

UPDATE: Quitter, the issue of the spread of normal values is a good one, so I looked it up here. Click on the icon below and it shows a chart of the normal range of T/E values for a large cohort of male athletes:

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Click on the second chart to see the variations in several athletes over several years:

i-50135d127d8e2f9e925d374f5c3ca624-te2.jpg

What you see is that while the majority of individuals — greater than 99% 95% — have values less than 6 4, some do not. What they emphasize in the paper is that with individuals who have natural values greater than 6 4, you have to look at historical testing, because those individuals should have stable values over time (as indicated in the second chart). These individuals appear to also have somewhat greater variability in their values, but in general if they had high values once they should always have them.

I have no idea what Landis’s historical or recent tests are, but I agree that they need to check that not only was his value high but it hasn’t been before. I guess I would speculate that it wasn’t or we would have heard about this before. As to whether it would help, your guess is as good as mine. Not being a cyclist, I wouldn’t know.


David Winter
, I read the bit about testosterone aiding muscle recovery, and I can’t find evidence on Pubmed for it either. The only trials I can find for supraphysiological doses of testosterone look at overall muscle strength. I think that this muscle recovery story must come from trials for hormone replacement in men with low testosterone, so it is not clear that they are comparable. I guess I would speculate that considering the typical time scale for testosterones action, it is unlikely that measurable effects would be observable that quickly. All the other studies with testosterone show effects over the course of several (10ish) weeks.

UPDATED: So I checked where I looked up the cutoff value for legal action, and I can’t find where I read 6. It says 4 in both the UCI and the WADA protocols. Hmmm. Sorry guys. I don’t know why I got confused.

Considering that the cutoff is 4, it highlights Quitter’s argument that the standard may be too strict. If you look at that bell curve, there are a bunch of people who have values over 4.

UPDATED: Floyd is, as they say, busted. He failed his isotope test. More here.

Comments

  1. #1 Chris
    July 28, 2006

    Frankly, I’m not sure what counts as doping or not anymore. People with naturally higher levels of testosterone, or EPO are at an advantage. Is boosting your levels to match theirs cheating?

    Training at higher altitudes can lead to higher RBC counts. Simulating the effects with tents and specially designed rooms is considered cheating in some sports, though.

    As we learn more about physiology, we come up with new ways to mimic the body’s natural responses and the line becomes harder and harder to draw.

    I just don’t see any way that anti-doping agencies can win this race (short of 24-hour surveillance)

  2. #2 jepalmer
    July 28, 2006

    Thanks for this. Every time a story about doping hits the news, I’m asked how the authorities can really be SURE the athlete did anything wrong, since testosterone (or RBCs) are naturally produced. This is a really helpful summary of the relevant research.

  3. #3 Scott Belyea
    July 28, 2006

    Very interesting … thanks.

    Just one point – from the linked article:

    a ratio of testosterone to epitestosterone greater than 4:1 is considered a positive result and subject to investigation. The threshold was recently lowered from 6:1.

  4. #4 wamba
    July 28, 2006

    I think it’s time to break out the conspircay theories. Considering the hoo-ha about Lance Armstrong a few months ago, is it possible that someone with access to the samples and possibly an anti-American bias has done some tampering in an attempt to discredit Landis?

  5. #5 PoliticalWarZone
    July 28, 2006

    Hi, I saw this at Townhall & linked it to our site, if you don’t mind?!!

    Thanks, so much!!

    PWZ

  6. #6 Jeff
    July 28, 2006

    John Eustice of ESPN is reporting that Landis’s high ratio was caused by a low epitestosterone (the denominator) level, not a high level of testosterone (the numerator). In other words, he doesn’t have a high testosterone level, just a high ratio because of a low denominator. How is it possible to get a low epitestosterone level and why? Would that help performance? What is going on?

  7. #7 Jake Young
    July 28, 2006

    Good question, Jeff. I looked up what answers were available and added an update at the bottom the post.

    Hi, Townhall.com people. Feel free to stay a while. If you have other technical questions, comment them here and I will be happy to answer them if I can.

  8. #8 quitter
    July 29, 2006

    This article is enormously useful. I’m concerned about the arbitrariness of their deciding on the 4:1 or 6:1 ratio however.

    What are the limits that they put on this ratio in relation to normal biological variability? Is it two standard deviations from normal? Three? Even if it’s 4 standard deviations from normal it will happen about 1 in 100 tests.

    I feel bad for the guy. There are a lot of explanations that fit that answer to the test that wouldn’t indicate doping. Not to mention, as you have pointed out, testosterone probably wouldn’t help a bicyclist that much that late in the game. Blood doping I understand, but steroids? How are they abusing steroids without developing all the sequelae that people like Ben Johnson, Barry Bonds and Arnold Schwarzenegger have gotten? The wide jaw, the big head, the generalized increase in muscle mass don’t seem to be present in these guys, and why would they want it? It would be like a jockey taking steroids, they depend on being so light, any weight gain would be a negative result.

    So, I don’t really believe he was taking roids. I’d only believe it if they show in an isotope test he is on something artificial.

  9. #9 David Winter
    July 30, 2006

    First up I’m with guitter on thinking it unlikely a road cyclst has much to gain from anabolic steroids.

    Second, although testosterone might help building up muscle in training it has also been suggested to help in muscle recovery (check out the bottom article here, published before the whole Landis afair broke. Though a quick glance at pubmed seems to offer little support)

    The timing of his results and the tests are a little worrying – blows up on stage 16, recovers overnight to blitz the peleton on stage 17 then tests positive?

  10. #10 quitter
    July 30, 2006

    Another athlete has failed this type of test. A sprinter that has been a big proponent of keeping sports drug-free no less.

    I’m thinking maybe their test is too stringent?

  11. #11 alyssa
    July 30, 2006

    Could Floyd’s low epitestosterone be due to the large amount of water he drunk during the stage?
    Obviously I’m way above my paygrade here.(grin)

  12. #12 Sidney
    July 31, 2006

    Great article.

    But the ratio of testosterone to epitestosterone is 4 to 1, not 6 to 1, a policy set by WADA.

  13. #13 Kevin
    July 31, 2006

    Something that wasn’t mentioned in the article is the fact that his overall testosterone level was reportedly low. A lower testosterone / epitestosterone level means that a smaller change in either one produces a larger difference in the T:E ratio. So while it may remain “relatively” constant, small changes could mean a big difference in the ratio.

    Also is there any research as to how the body responds with production of E and T after something like Landis’ bonk the day before. Not knowing anything about physiology it still seems reasonable to me that the body would selectively ignore certain things, say producing epitestosterone, in favor of more important recouperative tasks, say converting E to T.

  14. #14 J. Summers
    July 31, 2006

    The T/E ratio threshhold is no longer 6.0 but 4.0. For a good article on the “competition” between cheaters and testers, see: http://www.gladwell.com/2001/2001_08_10_a_drug.htm

  15. #15 Jake Young
    July 31, 2006

    People keep mentioning this bit about the threshold being 4 rather than 6. For some reason I remember reading in the WADA literature that if you have 4 it is deserving of scrutiny but not necessarily a failed test. Anything over 6 is a failed test.

    I will find it if I have a moment.

  16. #16 brian
    July 31, 2006

    UCI ratio is not 6:1 its 4:1 which is really low.
    What really gets me during the whole month of July no one was talking about cycling or the tour and now every Joe/Jane Schmo is talking about a sport they know nothing about.

  17. #17 Chris
    July 31, 2006

    It seemed Landis bonked on stage 16, neglecting to eat and drink enough during the race. Could this drop in blood sugar the previous day followed by a binge nutritional night cause the T/E ratio to go out of whack?

  18. #18 Skates
    July 31, 2006

    A shot of alcohol is usually 1 oz, and converting that to grams gives you 28.3495231 grams. Usig your estimated value of 140 grams and dividing that by 28.3495231 grams gives you a little less than 5 shots.

    That’s completely feasible for a human being without raising the blood alcohol level greatly!

  19. #19 Jake Young
    July 31, 2006

    Shots aren’t 100% alcohol Skates (unless the shots you are taking are much more interesting than mine). You have to factor in that Scotch is in the 80-100 proof area.

  20. #20 Scio
    July 31, 2006

    You article is using the assumption that the testosterone was used for muscle growth which can be the case. But if you are a close follower of professional cycling you would also know that testosterone patches are used to aid in recovery – especially useful during long stage races like the Tour de France.

    Coincidence that Floyd had blown up completly the previous day and lost 10 minutes and then the following day (Stage 17 – where he tested positive) blows everyone else away?

  21. #21 Jake Young
    July 31, 2006

    Scio,

    I can absolutely accept that professional cyclists are using it for reasons other than raising muscle mass. I was just reporting that in my literature search I was unable to find any evidence that it would be effective for aiding recovery at supraphysiological doses. (If someone finds one please let me know and I will post it.) This is also not to suggest that it isn’t effective — simply that I am not aware of evidence for it.

    With respect to the issue of coincidence, let me add a little background. For some time it was debated whether large doses of testosterone were effective at raising muscle mass. The evidence to that point had been largely anecdotal, and many people could still argue that the effect was a placebo that just motivated people to exercise harder.

    It is possible that testosterone aids recovery, though I stand by my assertion that I doubt it would be effective so rapidly. Most steroids do not act overnight.

    However, it is also possible that Mr. Landis took the drug, felt that he would have more endurance, and therefore pushed harder.

    I do not believe that we can at this time say whether it was coincidental, but I am prepared to believe that it was.

  22. #22 Pigilito
    July 31, 2006

    Nice post on the science behind the test. I found it very helpful in understanding what’s going on. One quibble: the ratio used to be 6:1. It is now 4:1. I’ve read that his ratio was 11:1. Going to be hard to make the booze hound argument if that was his ratio.

  23. #23 Scio
    July 31, 2006

    Here’s a short article on the use of testosterone in aiding recovery times for pro cyclists (bottom of page):

    http://www.cyclingnews.com/news.php?id=news/2006/jul06/jul07news3

  24. #24 S.Hinman
    August 1, 2006

    Is it possible that taking DHEA could alter the T/E ratio? It is not uncommon for people with hypothyroidism to also have low adrenal gland function. DHEA supplementation is sometimes used to offset the low adrenal function.

  25. #25 moby
    August 1, 2006

    Haven’t found any studies on the very short term (hours) performance benefits of testosterone(other than anecdotal reports from professional cyclists in the recent press). However all the experts who’ve been so willing to talk to the media and who are saying you need to take it for 12 weeks or longer might want to read this article that shows very high performance increases in 3 weeks:

    http://www.newscientist.com/article.ns?id=dn6265

    I expect it’s not that easy to set up and fund research on steroid use for ethical reasons etc; as well as the fact that it’s most often and most obviously associated with muscle building rather than performance in endurance sports. (Although by all accounts it’s widely used and fairly easy to mask, at least from the normal T/E ratio test – albeit not always successfully.)

  26. #26 Kim
    August 2, 2006

    Landis has a thyroid condition and takes a thyroid hormone daily. He also takes cortisone shots for his right hip. Could either of these drugs affect the findings?

  27. #27 Austin
    August 5, 2006

    Is it possible that someone could have slipped him testosterone without him knowing it so that he would flunk the test? It does not make sense from what you write that he would suddenly have an aberrant test result toward the end of the race when the benefit of the taking the drug would be so little and the consequences so devastating.

  28. #28 done in
    August 5, 2006

    Guilty, guilty, guilty. Good analysis, confirms the obvious. The guy is a liar and should justa admit it.
    Lance was just a little smarter.

  29. #29 Kevin
    August 6, 2006

    Landis tested negative two days before. As the yellow jersey weared on on the last two stages he would have been tested again. What were those results?? If testosterone is introduced to his system externally, how long does it linger?

  30. #30 miws16
    August 6, 2006

    One thing that is still not addressed is the fact that the synthetic testosterone/bad T/E ratio hasn’t been found in the testing that was done AFTER Stage 17. He had two more tests, four if you count both A & B samples. Why didn’t it show up in those? At a ratio of 11 to 1, it seems like subesequent tests would have to yield 8 to 1 or something like that.

    Also, I actually take Androgel (testosterone gel) due to implications from a pituitary tumor for low testosterone. On my last visit to my endocrinologist, he tested my HEMATOCRIT level. Apparently your hematocrit can be boosted by testosterone. I doubt this would occur immediately, but it certainly makes testosterone more appealing to cyclists, as the effect would be similar to EPO.

  31. #31 nathan.koenegstein@bchs.edu
    August 6, 2006

    If he was below the four to one ratio how much testosterone would you have to take get the E/T ratio to 11:1 to me that seems like an awful lot. The article posted by scio said cyclist use a patch on their scrotum for recovery but doesnot have much effect on blood testosterone levels…..to me the whole situation sounds a little fishy

  32. #32 mghorning
    August 8, 2006

    Obviously, there are many factors related to the ratio. Many of them “assumed”.

    I will put forth a reality that certain isolated, or contained populations, develope traits that are not common in the surrounding population physiologically.

    Given that Landis grew up in a Menonite community deprived of certain cultural exposure Alcohol, etc. He also would be significantly more likely to share an excessevily common parentage (gene pool) that is rare in eurpope, but not so much in remote or isolated communities elsewhere.

    There are certain known physiological conditions that exist in American aboriginal populations and Jewish lineages that are almost unknown amongst even within their broader population.

    Example: Alcohol has not been good to native populations in this country and is physiologically known that they do not metabolize it as their European counterparts.

    Given the religous communities that populated the northeast settlers abstention from alcohol prior to arriving in America coupled with 150 plus years of sexual and cultural isolation it might not be uncommon for an individual to have a greater increase of testosterone or a natuarlly low epitestostone level that would severely skew the ratio.

    If Landis produced 150% the norm for twenty grams of alcohol and had a twenty percent lower epitestorine level, he wouldn,t pass.

    The test seems tight given the latitude for production in diet, excretion and many unknown factors like that which I have just mentioned.

  33. #33 Frank
    August 9, 2006

    Jake, excellent coverage. I’m wondering how much information we have about how these are flushed out of the body. In 20 years of avid viewing, I have never seen a cyclist drink as much as Landis did on Stage 17. The commentators remarked on it, but hazarded that he was concerned about “cooking” again (confusing a blood-sugar “bonk” with dehydration, to my non-medical mind). I would estimate he drank 3-4 times as much as normal for the stage conditions.

    I wonder whether the huge fluid throughput would have affected either side of the T:E ratio, and which way. A failed attempt to flush some “naughty” testosterone away, or an attempt to stay hydrated (as per the commentators), but with the unintended consequence of lowering the Epitestosterone level?

  34. #34 truth machine
    August 10, 2006

    A failed attempt to flush some “naughty” testosterone away, or an attempt to stay hydrated (as per the commentators)

    That’s like “intelligently designed, or evolved?”. Hey two possibilities, must be an even call.

  35. #35 Anonymous
    August 11, 2006

    Well, Landis failed his failed his isotope test, didn;t he? there is little we can speculate or argues against that.

  36. #36 Anonymous
    August 12, 2006

    It sounds like nothing has been proven other than a highly questionable test or tests had positive results. How people react to these results indicates more about people than it does about Landis.

  37. #37 prologue
    August 16, 2006

    Awesome discussion. The dependance of a ratio allows for to many unknown variables to impact the result which can ruin the reputation of a rider.

    Cycling a Grand Tour is an insane demand on the human body. What the human body goes through during 23 days of a tour will remain a mystery. The pro rider Alexander Vinokuroff’s body hates rest days. The day after a rest day he looks like a club cyclist. The 2nd day after a rest day he looks like superman. What’s happening with Vino’s biochemistry?

  38. #38 david brower
    September 6, 2006

    It should be noted that the actual lab documents have not escaped the doping tsardom yet. These would be the “Final Analytical Sample Report” including a “Laboratory Documentation Pack”. The only data that has been reported is that on the one-page “adverse analytical finding” form, which may not be of much use.

    The final reports are expected in the next week or so.

    I personally don’t have quite as much faith in the tests as certain proponents would have the public believe. If they were as infallible as advertised, we would not see the apparently huge gap we do observe between the number of AAFs (lab reports) and actual santions, which is somewhere between 3:1 and 10:1 as far as I can tell.

    For those interested, I am trying to keep a rundown of Landis related news and research at http://trustbut.blogspot.com.

    TBV

  39. #39 Kevin Hannah
    November 20, 2006

    As many watching Landis comeback to win the Tour de France, I was suprised by the positive testosterone test. I have followed the stories related to the case and up until recently remained undecided as to whether Landis ingested synthetic testosterone or if there was some other reason for the high ratio (11:1).

    I am not a professional athlete, however I am subject to random drug testing at work. Recently (the past 5 months) a steroid panel was added to these tests that included a testosterone ratio. I submitted to a random test a couple of weeks ago and did not test positive for any of the anabolic steroids in the test. I was shocked to say the least when my testosterone ratio came back 14.9:1! The doctor at the lab said its the highest ratio he has ever seen. I am currently being retested with a new urine sample at the same lab as well as a second lab that will run more indepth tests. I have also had blood drawn by my own doctor to be tested on my own.

    I am a caucasian male, 37 years old. I work out five days a week and alternate between running (5-10 miles a workout) and weight lifting. I’m 5’11″, 170 pounds. Since this affects my career, I am searching for possibilities for my result. This is the first time I’ve been tested and have never taken any type of steroid, or any other performance enhancing drug. If anyone has any suggestions I’d appreciate it.

  40. #40 david brower
    December 31, 2006

    Congrats; this piece has been nominated for a science blog award at http://neurophilosophy.wordpress.com/2006/12/30/an-anthology-of-the-best-science-blogging-of-2006/

    Tomatoes: this piece has not been updated since Landis’ release of the Lab Documentation Package, and has not considered the various analysis of both the CIR and the TE testing. Starting points would be

    http://trustbut.blogspot.com/2006/11/duckstrap-zeros-in-on-right-arguments.html

    and

    http://trustbut.blogspot.com/2006/12/through-te-tests-looking-at-calibration.html

    TBV