A Test For The Future, And An Admission From The Past

by Rant on April 2, 2008 · 49 comments

in Doping in Sports

Got a couple of things to mull over tonight. First is news that a human growth hormone test will be available for use at the Beijing Olympics later this year. According to a New York Times story, test kits are already being manufactured by an unidentified European supplier.

According to the Times’ story:

A test for H.G.H. has been around for several years, but doping officials could not find a company to manufacture the kits on a large scale. Only a few hundred athletes were tested at the 2004 Games in Athens and at the 2006 Olympics in Turin, Italy. A few out-of-competition tests have also been conducted, although it is believed that only a small number of athletes, if any, have tested positive.

“We are pleased that the test will be in place for Beijing,” David Howman, WADA’s director general, said in a telephone interview. “The test has been around for a while; it was a matter of finding the manufacturer.”

Details about the test are hard to come by, and not much information is actually offered in the article quoted above. But there are a few things that can be deduced about any truly effective test. Including:

  • Because most of us produce HGH naturally, the test must be able to effectively distinguish between natural and synthetic HGH. One possible way to do that would be through the use of carbon isotope ratio testing — although there is no guarantee that this technique would be used, or that it is the only method for making the distinction. Edit: Actually, it appears that the test is based on the molecular weight of HGH, not a CIR/IRMS test. For more info, see the comments to this post.
  • The amount each individual produces is variable, so the criteria for a positive test must take that variability into account.
  • Most people produce progressively less HGH as they age, so the amount that would be normally present in a 20-year-old will be different than for the same person at age 40, for example.
  • The test should have been thoroughly vetted by peer review, and multiple studies with large enough test groups to draw statistically significant conclusions.

One suggestion in the Times article is that HGH can only be detected during a certain period of time. And no one is saying exactly how much time has to pass before the hormone is no longer detected.

Howman said that WADA had spent the past several months working with the company to ensure that the test was reliable.

“At least we can now proceed, but it had to go through the scientific process to make sure the kits were reliable,” Howman said.

WADA will not disclose how far back the test can detect the use of H.G.H., fearing that athletes may be able to determine how to avoid testing positive — although it is not believed to be more than a couple of days.

“We don’t want athletes to think if they use it one day, they are going to be O.K.,” Howman said.

Gary I. Wadler, an internist and a member of WADA, said that although the test could not detect the presence of H.G.H. many days after it was used, it would act as a deterrent because athletes needed to use the substance every day for it to be most effective.

Call me a skeptic, but if the test has only gone through a few months of testing, I have some questions about whether it is ready for “prime time.” Also, the few studies of HGH as a doping method haven’t determined if HGH is effective, or just how effective it might be. There is certainly a belief in some quarters (including amongst those inclined to cheat, and those looking to make a quick buck off those inclined to cheat) that HGH works. Most of what I’ve heard suggests that it’s effective when used in combination with other things — like various steriods. But I’m under the impression that more study needs to be done in this area.

Over time, I suspect, we will find out just how thoroughly vetted this test is, and the details of how it works will become more widely known. All it will take is one highly publicized case to put the HGH test into the spotlight. And if the test really does what it’s supposed to, and if there really are cheats out there using HGH, my guess is that we’ll be hearing about some time in the late summer or early autumn.

Alexi Speaks

When Alexi Grewal speaks, he always manages to say something that gets the attention of cyclists and cycling fans. Grewal, the only American man to win a gold medal in the Olympic road race (Los Angeles, 1984), has always been rather outspoken in his views. In the late 80s or early 90s, he once claimed that there wasn’t a single climb in the 48 contiguous states that needed a gear lower than a 42×19 (or perhaps it was a 42×17, my memory is a bit vague — and VeloNews doesn’t have online articles that go that far back). Maybe for him. But he comes from Aspen, Colorado and (probably still) climbs like a mountain goat.

Now, he’s back with a different story. One about doping during his era as a racer. And one thing he tells in an article in the print form of VeloNews seems to point a finger at a wide cast of characters, including a certain saint from Wayzata, Minnesota. Here’s the quote:

VN: Are you worried that your confession could cost you your gold medal?

AG: Repercussions? My gold medal got stolen a year or so ago, so I do not have that to lose. I am tired of the whole mess. Everyone I ever knew stepped over the line. Except maybe [Steve] Bauer. Shoot, give him the [gold] medal. It has never done me any good anyway.

As of this writing, the transcript of the interview between John Wilcockson and Grewal hasn’t been posted on the VeloNews.com web site, even though a note at the end of the article says that the transcript would be available there. Perhaps they will post it in the near future. What you will find at the VeloNews web site is an essay by Grewal about doping during his era, and the need for change.

In both the print interview and the online essay by Grewal, he appears to suggest that the only way that the doping problem in sports will end is when athletes who dope start having to serve jail time. Grewal notes that this won’t be a perfect solution, as there will always be a few people who will be tempted. But a large number of people, he believes, would be scared away from doping if they knew that being caught would land them in the slammer for a significant amount of their lives.

The print interview closes with this observation:

AG: […] It doesn’t take much to make the playing field very uneven, especially if the best guys are using the best stuff. If you’re one of the average guys, and you don’t have the same baseline, what are you going to do? I don’t think things will change significantly until some of the top guys do real time. Five years in prison will definitely make a difference. The larger majority, probably most of the guys, won’t do it. They’ll change their habits, and the sport will change. A few will break the rules, and they will, because there are always criminals. But it has to be approached as crime. Otherwise, you’re not going to be able to affect the consciences of men if they just see it as sport with no consequence.

Of course, if it’s approached as a crime and real jail time is involved, that would move the prosecution of doping cases out of the hands of the anti-doping agencies and into the hands of the justice system. This could have some unintended consequences, like forcing the practices of the anti-doping system into greater public view. And that would not be a bad thing, by the way, because the challenges to the system that would certainly happen (imagine the Landis case, but played out in a regular court, instead) would certainly force the whole anti-doping system to change. There would be a greater scrutiny of the testing methods involved, and that would ultimately serve to make those methods more robust.

But, at the same time, it does mean that a few guilty people might go free — at least, until the next time they’re caught. Alexi certainly has a point. I wonder if he realizes the full consequences of what he’s advocating? Take the time to find a copy of the full interview, and take a moment to read his online essay. If nothing else, one thing you can always say about Alexi Grewal is that he’s certainly an outspoken character.

Larry April 2, 2008 at 10:13 pm

On the HGH test: the best discussion I’ve found of how it works is at http://sportsillustrated.cnn.com/2008/writers/david_epstein/01/17/epstein.HGH/index.html.

I am looking for more information. But I don’t think that CIR testing is involved here. Synthetic RGH is not produced from plants, so there’s not going to be a carbon difference between synthetic and natural HGH, at least none that I can see. The idea seems to be that natural HGH comes in different molecular weights, and synthetic RGH does not. This is There’s some antibody that is used by the labs to separate out the HGH — details are a bit hazy.

I will look for more information tomorrow.

karuna April 3, 2008 at 1:31 am

@Larry
Am I right when I think that you gave up on your summary of the Landis evidence?
If so than I woulkd like to thank you again for all your work!! 🙂

Rant April 3, 2008 at 3:46 am

Larry,
Thanks for the link. I’d heard about the molecular weight difference. One thing I’d be interested in seeing is whether diet (specifically, a vegan diet, with only plant proteins consumed) has any impact on results. If it is a difference in molecular weights, it wouldn’t take too much effort on the part of those supplying illicit hormones to make some with a mixture of molecular weights. More expensive to create, perhaps, but not out of the realm of possibility.

William Schart April 3, 2008 at 4:41 am

Doing hard time for doping in sports is an interesting idea, but there are many questions about this. As mentioned in Rant’s post, putting these cases into the court system brings possibly new standards of evidence and proof, and hence can effect the outcome of cases. Quite possibly, some cases which would now result in a guilty verdict might result in acquittal.

But there are other questions I see. Cycling is an international sport, and each country would have to pass laws for this, including listing prohibited substances. This would almost certainly result in differences between countries; differences which riders could exploit. I don’t think a law could simply refer to the UCI or WADA list of banned substances; this would in effect allow these organizations to legislate. Here in the US, I would expect a constitutional challenge is such were done.

Then there would be a question of extradition. Tests take time to conduct. By the time a non=negative AAF was determined after say the Tour, a US rider could very well be in another country. Would that country extradite the rider back to France? Might not happen, especially if there were questions about how the tests were done, or how the French legal system compared to the country in question. (Note, I do not intend here to cast aspersions about the French legal system, but I do believe that it is based on different principals than the US system, or possibly other legal systems to. It is possible that one country might find these differences enough to not extradite, much as some countries will not extradite to the US if the death penalty is involved.)

Also, I have questions about whether or not the presumed deterrent of such a move would have much result. Hard time for other types of drug use has not seemed to have much effect, why should we think it would have an effect on athletes.

Finally, isn’t it a crime in the US to use prescription drugs without a prescription?

Thomas A. Fine April 3, 2008 at 6:00 am

Hi Rant,

I don’t think a carbon isotope test would fit in a “kit”.

Apparently, the hGH is a protein that comes indifferent varieties, or isoforms, and the synthetic version is only one variety. The test looks for too much of the synthetic one. Of course, it would be too easy if the synthetic one was the typically rare one. It’s of course the most common form, so both natural and doped states are mostly the same isoform. Doped profiles would just be more tilted towards one.

The different isoforms are produced by different genes. So in other words, each person’s natural proportions are determined by their own genetic pecularities. Who’s to say that a minority of people don’t have genes the produce a profile that matches doping?

Also, hGH levels vary widely, apart from reasons you suggest. One web site I found suggested 100-fold changes just based on sleep, stress, exercise, health, etc. One wonders if such widely varying natural production levels maintain a balance of production from one gene to the next, or if such changes can alter our natural balance of hGH isoforms.

Sounds like more of the same – oversimplified assumptions about a poorly understood production mechanism.

tom

karuna April 3, 2008 at 6:17 am

I have difficulty to put into words why I am against jailtime for dopers.
So let me put it like this: it FEELS to me that the balance “crime” versus penalty is way out balance when jailtime comes into the picture.

Concerning the HGH test.
When an antibody is used than it’s probably to bind the HGH to the antybiody to isolate it from other substances in urine or blood.
After the isolation the MS could be used to test for the molucule weight or a form of gel electrophoresis, like in the epo test.

Rant April 3, 2008 at 6:31 am

Tom,
Good points. Thanks.
Karuna,
Thanks. That’s along the same lines as what I understand about the use of antibodies.

Morgan Hunter April 3, 2008 at 7:48 am

Well – well, well – what a co-inkidink – since we are on the topic of hGH – lets look at what the Google advertisers say about it…sorry Rant – but I must assume that there is a perversity to this whole thing…This is the group of “Ads” that came along with your article here in Austria….

http://www.VitaminExpress.net — “HGH – so bleiben Sie jung” – (That’s how you stay young) — “Wachstumshormon (HGH) natürlich steigern ohne Nebenwirkungen” – (Growth Hormone (hGH) naturally raise your levels without harmful side effects)

****So let me get this straight – I can “safely take hGH WITHOUT SIDE EFFECTS!” Yet – I have just read your article Rant – WADA and the IOC have dumped bucks into this thing and it’s being advertised on Google?

http://www.1stplace-supplements.com — “Buy Human Growth Hormone
Buy Human Growth Hormone (HGH) Discounted Prices. Fast Shipping.”

****According to the implications in the article – this stuff is going to be and is “banned” – So what’s going on?

InternationalSupplements.com/H — “Huge Blowout Sale 60% Off
HGH Releasers “100% Pure” “Pharmaceutical Grade” High Potency”

******You know – anytime I go and by my drugs – I always insist on pharmaceutical grade quality…

http://www.HumanGrowthHormone.com — “HgH.com AntiAging
120 Day Guarantee Ships same day- Buy 2 Get 1 Free”

AstroNutrition.com — “Human Growth Hormone
Weight loss, lean muscle, immune All HGH products now 30% off!”

*******Hey – what is wrong with you guys? What exactly do you have against us old geezers losing some access body fat – packing on lean meat rather then a normal beer belly? And – I can GET IT ALL AT A 30% DISCOUNT – What – are you all anti-capitalists or what?

Rant – this is not meant as any form of criticism – it is merely my attempt to bring something to your attention…As you can see – Google world amok! – Lets play a game – write some other articles and see if some idiot has written a program that will attach itself to whatever you come up with…

As to the article – I’ve got just one small observation – WADA is doing the “same old/same old” – it seems determined to become internationally known as an authority on the moral standards of every one – aren’t they just so precious? How about if we hook them up with the Advertisers for the very product that they are banning for us?

Just a thought……

Rant April 3, 2008 at 8:40 am

Morgan,
It is perverse. It’s the perversity of Google Ads. They parse the content and put up ads they think are “appropriate.” Of course, I can filter these beasts out, and will, but I can’t do it pre-emptively. Now, the ones you’ve pointed out are soon to be filtered.

Morgan Hunter April 3, 2008 at 9:50 am

Rant – I was making no comment against you or the Rant Line – I implied no responsibility or collusion – I just thought that it is truly macabre – what is truly perverse is the situation that these ads are up out there, here comes WADA world doing its thing and all any one needs is to Google any subject and bingo! – you got access…

Michael April 3, 2008 at 9:51 am

How can a test be scientifically vetted if we can’t find any record of this process on the web? I guess we’re just supposed to trust WADA? I am left thinking that this test is as bogus as the one that indicted Tyler Hamilton.

Based upon my rudimentary understanding of hGH:

What will WADA measure? Testing HgH values is currently possible but a top end baseline is not relevant (a typical male could have values for hGH in blood between 0 and 5 ng/ml but it is not unusual to be as high as 30 ng/ml). hGH is released into the blood in doses (as opposed to continually) when people are sleeping, and is only in the blood less then an hour. In the liver most of the hGH is bound and some is converted into somatomedin-C, AKA Insulin-like Growth Factor- I (IGF-I) – I think. Once produced, IGF-1 remains in the body for more than 24 hours. In 2001, Dr. Jenkins at Cambridge University studied seven athletes with an average age of 23, who continued their training programs after starting HGH supplementation (sorry I couldn’t find a link). This test lasted 2-weeks, and showed that IGF-1 levels were doubled. This test confirmed a test that was done at the University of Vienna in Austria in 1993. Is IGF-1 what WADA will be monitoring? Another interesting aside, these studies both showed that hGH does not benefit weight training. In fact the opposite may be the case, given enough time. But the studies were way too short to show the real effects of hGH supplementation. Anecdotal evidence shows people get best results after months of use.

Monitoring IGF-1 has it’s own problems. Things that effect IGF-1 levels (and also hGH) include nutrition, stress, athletic activity, body mass index, time of day, estrogen levels, or any insulin related issues (like eating 85% of your calories in the form of carbs). In these cases the liver will not produce IGF-1 in a way that mirrors the HgH introduced into the blood. Additionally, IGF and hGH levels and their proportions vary with age. So a test may reflect high IGF-1 levels, but this would not be proof of hGH use; the ADA’s would need to have a baseline IGF-1 level for the individual.

If I were inclined to take hGH to gain an edge, perhaps I would take IGF-1 instead. If they are actually testing for the proportions of the varieties of hGH (the theory stated by Karuna) then I would definitely cut out the middle man and go right to the IGF-1. The big question I have, if Karuna’s theory is correct, how many people and athletes did WADA test to verify if the proportions of hGH are reliable and stable? And was this testing done independently, or was it done by someone who had a vested interest in the test’s success?

“And here’s the final and most compelling reason why IGF-1 is being used right now, and why the demand for this hormone will increase exponentially as time goes by: IGF-1 is undetectable by both blood and urine testing. Because IGF-1 can be injected directly into the muscle, it never enters the blood stream. Therefore, a muscle biopsy is the only way to determine if a person has used IGF-1. And the anti-doping forces will never, ever be allowed to take muscle biopsies from athletes.” See: http://www.thesage-speaks.com/igf-1-insulin-like-gowth-factor-explained/

ludwig April 3, 2008 at 10:00 am

Anti-doping laws have been enacted or are being considered in a number of European nations. Usually, it’s the leftist parties that advocate such laws, while the conservative/nationalist parties block them (ie Puerto may not have been possible without the Aznar government, etc). Part of the reason nationalists oppose doping laws is sporting nationalism–they feel that if you enact doping laws, their own athletes would be at a disadvantage.

I’m not sure what to think about these issues (partially because I’m a skeptic on the usefulness of the drug war against recreational drugs) but I suppose it’s true that if you want this behavior to be considered anti-social and irrational, then criminal penalties for doping might be the way to go.

Again I think a distinction between amateur and professional is key here. It’s clearly in the interest of the state to prevent amateurs at the collegiate or even Olympic level from being forced to take drugs in order to compete. The question is whether professional sport is another matter (especially in cycling, where, as we know, doping has always been present and is very difficult to eradicate). A possible solution might be drawing a line once and for all and keeping professional athletes (ie dopers) out of the Olympics and similar events, as well as enacting anti-doping laws against amateur doping.

Rant April 3, 2008 at 11:38 am

Morgan,
No offense taken. Google Ads don’t allow you to block entire categories of ads. If they did, I’d have blocked ads for steroids, various “supplements” and things like HGH a long time ago. It’s a catch-as-catch-can proposition. Every time I see an an ad that I don’t think should be here, I add it to the blocked list. Even then, it can take some time before those sites get blocked.
Michael,
Good info about IGF-1. If I were hell bent on doping, I’d certainly want to skip the middleman, so to speak.
Ludwig,
I’m with you on separating out the pros from the amateurs in the Olympics. Adding pros to the mix has made a mess out of what the former “Olympic Ideal” was all about — competing for the love of the game (or sport).
I share the skepticism on whether making doping illegal would really work. The so-called “War on Drugs” is a good analogy for how such policies can be ineffective (or complete failures).
One of the problems with criminalizing doping is this: Some things that are considered doping drugs/products are quite legal for uses in other contexts. For example, finasteride — which many men use to treat thinning hair. Now, someone somewhere postulated that it could be a masking agent, and added it to the list of banned substances. So, would an athlete who tests positive for finasteride be sent to prison, while the rest of men in our society could use the drug with no consequences? That seems pretty bizarre to me, but a real possibility. One has to wonder whether such a regulation could stand up to the legal process, too.
In criminalizing doping, a lot of thought would have to go into exactly what types of doping would be illegal. And, for the many (perhaps most) of the likely suspects, there are already laws (in our country, at least) against the use of the products without proper prescriptions, and laws against distributing these products improperly, too. (Of course, the “supplements” industry has found a way around some of these laws, but that’s another story.) So, in those cases, do we even need any new laws? How about we just enforce the laws that are already on the books?

karuna April 3, 2008 at 12:44 pm

Michael
This is how I understand the HGH test based on the article Larry gave us.
All HGH (endogenous and exogenous) is bound to an specific antibody to isolate the HGH from the other substances in the blood/urine.
After that they will try to make a distinction between endogenous end exogenous HGH by the difference between the molecule mass in exogenous and endogenous HGH.
Theoretical the endogenous HGH exist for 80/85 % out of heavy molecules.
Exogenous HGH has always heavy molecules.
Using exogenous HGH will mean that the 80/85% will rise to 90 or so %.
That is what they will try to measure maybe with the MS which measures molecule mass or a gel electrophoresis.

As far as I know have all hormone systems a feedback system. This means that when the, for the body necessary, level of the hormone is already in the body, the body will stop with making the hormone.
It is true for EPO for instance. That’s why there are stories that there were riders with no endogenous EPO in their urine or blood.
That system is also responsible for the fast decrease of the effect of EPO: the body stops making EPO until the level of red blood cells are back to what the body “thinks” it needs.

Because of that system it is possible that the HGH measured could even have 100% heavy molecules.

Forgive me the use of simple words, I really lack the words when trying to explain something technical, so I go back to simple English.

Jean C April 3, 2008 at 1:59 pm

France has already criminal laws for doping. But that is the providers who are risking the most with from 3 to 6 years jail!

Apparently last year on TDF the costs were 70k euros to deliver fresh blood on TDF. A price related to the high risk for the people carrying the blood in France across the border.

For athletes, the common laws should be applied, I don’t see a difference between stealing a car , money or stealing the prize money of a sport event. Prejudices seems similar for victims!

karuna April 3, 2008 at 2:52 pm

Jean C

You are actually giving me a good example.
The use of doping could be compared to stealing a car/prize money.
I don’t know because I have never tried it :), but I don’t think that stealing a car could result in the Netherlands to time in jail.

Besides that, imagine this: HGH use is not proven to give a better performance.
The use might very well be just psychological (there is research going on right now to the psychological factor of dope use) if any effect at all.
So although using there is no “real” effect from the HGH use as a substance.
And then the use might result in time in jail?
I think the balance between “crime” and penalty is completely lost in such cases.

William Schart April 3, 2008 at 5:09 pm

Jean:

I am not sure that doping is necessarily the same as stealing. I guess you could argue that someone how placed well enough to get prize money while under the influence might be obtaining that under false pretenses, but that would be fraud. And what about the domestique who dopes so he can beat the time cut off. And would you jail athletes who cheated in other ways? Maybe we should send Belichek up the river?

Regarding the Olympics and amateurism: I have seen the idea that the amateur “ideal” was largely a matter of class. That is, the only ones able to compete in such a competition without financial reward was the upper class; amateurism served to guarantee that the unwashed masses would not sully things. I am of the opinion that, with all the politics, boycotts, etc., the Olympics are past their prime and should be retired. If a true amateur code was instituted, it would probably die. Few athletes, at least in “big” sports are truly amateur. A number of years ago there was an attempt at a professional track and field league, one of the reasons it failed is the fact that “amateur” athletes would have to take a big cut in pay to compete at the professional level, so the league was mostly the over the hill gang.

karuna April 4, 2008 at 12:50 am
Jean C April 4, 2008 at 2:44 am

By the exemple of stealing I just wanted to say that the common law could be used, a jury or a judge could judge and evaluate the prejudice and give an adequat punishment. That could be jail, fines and money for victims!

Jean C April 4, 2008 at 2:47 am

Karuna,
That is the better for sport, the number of spectators will increase drastically
http://www.steroidreport.com/2008/04/01/swimmers-must-compete-naked-swimsuits-give-unfair-advantage/

karuna April 4, 2008 at 2:48 am

I just read in a newspaper that the laywer Mino Aulette (italian, 78 years of age) is chosen to be the president of CAS until 2010.

karuna April 4, 2008 at 3:38 am

I found this article trough a university link (so I can’t give a link, that requires a id and password):
Maybe it’s helpfull. The thext is the abstract:

A. Kniess ・ E. Ziegler ・ J. Kratzsch ・ D. Thieme ・
R. K. Muller
Potential parameters for the detection of hGH doping

Published online: 16 May 2003
c Springer-Verlag 2003

Abstract The aim of our hGH application study with
non-competitive athletes was the investigation of selected
serum parameters from different processes affected by
hGH. Fifteen athletes (age 21–33, mean 24) were treated
with 0.06 IU hGH/kg BW per day or placebo (10 hGH,
5 placebo) respectively for 14 days. Blood samples were
taken prior to, during and until 10 weeks after treatment.
The concentrations of the following markers were determined
in relevant serum samples: IGF-I, IGFBP-3, ALS,
PIIINP, PINP, osteocalcin, and leptin. The IGF-I concentration
increased rapidly within the hGH treatment group
and showed significantly higher levels compared to baseline
even 3 days after application. The response of the
IGFBP-3 to the hGH applications was lower in comparison
to IGF-I. The hGH group showed an increasing IGFBP-3
compared to baseline from day 4 till day 15. The response
of PIIINP to hGH is clearly delayed compared to the IGF-I
axis, but the PIIINP concentration remains on an increased
level for a longer period (from day 4 until day 21). The
time course and the extent of response varied strongly interindividually.
PINP and osteocalcin showed only a small
response to hGH applications. These parameters are characterised
by a strong scattering of base values compared
with the small response. In the hGH treatment group very
different leptin concentrations were found at the beginning
of the study, but after treatment decreasing leptin levels
were observed in all cases.
The determination of only one parameter will not be
sufficient for detection of hGH abuse. A combination of
markers by mathematical methods can be helpful to distinguish
between placebo and hGH-treated athletes. By using
the suggested discriminant function the data sets of hGH
and placebo-treated athletes could be separated without
false positive results. markers by mathematical methods can be helpful to distinguish
between placebo and hGH-treated athletes. By using
the suggested discriminant function the data sets of hGH
and placebo-treated athletes could be separated without
false positive results.

karuna April 4, 2008 at 3:44 am

There is something interesting in the introduction too about the use of anti bodies:

Introduction
Human growth hormone (hGH) is abused as an anabolic
hormone among athletes to enhance their physical performance.
Although prohibited in sports there is not yet an
approved method to detect hGH abuse. The simple quantification
of hGH in serum is not capable to detect growth
hormone abuse as hGH is secreted in a pulsatile manner
[1].
Many attempts have been made to detect hGH doping
in the recent years. The quantification of hGH in urine in
order to detect doping is not useful due to the proteinuria
during and after heavy physical activities [2]. Other hGH-related
parameters (e.g. insulin-like growth factor I [IGF-I],
insulin-like growth factor binding protein 3 [IGFBP-3])
are excreted in urine in very low concentrations with large
inter-individual variations [3]. Due to its very short halflife,
the determination of exogenous recombinant hGH
(rhGH) in serum by differentiation between recombinant
and pituitary hGH by using special antibodies is only effective
for approximately 1 day after the last hGH injection
[4].
The serum concentrations of IGF-I and its binding proteins
are altered in response to hGH applications. However,
the ratios of IGF binding protein-3/IGF binding protein-
2 (IGFBP-2) and IGF-I/ IGFBP-2 are insufficient to
prove hGH doping because of their enormous inter-individual
differences among untreated athletes [5]. In contrast,
IGF-I/IGFBP-3 ratios calculated from molar concentrations
of both proteins are reported to be significantly
increased in response to hGH applications [6].
The bone and soft tissue collagen metabolism is also
increased in response to hGH treatment. A long-term hGH
treatment study with healthy subjects aiming to develop a
detection method of the hGH abuse has shown that bone
markers scatter across a wide range inter-individually [7].
The authors published a discriminant function including
serum levels of different bone markers as well as of the
soft tissue marker N-terminal propeptide of type III procollagen
(PIIINP). By using this discriminant function the
authors distinguished between treated and untreated subjects
with approximately 2% false positive results [7].
Leptin, a polypeptide secreted mainly by adipocytes, is
also affected by hGH. However, its role as an indicator of
hGH action in healthy athletes remained unclear so far.
The aim of our hGH treatment study was to evaluate
biological parameters in human serum in view of their response
to hGH applications and of their intra- and interindividual
variations, and to develop a preliminary discriminant
function for distinguishing of hGH- and placebotreated
subjects.
For this purpose, IGF-I, IGFBP-3, N-terminal propeptides
of type I and III procollagen (PINP, PIIINP), osteocalcin
and leptin were measured in a blind, placebo-controlled
study with male, non-competitive athletes treated
with hGH in physiological dosages for two weeks.

karuna April 4, 2008 at 4:20 am

An overview. For the full text is an id and password needed again.

http://pt.wkhealth.com/pt/re/bjsm/abstract.00002412-200607001-00009.htm;jsessionid=H2bVHfsmv5hXqvKWWdvzDpnTTF2Jrjphx4LxyQN0klVnxhhk0bj7!172353749!181195629!8091!-1

When anyone is interested I can come up with relevant parts of the full text.

karuna April 4, 2008 at 5:06 am

JeanC
Hihi, isn’t brilliant!

I thought that it might be easier just to give the overview.
For those not interested in the test, just skip this post.
After this I promise to leave you all at peace 🙂

-The indirect method is the same I posted at 3.38 am.
-The indirect method is the method I had a theory of yesterday (although it is not possible for urine) in the post of april 3 12.44 pm.

The blood strategies
Two main strategies are currently being followed to detect hGH doping using blood: the indirect and direct approaches.

The indirect approach
Increasing knowledge about the naturally occurring variability of several hGH dependent factors (that is, IGF-1, the different IGF binding proteins (IGFBPs), or several markers of the bone turnover), individually or in combination, could provide a database of normal ranges for the concentration of these factors. This may lead to establishment of cut-off levels and description of so-called abnormal values outside the normal constellation of measures.

This approach, proposed in the mid-1990s, was investigated by an international panel of endocrinologists, but did not lead to a final solution for detection of hGH doping.28–30 The advantage of an indirect approach to target GH use is certainly that these biological factors are less variable or less sensitive than GH itself and should have a longer half-life in the body. A main objective of the study was to investigate the variation of these secondary variables during or after exercise. IGF-1 and IGFBP-3 in the hGH biological cascade as well as selected peptides involved in bone metabolism (for example the N-terminal peptide from the pro-collagen named PIIIP) or osteocalcin were considered as good biological markers of GH doping. These variables showed slight but significant changes after acute exercise. Moreover, the interindividual variability in the reaction to GH administration makes the use of indirect measurements almost impossible in a forensic description of GH misuse. It is obvious that rather than depending on the observation of a single value, a solution may be found in an algorithm combining all the biological variables from the cascade. Nevertheless, all these investigations clearly show that the indirect approach can certainly be used for screening and targeting purposes when a biological follow up of athletes will be acceptable in the sport community. But it cannot stand in front of a court as an absolute proof of doping. The regular evaluation of individual normal ranges in sportspeople could in fact lead to, as is currently done with haematological substances, better screening and targeting of the athletes and direct detection of hGH misuse as proposed in the following section.

What this study adds
The direct method of detection, based on double immunological tests needs to be well evaluated and validated. This review has described the difficulty sports authorities will face to prove hGH doping. At present, the short time window of detection of any method and the effect of exercise on natural hGH secretion still make any approach quite risky.

The direct approach
The Strasburger–Bidlingmaier group in Munich developed a so-called direct method for the detection of hGH doping.4,6 Two specific immunoassays have been developed to quantify several types of hGH isoform. Recombinant hGH is exclusively represented by the native 22 kDa form whereas the circulating hGH in the human blood is present in several forms (table 1). When the recombinant form is injected in the body, this increases, for a period of time, the proportion of the 22 kDa form in comparison with all other circulating forms. Moreover, with long term use, classic back regulation of the endogenous secretion of natural hGH occurs, which favours the proportion of the major 22 kDa sequence.

The proposed test was used during the Olympics in Athens (2004) and in Torino (2006). To fulfil the requirements of the World Anti-Doping Agency (WADA) code and the standards for laboratories, two double tests were applied to serum samples: the first test quantified specifically the 22 kDa form and the second test was a comprehensive assay measuring all forms present in the serum (see fig 1). The ratio was established and a cut-off defined to differentiate normal subjects (negative samples) from those having a significant higher proportion of 22 kDa hGH (positive samples). A second double sample test was used for confirmation purposes. The time window of detection for these tests is claimed to be between 24 hours and 36 hours after the last injection, depending on the dosage used. It is thought that hGH doping, to be efficient, needs multiple injections. Environmental influences, such as exercise, have been evaluated by Wallace et al.31 These authors measured total, pituitary, 22 kDa, recombinant, non-22 kDa, 20 kDa, and immunofunctional GH. They concluded that all isoforms increased during exercise, peaked at the end, and declined after exercise. At peak exercise, 22 kDa GH was the predominant isoform. After exercise, the ratio of non-22 kDa/total GH increased and that of recombinant/pituitary GH decreased. But it is considered that these changes will not invalidate the test after competition. Moreover, even if GH was used out of competition, this test should act a deterrent for its use. Since the test was introduced in 2004, no adverse analytical findings have been declared from any of the WADA laboratories that have validated the tests.

CONCLUSION

With new biotechnology products on the market, such as rGH and its precursors, the fight against doping must evolve with new analytical techniques and strategies based on different biological matrices. These new methods will need to be fully validated forensically before being submitted to any court challenge.

Larry April 4, 2008 at 7:10 am

Karuna, my real life has intervened in a major way, but I do plan to write a few more pieces on the Landis evidence!

Rant April 4, 2008 at 8:25 am

Karuna,
I haven’t had time to read every one of your posts, but what I’ve read so far is very interesting. Thanks!

bitch slap me back! April 4, 2008 at 9:21 am

I am soooo disappointed: the fireworks would have been fun:

http://www.velonews.com/article/74117/mino-auletta-named-president-of-cas

susie b April 4, 2008 at 9:27 am

Rant,

What do you think is behind the FFC’s request (demand?) to the ASO to get Paris-Roubaix on a UCI calendar pronto? Is it that they now realize the difficulties of “governing” a race, thanks to their experience with Paris-Nice? Or because the UCI was coming after THEM & they have NO money to fight them off after losing that recent court case?

Are you surprised or did you expect something like this? Do you think MAYBE this could be to Astana’s advantage? If the ASO races go back on the UCI calendar & the UCI insists all Pro-Tour teams can participate…. I guess that’s being foolishly optimistic as I just SO much want Astana in the Tour this year. Thanks to all the blood shed (how appropo..) in this escalated feud, I doubt the ASO would back down now, just “on principle”. They would lose face.

However, if the FFC refuses to “govern” the TDF, it would seem the ASO would HAVE to bend. At least for races in France, the FFC appear to be THE one group that can make the ASO & UCI come to some sort of working arrangement again. What do yo think?

And one more question – on a different topic. Which statements by Dick Pound caused the UCI’s anger & WHEN did he say them? I was outraged 2 YEARS ago over the stuff he was spewing & then last year before & doing the Tour (I think). Did Dick say something recently? And if they are statements he said months/years ago, what prompted the UCI to go after him NOW? Is it just because he is no longer the head of WADA? Isn’t the UCI busy enough fighting the ASO?! I’m thinking there’s MORE to this story.

karuna April 4, 2008 at 10:13 am

Thank you Larry,
I hope your real life is “only” busy and nothing “more serious”.
I am looking forward to your posts!

Michael April 4, 2008 at 10:46 am

Karuna, Thanks. Some good stuff.

But of course, none of these are actual tips regarding what WADA did to confirm the viability of their test. . .

Jean C April 4, 2008 at 3:06 pm

Susie,

Sometimes It try to imite badly Rant

To run Paris-Roubaix, it’s not a difficult job for FFC and they can earn some money in that case! That is just referees and some bureaucrat job. But there is no reason for FFC or ASO to keep for ever UCI out of their races… ASO just want to keep the control of their races.
Do to put P-R on historic calendar is just a political move, probably to reopen negociation that McQuaid refused!

For Astana, don’t hope. As you pointed there is no reason for ASO to change, especially when they risk to lose face!

Anger of UCI was the results of Dick stating that UCI was not fighting doping!

Rant April 4, 2008 at 6:36 pm

Susie,
First, sorry that your comment got stuck in moderation for a bit. Not sure how that happened, but it does every once in a while. My apologies for any inconvenience.
About the FFC wanting the ASO to put Paris-Roubaix on the UCI calendar: Don’t know what to make of it, though there is a part of me that thinks they’re doing it to get the UCI to back off the sanctions. It is a move that does give the impression that they’d like to work within the current structure, rather than create a whole new “league” from scratch. And perhaps they’d rather not have the headache of co-ordinating all the logistics (race commissaires, arranging for the anti-doping testing, etc.). Jean may well be right, it could be a political move.
And, as Jean says, don’t expect Astana to be invited to any ASO races this year. They would really lose face if they turned around and asked Astana to race, having already said basically, “Fool me once, shame on you. Fool me twice …” I don’t expect that Astana will be starting the Tour or any of ASO’s other major races. And, if they do invest in the Vuelta, there may even be pressure to keep Astana out of that race, too. (But that’s a ways off, and who knows what state those negotiations are in.)
I’m not sure if the FFC would try to maneuver a way to get the ASO to bend. But, this is the kind of thing that would help the ASO save face if the were to give in a bit. It would appear, at least on the surface, that they had to in order to make the race happen. And in the current state, one side or the other is going to have to give in if there’s to be any future negotiations. I’m not sure what scenario could play out to give the UCI room to bend — although Hein Verbruggen’s comments that the ASO had won certainly afforded a bit of an opportunity there. McQuaid pretty quickly squelched that story, though.
With the UCI’s lawsuit against Dick Pound, I see two possible motivations. More and more, I wonder if it was designed to scuttle his bid for the CAS presidency. They might really be after him for things he said over the years, but that really makes very little sense (does McQuaid ever?). The timing is odd, to say the least. But scuttling Mr. Pound’s attempt to head up the CAS? There’s an intriguiging possibility. From what I gather, the person who gets elected can’t be involved in any litigation. And if the UCI does go through with their lawsuit, Pound is in for a bumpy ride (as are McQuaid and company). I’ve got to wonder, are the Swiss courts a “loser pays” sort of organization. Meaning: If the UCI loses the suit, will they have to pay for Pound’s defense, too? If that’s the case, this whole lawsuit is a pretty risky adventure.
I’m not sure that Pat McQuaid and company are smart enough (or crafty enough) to have launched their lawsuit with the idea of torpedoing Pound’s chances at the CAS presidency. They’ve been so clumsy in other areas, that it’s a bit out of character. But then again, truth has a way of being stranger than fiction.

karuna April 5, 2008 at 1:23 am

I think that what the FFC says is what the ASO wants.
Maybe the move of the FFC is an answer to the Verbruggen’s threat: When you make a new federation, then we step aside, meaning you not just do the nice work like organizing a race, but you also do the OoC, sanctioning etc.
I don’t think that is what the ASO wants. They like the UCI to do the things they don’t want to do money wise and status wise.
Like this the ASO safes face, like Rant says and the FFC/ASO can “show it’s good will” in this conflict.
I think what happens lately looks different on the surface but is just another version of the same war.

I also wondered how the ASO could form a new federation, even when they really wanted to.
For organizing races they don’t need anybody. But what about the doping controls, what rules do they use in general and (more important) doping wise?
Can they just use the WADA rules? Shouldn’t that new federation need approving from the IOC?
In that case they are not lucky with Verbruggen being a member of that IOC.

karuna April 5, 2008 at 1:45 am

Michael

— But of course, none of these are actual tips regarding what WADA did to confirm the viability of their test. . .””

You are absolutely right. We don’t know anything about the way the test is being validated. If, and it looks like that, the WADA is using the “˜direct method’ with the antibodies, than the test should only be valid for one day after the fact. Since we know nothing about the criteria being used for declaring a “˜non negative’ finding, we have no idea how the test would holds under scientific scrutiny.

Like more things WADA comes up with it seems to me that “˜the frightening factor (for the riders: we can CATCH you)’ and “˜the reassuring factor (for the public: we CAN catch them)’, is more important than the “˜we are scientifically right factor’.

Jean C April 5, 2008 at 6:30 am

An other Joe Pap but older:
From http://www.cyclingforums.com/t-271814-20-1.html

I took 175 mg of testosterone per week by injection for one season.The ability to recover after repeated hard days was unreal. This dose of testosterone put my testosterone level above 1000ng/dl…about twice what a normal male puts out.
This is what the test does….it helps you recover. You can also get down below 6% body fat without loosing any muscle mass. On the down side test, and all steroids, will make you hold water weight and I was holding about 5 pounds I think. The water, however, is mainly intramuscular and it helps with strength a lot.

Sides…..acne, lost a bit of hair, and of course even a small dose of testosterone will shut down your natural testosterone production completely. When you stop it takes a while before your natural testosterone level comes back and you feel tired and with no sex drive at all.
Testosterone and all steroids will make your good cholesterol(hdl) basically disappear as well while “on” the stuff.

I also used EPO for 4 months 4000 iu’s injected sub Q in the lower belly fat once a week to build, and then 1000 a week to hold. 4000iu’s will bring your hematocrit up 1% a week.
I went up to 54% but even at 50%, the legal limit in the pro ranks , my performance was unreal.
My sustainable power output went from 350 to 420 in three months!!! That’s a 20% gain!!!
….more to read

and later

When I stopped my crit went down slowly over the weeks to my normal, which is about 43%. After stopping the testosterone it took about a month before my natural test levels returned to my normal, and a typical normal of 550nd/dl. I took clomid, an estrogen blocker, after stopping the testosterone, and this helped “kick start” the testes. I learned this form a bodybuilder. So my testosterone levels rebounded pretty quickly. But I did feel a little fatigued and my sex drive wasn’t good for a few weeks while I waited for my natural testosterone level to return. I felt crappy on the bike at this time.

I was able to keep some of the power gain that I got from the epo and testosterone. I slowly dropped down to a sustainable power output close to 400 watts, which I then held with proper lactate threshold work on the bike. So the drug use did have some lasting effects on my body.

The testosterone allowed me to recover from repeated HARD workouts….four a week on a steady long term basis.

William Schart April 5, 2008 at 7:56 am

I have been think some more about the idea of hard time for sports cheaters, including dopers. Here in the US, I believe that by and large, sports are left to police themselves. There are some exceptions, in particular, “fixing” an event is usually treated as a crime. This probably relates to betting and connections with organized crime. In some cases, I believe, NCAA coaches have been prosecuted when violations involve use of mail or telecommunications for fraud, as when fraudulent academic records are used to make or keep a player eligible. However, as best I know, legal authorities are not concerned if a coach calls a recruit too many times, or if a local booster gives the player a job. There have been a few prosecutions of hockey players when sever injuries have occurred from flagrant hits, but the idea here is that what occurred was an assault, and not so much that what occurred was ”
cheating”.

In general, I would suspect that most PEDs are controlled substances and that use without proper prescription is probably illegal in most countries. Of course, what is or is not illegal can vary from country to country. Also, some athletes have been sanctioned for doping when use of what is otherwise perfectly legal, even OTC, substances resulted in an AAF due to minor amounts of banned substances – like the skier who used a Vicks inhaler, not realizing that the US version container trace amounts of a banned substance.

If doping violates existing drug laws, then by all means the authorities with jurisdiction should investigate and prosecute when appropriate. This should be in addition to whatever internal sanctions the sport involved might make. So if a rider in the TdF uses EPO, and using EPO without prescription is illegal in France, then the French authorities well might take action. Of course, there well may be different standards regarding admissibility of evidence, standards and burden of proof, etc., such that an athlete who is sanctioned by the sport may not be convicted, indeed, may not even be charged in the criminal justice system, and perhaps vice versa.

My feeling is that in general, most sport governing bodies want to control how they deal with athletes who violate the rules of the sport. The NHL has rather tended to oppose criminal action against players who make vicious hits. And I doubt that the police and court system are really anxious to start prosecuting pitchers who “load up” the ball, or batters who cork their bats. I don’t think we need to have laws which specifically address the idea of cheating, even doping in sport, beyond what sorts of behavior would otherwise be illegal. If some guy down at Gold’s Gym uses steroids for no other reason than to “pump up” to impress women is subject to prosecution, then athletes should be on the same basis. However, if that guy at Gold’s is not liable to legal action for using a Vick’s inhaler, than an athlete shouldn’t.

Morgan Hunter April 5, 2008 at 8:42 am

You know folks – it really serves no purpose 2presenting” stands on the issues of “doping and punishment” – when we don’t even seem to be able to have a FAIR and UNBIASED “governing body” to run it all…

Perhaps – some of you all haven’t connected a singular factoid that was “let slip out” in a Cycling News article, — “…2007 death of CAS founder Kéba Mbaye, was chosen over Pound, Swiss lawyer Robert Briner and Sweden’s Gunnar Werner. He will now fulfill the remainder of Mbaye’s term, ending in 2010 at which point the CAS will hold another election.”

Is no one aware what this implies? One can only suppose that there is damned good reasons for “a lack of transparency” in the “governing bodies” involved in cycling…

May I repeat – “…Pound, Briner and Werner will remain members of the court.” — Pound is a “member of the court of Arbitration!” Hello – people…and if I am correct – so is Tygart – yep – the SAME TYGART that is responsible for “WRITING ALL THE RULES” that supposedly GOVERNS the whole cycling scene…

Maybe it is just me – but I have to tell you all that bringing “Joe Papp and French Law and arguing the pros or cons” of the existing system seems a bit idiotic!

Don’t you all realize that EVERY accused athlete – once he or she is “targeted” has no chance at all to “fight the accusation” – not when all the people who are involved in “governing” – “prosecuting” and punishing ANY ATHLETE – are the very same people who produced this whole mess to begin with…

Arguing over the merits, the pros and cons of existing issues seems like a complete waste of air…

michael April 5, 2008 at 8:59 am

Morgan you depress me.

Now I am going to go out and ride in the rain and cold. Maybe a little hypothermia will cut the edge.

Knowledge of the depth of cycling’s and WADA’s problems is way too demoralizing.

Morgan Hunter April 5, 2008 at 9:16 am

Michael,

It is not my wish to depress you – but if you insist on blaming me for your need to burn some rubber out in the rain – go right ahead (:-))) – I’ve never bothered running my life on what the alphabet soup decides to hit the public with – I just don’t intend to go “silently.”

Michael – keep the head covered – use good wool – hypothermia is no fun – I once got caught 30 miles from home between Kalispell Montana and Ferndale Montana where I lived – I swear – there was not a cloud in the sky – Alcohol does not help – since it makes you dehydrated – but what the heck – a nice shot will get you thinking you can outrun a grizzly…

Have fun Michael – hope the roads are smooth and debris free and the curves are not flooded…

Larry April 6, 2008 at 7:21 am

Gang, consider that the FFC has not paid most of the riders for the 2007 Tour de France. There may be a connection between the apparent financial difficulties at FFC and the FFC’s seeking to get Paris-Roubaix on the UCI calendar.

Morgan Hunter April 6, 2008 at 8:16 am

Larry,

Well – it looks to me like this circus will have to go into a legitimate court of law – one way or another – if the riders aren’t getting paid – this is a real reason – and as far as I know – both ASO and the UCI are responsible for this aspect of the situation – and therefore they have left themselves open to a real trial…

Morgan Hunter April 6, 2008 at 8:17 am

I’d love it if the Books from ASO and the UCI were to be opened for inspection…

William Schart April 6, 2008 at 12:02 pm

If one were to write a novel plotted like this and try to get it published, you’d probably get turned down for having too improbable a plot.

Jean C April 6, 2008 at 1:08 pm

Normaly that is ASO who is paying UCI or FFC for their “services”. So I doubt strongly that the reasons to put P-R on UCI historical calendar could be financial.

Larry April 6, 2008 at 9:32 pm

I can’t do the research at the moment, but my understanding is that ASO fully paid the 2007 TdF prize money to FFC before the race started. My understanding is that the problem is with FFC and not ASO.

I also recollect that FFC had to pay out a large settlement recently as part of some litigation, and that FFC has publicly admitted that they’re in bad financial shape.

I will try to research this further when there’s time.

karuna April 7, 2008 at 12:56 am

The official version of why the money is not paid to the riders is, according to a Dutch newspaper, that the ASO has ‘stalled’ the money with the FFC until the Rasmussen, Moreni etc cases are officially ended.

Jean C April 7, 2008 at 2:14 am

Larry,

I agree with you. Prize money were in the hands of FFC…

Karuna,

To give prize money, rankings need to be definitive. But some rankings should be unaffected by all doping cases (Rasmussen, Vino, Mayo, and Moreni).

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