Friday, 14 December 2018

An overview of the last five years of drugs in sport and doping science

Run, Swim, Throw, Cheat has just been published in a Japanese edition. I am very pleased that there is still interest in a book published in 2012. When introducing this edition, I felt it was worth writing an extended update of the doping science scene during the last six years - or at least the five years since I write a new introduction for the 2013 paperback edition of the book. I thought it also might make an interesting – if somewhat lengthy – blog entry for readers of this blog who can’t read Japanese. So here is the English version of the introduction. 

Introduction to Japanese edition of Run, Swim, Throw, Cheat 

Run, Swim, Throw, Cheat was published just in time for the London 2012 Olympics; this was not a coincidence of course!  However, most of its subject matter does not date rapidly and everything you will read in this Japanese translation is as sound scientifically as it was when written. Minor updates on new drugs and testing methods were included in the blog I write (and occasionally update) at www.runswimthrowcheat.com.

What does change is the stories that illustrate the science. Most notably the Lance Armstrong Tour de France scandal came to light the year following that in which the book was published. There is not even a hint of his wrongdoing in the original printing of the book. This was remedied in the 2013 paperback version and much of the introduction I wrote for that edition is given over to discussing the Armstrong saga. 

The London 2012 Olympics itself had few doping scandals during the event itself, although I did manage to witness the one medal that was overturned. The culprit was the Byelorussian shot putter, Nazdeya Ostapchuk (when you read this book you will realise that it is not surprising that shot putters, especially female ones, are particularly able to benefit from doping). At the time I was sat in the Olympic stadium next to a New Zealand journalist who was cheering for Valerie Adams to retain her gold medal. She did just that, but only received it much later when Ostapchuk was disqualified by the International Olympic Committee (IOC) for doping.

The drug Ostapchuk had in her system was the anabolic steroid, metenolone. Athletes seem to favour this steroid as it is claimed to have fewer androgenic (i.e. sexual) side effects. I was surprised that Ostapchuk was caught at the games. I stress in this book that careful planners will stop taking a drug long enough before a prestigious event so it is out of their system when they compete. Although Ostapchuk has never admitted her doping, I thought at the time that she – or her team – must have made a miscalculation. Indeed at her disciplinary hearing she was given a shortened one-year ban, as it was claimed her coach, Alexander Yefimov, had drugged her food. In the words of the head of the Belarusian anti-doping agency, Alexander Vanhadlo, "Yefimov confessed that he added the banned drug metenolone into Ostapchuk's food because he was worried by her unimpressive results ahead of the Olympics”. Yefimov was then banned for four years by the Belarus' national anti-doping agency.

However, subsequent events show it was not an isolated incident. Recent re-tests of old urine samples using more modern and sophisticated techniques mean that eight athletes, including Ostapchuk, have since been found guilty of doping at the 2005 World Championships in Helsinki by the International Association of Athletics Federations (IAAF) and at the 2008 Olympic games in Beijing by the IOC. The emerging story is that Ostapchuk (or her team) were using drugs that at the time they thought could not be detected. It now looks like improvements in analytical techniques mean they got their timings wrong for when she should come off the drug. Strike one up for the anti-dopers!

There is a depressing note associated with this story. Immediately after the shot put final, the UK discus thrower, Brett Morse, tweeted from the Olympic village that Ostapchuk must be doping; his evidence was primarily that she looked like a man. Readers of my blog will know how much I disagree with unsubstantiated accusations about named athletes. This just tars everyone, even clean athletes, with the doper’s label. Quite rightly Morse was criticized at the time and the offending tweet removed. The fact that Ostapchuk was stripped of her medal was, of course, not surprisingly subsequently seen by Morse as a vindication of his tweet. Since writing this book, I have met many clean athletes unfairly accused of doping – especially on the internet. Morse’s tweet, especially as its substance did proved correct, might have the undesirable effect of leading to more of these unfair accusations.  Indeed during London 2012, the biggest “doping” scandal was centred on the Chinese swimmer Ye Shiwen who has never tested positive for doping before or since these games. The suspicion was merely based on her breaking the world record. In the current suspicious times, it pays to not win your event by too large a margin….  

Yet, the real scandal of the 2012 Olympics was only revealed five years later, when the full extent of Russia’s state doping system was revealed by a combination of the whistle blowers Grigory Rodchenkov and Yuliya Stepanova, the German reporter Hajo Seppelt and the Independent Commission reports of the World Anti Doping Agency (WADA) chaired by Dick Pound and Richard McLaren. Exactly how many Russian were doping in London 2012 (and of course later in the 2014 Winter Olympics in Sochi) will never be known, but as a consequence of retesting, 29 London medals had been returned for doping offences, 13 of which were from the Russian team. As a personal experience visiting the London games in my home city were an amazing uplifting experience, with some of the happiest crowds I had ever seen in the city. How they would have felt if they had known at the time that this level of cheating was occurring is not difficult to imagine. I should mention at this point that Russia still denies it was involved in a “state sponsored” doping regime. This denial is why - as of 2018 – the country is still banned from the Paralympics by the International Paralympic Committee (IPC), although the International Olympic Committee (IOC) has seen fit to reinstate them into the Olympic community. 

What is clear from London 2012 and Sochi 2014, is that, however clever the drug testing, it is irrelevant if the testers themselves are corrupt; and the state have a unique ability to cover up this kind of cheating. Clever science will always be trumped by clever politics. What is perhaps more interesting from a scientific point of view is that the kind of doping Russian athletes were involved in was not too different from what was found to be effective over 40 years earlier by the East German state sponsored system. Whilst there were some newer drugs of potential - if not scientifically verified - performance benefit such as meldonium, the core of the program was anabolic steroids to increase strength and power in, especially, female athletes. In fact the main difference was possibly the use of lower doses so that the female athletes were less obviously over muscled, decreasing suspicion that they were doping. Where there was a difference is that the effectiveness of blood doping (EPO, blood transfusions) had been discovered since the East German program; this benefitted both male and female athletes. It is one of the conclusions of my book that the real “game-changing” benefits of doping come from anabolic steroid use by female athletes in “power” events and blood doping by male and female athletes in “endurance” events. This conclusion, has if anything, been confirmed by what the Russian whistle-blowers and WADA reports revealed of the Russian program. 

There was a backlash against WADA, IOC and IPC led by the Russian government and various hacker groups such as Fancy Bears.  The Russians complained that they had been unfairly singled out as there was widespread doping elsewhere. This could perhaps be called the “Lance Armstrong” defence. Armstrong claims he should keep his seven Tour de France titles as his rivals were cheating at the same time. Although, in my opinion their abuses were generally more flagrant then their rivals, the Russians and Armstrong were correct that cheating is widespread in sport. Two other Tour de France winners lost their titles due to a doping offence and - if 13 out of 29 London 2012 medal cheats were Russians - 16 out of 29 were obviously not. In May 2016, at the same time as Russia was being investigated, the Anti-Doping Agency of Kenya was declared non compliant by WADA due to concerns about the implementation of its anti doping programs; Kenya only regained its compliance a day before the start of the 2016 Rio Olympics.  In August 2013, Renee Anne Shirley, the former executive director of Jamaica’s Anti-Doping Commission (JADCO), revealed her concerns about a lack of adequate out-of-competition drug testing prior to the London 2012 Olympics. This led to an official audit of JADCO by WADA in November 2013, the resignation of the entire JADCO board, and subsequent improvements to the Jamaican anti doping program, following a new partnership with the Canadian Centre for Ethics in Sport.  Although the situations described do not mean that individual athletes in these countries are guilty of doping, the lack of effective anti doping regimes in some countries will always make it harder to be confident that a sport is clean. 

The more interesting backlash, at least scientifically, came from the Fancy Bearshackers. They exposed the use of the Therapeutic Use Exemption (TUE) in athletes, claiming these were a form of “legalised” doping. None of the athletes concerned had committed any doping offence. Indeed, in many of the cases revealed by the cyber hackers, it is hard to see how the drugs taken could be beneficial to performance. But there is still an interesting discussion to be had around the science. TUEs are given for drugs designed to treat an athlete’s medical condition without enhancing performance; being performance “enabling” the intent is that they allow an athlete with a pre-existing medical condition to compete on a level playing field with their healthy peers. A concern is that athletes, their coaches and/or doctors, might “game” the system to their benefit. This was an accusation levelled at the British Olympic and Tour de France Champion cyclist, Sir Bradley Wiggins, over the unusual medication used to treat his severe seasonal hay fever, triamcinolone. Although not a first line medical treatment, as a powerful long lasting anti-inflammatory corticosteroid, triamcinolone is used by some doctors for treating hay fever and rhinitis. The critics’ claim is that a side effect of triamcinolone is weight loss, enabling a rider to lose weight but not power, a potential advantage for a cyclist in a climb. Although this is an interesting idea, the scientific evidence supporting this is weak and Wiggins and his then employers, Team Sky, strenuously denied any performance benefit for what was, it should be remembered, a WADA approved  therapeutic use exemption.

Another area that is causing current concern in Britain is the inhaled bronchodilator salbutamol, required for many athletes with asthma to breathe freely.  A TUE is only required for salbutamol if you need to take an excess in a short period (essentially this equates to eight “puffs” in a eight hour period). It is not clear that exceeding this level is performance enhancing; there is little if any performance effect in short term studies, although WADA claim that over time at high dose it might increase muscle mass. However, once a limit is set, it must be policed. The British multi Tour de France winner, Chris Froome was recently investigated due to the high level of salbutamol recorded in his urine sample during his La Vuelta victory in 2017. The WADA doping threshold in a urine sample (1,000ng/ml) was set to be impossible to reach unless an athlete inhales more than the eight puff limit. However, this has been disputed by some recent scientific research, which shows that the rate of salbutamol transfer from drug inhalation to appearance in the urine is highly variable and it is indeed possible to exceed the limit when an individual is not exceeding the permitted inhalations.

Froome and Team Sky disputed that he took too high a dose. The resultant case was all about the science. Could Froome convince the authorities that there is a plausible explanation for the anomalous urine reading? Is it possible given the conditions at the time for Froome to have exceeded the urine threshold whilst only taking the approved levels of the drug? Froome was under the doping limit throughout the rest of the Vuelta and indeed the whole season despite multiple testing in competition, so it seems highly unlikely that he was attempting the kind of long-term use that WADA claim can be performance enhancing.   It is notable that few people reporting this case – even the Froome critics – claimed that he would have received a short-term performance benefit for any one off salbutamol abuse. The discussion focused on the science of the test and whether a rule was broken. A week before the start of the 2018 Tour de France, the cycling authorities (UCI) ruled that they were satisfied that Froome did not commit any offence, and WADA decided not to appeal the UCI’s decision. The UCI’s decision was based on experts’ interpretation of data provided by Team Sky and WADA including information about the specific circumstances of Froome’s metabolism of the drug. Sometimes it feels that following elite cycling is as much about the underpinning science as the action itself. It is perhaps no surprise that when I have given presentations about my book, the cycling fans are the most knowledgeable in the audience! 

Another area of sports science that has become a current hot topic since I wrote this book is the hyperandrogenism and transgender athletes in female sport. Hyperandrogenism is defined as a female with higher than average levels of the sex hormone tesosterone (i.e. in the male range), provided it has also been shown this hormone is able to be exert its physiological effect. 

This is not a doping issue; no one is claiming the athletes are cheating. However, some of the science is related. Most sports have separate male and female categories. Given the cynical view that some athletes will cheat if they feel they can get away with it, there has been concern as to whether males can get an advantage by masquerading as females. As I discuss in the book, the history of how to “police” this gender boundary has historically been fraught with difficulties and prejudice. In most sports the issue has been quietly forgotten about. However, changes in society have made this veil of ignorance harder to maintain. There is an increasing acceptance of transgender and intersex people as individuals that should not suffer prejudice for who they are. There is also an increasing number of countries where gender can legally be self-determined. These facts have brought sex and gender politics back to the forefront of the sporting regulators. 

The IAAF and – more recently – the IOC have attempted to scientifically categorise their female separate sports categories. Approved by the IAAF in 2011, the “Regulations Governing Eligibility of Females With Hyperandrogenism to Compete in Women's Competition” state that any female athlete with a level of testosterone above a stated value (i.e. in the “male range”) will not be allowed to compete until they had taken measures to reduce this value. Usually this would require some form of hormone or drug treatment. The IAAF argument was that the difference in sporting performance between elite men and women is predominantly due to higher levels of testosterone in men. This is why women tend to get excess benefits by doping with anabolic steroids (such as testosterone) when compared to men. Therefore it is “unfair” for someone with a natural high level of testosterone to compete as it gives them benefits akin to doping. Note that at no point did the IAAF blame a “hyperandrogenic” athlete nor argue that they were not a woman - just that they should not be allowed to compete in elite women’s sport without corrective treatment.

An Indian sprinter – Dutee Chand – refused to lower her testosterone level and challenged the legality of the regulations at the Court of Arbitration for Sport (CAS). On 24 July 2015 CAS issued an Interim Award in the arbitration procedure. They suspended the regulations for two years to give the IAAF the opportunity to provide scientific evidence about the quantitative relationship between enhanced testosterone levels and improved athletic performance in hyperandrogenic athletes. To summarise a long case, essentially the IAAF had argued that natural (endogenous) testosterone gave a female athlete the equivalent benefit that dopers achieved using unnatural added (exogenous) testosterone. CAS did not dispute this idea in principle, but wanted to see proof. In the meantime, from 2015 onwards, female athletes were once again allowed to compete with no checks on their high testosterone levels. 

The CAS ruling led to a IAAF and WADA funded study that looked at over two thousand observations from elite athletes competing at the 2011 and 2013 IAAF World Athletics Championships. Measurements were made of blood levels of testosterone and comparisons made to performance. The key finding is that after dividing the athletes into thirds – high, medium and low testosterone – women in the highest testosterone category performed significantly better in 400m, 400m hurdles, 800m, hammer throw, and pole vault. In the 400m, 400m hurdles and 800m there was also a correlation between the higher testosterone levels and the amount of the blood oxygen carrying protein, haemoglobin. This pattern was not seen in any male events.  In a separate study, female athletes with serum testosterone concentrations in the normal male range performed on average 5.7% better when their serum testosterone levels were unrestricted, compared to when their serum testosterone levels were suppressed. 

This new science led to the new IAAF eligibility rules for athletes with differences of sex development(DSD), requiring any female athlete with DSD to maintain her blood testosterone level below five (5) nmol/L to compete internationally in the 400m, 400m hurdles, 800m and 1500m. This means that athletes such as Castor Semenya will need to have drug therapy to reduce their tesosterone levels, if they still want to compete in their preferred events. The IOC looks set to incorporate these same levels into their new guidelines for transgender athletes. In the latter case the justification, at least in part, is that current best medical practice is to target these lower levels as part of the transition from male to female for transgender individuals. 

How does this relate to the doping issues I discuss in this book? London 2012 was the first Olympic games when hyperandrogenic athletes, including world champions such as Castor Semenya competed under regulations restricting their tesosterone levels. Their running times did increase, though Semenya still won the 800m title. However, in the actual race she came second. First past the line was the Russian athlete, Mariya Savinova.However, in 2014 Savinova was caught in undercover video footage appearing to admit to injecting testosterone and taking the banned steroid oxandrolone. This led to a WADA re-investigation of her blood samples, which found that she had used blood doping between 2010 and 2013.  She was subsequently banned by the IAAF for four years, a decision upheld by the Court of Arbitration for Sport (CAS) in February 2017. Savinova is currently appealing this decision, but as it stands, her London result has been forfeited and Semenya awarded the gold medal. So Savinova beat Semenya, but apparently (appeal pending) only by resorting to cheating, taking steroids to increase her muscle mass and blood doping to increase her haemoglobin levels. The 800 m is an event that requires both power (muscle mass) and endurance  (oxygen delivery). Tesosterone gives males from birth increases in both muscle mass and blood haemoglobin. Doping or hyperandrogenism mimic these male advantages. 

If I was writing the prologue to my book again, I would focus not on Ben Johnson’s 100m Olympic win in Seoul nor even the five runners who passed the line one after the other in the 1500m final in Helsinki and who each at some point in their careers was found guilty of doping. Instead I would showcase the London 2012 Olympic games 800m race. Yes, there is complexity in the science of doping and, hopefully, my book will help you understand this and entertain you at the same time. But the key message is simple. What really works – and what is game changing – is the use of anabolic steroids to increase muscle mass (especially in female athletes) and the use of blood doping to increase haemoglobin content in all athletes. Everything else is just noise. 

It is not clear whether these new IAAF DSD regulations will stand the test of time or whether they will face a new legal challenge. Is it ethical to focus on just one genetic difference that enhances performance? Testosterone is the key sex defining hormone, but it is not the only performance defining molecule in females or males, many of which will be similarly genetically determined. Ultimately the answer will not be down to the science, but to what society will accept. I was fortunate enough to be back in the London Olympic stadium in 2017 for the World Athletics Championships. This event took place during the period when the IAAF hyperandrogenism regulations were suspended. I, along with 60,000 other sports fans, cheered Castor Semenya home to the 800m victory she was denied in London 2012. The same crowd that had roundly booed ex-doper Justin Gatlin’s victory in the 100m race, rose to their feet to support Semenya. The lack of any hyperandrogenism regulations did not seem to be stifling their cheers. It certainly did not feel like an unfair victory to those in the stadium. 

Friday, 26 October 2018

Pseudoephedrine: does it work and why is it banned in sport?

I have just published an analysis of the scientific literature on the effectiveness of the banned stimulant pseudoephedrine in sport [1]. The full paper is free to read and can be accessed via this link: rdcu.be/8EtB Like most research it was a team effort. The original research was undertaken by two talented ex-undergraduate students of mine - Maria Gheorghiev and Farzad Hosseini - as part of their University of Essex degree. An Essex PhD student Jason Moran (now at Hartbury University) re-analysed and re-interpreted the data, adding greatly to the final outcome.  

Being a scientific paper, I was forced to write in a somewhat formal style and rein in some of my more florid expressions. However, hopefully it should still make interesting reading for the intelligent layperson. 

The key points from my paper were 

·      Pseudoephedrine use increases heart rate during exercise, but there is no significant effect on time trial performance, perceived effort, or biochemical markers (blood glucose and blood lactate).

·      A small performance benefit could not be completely ruled out, especially in the younger and well-trained athletes of most concern to anti-doping agencies, 

·      However, any performance benefit of pseudoephedrine is marginal and certainly less than that obtained through permitted stimulants such as caffeine

For those of you who are unfamiliar with pseudoephedrine it is the safest and most effective nasal decongestant available. It clears up the symptoms of blocked nose and sinuses during colds and flu, although it has no effect on the overall progress of the disease. Although available in most countries over the counter, its use is restricted, primarily over concerns that it is used as a precursor in the production of the recreational drug “crystal meth”. For those of you familiar with the TV show “Breaking Bad”, it is the “pseudo” that the characters use to make meth in their RV, before switching to more productive precursors when they move to industrial level production. 

In sport, as outlined in my article, the regulation of pseudoephedrine has a chequered history. It has been banned, unbanned and then banned again. As I say in my book, the most tragic case was that of the sixteen-year-old Rumanian gymnast Andreaa Răducan. At the 2000 Sydney Olympics the Rumanian women’s gymnastics team obtained a clean sweep of medals in the overall event. Răducan took the gold. However, she subsequently tested positive for pseudoephedrine; her gold medal was withdrawn. The drugs test was as a result of a cold that had struck many members of the Rumanian team. The team doctor had prescribed the painkiller Nurofen, which in its form as a cold medication contains pseudoephedrine. The minimum level of pseudoephedrine allowed in a urine drugs test is not corrected for body mass. Răducan, being the lightest gymnast, registered over the limit; her teammate Simona Amanar, who finished second, also tested positive for pseudoephedrine, but was below the banned level. Amanar was consequently awarded the gold medal – but she then boycotted the medal ceremony claiming that Răducan was the true champion. 

Given what we know was going on at the Sochi 2014 Winter Olympics games, it is rather ironic that the most high profile positive test actually reported at the Games was not for anabolic steroids or blood doping, but a humble nasal decongestant. The Swedish ice hockey team were deprived of the use of the star player Nicklas Backstrom, just before the gold medal ice hockey game. Shorn of their star player, Sweden were convincingly beaten by Canada 3-0. Backstrom had tested positive for pseudoephedrine. He was taking (and declared on his doping control form) Zyrtec-D, a pill that contains both an anti histamine and pseudoephedrine. It seems that he had been taking it every day for seven years. WADA does have a lower limit of pseudoephedrine that does not result in a ban. When tested, Backstrom’s pill put him just over this limit. There are a issues about the timing of the Backstrom ban (just before the ice hockey final) that have caused a lot of upset in Sweden. The controversy did not end after the Games. Originally not awarded a silver medal, the IOC reinstated him and awarded his medal in March 2014. WADA then appealed this decision to the Court of Arbitration for Sport in November 2014. Finally in January 2015, the dispute was settled and Backstromended with a reprimand, but was allowed to retain his medal.

I know WADA have more pressing issues to deal with at the moment (to put it mildly!). But it does seem to me that the WADA banned list could do with some significant pruning to remove these drugs and medicines such as pseuodoephedrine that - even if they are potentially performance enhancing - are clearly not “game changing” compared to current, legitimate supplements and methods that athletes are allowed to make use of. The asthma medication Salbutamol, as used by Chris Froome in the Vuelta a Espana -  could probably also fall into this category. But that is a subject for my next blog. 


Wednesday, 18 October 2017

“Gender doping”: should women with high testosterone be allowed to compete in athletics?

At the University of Essex we have just started a new MSc. in Sports and Exercise Science [1]. As part of my drugs in sport module, I am getting my students to examine a “hot” research paper each week. They do the background reading and then we discuss the paper together asking the questions: Why was the research done? What did the research find? What were the problems and limitations of the study? What are the consequences for sport?

I am really enjoying this type of small group teaching. The nine students are a mix of UK and overseas, some straight from undergraduate degrees and others with real world experience. The discussions are lively and they all bring different ideas to the table.

The first paper we discussed [2] was one about a condition called hyperandrogenism  - where someone has excess levels of the natural anabolic steroid testosterone. The paper is about to play a key role in the upcoming (any day now!) verdict from the Court of Arbitration of Sport with regards to the IAAF’s hyperandrogenism regulation. Approved in 2011 [3], the “Regulations Governing Eligibility of Females With Hyperandrogenism to Compete in Women's Competition” state that any female athlete with a level of testosterone above a stated value (i.e. in the “male range”) will not be allowed to compete until they had taken measures to reduce this value (usually this would require hormone treatment). The IAAF argument was that the difference in sporting performance between elite men and women is predominantly due to higher levels of testosterone in men. This is why women tend to get excess benefits by doping with anabolic steroids (such as testosterone) when compared to men. Therefore it is “unfair” for someone with a natural high level of testosterone to compete as it gives them benefits akin to doping. Note that at no point did the IAAF blame a “hyperandrogeic” athlete nor argue that they were not a woman - just that they are not allowed to compete in elite women’s sport (there is a distinction here if you look hard enough I guess).

An Indian sprinter – Dutee Chand – refused to take treatment to lower her testosterone and challenged the legality of the regulations at the Court of Arbitration for Sport (CAS). On 24 July 2015 CAS issued an Interim Award in the arbitration procedure [4]. They suspended the regulations for two years to give the IAAF the opportunity to provide scientific evidence about the quantitative relationship between enhanced testosterone levels and improved athletic performance in hyperandrogenic athletes. I can recommend reading the full award; it is a fascinating discussion of this difficult area [5]. However, to summarise a long case, essentially the IAAF had argued that natural (endogenous) testosterone gave a female athlete the equivalent benefit of unnatural added (exogenous) testosterone. The IAAF did not dispute this idea in principle, but wanted to see proof. Hence the two-year study that culminated in the research paper I discussed with my students [1, 2]. In the meantime with the regulations suspended Dutee Chand and other hyperandrogenic athletes were allowed to compete with their natural (high) levels of testosterone [6].

The IAAF and WADA funded study was published in the British Journal of Sports Medicine [2]. The study looked at over two thousand observations from elite athletes competing at the 2011 and 2013 IAAF World Championships. Measurements were made of blood levels of testosterone and comparisons made to performance. I have some potential issues with the statistics used in that they seemed a bit too generous towards finding a performance association, but perhaps that is a story for another day. The key finding, that no doubt will be forwarded to CAS, is that after dividing the athletes into thirds – high, medium and low testosterone – women in the highest testosterone category performed significantly better in 400m, 400m hurdles, 800m, hammer throw, and pole vault with margins of 2.73%, 2.78%, 1.78%, 4.53%, and 2.94%, respectively. This pattern was not seen in any male events.  

So what did my students think of it? Well they made some great observations. Perhaps the most interesting was that the effects were restricted to so few events. Results in many power-based events showed no association with increased testosterone. Indeed in the 100m, 100m hurdles and 200m those with the highest testosterone performed worse than those with the lowest testosterone. The difference was not scientifically significant, but clearly is heading in the wrong direction for the IAAFs case. However, it could be legally significant given Dutee Chand  - who bought the case after all – is a 100m sprinter! 

Actually what was not observed is almost as important as what was. Across female track and field events there was no association of testosterone levels with discipline i.e. elite female athletes in strength events such as shot putters and sprinters do not have higher testosterone than those competing in distance events like the 10,000m and marathon. Even more surprising (at least to me as an oxygen “expert”), the levels of the oxygen carrying protein hemoglobin were not greater in the “aerobic” events. This result is hidden away in Supplementary Table 8 if you want to find it. There is a trend for sure, but I would have expected the difference to be more evident, given that we know that long distance runners are doing all they can within the rules (altitude training, sleeping in low oxygen tents) and without the rules (EPO, blood doping) to increase their hemoglobin; something sprinters don’t bother with at all.

The fact that a biochemical marker like hemoglobin that athletes can manipulate and that is known to affect performance shows such a poor association with performance, does question the whole idea of these kind of “association studies” even when they include so many athletes.

Of course the real problem with this study is that it is – quite rightly - limited by ethics. None of the female testosterone values in this study were in the “male” range. Otherwise the athletes would have been banned at that time of course. The best way to prove that hyperandrogenism is equivalent to testosterone doping is to dope elite athletes with testosterone for a short time. Then look at their performance when they are on and off the steroids. Does the increase and decrease mirror those seen when a hyperandrogenic athlete comes on and off hormone therapy to vary their natural levels of testosterone? Good luck getting that study through a university ethics committee!

One final point is that the paper also looked at male athletes. Unlike with women, the study did find that male sprinters had increased testosterone levels compared to other events. However, in no event was there any association of an individual’s testosterone level with performance in that event. In the discussion the authors’ suggest there is “sigmoidal” curve associating testosterone levels and performance. For women this means that increasing testosterone can have a large effect on performance (the association curve is steep), but at the higher values seen in men the relationship smooths out and is undetectable. Of course this begs the question. Why is taking testosterone and other anabolic steroids banned for male athletes, if the performance benefit is so marginal as to be unmeasurable? I am not sure the IAAF and WADA can have things both ways. If associations with performance can be used to ban female hyperandrogenic athletes from performing, then surely the lack of such an association can be used to unban male anabolic steroid dopers? I think Shakespeare called this being hoist on your own petard [see Hamlet Act 3, scene 4).

What ever CAS decides, at least my students enjoyed discussing the paper. “Much better than my undergraduate teaching said one”. Given I taught him as an undergraduate, this was a somewhat back handed compliment, but I’ll take it anyway!  

Onwards and upwards ….next week we are discussing a controversial paper that suggests  that  blood doping does not increase performance in long distance aerobic sports events such as cycling [7]. Can’t wait……


[1] MSc. in Sports and Exercise Science, University of Essex, UK


[2] Bermon S, Garnier PY (2017) Serum androgen levels and their relation to performance in track and field: mass spectrometry results from 2127 observations in male and female elite athletes. Br. J. Sports Med. 51:1309-1314.


The paper can be downloaded from the IAAF web page: https://www.iaaf.org/news/press-release/hyperandrogenism-research


[3] IAAF to introduce eligibility rules for females with hyperandrogenism ; IAAF news April 2011


[4]  CAS media release: CAS suspends the IAAF hyperandrogenism regulations Lausanne, July 27, 2015


[5]  Dutee Chand v IAF and IAAF, Interim Arbitral Award delivered by the Court of Arbitration of Sport,  July 27, 2015


[6] The most famous current elite female athlete is the South African World and Olympic 800 m champion, Caster Semenya. Since the lifting of the IAAF regulations her success has come under some criticism from fellow athletes.


However, it was notable that this is not necessarily shared by the athletics watching public. I was at the London Olympic Stadium two months ago when the crowd were right behind her during her race, in her post racer interview and during the medal ceremony.



[7]  [Heuberger J, Rotmans JI, Gal P et al (2017) Effects of erythropoietin on cycling performance of well trained cyclists: a double-blind, randomised, placebo-controlled trial. Lancet Haematol 4:e374-e386.


Friday, 21 October 2016

DENY, DENY, DENY. Gene doping: the future of theatre?

Deny, Deny, Deny is written by Jonathan Maitland and is due to open at the Park Theatre, London on November 2nd. I was the scientific advisor for this play, which deals with a female sprinter tempted into experimenting with gene doping. I wrote a short piece for the program notes, which I reproduce below [note that the last line does not mean I particularly think any athlete is currently gene doping, although this possibility can’t be ruled out entirely].

“In 2006 anti doping agencies got the information they had always feared.  Police raiding the home of famous German athletics coach, Thomas Springstein, found this email on his computer: The new Repoxygen is hard to get. Please give me new instructions soon so that I can order the product before Christmas.” Repoxygen was an experimental drug developed by UK biotechnology company Oxford Biomedica. It was designed to treat anaemia by injecting extra copies of the human erythropoietin (EPO) gene.

EPO is a small protein that increases the number of oxygen carrying red blood cells in the body. Activating the EPO gene increases the levels of EPO protein, increasing the number of red blood cells, enhancing oxygen delivery and improving performance in long distance “aerobic” sports. Clean athletes try to increase their own levels of EPO by altitude training. Others, like the cyclist Lance Armstrong, injected synthetic EPO directly - a process explicitly banned by the World Anti Doping Agency. Synthetic EPO is detectable, albeit with difficulty. It also needs multiple injections. How much better coach Springstein thought to inject the EPO gene itself? This gene would continue to make increased undetectable levels of EPO, creating a gene doped super athlete!

We don’t know whether Springstein ever got hold of his black market Repoxygen. We do know that Oxford Biomedica stopped making it; a combination of poorer than expected animal trials and the ready availability of new versions of cheap, synthetic EPO protein made further development uneconomic. Market forces, rather than the vigilance of anti doping agencies saved the day for clean sport in this instance.

Gene doping sits at the heart of Deny, Deny, Deny. So what is it and is the plot scientifically feasible? Gene doping is the bastard child of gene therapy. It uses the same molecular tools but aims at different outcomes. Whilst gene therapy attempts to cure genetic diseases such as cystic fibrosis and thalassemia, gene doping aims to improve how well elite athletes can run, swim or throw.

In the 1970s gene therapy was touted as heralding a new age of medicine. Is gene doping a similar game changer in sports cheating? The basic science is scarily cheap. You can teach students the principle in a school project and even get them to make a “dummy” gene construct. There is an analogy here with nuclear weapons. Everyone knows the basic theory of how to make one. But the problem - and expense - lies in the fine details of the engineering. In gene therapy the multi million pound expense is not in creating the new gene, but in making the final product effective and safe. As a result there are only a handful of genetic diseases that are currently treated by gene therapy; the cost of gene therapy per patient runs into the hundreds of thousands of pounds.


It is easy to envisage gene doping increasing the speed of female sprinters. It would only require injecting a gene that causes a slight increase in levels of testosterone – the natural male anabolic steroid - to increase female muscle mass and enable a sprinter to power to victory in the 100m or 200m. But given the costs is gene doping too expensive and impractical to be successful without the backing of Big Pharma or a rogue state? I think not. If you had “looser” ethics and were willing to trade off safety for low cost and high performance, it is easy to envisage an unscrupulous coach persuading a scientist to inject a gene that would increase the performance of a female sprinter. Perhaps they already have …….”