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:

[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 …….”

Wednesday, 31 August 2016

Bloody Olympics: Rio, 2016, and the history of illegal blood doping

The below is a reprint of a bog I wrote for Oxford University Press to coincide with the Olympics. Nothing new really, but it was nice to put things in a historical context. To see the original story (with pictures) go to

Throughout history blood has been imbued with magical properties. Drinking blood was viewed as a source of power for many mythical beasts centuries before the invention of the modern vampire myth. In Greek mythology Odysseus can revive the dead by giving them blood to drink. But all blood is not the same – the blood from the veins on the left side of the snake-headed Gorgon Medusa is deadly, that from the right side is life-giving. In 1489 the Italian philosopher Marsilio Ficino, proposed that drinking the blood of healthy young men could rejuvenate the sick and elderly. Indeed it seems that an attempt was made to cure Pope Innocent VIII of his stroke by giving him blood from three ten year old boys. More dramatically the Hungarian princess and serial killer, Countess Elizabeth of Bathory, was alleged to have drained all the blood from over 600 young girls to feed her restorative blood baths.

Drinking fresh blood was supposed to give you strength, maybe eternal life if you were a vampire. Even in the post-enlightenment age, the first blood transfusions had nothing to do with the modern notion of enhancing oxygen supply; instead they were supposed to heal by replacing old bad blood with strong healthy animal blood.

Sport has long had a fascination with blood. The blood of the Roman gladiators, moppped by a sponge from the arena, fed a profitable business; perhaps the athlete’s ultimate commitment to promoting their brand? Today blood is even more relevant to sport. Indeed arguably its use and abuse in sport today has come close to destroying the Olympic movement.

The modern fascination with blood in the Olympics arose from the new discipline of sports science in the 1960s and 1970s.  A key driver was the 1968 Mexico City Olympics where physiologists recognized the difficulty of getting sufficient oxygen to tissue in the rarefied 2km high air. Red blood cells transfusions increase the amount of oxygen given to people suffering from trauma or anaemia. It was therefore argued that healthy athletes could be given “excess” blood to increase their ability to deliver oxygen to tissue, and hence enhance their performance in endurance sport?

Scandinavian scientists were first to prove this - in 1972, Bj√∂rn Ekblom at the Institute of Physiology of Performance in Stockholm, showed a 25% increase in stamina after a transfusion. It was subsequently alleged that Scandinavian athletes were putting this laboratory method into practice. Lasse Viren won double gold medals on the track in 5,000m and 10,000m at the 1972 and 1976 Olympics. Unproven allegations of blood doping dogged Viren, who always denied them claiming that altitude training and “reindeer milk” were the keys to his enhanced performance. Some of his teammates did later confess to blood doping, however, most notably Kaarlo Maaninka at the 1980 Olympics. Maaninka received no sanction, which might surprise today’s readers given that blood doping is one of the main reasons we will not see the Russian track and field team competing at these Olympics. However, although in the 1970s and 1980s blood doping was viewed as morally dubious, it did not break any rules. The anti doping effort of the time focussed more on amphetamines and anaboloic steroids.

This would change in the 1980s. The LA Olympics in 1984 was the watershed event. There was extensive use of blood transfusions including by several members of the highly successful US cycling team. Again no rules were broken, but the IOC had had enough and banned blood doping in 1985. However, they had no way of testing for this form of cheating, so it presumably continued in secret. In fact the ready availability of genetically engineered EPO in the late 1990s, a difficult to detect drug that increases the number of red blood cells more gradually and naturally than a blood transfusion, undoubtedly increased the use of banned methods. I could fill most of the rest of this article with a list of Olympic athletes who are confirmed or strongly suspected of using EPO and/or blood transfusions to aid their performance.

So where are we now? Blood is a part of the Olympics and always will be. Whilst not imbuing you with the mythical life giving properties of Odysseus, optimizing your number of red blood cells is a key part of success in endurance events. I can guarantee that every medal winner in a long distance endurance event will have had their blood measured frequently by support scientists to conform the success of their training program, whether that program uses permitted (altitude training, sleeping in low oxygen tents) or banned (EPO, blood transfusion) methods.

So much for Rio, what about PyeongChang and the Winter Olympics? This is, if anything, an even richer source of stories than the summer games.  There are claims of athletes chosen for ski teams solely so that are the right blood group to donate blood to their team leader; in 2006 a disgraced ex Austrian ski coach crashed his car into a roadblock in the Italian alps, whilst attempting to escape the police. But that’s a blog for two years time ……..

Rio Olympics 2016 and doping stories

Most of the interest for me happened pre the Games of course and the "will they, won't they" allow Russia to compete saga. Not surprisingly during the games my TV and radio interviews weren't about science, but about athletes response to other athletes. The extent of finger pointing was unusual for the Olympics,  but less extreme than has happened at some other events e.g. Paula Radcliffe unfurling her "EPO cheats out" banner at the 2001 World Championship [1]. Still it was the Olympics so news outlets inevitably focussed on incidents such as the finger wagging between Yulia Efimova and Lilly King [2]. Until of course the light relief/black comedy provided by Ryan Lochte and his co-conspirators [3].

The main story in my opinion though was the IPC being brave enough to ban Russia completely from the Paralympics. The world didn't end and the ban was even upheld by the Court of Arbitration for Sport.  This rather put the lie to the IOC's passing of the buck to the national sporting organisations with its ridiculous one week timescale and wilful misreading of the nature of the McLaren WADA report [3].

I didn't get asked much about the IPC decision  though I did try to bring the contrast with the IOC into some of my interviews. Still I am now really looking forward to the Paralympics. Not clean, but cleaner......





Friday, 11 March 2016

Sharapova, Pound and Seppelt: Tacking Doping in Sport 2016

I’ve just come back from this two-day conference at Twickenham stadium. To get there I waited once again at the bus stop I used to spend my teenage life hanging around – a situation made me feel both strangely young and old at the same time. But what of the conference? You might expect a set of talks from regulators and lawyers to be dry and drab. However, at times more sparks flew than even at the most vitriolic academic meeting. Actually the latter are usually sedate – though intellectually stimulating events – with tempers and egos well in check (at least until the bar opens).

So what caused the fuss at Twickenham? Surprisingly it wasn’t the Maria Sharapova meldonium affair. This just led to incredulity as to how someone would keep taking a drug – for whatever reason – when it was so clearly advertised as coming on to the banned list and an effective test had clearly been developed. The fact that Sharapova has been joined by 99 other athletes in the space of a few months suggests either a massive breakdown in anti doping education or a significant level of stupidity amongst dopers.

So who did get everyone excited? Not Dick Pound for once with his usual erudite exposition of Russia’s recent failings. Not even Jonathan Taylor from Bird & Bird who did his best to wind up – well everyone really. No they were both upstaged by the showing of Hajo Seppelt’s new ARD documentary; this revealed that banned coaches were still active in Russia. He followed this up with some direct barbs at the WADA president, Sir Craig Reedie, accusing him of firing one of his top investigators and having a conflict of interest between his role at WADA and the IOC (where he is a Vice President).

I felt a little bit sheepish giving my own talk immediately after Hajo’s Tour de Force. Especially as what I was talking about essentially amounted to studying not doping. I discussed whether much of doping’s effectiveness could be due to the power of the placebo effect i.e. the athlete runs faster because they believe they have a secret advantage. This contrasts with the nocebo effect, where the athlete runs slower because they believe their opponent is doping and hence can’t be beaten. The problem is to do the definitive placebo doping study I would need to give EPO to a elite athletes whilst telling them I was giving them a meaningless injection. This would reveal exactly how much of EPO’s benefit is due to its biological, rather than its psychological effect. But it is hard to see a research ethics committee agreeing to this level of deception. Such a pain when morality gets in the way of a good piece of science!