| DWAIN CHAMBERS is a leading British sprinter. Having failed to achieve
his potential at the World Athletics Championships in Paris last month,
missing out on an individual medal, he is now at the centre of controversy
having been reported to have tested positive for tetrahydrogestrinone
(THG), a derivative of gestrinone and the latest “undetectable” anabolic
steroid (see “What is THG?” panel). Mr Chambers has denied
wilfully taking any banned substance.
What is THG and what does it do?
Tetrahydrogestrinone (THG) is a derivative of an
existing steroid gestrinone. A licensed version of gestrinone
(Dimetriose, Florizel) is available for treating endometriosis.
Dr Alan George, of the Liverpool school of pharmacy, explains: “The
parent compound, gestrinone, has antiprogestogenic and antioestrogenic
effects, with some androgenic activity. The androgenic potency of gestrinone
has never been quantified.”
He says that three major types of modification can be carried out on
testosterone-derived steroids. THG shows two of these. Modification of
gestrinone at the 17a-position confers oral activity, like ethinylestradiol,
and THG has been reported to be administered under the tongue. “THG
is a 19-nor-testosterone derivative, rather like nandrolone, and in the
same way it is not converted to estradiol by aromatase. This means it
has no feminising effects. I suspect that it also has far fewer masculinising
effects in women.” The other modification affects metabolism. “Like
gestrinone, THG would be resistant to metabolism and probably has a long
half-life. The plasma half-life of gestrinone is 27.3 hours.”
Buccal administration would also reduce first-pass metabolism and probably
produce a different metabolite profile to intravenous administration,
in a similar way to which morphine has different metabolites following
oral or intravenous administration.
“ The biggest problem with THG is likely to be that 17a-modification is
known to produce liver toxicity problems for other orally active steroids,” Dr
George says. This would be added to the general problems of undocumented quality
and safety for any illicitly made product.
Further details of anabolic steroid modification and use are contained
in the 3rd edition of ‘Drugs in sport’, pp138–88 (2003.
London: E. & F. Spon).
|
Professor David Mottram, of the school of pharmacy at Liverpool John
Moores University, is editor of ‘Drugs in sport’ (full details
see Panel). He says that the interesting thing about THG is that the
changes made to produce its structure also affect its metabolites. The
screening processes used in anti-doping tests measure the levels of key
urinary metabolites of specific drugs, including anabolic steroids. Altering
the THG metabolites means that it did not give the normal fingerprint
seen in mass-spectrometry tests, rendering it, in practice, “undetectable”.
THG is not currently on sporting authorities’ prohibited lists
but is covered by an “and other related substances” clause
for anabolic steroids. The THG story started in the United States earlier this year. The United
States Anti-Doping Agency (USADA) received information that various international
and American athletes were using an “undetectable” steroid.
Subsequently, a used syringe containing a residue of this substance was
sent to the USADA which passed it to its accredited laboratory at the
University of California at Los Angeles (UCLA).
Dr Don Catlin, head of the UCLA laboratory, identified the substance
as THG, resynthesised it to ensure that it had been correctly identified,
and then developed a test for it. Testing of both in- and out-of-competition
samples in the US found a number of positive results.
Terry Madden, USADA chief executive, said: “What we have uncovered
appears to be intentional doping of the worst sort. This is a far cry
from athletes accidentally testing positive as a result of taking contaminated
nutritional supplements.”
USADA says that the source of THG was BALCO (Bay Area Laboratories Co-operative)
of Burlingame, California, a company specialising in nutritional mineral
supplements for athletes. BALCO is currently being investigated by US
authorities.
Official tests for THG have now been developed and are being used by
authorities at the Rugby World Cup running in Australia. Retrospective
testing is also being done of stored samples from other events. Athletes
can be required to give urine samples for drug testing at sporting events
and at out-of-competition training sessions. In the three months to 30
September this year, British authorities carried out tests on 1,416 samples,
of which 15 required further action to be taken.
Dr Alan George, of the Liverpool school of pharmacy, contributed the
chapter on anabolic steroids to ‘Drugs in sport’. He says
that novel steroids do appear. Dr Caplin of UCLA identified norbolethone,
another anabolic steroid, last year.
“There must be many steroid compounds described in the archives of pharmaceutical
companies that were synthesised and investigated but then not developed
for commercial reasons,” Dr George says. If other persons produced
such compounds then they would not be subject to the normal standards
of testing, safety or manufacturing required for licensed products.
Professor Tony Moffatt, the Royal Pharmaceutical Society’s chief
scientist, has conducted extensive work on drugs in sport. He agrees
with Dr George, saying: “Clearly the manufacturer [of THG] achieved
what it wanted up to now, which is having a steroid that was not detectable.
However, the product may not have any androgenic activity and has an
unknown toxicity profile. Athletes who used THG have put both their health
and their careers at risk for no known benefit.”
The key to the whole issue is, of course, money. Sports stars earn huge
amounts in endorsement fees and are under tremendous pressure to perform.
There will always be those seeking to cash in by offering short cuts.
Resisting the siren call of “undetectable” performance enhancers
is hard and the testing authorities are always hot on their heels. This
looks like being a race without an end. |
