Read more from MESO-Rx: Erectile Function and Fatigue- What Happens When Testosterone Replacement Fails to Improve Them?

The testosterone doping test is flawed. The EPO test is flawed in more ways than one. Peptide hormones such as human growth hormone (HGH) and insulin-like growth factor (IGF-1) are currently undetectable. And this does not begin to address other current and emerging synthetic blood boosting techniques being used by cyclists.

It seems that anti-doping agencies are happy to assert that they are winning the war on doping while neglecting issues such as biogeneric/biosimilar erythropoietin (EPO) stimulating proteins (ESPs); blood oxygen carriers: perfluorocarbon emulsions (PFCEs) and hemoglobin based oxygen carriers (HBOCs); hydroxyethylstarch (HES/HAES); and before long, if not already, EPO-mimetic peptide (EMPs).

The newer blood boosting techniques like PFCEs and HBOCs do not increase hematocrit levels; so these drugs have performance enhancing effects without risk of exceeding the 50% hematocrit cutoff. Furthermore, the performance enhancing effects of PFCEs and HBOCs are instantaneous. The HES/HAES are actually plasma expanders and would dilute the hematocrit concentration.

Occasionally, the press reports on these substances e.g. when the U.S. Postal Team was caught with Activegin and subsequently admitted taking Activegin to the 1999 Tour de France prior to its ban and when Mauro Gianetti almost killed himself using PFCEs during the 1998 Tour of Romandy. (Ironically, Mauro Gianetti is the team manager who was “duped” by riders on the scandal-plagued Saunier Duval-Scott cycling team).

And while most of us just learned about a third generation version of EPO called Mircera, a “fourth-generation” version of EPO belonging to the class of drugs known as EMPs may receive FDA approval within the next 2-3 years; it is unknown whether athletes are currently experimenting with Hematide or Hemomer.

Blood oxygen carriers: perfluorocarbon emulsions (PFCEs) and hemoglobin based oxygen carriers (HBOCs)

Actovegin (Nycomed)
HemAssist (Baxter Healthcare)
Hemolink (Hemosol)
Hemopure (Biopure) *
Oxyglobin (Biopure) *
Oxycyte (Synthetic Blood International)
Oxygent (Alliance Pharmaceutical Corp)
PHER O2 (Sanguine Corp)
PHP (Curacyte)

Hemospan (Sangart) – added May 6, 2011
Polyheme (Northfield Laboratories) – added May 6, 2011

* Biopure assets were sold to OPK Biotech

Plasma expanders: hydroxyethylstarch (HES/HAES)

Dextran (B. Braun Medical)
Gentran (Baxter Healthcare)
Hespan (B. Braun Medical)
Voluven (Fresenius Kabi)

EPO-mimetic peptide (EMPs)

Hemomer (AplaGen Biopharmaceuticals)
Hematide (Affymax/Takeda Pharmaceutical)

***

Cyclists will continue to use performance enhancing drugs. They will continue to remain ahead of the anti-doping agencies. By only giving credence to official statements from WADA, AFLD, etc., one would believe this was all but impossible. But the evidence that doping continues is everywhere.

For example, here is an experpt from a post at RoadBikeReview.com regarding how doping is still possible given all the doping controls:

HGH, IGF-1 and Actovegin are pretty much the minimum that riders take. Ok…a few might just be on HGH because after all HGH converts in the liver to IGF-1. NONE of these drugs can be dectected…

[...]

Now for a one day classic they just come to controls with a 49% hematocrit. They can get there with blood doping or Dynepo use (human identical epo) After morning controls they have about an hour, and sometimes a little more, to blood dope. Units of their own blood are slammed into them with blood pumps. You can infuse a litre of packed cells in about an hour with no issue. This is at least 3 units of pure red cells. This will boost your hematocrit by at least 5% and sometimes 8-9%! The top riders then line up at the starting line with a 55-59% hematocrit!!!

After the race the extra blood is taken out, the plasma is spun off and the red cells are frozen as above. They end up with a 50% hematocrit. Alternatively they can just bleed the extra blood out of you until you are at 50%.

[...]

In grand tours you have to pass morning controls with no more than a 50% hematocrit, just like for any race, so they either take the extra blood out of you after the stage and save for re-infusion after morning controls, or they simply jack you with IV saline and volume expanders like Hespan right before morning controls so your hematocrit is diluted to 49-50%. You still have the same O2 carrying capacity that you had at say 56% …the blood is just diluted down. This extra fluid also comes in handy in the stage.

If you blood dope for any length of time you must supplement with very tiny doses of epo and only via the IV route. Blood doping shuts down your own red cell production so you will have next to zero retics (immature red cells) in you …and if control sees this they will know you are blood doping.

Is WADA really winning the war against doping in sports?

The arrests came after a two-month investigation prompted by a tip, Grapevine police Lt. Todd Dearing said. Matthew Wong, 17, of Grapevine was arrested April 10 on suspicion of possession of controlled substances and dangerous drugs and on suspicion of delivery of controlled substances. The charges range from state jail felonies to second-degree felonies, Dearing said. Wong remained in the Tarrant County Jail on Tuesday with bail set at $26,000.

Police say Wong sold an undercover officer steroids numerous times. According to an arrest warrant affidavit, Wong most recently met the undercover officer on Feb. 21 in a restaurant parking lot, where the officer bought 21.8 grams of Oxymetholone, a strong steroid, and 19.6 grams of testosterone from Wong for $310.

STEROIDCONFIRM™ enables sports trainers, employers and parents to test individuals who they suspect may be abusing steroids. Simply take a urine specimen at home, in the workplace or at school, and mail to our laboratory using the pre-paid shipping pak. You have the option to perform a confidential test (no personal information is required) or a test with a Chain of Custody…

Using Liquid Chromatograph Tandem Mass Spectrometry (LC/MS/MS), the most sophisticated and sensitive technology available for the steroid testing community, STEROIDCONFIRM™ can accurately quantify substances well below the cut-off levels. Each specimen is tested directly with this instrument – there is no screening process.

Confirm Biosciences claims the SteroidConfirm steroid testing kit is comparable to the steroid panels used by the World Anti-Doping Agency (WADA). This may be misleading.

STEROIDCONFIRM™ is comparable to World Anti-Doping Agency (WADA) panels, detecting a full list of prescription androgenic anabolic steroids, prohormones, designer anabolic steroids, essential masking agents, anti-estrogen agents and diuretics.

But the SteroidConfirm description only claims to identify 11 anabolic steroids, 5 metabolites, and 1 beta-2 agonist. This doesn’t come close to approaching the number of anabolic steroids included in the WADA doping tests. SteroidConfirm advertises the detection of the following 17 substances (mostly steroids and their metabolites).

» Tetrahydrogestrinone (THG)
 » Boldenone (Equipoise)
 » Hydroxyboldenone (Metabolite)
 » Clostebol (Steranobol)
 » Clenbuterol
 » Dehydroepiandrosterone (DHEA)
 » Testosterone
 » Epitestosterone
 » Oxymesterone (Oranabol)
 » Oxandrolone (Anavar)
 » Methyloxandrolone (Metabolite)
 » Stanozolol (Winstrol)
 » Hydroxystanozolol (Metabolite)
 » Flouxymesterone (Halotestin)
 » 6B-Hydroxyflouxymesterone (Metabolite)
 » Androsterone
 » 19-Norandrosterone (Metabolite)

Several popular anabolic steroids are apparently not included in the testing. These include Anadrol (oxymetholone), Dianabol (methandrostenolone), Trenbolone, Masteron (drostanolone propionate), Primobolan (methenolone), and Proviron (mesterolone).

Deca Durabolin (nandrolone decanoate) is not included either; however, I think a positive result for the metabolite 19-norandrosterone will effectively detect the use of any nandrolone based steroids (Deca, Laurabolin, Dynabolan, Anadur, etc).

It is possible that some of the steroids I mentioned will be detected by discovery of some of the 5 metabolites that SteroidConfirm does test for. But it would seem that the Confirm Biosciences marketing department would be certain to mention this if it were true.

Otherwise, I think suggesting that the steroid testing kit is comparable to WADA panels is a bit of a stretch. The steroid testing kit is not nearly as comprehensive at the company would like you and your $145 believe.

(Hat tip to Steroid Nation for link to CNBC story.)

WADA refuses to worry about trivial genetic factors. WADA is loath to do longitudinal tests of athletes. WADA might find a variable that might refute their laboratory findings or challenge their presumption of laboratory perfection. WADA would never invest time and money doing pedigree studies to determine if a single metabolite above threshold for exogenous testosterone is a trait common in a family, or among a group of people found in a geographical region. But idiosyncratic individual differences in medicine have been documented in many pedigree studies. For example, hematocrit levels above 50% have been found in fathers and sons of elite cyclists. These hematocirt levels are inherited tendencies, not based on EPO doping. The same is true for testosterone/epitestosterone ratio(s) and may be true for Carbon Isotope metabolite delta/delta scores.

Personally, I’ve always been suspicious and critical of the arbitrary 50% hematocrit level as an indicator of EPO doping. Why? My hematocrit level has regularly and consistently exceeded 50% for the past 15 years and I’ve never used EPO. I may be an outlier, but I would venture to guess that a significant percentage of elite endurance athletes fall into the outlier category on various physiologic parameters.

The unreliability of the testosterone:epitestosterone ratio test (T:E ratio) and WADA’s insistence on its infallibility only further undermines the credibility of WADA.

It would be nice to believe that the isotope ratio mass spectrometry (IRMS) [used in the carbon isotope ratio testing (CIR) to detect exogenous testosterone use] is 100% reliable as WADA would suggest. But Velo Vortmax explains why we shouldn’t just trust WADA with this test.

The IRMS is an instrument that requires very precise controls of operation. The results of an IRMS is only as good as the laboratory performing the tests. Inexperienced laboratory personnel who cannot follow sequential steps in testing cannot be expected to arrive at the correct results. A valid IRMS is also only as good as the science behind the tests. A valid IRMS is only as good as the criteria required in WADA technical documents, by international standards, and by standardized criteria as to constitutes a positive result. WADA has failed in all these areas.

One hundred years from now will the scientists of the future shake their heads in amazement at our ignorance. Will they abhor the stupidity and mistakes of the anti-doping crusade? Will they be forced to restore the honor to “fallen” athletes?

Is it any surprise that there is a fair amount of skepticism regarding WADA’s new human growth hormone testing kits?

Source: Wikipedia

The scientific and anti-doping community continue to struggle with the development a test for exogenous growth hormone in athletes. They haven’t even been able to produce scientific evidence that growth hormone enhances athletic performance in spite of anecdotal evidence [from athletes and strength coaches] that this is the case.

But science continues to do a good job at finding weakness in the doping controls currently in place. Tip of the hat to Trust But Verify for alerting us of a new study which, among other things, tells us exactly how much exogenous testosterone some athletes can use and still pass the drug test.

The study reveals serious weaknesses in the testosterone:epitestosterone ratio test used by WADA and other anti-doping organizations (“Doping Test in Sports Confounded by Common Genetic Trait,” March 21).

The current first-line defense for detecting testosterone abuse in sports is to measure the ratio of two chemicals in a spot urine test: testosterone glucuronide (TG) and epitestosterone glucuronide (EG). TG is a by-product of testosterone in the body; it increases as the amount of testosterone increases. EG is unrelated to testosterone metabolism, and serves as a reference point in testing.

In doping tests, any ratio above four, according to the International Olympic Committee, should be considered suspicious and lead to further testing.

It appears that certain genotypes are more likely to have false negatives (athletes use testosterone but don’t get caught)and other genotypes are more likely to have false positives (innocent athletes test positive for steroid use).

The production of TG from testosterone, however, is primarily controlled by an enzyme (UGT2B17), which is produced by a specific gene. Common variations to this gene may give rise to wildly different testing results, even when the same dose of testosterone has been taken.

For their study, the researchers screened 145 men for the insertion (ins) or deletion (del) of this gene. Among the participants, 15 percent had no copies of the gene (del/del), 52 percent had one copy (ins/del), and 33 percent carried two copies (ins/ins).

From this group, the researchers selected 55 men (17 del/del, 24 ins/del, and 14 ins/ins) to receive a single 360 mg dose of testosterone. The men were then routinely tested over a 15-day period for the telltale signs of doping.

If you’re a genetically gifted athlete (i.e. you lack the gene that produces the enzyme UGT2B17), you can take an whopping injection of at least 360 milligrams of testosterone without getting caught by the testosterone:epitestosterone ratio test (T:E ratio). This testosterone loophole in drug testing has been known by athletes for decades (anecdotally). It is nice to have solid scientific evidence to confirm it.

A full 40 percent of the del/del subjects never reached the detection threshold in a standard doping test. “Nearly half of the individuals in our study who carried this genetic variation would go undetected in a regular doping test after a single 360 mg dose of testosterone,” said Dr. Schulze.

If you were born without the genetics to beat a drug test, then you have a fair chance of failing the drug test even if you are innocent.

Of equal interest, 14 percent of the ins/ins subjects were naturally over the detection threshold even without receiving a testosterone injection. Based on an earlier study, the researchers estimate that this would give a false-positive rate of 9 percent in a random population of young men. “False positive results are not only of concern for the legal rights of the sportsman,” said Dr. Schulze, “they also yield extra workload for the doping laboratories.”

Maybe athletes will start taking advantage of relatively inexpensive personal genome services to learn things like the likelihood of side effects from anabolic steroids and the likelihood of being able to get away with using banned substances?

Most importantly, this study provides solid evidence that innocent athletes can be falsely accused when relying on the T:E ratio test.

A few other things learned:

• A level playing field doesn’t exist even at the genotypic level even when it comes to the ability escape doping detection

• Could there be a rogue chemist who discovered a pharmaceutical drug that can block the UGT2B17 enzyme?

• Certain “ethnic populations” are more/less likely to get caught when using banned substances like testosterone (e.g. East Asians and Swedish Caucasians).

I look forward to reading the full text of the study when it is released.

The paper “Doping Test Results Dependent on Genotype of UGT2B17, the Major Enzyme for Testosterone Glucuronidation” will appear in the June issue of [Journal of Clinical Endocrinology & Metabolism] JCEM, a publication of The Endocrine Society.

Landis, 32, has spent millions of dollars on a defense that tried to cast doubt on the scientific validity of doping tests and the procedures followed at antidoping labs. But last September, in a 2-to-1 ruling, a United States Anti-Doping Agency arbitration panel concluded that Landis had used synthetic testosterone to achieve his comeback win at the 2006 Tour. As a result, he was barred from racing until January 2009….

In its 84-page ruling last year, the United States Anti-Doping Agency panel accepted Landis’s argument that the French antidoping lab that tested his urine samples from the Tour was sloppy in some of its operating procedures, and in how it documented its work. But the panel also found that a more sophisticated second test, conducted after the initial screening proved positive, was accurate.

But make no mistake about it, this isn’t just about Floyd Landis. It is also about the World Anti-Doping Agency (WADA), the anti-doping organization and program that is held as the model for drug testing around the world.

Former NFL running back Femi Ayanbadejo has filed a lawsuit against Author L. Rea of ALR Industries. He claims an undisclosed ingredient in ALRI Max LMG caused him to fail an NFL doping test leading to his release by the Arizona Cardinals and Chicago Bears. Ayanbadejo tested positive for a “form of nandrolone.” Ayanbadejo’s attorney is blaming the positive steroid test on the manufacturer for possibly intentionally “spiking” the supplement with banned substances or contamination from the manufacturing facility.

I have not had a chance to review legal documents in the case. The owner of ALR Industries did not seem to be aware of the lawsuit and could not provide me with any insight into the case.

But on the surface, I’m not sure it has merit from a legal standpoint. Keep in mind that substances prohibited by the NFL (or WADA) are not necessarily prohibited by DSHEA as over the counter supplements (nor should they be). It does not appear that ALR Industries is guilty of producing supplements unintentionally contaminated with steroids or supplements containing undisclosed steroidal products unless there is evidence other than the failed drug test.

It appears that the ingredient that caused Ayanbadejo to test positive on the NFL’s steroid test was clearly listed on the label and/or marketing materials and identified as a legal progestin similar to other progestin-based steroids like trenbolone and nandrolone.

The active compound in Max LMG is 13-ethyl-3-methoxy-gona-2,5(10)-diene-17-one… It is legal because it is a progestin, and before anyone thinks “birth-control”, remember that trenbolone, nandrolone, methyltrienolone and Methyl-Dien all are also progestins. I doubt anyone will disagree with the effects of these compounds upon favorable body composition.

In addition, the label warned consumers about androgenic side effects.

Possible side effects include acne, hair loss, hair growth on the face (in women), aggressiveness, irritability, and increased levels of estrogen.

When an ingredient is said to be in the same class of compounds as banned steroids “trenbolone” and “nandrolone” (legality notwithstanding) and the side effect of “hair growth on the face (in women)” is listed on the bottle, I think this would be indicative of a dietary supplement that a drug-tested athlete would be wise to avoid. In other words, Ayanbadejo made a mistake and should have known better.

My opinion is based on the following assumptions:

1. Max LMG is not contaminated with undisclosed steroidal hormones, either intentionally or unintentionally.

2. The active ingredient in Max LMG is accurately disclosed as 13-ethyl-3-methoxy-gona-2,5(10)-diene-17-one.

3. A metabolite of 13-ethyl-3-methoxy-gona-2,5(10)-diene-17-one resulted in Femi Ayanbadejo’s positive steroid test for a “form of nandrolone.”

4.  The compound 13-ethyl-3-methoxy-gona-2,5(10)-diene-17-one was legally permitted under DSHEA and the Anabolic Steroid Control Act of 2004 whereas the “term `anabolic steroid’ means any drug or hormonal substance, chemically and pharmacologically related to testosterone (other than estrogens, progestins, corticosteroids, and dehydroepiandrosterone).”

Given these assumptions, there does not appear to be a violation of law nor a failure of enforcement (of DSHEA).  Comments are welcomed.

Gaffney takes note of the lack of empirical research examining the performance enhancing effects of drugs that has historically resulted in mainstream medical organizations failing to recognize performance enhancing drugs. Given this along with results seen in “experiments of nature,” Gaffney feels it is reasonable to conclude that GH has performance enhancing effects:

Consider that until 1984, testosterone — now the paragon of a PED — was not labeled a PED by the American Academy of Sports Medicine. Consider that most PED studies look at ‘weekend warriors’ and not elite world class athletes. And consider that no scientist has studied the effect of any PED on home run production in a double-blind placebo-controlled cross-over pharmacological study. Considering all these points, saying PEDs affect MLB home-runs — or any athletic task — constitutes a classic inductive leap. But a reasonable conclusion in my view.

Gaffney discusses the importance of syngergism in the use of performance enhancing drugs. Bodybuilders have long recognized and exploited the synergism amongst various combinations of anabolic steroids, growth hormone and other peptides, and other performance enhancing drugs and have coined the term “stacking” to describe it. But Gaffney is one of the few doctors I’ve seen that has appreciated the concept of synergy in the context of PEDs in baseball and other sports outside of bodybuilding.

In the complex physiological milieu that constitutes human biology, hormones like HGH do not act alone. Neurotransmitters, hormones, growth factors, and other biochemicals act in concert with a multiplicity of biological variables to produce behavior, performance, emotions, and the other functions that we call life…

Many experts contend that HGH by itself my not increase strength or athletic performance. However, athletes take the drug in combination with anabolic steroids, thyroid hormone, insulin, IGF-1 (insulin-like growth factor), and other ‘stacked’ PEDs. The effects of these drugs appears to be synergistic…

Experts on metabolism and endocrinology suggest that androgenic hormones modulate the response to HGH — ie. a synergistic effect. The response to HGH becomes even more complicated because another hormone IGF-1 may actually be performing much of the cellular dirty-work for HGH.

In 1999, my friend Bryan Haycock wrote a groundbreaking article on the synergism between growth hormone, insulin-like growth factor 1 (IGF-1), insulin, thyroid, and anabolic-androgenic steroids.  The lengthy series offers incredible insight in the synergy of performance enhancing drugs.

In the first installment of this series we discussed the mechanism by which human growth hormone (GH) exerts its anabolic effects in the body. We also discussed the important role of insulin-like growth factor-1 (IGF-1) in the anabolic properties of GH. In part two we discussed the role of androgens in GH secretion and sensitivity in a hypothetical pharmacological regimen aimed at dramatically increasing skeletal muscle growth. Based on research looking at the effects of androgens on GH secretion and IGF-1 sensitivity, it was deduced that the testosterone esters should provide the most potent anabolic stimulus compared to other androgens, especially those that do not aromatize. Now, in the final installment, we shall look at the feasibility of using GH, IGF-1, Insulin, and perhaps tri-iodothyronine (T3) to enhance the anabolic properties of androgens.

Athletes, particularly bodybuilders, will always be far ahead of the scientific community when it comes to experimentation with performance enhancing drugs. Bodybuilders usually are the first to establish trends in the types of anabolic drugs used and the manner in which they are used. The body of knowledge amonst bodybuilders continues to advance through real world trial and error.

There is no prohibition on performance enhancing drugs in bodybuilding which completely eliminates the ethical considerations faced by researchers and physicians and even athletes subjected to doping controls. As a result, anyone who wants to learn about performance enhancing drugs just needs to investigate bodybuilding to learn what is on the leading edge.

So, I have to give credit to the few journalists who “try” to explain the difference between growth hormone and anabolic steroids like testosterone e.g. The Growth Hormone Myth:

The media haven’t spent much time making a distinction between HGH and steroids. An AP story, titled “After BALCO, Another Steroid Scandal,” glosses over any differences between the two, drawing a straight line from the BALCO investigation to the busts in Florida. But Jerry Hairston isn’t Barry Bonds. Sure, both of these guys probably took banned substances in an effort to boost their stats, and both were involved in major drug busts involving large numbers of Major League players. But it’s just plain wrong to put growth hormone in the same category as anabolic steroids. In the sports version of the war on drugs, Bonds was shooting heroin while Hairston was smoking marijuana.

Hairston used growth hormone; Bonds used a variety of anabolic steroids. The author of the article makes the analogy that steroids are like heroin as growth hormone is like marijuana. The implication is that not only are they different classes of drugs, but that one (anabolic steroids) is significantly more dangerous than the other (growth hormone).

Unfortunately, this may not be true. At the very least, it is not a certainty according to experts. The anti-aging physician Karlis Ullis, M.D. who has prescribed both testosterone and growth hormone in the course of his practice suggests that growth hormone may be a riskier proposition than testosterone:

Don’t get me wrong – I still use both growth hormone and testosterone as part of overall anti-aging programs in my patients. This article is not meant to say one hormone is “good” and another is “bad”. It is just my opinion at the moment that the overall benefit/cost ratio for improving body composition is higher with testosterone than growth hormone. By cost, I mean both the monetary price – testosterone is far cheaper than growth hormone, and the side effect/safety profile – testosterone is safer than high-dose growth hormone use.

Since growth hormone is extremely expensive and perhaps riskier than testosterone, I screen patients very carefully and only recommend it to those who either have very low IGF-1 levels and fail growth hormone stimulation tests, or those who have failed to respond to testosterone or other therapies. The new research has also made me confident in encouraging more and more patients to go on testosterone. However, we must keep constant track of the new research to better refine both anti-aging and bodybuilding programs. The science of hormone supplementation is still in its infancy, and there is still a lot more questions that need to be answered.