Tuesday, September 04, 2007

Another Theory

EMailer BK Sanders has sent us some references and links to cases we haven't really figured out how to introduce, and rather than wait for inspiration, we'll just put it out here for your consideration. Unverified, and certainly not to be taken as an "official" Landis position, but worth a look.

Do Non-Steroidal Anti-Inflammatory Drugs Influence the Steroid Hormone Milieu in Male Athletes?

Med Hypotheses. 2007 Mar 23; [Epub ahead of print]

Sex, drugs and sports: Prostaglandins, epitestosterone and sexual development.


College of Letters and Science (Alumnus), University of California, Berkeley, CA 94720, United States.

Amateau and McCarthy's findings published in Nature Neuroscience (June 2004) are noteworthy for suggesting a role for prostaglandins in sexual development. However, evidence suggests that in manipulating PGE2, they unknowingly implicated 3alpha-hydroxysteroid dehydrogenase [E.C.], 3(or 17)alpha-hydroxysteroid dehydrogenase [E.C.] and their respective products, androsterone (ADT) and epitestosterone (EpiT), in the developmental masculinization of sex behavior. EpiT is generally regarded as a hormonally inactive 17alpha-epimer of testosterone (T). In rats, the kidney is the primary site of EpiT formation, whereas in humans it originates from the gonads, with only a small contribution secreted by the adrenals. Because the ratio of T to EpiT is nearly constant, it is presently used for assessing steroid abuse in competitive sports, where the World Anti-Doping Agency (WADA) considers a T/EpiT ratio > 4 evidence of T doping. Despite its central role in the detection of illict anabolic steroid use, our knowledge of factors effecting EpiT production is poor. Clues in the literature, however, reveal that prostaglandin-mediated processes, such as LHRH release, may influence its production. Antimycotics, NSAIDs, and opioid analgesics used in sports medicine are all known to effect prostaglandin E2 synthesis. Primary PGs are potent inhibitors of ADT oxidation, while indomethacin, a prostaglandin blocker, powerfully inhibits 3alpha-HSD reduction and ADT oxidation. This is significant because ADT inhibits the oxidation of EpiT, and may modulate its antiandrogenic and neuroprotective effects. It is hypothesized that the T/EpiT ratio is increased by COX-2 inhibitors and opiod analgesics, and decreased by antimycotics that do not impair testosterone biosynthesis. Given the devastating personal and career consequences that may result from false positive drug tests, substantive research on the effects of PGE2 manipulations on EpiT is warranted.

Int J Sports Med. 2007 May 11; [Epub ahead of print]

Do Non-Steroidal Anti-Inflammatory Drugs Influence the Steroid Hormone Milieu in Male Athletes?

Unit of Endocrinology, Department of Health Sciences, University of Rome “IUSM”, Rome, Italy.

Prostaglandins modulate the hypothalamus-pituitary-adrenal and -gonadal axis pathways. We explored the effects of a single course of treatment with acetylsalicylic acid (ASA), an inhibitor of prostaglandin synthesis, on the steroid milieu in athletes. Morning plasma cortisol (F), dehydroepiandrosterone sulphate, free-testosterone, testosterone (T) and their ratios were evaluated before and after the administration of either ASA or placebo in twelve male athletes, when affected by minor musculoskeletal trauma and, as control, after a five/six week wash-out in healthy conditions respectively. One tablet of ASA (800 mg), or placebo, was administered two times daily for 10 days during treatment. All the volunteers suspended exercise training during treatment. The results revealed that compared to placebo, plasma F was significantly lower after ASA treatment (p = 0.023). Furthermore, the comparison of hormone's absolute and percentage of variations (Delta and Delta%) between ASA and placebo treatment showed significant differences respectively for DeltaF (p = 0.045), for DeltaT (p = 0.047), for DeltaT/F (p = 0.042), for DeltaF% (p = 0.04) and for DeltaT% (p = 0.049). Our data suggest that in comparison to placebo, a short-term ASA treatment is able to influence the plasma steroid milieu in athletes. Due to the observed variability of the individual hormonal patterns, further research is required to substantiate these findings.

Neuroscience. 2006 Jul 7;140(3):929-37. Epub 2006 Apr 3. Links

Single opioid administration modifies gonadal steroids in both the CNS and plasma of male rats.

Pain and Stress Neurophysiology Laboratory, Neuroscience and Applied Physiology Section, Department of Physiology, University of Siena, Via Aldo Moro, 2, 53100 Siena, Italy.

While morphine remains one of the most widely used opioids for the treatment of painful conditions, other opioids are also commonly employed. Because of the interactions between opioids and gonadal hormones, in particular opioid-induced hypogonadism, this study investigated the effects of widely used opioids on plasma testosterone and estradiol levels and brain testosterone levels in male rats. Animals were s.c. injected with two concentrations of morphine (5 or 10 mg/kg), fentanyl (0.05 or 0.1 mg/kg), tramadol (10 or 40 mg/kg), buprenorphine (0.05 or 0.1 mg/kg) or saline (0.7 ml/kg). Four or 24 h after treatment, the rats were deeply anesthetized to collect blood samples from the abdominal aorta and to perfuse the brains with saline. Plasma and brain hormone levels were measured by radioimmunoassay. In rats studied 4 h after treatment, all the opioids except tramadol 10 mg/kg decreased plasma testosterone in comparison with saline administration. At the same time, plasma estradiol levels were lower than control in the groups treated with the low doses of morphine, tramadol and buprenorphine, while estradiol remained at control levels in the other groups. Twenty-four hours after treatment, plasma testosterone levels were different (higher) than control in the animals treated with the low doses of morphine, fentanyl and buprenorphine. Estradiol was lower than control in the low dose groups, while the high doses did not produce any changes with respect to control. Four hours after treatment, brain testosterone was drastically decreased in all groups except buprenorphine, in which it remained at control levels. All groups returned to control levels at 24 h after treatment. In conclusion, opioids exert important effects on plasma and CNS sex hormone levels. The different magnitude and time-course of the effects of the different opiates on testosterone and estradiol levels are likely due to their different mechanism of action.


The attached news reports and research articles suggest that anti-inflammatory drugs, which are prohibited substances in certain circumstances (see WADA list/USADA Guide), may be an unidentified cause of positive tests for steroids:
Thorpe cleared on drugs
Thorpe making progress after broken hand http://www.abc.net.au/news/newsitems/200605/s1636288.htm
Glandular fever (Infectious mononucleosis) http://www.medinfo.co.uk/conditions/glandularfever.html

There is no specific treatment for glandular fever. Antibiotics are not helpful, as this is a virus infection. In fact there is one antibiotic, ampicillin, which is more likely to cause a rash if given to people with glandular fever.

You can treat the symptoms of fever and pain with pain killers (analgesics) such as paracetamol or non-steroidal anti inflammatory drugs such as ibuprofen or aspirin (16+ only). You will probably need more rest and sleep than usual for a prolonged period.

Gatlin got injection he thought was vitamin B12 before positive test

(AP) — The top assistant to track coach Trevor Graham gave Justin Gatlin an injection, which he believed to be vitamin B12, two weeks before the world record-sharing sprinter tested positive for steroids.

After Randall Evans gave Gatlin the shot, the sprinter was given what he was told were anti-inflammatory pills as a follow-up, a person with knowledge of the case told The Associated Press on Monday.


Mike Solberg said...

Ah, sorry, you can't challenge the science.


jamesdemien said...

I agree with and would like to extrapolate on marks comment. If only a little.

What we have here is a theory as to why the ratios would be outta whack. The defense's case showed that there is no way to know whether it was in or out of whack because they botched the tests.

Interesting theory indeed, but lets stick to a singular attack plan.

Valery said...

Natural hormone balance is the most important part in your health! Take care of that!