Dr. John Amory, Direct by Jacobs.
q: where employed.
a: UW Seattle.
q: what do you do:
a: physician, scientist in andrology
a: testosterone replacement, and hypergonadism.
q: where edu?
a: Harvard, UCSF.
q: in andrology, awards?
a: Young (less than 45)
FAILURE ALERT! The HTML monster ate a bunch of stuff here, sorry.
...very rigorous paper in NE Journal of Medicine.
q: testosterone and endurance - papers.
a: August last year...
GDC 621. Effect of multiple oral doses on endurance performance, Baume et. al, including Saugy.
a: study of trained athletes with t/placebo/exercise, treadmill performance. conclusions were that no benefit compared to placebo.
q: familiar with reviewed papers on recovery?
a: two old ones from the 80's. Neither showed any benefit.
q: Don Catlin testified that T wuld benefit recovery. Has he written papers on that?
a: unaware of data to substantiate that claim.
q: Joe Papp took bunch of stuff... and microdosing androgel, and he said androgel gave recovery benefit. Is there a benefit to recover.
BARNETT: objection mischaracterizing testimony.
q: do you have opinion if the androgel would give recovery bneefit.
a: my review of literature says no; of the list, the glutein (?) does give recovery benefit.
q: how does T affect someone psychologicall -- papers?
a: O Conner
a: 200 ng by injection, followed by questionaires -- no changes in normal; those sub-normal became less hostile and irritable.
q: show where in paper?
a: table 3, page 561.
q: explain table.
a: person and partner reported scales on aggression/anger/hostility; doesn't seem to have any affect.
q: familiar with t/e ratio and how used in anti-doping?
a: in cases I've judged for ADRBs, they've been triggered by t/e ratios.
q: what affect does T have on T in the short term?
a: changes the ratio?
q: affect of single use?
a: no, some studies of chronic and intermittant, including Cologne study.
EX 34 cologne.
q: not peer reviewed, correct?
q: do you now what review has been given?
a: presented in conference in the last year.
q: what does it show about t/e ratio?
a: has a marked and stable increase in t/e ratio.
q: some or all?
a: most over 4, some less than that.
q: for those who did not have it go over 4, what did it do to t/e over reference range.
a: tend to increase over their normal range?
q: how many participants?
a: 18 -- gcms, 2 checked by irms.
q: significance of cologne study looking at Landis' t/e values?
GDC 1363 2.8/ 1.3 / 2.5/ 1.5/ 1.8 / 11 / 2.5/ 1
a: what you see here, all less than 4, and the value of 11 is out of range. In the cologne study, if they went above 4, it would stay above 4.
q: low mode vs. high mode individual?
a: high mode have a t/e around 1. low mode because of low e have ratios perhaps around .1; you are either one or the other. Don't switch.
q: If the contention is that T gel was used on these occasions, and looking at the t/e ratios, does this l ook consistent.
a: if gel was used on all those dates, I'd expect a higher t/e ratio. t/e is a sensitive marker for t gel. I don't consider these results consistent with T gel use over that period?
q: what if injections some days, gel others, oral others.
a: would be surprised to see these results, but not impossible.
q: looking at actual T concentrations,
a: these are frankly low, others are low.
q: what it the significance of these numbers?
a: fairly consistent, in the low range of normal.
q: anything in the E numbers striking?
a: quite low. these are below lower range of normal. with excretion of t and e there is a circadian rhythm involved. Lowest in mid-afternoon, almost 10x lower than rest of the day -- 5pm is the time reported.
q: in the work you do with ADRBs, are you familiar with CIR tests?
a: yes. Classically used as a confirmatory test, to see if T is exogenous.
q: if exo-t used, explain metabolization.
a: complicated stuff. Metabolites used as markers for doping control.
q: do you expect relationships between them.
a: they should relate close to each other. the 5a and 5b should go toghether and in tandem.
q: are there papers to support that.
a: best is shackleton.
q: EX 40 at USADA 1241. Is there a portion to look at?
a: see fig 4 on page 383, this shows 5a and 5b fall dramatically, to about -4only later do they vary much.
q: in you opinoin, is there basis to believe that exo-T would affect one diol in a significantly way than another?
a: none in the published literature?
q: what's the maximum difference you'd expect to see?
a: very surprised to see it > 2.
q: what about cologne?
a: did do irms on two individuals over time. page 14, figs 18-21 the irms results. Fig 18 shows patient 10,
the t/e ratio is up all the time it is administered; good correlation of t/e with irms data.
q: other figures of interest?
a: fig 20 and fig 21, this is person 9 doing intermittent gel application. the irms differences are about as you'd expect, but not as sensitive as we'd like.
q: other points?
a: fig 21 A-diol vs B-diol. so there is a little difference between the A and B diols, but still moving the way you'd expect.
q: jul 20 -6.39 and -2.65. consistent with exo-t use?
a: no. difference of 4 is way out of line with studies.
q: jul 22, -4.8 and -1.67. consistent with exo-t?
a: no, doesn't look like anything we've seen -- exceeds 3.
[ problem case is 7/13 -4.62 and -4.09 ]
q: do you believe these results are accurate?
a: I don't think they can be used to confirm doping occurred. While 7/13 looks bad IRMS, it doesn't make sense T/E. There's no point where they are both positive.
q: if this t/e 11 is right, you wouldn't expect a 2.5 on jul 22?
a: no you would not expect that.
q: on the andro -11k, and e-11k, would you expect similar changes there?
a: they should parallel. these all look normal. the values on the 23 are confusing.
q: you've seen all the values from cologne. Are any of those values consistent with what we see here.
q: if low mode, then t/e is always going to go to normal.
q: if high mode, it'll go from normal to > 4
q: how many studies have you done with urine steroids.
q: so when it comes to urinary metabolism you rely on someone like shackleton?
a: I rely on the literature.
q: you said that you have work on USADA cases with t/e and irms?
a: around 2 or 3 of 10 cases.
q: that would be the only time in your career when you've have occasion to look at ratios?
q: the only occasion you've looked at irms results like 5a dna 5b.
q: your experience working with deficient patients is mostly blood.
q: depending on urine/blood the method of application affects metabolization.
a: yes. injection fast, gel, oral more steady state.
q: time after administration makes a difference?
q: are you aware of studies showing mixed administration?
a: some data in cologne, at different times.
q: if you were an athlete who wanted to keep t/e down, methods would be E cream.
q: could make it go down or stable.
a: yes. I'd expect the absolute value of T to be relatively high.
q: if you were using one or more T products, like fast acting pill, that would have a signficant effect.
q; if your e was fairly low, then it wouldn't take much administered to change ratio.
a: yes, it could change very markedly.
q: if you did that, you wouldn't see marked difference in absolute amount of t.
a: not if you were using E cream
[ i didn't follow this ]
q: are you aware of any studies that show that during a long event that an athlete's T drops.
a: no studies, but not surprising.
[landis, chin in hand ]
q: EX 43, USADA 804, whatever opinions you have on t and e may be affected is based on reading, not work you've done.
q: have you seen this study?
a: same group as the endurance study earlier.
q: you said you reviewed exhibits, did you get ours/
a: I have many binders. Can't say specifically.
[ blows up abstract ]
q: look at F1, p 367. look at individual S1, somebody after his first pill, t/e not affected in 24 hrs.
q: 5a and 5b drop together in 4 hrs, back to normal in 24 hrs.
a: clearly a low mode individual, baseline 0.1. This drug is used 3x day in europe.
q: so this would be a good way for an athlete to take T?
a: good for hiding, but bad for effect; you might evade detection, but get no benefit.
q: Subject 5, takes Oral T, gets a TE spike to 17.31, high mode.
a: what you'd expect.
q: 8 hrs. back to normal. 5a and 5b go together, gone in 8 hrs.
a: a great slide. t/e go up and down in almost exactly the same as the delta go down. Here they corroborate each other very well; inconsistent with what we see in Landis.
q: so this athlete could take oral T every day before bed and you wouldn't find it an after race test.
a: yes, this individual would never even screen positive.
1241/ USADA 1245 shackleton
q: Subject 5 of this study, the 5a and 5b behave differently.
a: i think there's a difference of 1 or more, at most 2. so actually difference only after 13 days, single data point do you get that large difference.
q: this is a single large injection. different people metabolize differently.
a: patterns are very similar. reproducible pharmokinetics.
q: would you expect 5a and 5b to behave differently dpeendingn on whether the product was administered orally or through skin.
a: apriori, I might; the one subject is hypothesized to be that way in the cologne study. That explanation is incorrect. I have give t-gel to 100s of men. We don't see that in these studies. We did see this with patches, but not gel. So that explanation doesn't make sense.
q: you've never measured how 5a and 5b react after administration of gel.
a: no. lots of data on serum testosterone and DHT.
q: do you look at E in blood?
q: medical purpose?
a: looked at for research.
q: USADA 122, is this the paper article you referred to?
q: you're quoted as saying men ordinarily produce 1E for 1T. true?
a: I don't think she understood our discussion.
q: "there are peple likt what who would like to see an American...disgraced. That's why the Coc has to be codified"
a: may have some resemblence to what I said, but certainly not this.
q: how would someone squirt something?
a: I don't think that's what happened.
NO QUESTIONS -- no, one more
q: you said earlier use of T increases RBC, so using hematocrit and hemoglobin to go up.
a: if started anemic, improve to baseline.
q: did mr. landis tell you he had a list of blood test results from UCI?
a: have not seen such a list.
[ This was something he alluded to with Catlin ]
JACOBS RE-DIRECT: FTR, I'm not clear what blood test list Mr Young is referring to.
q: NYT article, CoC documents important when doing ADRB work?
q: Also lab documentation.
q: when you got lab documentation, did you do that?
a: there are some errors
a: in a medical context they'd throw it out and force a retest.
q: GDC 1363, summary chart. asked about E cream as a masked t use. Are the E values here consistent with an E cream.
a: these are very low values. I can't see taking E cream to get these low values. this is my opinion only. based on no published data, it seems consistent with all values. Doesn't seem consistent with use of any use of a supplement. None are high, they are all low.
q: you were shown EX 43, USADA 807. Look at subject 1. Is the data consistent with in this case?
a: not at all.
q: why not?
a: low mode; Landis is high mode.
q: S2. consistent with Landis?
a: no. illustration why you expect t/e to go up while 5a and 5b go down.
q: S3. consistent with Landis?
a: no. none of these are even abnormal.
q: S4. consistent with Landis.
a: no. again, the two tests back each other up.
q: S5. consistent with Landis?
a: no; same reason.
a: once again no, same reasons.
a: no. same reasons. at no point is there a discrepency between the two tests.
q: Shackleton paper. Fig 4a, 4d, 4e, 4f.
a: no. the metabolites should corroborate each other. Nothing as large as the 4 seen in Landis.
q: is there any reason to believe a cyclist would metabolize T different than anyone else.
[ landis yawns, deeply ]
q: focus on second graph, 11ha-adiol (don't knwo which person, looks like intermittent use). Week 7, what would you say the 11ha value is?
q: week 8
q: so the 5a is more than 4x bigger than the 5b?
a: only two individuals underwent irms, the problem with this study is that there is a endogenous compound and only one individual. This is shingling past the edge of the roof.
q: there are 2 others in the appendix.
q: p3 and p10 at 14 also has irms results, figure 18?
q: when you look at p9 and p3, you see you can get variations?
a: and at every point you get a t/e positive.
q: this is after gel for..
a: 6 weeks for one, and on and off for the other.
q: did you listen to Mr. Papp?
q: would is surprise you to pass t/e screen on androgel?
a: with a lot less, maybe not; with large dose yes.
BRUNET: Scheduled to run till 5:00, Landis cross I don't expect cross less than 30 minutes?
SUH: After Landis, we will call Simon Davis, last witness, 2-3 hours.
BARNETT: may have one or two rebuttal witnesses.
SUH: Identify rebuttal witnesses?
BARNETT: Later tonight.
BRUNET: Provide within next hour.
RECESS till 9:30am
September 07: Hearing Award
October 07: Hue's Hearing Appraisal
November 07: Major document Release
January 08: Larry's Curb Your Anticipation
Monday, May 21, 2007
Dr. John Amory, Direct by Jacobs.