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Eberhardt Nieschlag: So we heard the presentations, we heard the cases, now you can ask the questions.
Audience Question: Dr. Morgentaler, what if the PSA starts rising after you give testosterone to this patient because I am aware of good studies where PIN patients have been given testosterone and nothing has happened. But PIN with high-grade PIN and that, too, with high PSA, are the risk factors of the population which are expected to progress to malignancy. And what if you give testosterone to these people and the PSA starts rising.
Dr. Morgentaler: Well, the question, if I hear you right, is if the man has PIN and the PSA rises, what do you do? And I would say that the answer is the same whether the man has PIN or not and whether the man is on testosterone or not. If a man has a rising PSA, it is a reason to do biopsy period for every man on testosterone or not. And of course we have to be careful, but remember that the PSA change that we see with testosterone replacement therapy happens very early within a couple of months and it gets the level of eugonadal men and no more and then the changes that we see, we saw some of the Nebido® study before and some of the other ones, there is very little rise in PSA after the initial six months. Let’s remember: we worried about prostate cancer. PSA for us is just a reason to do a biopsy. So once you do the biopsy and there is no cancer, all you can do is follow him and that is his new base line and I do that for my patients who are not receiving testosterone therapy, too.
Audience Question: One more question to Professor Behre. Regarding your indications for testosterone replacement treatment, you have mentioned one: delayed puberty. Now I would like to ask if it is a delayed puberty, would you not likely use a hCG kind of compound which increases FSH, LH, in addition to testosterone and give only testosterone?
Dr. Behre: I think there are quite good data in delayed puberty if you give testosterone to induce the puberty more or less. You give the treatment for inducement of puberty. There are quite good studies showing this. I think this is the reason why you give testosterone preparations. HCG I think is the treatment of choice if you have secondary hypogonadism; for example, in patients with Kallmann Syndrome, with low GnRH or pituitary disease and you combine hCG and FSH treatment for stimulation of the testis and the two gonadotrophins will stimulate spermatogenesis to induce fertility, to induce testosterone production.
Audience Question: Excuse me, but then, you see, puberty is when there is a surge in the luteinising hormone. If you give testosterone, you are trying to give a negative feedback to the luteinising hormone.
Dr. Behre: You are right. I mean, it is quite important your point. If you use testosterone for delayed puberty, you take very low doses so that you don’t have negative feedback, but only something like a priming for the puberty. That is an important point.
Audience Question: It’s a bit of a comment, but open to all of the panelists. It’s the cut off of 12 for total testosterone, in our centre; we chose a cut off of 15 in part by looking at the literature, part for cost containment, wherein if the first level was above 15 we didn’t do a bio-available testosterone. And while it is true that a pre-test probability of a low bio-available greater below 12 or 13, it is not zero above 13, 14, 15, such that three years ago we had to drop that. We have seen many, many men with values of total testosterone in the high 20s with low, if not sometimes immeasurable bio-available testosterone levels. Could you comment?
Dr. Morales: Well, I can, I always love to make a comment on this. I feel very strongly that we have published in that regard. Again, what Abe said and I said it earlier today, you have to believe in your patient and not in your biochemist. If there are any biochemists, please do not take this personally, but you talk to the biochemist and there are a lot of problems in the biochemistry clinical labs. I am not talking about the research labs that is a different story, but the regular biochemistry labs, when we sent our samples, there are huge problems of many of us are not aware of what is happening there so, Richard, I agree, you really have to listen to the patient.
Dr. Behre: I did not mention this, but you are quite right. If you use different methods for measuring testosterone and although you have good quality control, internal quality control, external quality control, different available methods will result in different testosterone levels and we are all aware of this and that is a clear recommendation that each laboratory should establish its own reference range, depending on the method you use. I think this is an important message for the audience. But you should establish your own range and then you can decide who you will treat.
Dr. Morgentaler: I have strong feelings about this and I think your clinical suspicion is the right one. There is not one paper to my knowledge that has looked at testosterone replacement therapy in trials that has looked to see if men with T above, let’s say, 340 or 350, whatever you want to say, have done less well if they were symptomatic to enter the trial. What we do in our practice is we measure total testosterone and free right together and we will treat men who have, who are either low or lowish on either one, but symptoms are paramount and we have some men, a lot of men, who have T levels above 350. Total Ts, there is the free T that sort of tips us off and makes us feel more comfortable treating them, but a lot of these guys have T levels that are above 500, not a lot, but some and it depends on SHBG and all this. So understand that the thresholds have come from statistical measures of populations, two standard deviations from the mean. What that means is the lowest 2.5% of males are called low. Well, who is to say that the prevalence of hypogonadism is exactly 2.5%? That is the problem. So go clinically.
Audience Question: One has to do with sleep apnea. It is totally counter-intuitive why sleep apnea shouldn’t improve with testosterone replacement therapy as we improve people’s body mass index, etc., etc. The idea that there is some sort of idiopathic or idiosyncratic response to testosterone that causes sleep apnea to begin de novo, it just doesn’t make any sense, and I would appreciate some comments.
Dr. Morgentaler: Well, you know, I dealt with risks so I’ll just say this. I wish we never had sleep apnea come up in the testosterone talks. It is unavoidable; the world literature is something like less than 30 patients. It has never been an issue about which I would say if I ask, I ask everybody now, 15%, 20% of my patients who walk in the door say they have sleep apnea. We treat them anyway. It is not an issue and I don’t know what to do with it otherwise.
Audience Question: The second question has to do with the PSA from Dr. Behre’s case. One of the options not offered was with a PSA of 3.6 in a 61-year-old male, would you biopsy him before you, would that be part of your further work-up? That was not offered as one of the choices and the sort of discussion was that that was a little on the high side for a 61-year-old guy and might warrant some further investigation just to rule out prostate cancer.
Dr. Behre: I would agree, there should be a follow-up, but this patient will not receive testosterone therapy, as I said.
Audience Question: You would wait until you . . .
Dr. Behre: And he would have follow-up in the office, PSA and probably biopsy.
Audience Question: It is regarding the third case that was the case from Dr. Morgentaler. I have been one of those who voted for the considered testosterone replacement therapy, but I have learned during this meeting that maybe the PSA velocity, the PSA in motion, would help us besides the biopsy. What do you think about that?
Dr. Morgentaler: If PSA is going up, watch out. You have to do both. I mean the arguments about why velocity is useful is because there are so many men now who already have had PSAs drawn over the years and even within what is called the normal range we see changes and it may still be below a threshold but the velocity is now an indicator that there may be cancer.
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