Overview of the 7th World Congress

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Dr. Mark Perloe: “I’m here with Eric Thomas who is Co-Chair of this wonderful 7th World Endometriosis Society meeting in London, England. I hope we have a chance to come back for maybe the 8th or 9th one here; this has been an excellent program and a wonderful city to visit. What would you say have been the highlights of the meeting so far?”

Professor Eric Thomas: “I quite like the structure of this week. For the first time we experimented with the structure and have the first lecture which would be just the basic science and the biology of the problem, and then how that was then related to endometriosis as the second lecture, and then the clinical management is the third, and that’s worked well where we planned it. I thought this mornings talk on new therapeutic agents, particularly with Professor Smith and Professor Osteen, was very forward
looking and gave some potential anti-angiogenics and matrix metalloproteinase modulators and all in all the high standard of presentations in areas of interest.”

Dr. Mark Perloe: “One of the things that I think we heard repeatedly was that the pharmaceutical companies are losing their interest in women’s health, and we have to wait until a drug comes out for breast cancer or metastasis in another sort of cancer. Then we experiment with it and see if it has application. You had talked about some areas of hormonal modulation or manipulation, and I wonder if you might review some of the things that you touched on in your lecture.”

Professor Eric Thomas: “To come back to the point about the pharmaceutical industry, I think they have to make very, very hard
commercial decisions, there’s a lot of investment going on and they need to know that they’re going to get some repayment. So that’s why they’re, I think, a bit worried with the female health market at the moment but in terms of the estrogen modulators, I reviewed both the new anti-estrogens, which we’re still really waiting to see what their potential is. The aromatase inhibitors which I felt in the end are probably not going to be helpful drugs in reproductively capable women but certain selective estrogen
receptor modulators - the serums look as if they may well be very effective in the treatment of endometriosis, and also, you would be able to treat endometriosis and still preserve bone which would be very advantageous.“

Dr. Mark Perloe: “One of the things with the serums has been that the raloxifene which is commercially available in the United States is associated with increased patient complaints of hot flashes and the vasomotor side effects. There are some serums that are coming down that may not have that. What about the side effects from this, do you see these as drugs that would be used alone or perhaps as an add-back therapy agent in conjunction with the GnRH analogue or antagonist?”

Professor Eric Thomas: “I would sooner have it being used alone, the animal model both in the rhesus monkey and in the rabbit with experiment in endometriosis shows that raloxifene will affect those. Now there’s a tolerability issue with raloxifene in particular, it may be that if there are other serums that don’t have this vasomotor symptoms then they would be more helpful but the thing that really limits the length of time you can use a hypoestrogenic approach is, of course, bone demineralization and raloxifene does not affect bone.”

Dr. Mark Perloe: “One of the things that we haven’t heard talked about yet is the extension of the add-back therapy or initiation of add-back therapy earlier. Traditionally, we’ve been using a six-month course of lowering the estrogens and then getting off, and I think there’s good evidence. Dr. Evers showed some wonderful slides on how you can grow great endometrium in a woman who hasn’t had estrogen for fifteen years so six months isn’t going to do it but what about add-back, are we going to learn how to use that more appropriately to get a longer term benefit?”

Professor Eric Thomas: “My understanding of the literature as it stands at the moment is that there is no evidence that giving add-back from the very beginning makes any difference to the effectiveness of the drug. I think in a sense, the deal is done, you should just prescribe add-back with the six month course of GnRH analogue because women are needlessly having their hot flashes.”

Dr. Mark Perloe: “What about continuing beyond six months?”

Professor Eric Thomas: “I think it’s logical. To be perfectly honest with you, I think the issue is a cost issue for the physician or for the healthcare system in that these compounds are still in UK terms about a 100 to 150 pounds a month. That’s quite expensive treatment over a period of a year or two years, so I think there is an issue related to cost. I don’t normally use them long term except in people with really very debilitating chronic disease.”

Dr. Mark Perloe: “We’ve had some experience in those patients and the cost issue comes out at about a two- to three-year breakthrough so that if you’re going to continue someone longer than three years, then surgery may be a benefit. What are your thoughts on the angiogenic factors and MMP’s?”

Professor Eric Thomas: “I thought they’re very exciting. It’s wonderful in a sense that only reproductive women have angiogenesis and so you’ve already got an immediate targeting, it’s targeting straight away. I thought that the data from Professor Smith and Professor Osteen really looked very attractive as possible modulators of endometriosis in the future.”

Dr. Mark Perloe: “We’re starting to again think of endometriosis as a metastatic condition and that offers a whole new range of drug treatment possibilities. When we look at the cardiac vascular conditions, on the other hand, the VEGF and angiogenesis plays a supportive role and when we look at metastasis, we want to block that system. Are we going to run into problems that by treating one system we perhaps increase risks elsewhere?”

Professor Eric Thomas: “I don’t know it’s the answer, I don’t know that. I don’t quite know what the impacts of anti-angiogenics are on the cardiovascular system but of course you’re not laying down blood vessels. You and I aren’t creating a blood vessel at the moment, and so realistically you’re only going to affect new blood vessel formation. Realistically, that only happens in the adult female in the endometrium and in the ovary.”

Dr. Mark Perloe: “So there are a lot of therapeutic options for this new approach.”

Professor Eric Thomas: “Yes.”

Dr. Mark Perloe: “Anything else about the meeting that we need to let people who haven’t had the opportunity to come learn about?”

Professor Eric Thomas: “I think we’ve had a very interesting symposium on the things that matter clinically, on pain and damage formation and how you get adhesions and the treatment of adhesions. I think one lesson from that was we still don’t know how to stop adhesions forming and we’re still in difficulties treating them so there’s a long way to go.”

Dr. Mark Perloe: “I think we’ve put the nail in the coffin about minimal endometriosis causing infertility.”

Professor Eric Thomas: “I think that nails been in the coffin for a long time, hasn’t it?”

Dr. Mark Perloe: “I think people are still not necessarily willing to accept that. Although that’s the case, I still think those patients who present are going to be treated as having unexplained infertility. What about other areas and more aggressive stages of endometriosis in infertility or is there no place for a symposium on infertility at a endometriosis conference?”

Professor Eric Thomas: “No more than endometriosis causes damage to the tubes and ovaries and that’s how you can end up getting infertile. The evidence is really very clear now that certainly medical treatment does not benefit fertility, absolutely, and there’s some conflict about surgical treatment with one study showing no benefit and another study showing some.”

Dr. Mark Perloe: “Do you want to address some of the controversy around the Endo-Can study because right now that is the best designed study we have, yet people are leery about believing the results.”

Professor Eric Thomas: “I think what the issue with that study is the low pregnancy rate in the control arm, and you saw data today showing pregnancy rates of around about 40% in the control arm of those medical studies when Professor Evers aggregated them all together. So the issue is why is there such a low pregnancy rate in the control arm at 19%? Also, if I remember right, that study wasn’t just unexplained infertility there were other manipulations that took place.”

Dr. Mark Perloe: “They did deal with adhesions in the group with endometriosis, yet not in the control group, although they looked at that in the subsequent analysis. It also may not have been clear as to exactly which cases entered into the study but the issue of surgical management, again, ought to be just to restore anatomy?”

Professor Eric Thomas: “We’ve discussed the issues around the Endo-Can study and the Italian study – GRSE didn’t show any impact of surgery. I think the difficulty is that it’s difficult to see a mechanism, it’s often endometriosis and you blast it - how does that make you more fertile?”

Dr. Mark Perloe: “The term ‘epiphenomenon’ was used, do you think this is a epiphenomena that there may be some factor allowing endometriosis that also makes infertility more likely?”

Professor Eric Thomas: “You could say infertility causes endometriosis. We know that there is strong evidence of a relationship between your likelihood of getting endometriosis and your exposure to menstruation. Now by definition, infertile women have a long unbroken exposure to menstruation because they’re infertile whereas other people are having pregnancies so it might actually be that because you’re infertile you’re more likely to get endometriosis, and not the other way around.”

Dr. Mark Perloe: “What about the patient going through planned IVF, what’ s your approach if there’s an endometrioma present?”

Professor Eric Thomas: “I think it depends upon the size, if it’s very big you can’t get at the eggs. In general, I think it’s probably a good idea to have it drained or excised.”

Dr. Mark Perloe: “One of the other issues that I think we’ve seen some conflicting evidence is the value of removing both ovaries at the time of hysterectomy. What is your approach and understanding of the literature?”

Professor Eric Thomas: “My understanding of the literature is that it’s pretty sparse. The work I know best is the work that was done by John Stud?? who looked retrospectively at women with endometriosis who had had their ovaries removed at the time of hysterectomy and those that hadn’t. The reoperation rate in those that hadn’t had their ovaries removed was in the order of between 40%-50%. In other words, 40%-50% of those women required another operation for the persistence of symptoms yet the ones that had had their ovaries removed, the reoperation rate was 5%. That’s a pretty clear difference, and what I do is I advise my patients of those figures and then discuss with them how they feel about it.”

Dr. Mark Perloe: “Are you utilizing a progestin in your hormone replacement protocols afterwards? Do you believe that that may be a benefit or estrogen only?”

Professor Eric Thomas: “I just give estrogen only because in many respects most of the side effects of HRT are progestogenic. There is some issue about the breast, isn’t there, and whether or not the progestogen helps in terms of breast disease.”

Dr. Mark Perloe: “I think going back to the Gambrell study and the other studies have shown that when these people do repair, removing the estrogens may be beneficial if the symptoms are seen following this. Thank you so much for coming up and speaking like this. I look forward to seeing you in San Diego in two years.”

Professor Eric Thomas: “It’s been a pleasure.”

Dr. Mark Perloe: “Hopefully back in London again soon.”