Advancing the Science and Surgery of Endometriosis
Monday and Tuesday, April 18-19, 2016
The Union Club, New York
Audience Member: I have a question for Dr. Asgi Fazleabas. Thank you very much for your talk. I was just curious if you have animals that you inoculate who do not get the disease and how they differ from the animals who do get the disease?
Asgi Fazleabas, MD: Generally, we overpower the system so 100 percent of the animals will get the disease but they can vary in terms of number of lesions. On average there are between seven to 12 lesions that we see after one to three months and then they continue to develop over time. What we found is that we need two inoculations. If one inoculation is not sufficient they will develop a little bit of disease but they do not develop complete disease for the extended period of time that we have it. The other interesting thing is that they have to be menstruating. Because we have done some experiments where we have ovariectomized the animals, given them hormonal replacement therapy, did a progesterone withdrawal bleed and then inoculated them with the menstrual tissue after progesterone withdrawal. And then put them on estrogen implants, only estrogen implants, or controls, with silastic implants and unless they are menstruating we will see lesions for about three to five months and then they disappear. The importance of re-seeding from menstrual tissue seems important to sustain the disease. But two inoculations with lots and lots of tissue, we put in an average of about six pipefuls. A baboon is never going to see that much menstrual tissue in their entire lifetime so we are really forcing the disease.
Audience Member: I have a question for Dr. Asgi Fazleabas as well. In the New York Times a few weeks ago they talked about testing menstrual blood for different diseases in women. And that in you are using this to inoculate women do you think we could use menstrual blood to test for endometriosis in the future?
Asgi Fazleabas. MD: I do not know whether Peter talked a little bit about it yesterday. There has been some work that has been done at Long Island, work that Tamer has been involved with in trying to look at stem cells in menstrual tissue. Caroline Gargett in Australia has been looking at that too because there is certainly, and you will later on today or tomorrow, hear from Hugh Taylor with regard to the origin of stem cells. He has some very interesting data suggesting that the stem cells from the ectopic tissue actually can then be transferred to the utopic. Certainly there is plenty of evidence to suggest the menstrual tissue from women have stem cells. Perhaps that is important in terms of a diagnosis. It is an easier tissue to get if you are going to be able to diagnosis this but there is nothing definite yet. The one thing I can tell you is that when we looked at our baboon model with regard to menstrual tissue there is a greater preponderance of genes that are involved with the adhesion, vascular genesis like VGF, CYR61 and all of these other genes that are involved. So there is a greater increase in the menstrual tissue of these animals that have the disease.
Audience Member: Thank you, that was a great talk for everybody actually. This is a question also for Dr. Asgi Fazleabas. Any future research basically for looking at microRNA to explain why some women have more painful endometriosis and still have say stage four but less painful so it is not correlation really to the staging that we do.
Asgi Fazleabas, MD: That is really a tough question basically because as you know the extent of disease and pain are never correlated. Our problem with our models is that pain is one of the most difficult things to assess. These animals are amazingly stoic and they have very little pain so that is the disadvantage of the model is that it is very difficult to assess pain. Ideally we would like to there have been some really nice mouse models and rat models that have been developed now to assess pain and somewhere down the line but at this point we are not really trying to correlate any of those because it is so difficult. I am not a behaviorist. I do not understand how to study pain. I think that has been a real big issue and something that we have discussed. I think Lone has been involved with a lot of the discussions in terms of as this field moves I think we need to bring in pain specialists and we need to bring in people that are specialized in really trying to understand this and work together in terms of trying to understand that. But no, we do not have evidence to show that.
Audience Member: This is a question for Dr. Appelbaum. Yesterday we talked a little bit about adolescents as well and using Nexplanon in patients with endometriosis. I am just curious because we know it is the least suppressive for ovarian function in terms of the hormonal methods. I find that my non-endometriosis patients barely tolerate the irregular bleeding and cramping that go with it. My endometriosis patients absolutely do not tolerate it at all. I am just wondering what your experience is.
Dr. Appelbaum: I have very limited experience using Nexplanon in general. I have a lot of patients that just do not take to it. They do not like the concept of Nexplanon so I do not really want to comment. It is based on a very small cohort of patients. But I think the concept is that it is a progesterone type of treatment and with the systemic effect and therefore should have some of the effects that we see from the oral progesterones like decidualization and suppression of the endometrial implants.
Audience Member: I get the theory and I guess my only comment is the only thing worse than scheduled bleeding is unscheduled bleeding, especially for endometriosis patients. I just find it more difficult.
Dr. Appelbaum: Agreed, I think we need to look at it a little bit more.
Moderator: There are not really any studies on that just yet.