Current Research on Endometriosis: an Interview with Idhaliz Flores, PhD
“Endometriosis is a complex disease and its treatment must be multidisciplinary and the research as well.”
Teresa Götz: Welcome. Thank you for taking the time to speak with us. I can introduce myself briefly. I’m Teresa and I’m the psychologist for the German Endo-App and the German Endo-App website. Could you please introduce yourself to our readers?
Idhaliz Flores: My name is Idhaliz Flores, and I am a professor of basic sciences at the Ponce Health Sciences University in Puerto Rico. Puerto Rico is an island in the Caribbean, which is a commonwealth territory of the United States.
I did all my training in Puerto Rico, then went to the United States for my PhD in molecular genetics and microbiology. After that, I returned to Puerto Rico and have been a professor here for nearly 30 years.
For 20 years, I have been researching endometriosis and women’s health. It came to be that way because I was diagnosed with the condition back in the 1990s, and as a scientist, I was curious to know what was out there, what the scientific knowledge about this disease that I’d never heard of before my diagnosis. I was quite impressed to see that there was very limited research at the time. I had to face this reality and say, “What are you going to do about it?” Now that I have the diagnosis, why are you going to be about it? I am a molecular biologist. I should be able to answer some of these questions. They called it at that time enigmatic disease, and it is still being called an enigmatic disease. That’s how my research and program was born.
Teresa Götz: You have a lot of experience as a scientist, but also as a patient yourself, though. You know both sides.
Idhaliz Flores: Absolutely. It drives me, it helps me focus on what’s important. Also, when I talk to the research subjects, the participants of the diverse studies that we have conducted, they call here, they talk to me, and I understand their concerns. I listen to them with an open-up eye, but I can understand them. They feel relieved to know that I can understand where they’re coming from.
Teresa Götz: What is the biggest challenge in the field of endometriosis now?
Idhaliz Flores: Well, there are two huge challenges.
One is diagnosis. We desperately need to know how we can diagnose endometriosis better. How can we follow up with these patients to know that the treatments are working? Who is at risk and how can we identify these individuals early on? (The current challenge is to find a biomarker.) Until we have some biomarker that we can reach in a non-invasive manner, whether it’s in blood, urine, or even menstrual fluid. Probably it will be more than one biomarker. I think it will take some algorithm that will include several biomarkers and then the clinical symptoms, and history.
The second major challenge is treatment because right now the most used treatments are hormones such as the contraceptive pill. The modulators of the GnRH (gonadotropin-releasing hormone) have some issues (GnRH is a brain hormone regulating sex hormone release). Not all patients respond to them. In most cases, you cannot take them for the long term because there are side effects associated with them. They are contraceptives, so patients who want to get pregnant have issues taking those drugs. Therefore, I believe we desperately need other non-hormonal treatments. Some of the things that we have been doing in my lab are looking at signaling pathways and different other mechanisms, receptors that we know are upregulated. However, in addition to non-hormonal pharmacological treatments, we will also benefit from non-pharmacological treatments, things that patients can use to supplement medical treatment.
Teresa Götz: At the congress, you presented your research about environmental enrichment. What does your research focus on in general? How would you describe your research?
Idhaliz Flores: How can I define my research? Unfocused. Because I’ve been doing so many things in the past 20 years.
Initially, I investigated the epidemiology of endometriosis in Puerto Rico because it was not known how common it was, what its clinical symptoms were, etc.
Then I studied the genetics of endometriosis. We found some correlations with chromosome 10 and chromosome 19 and some specific mutations that are highly prevalent in patients but not in controls.
In addition, we have studied epigenetic factors. These are factors that modulate gene expression but do not represent actual mutations on the DNA but affect how genes are turned on and off. Further, we have studied different signaling pathways. For this purpose, we use cell models and tissues from patients who kindly provide us with these tissues.
Furthermore, I have been looking for a biomarker for endometriosis for many, many years, and it has been a great challenge. Recently, I’ve started looking at some factors in menstrual effluent because it’s a non-invasive way to get a biological sample that can give insight into what’s going on in the pelvis. We have found some potentially important biomarkers, but they have not yet reached the percentage of specificity and sensitivity needed to become standard or clinically useful. We have some potential biomarkers, but I think we need more than one, or a combination.
Also studied was the utilization and cost of endometriosis treatments in Puerto Rico. We studied that in collaboration with the public health department. In collaboration with the Department of Psychology and Neuroscience, we have been looking at stress and its effects on endometriosis. We were one of the first to systematically show that stress exacerbates the disease using an animal model (rat) for endometriosis. It’s very well-established and widely used. It represents many of the endpoints of endometriosis in women, and we used it to show that stress exacerbates the disease and increases inflammation. We looked at some mechanisms at the central level and found that the HPA axis, which is the axis that produces the stress hormone cortisol, could be a potential target for treatment.
We pursued this in two ways. First, we have pursued stress management through what we call environmental enrichment. This is an intervention that has been used to ameliorate symptoms of neurological disorders, and stress-related disorders such as irritable bowel syndrome, pain disorders, etc. but has not yet been tested in endometriosis. We have also looked at the pharmacological blockade of the HPA axis using an inhibitor of one of the hormones or factors in this pathway. Again, we have shown in animal models that this alleviates symptomatology, inflammation, and pain. We are pursuing this pharmacological pathway and have patented it. We have a biotech spinoff company that wants to pursue this pathway.
I joke that I’m very unfocused because I’ve been dealing with so many things, but fortunately, some of those doors have opened so I can continue to do research for the benefit of women.
Teresa Götz: Could you describe the environmental enrichment in more detail? What did the patients do exactly?
Idhaliz Flores: We had shown in the rat model that stress exacerbates the disease, but we also showed that managing the stress improves the disease in this animal model. We looked in the literature and found out something about environmental enrichment. In the rat model, the cages are bigger, there are more rats per cage, and they have toys to play with that are constantly changed, which means novelty.
We transferred that to humans. And what did we do?
We have done some support groups, so those are the social aspects of environmental enrichment that are very important. They support groups in an open environment.
We had the advantage of being on an island in the Caribbean, and we had places like beaches, lakes, gardens, and the countryside; other countries also have beautiful open and natural places to conduct this intervention.
Third, we learned some new stress management strategies. We did yoga on the beach and art therapy by the lake, and we did dance therapy, which is a nice physical exercise. Also, at a retreat, we had drama therapy in nature or aromatherapy in a park. The environment, the trainer, and the activities were new. What was not new, was the group. Then they had WhatsApp chats so they could continue getting support from each other through the whole intervention, which lasted three months. We met again three months later, and we did some of those same measurements. We measure stress, quality of life, depression, and anxiety. We did that before the start and at the end of the intervention. Then, three months later, we met again and did this measurement again.
Teresa Götz: Did you use EHP (Endometriosis Health Profile app)?
Idhaliz Flores: Yes, we used the EHP. It is very useful; it contains a lot of information.
Further, we obtain saliva. We’re trying to see whether there were some effects on the cortisol levels. Cortisol levels are meant to be high in the morning and low in the afternoon. From saliva, we wanted to find out whether there is some kind of dysregulation of the cortisol level. The serum was also screened for inflammatory cytokines. What was important was that we had a control group. This control group had not participated in the intervention, but we also got all the measurements from this group. That’s important because you want to do a control comparison to make sure that other factors are playing a role. That’s the most rigorous way to show that an intervention works.
Teresa Götz: You told us a little bit about it, but what are your future research goals? What are you doing next?
Idhaliz Flores: Before I go into that, I wanted to tell you about the results. We have observed very good and significant effects. We have seen, through the intervention, long-term effects on depression, stress, and quality of life. We were successful in this trial, and we want to make this a manual of procedures that we want to make available for other countries and other people to use.
In terms of research, I am now looking at the immunological aspects of the disease and we are looking at some potential immunotherapeutics. We continue to look at utilization and causes and impact. We are looking at the stigma of endometriosis and trying to find ways to use psychological interventions like CBT (Cognitive behavioral therapy). In addition, we have found that catastrophizing pain plays a very important role in the severity of reported pain. We also want to find out if we can promote pain catastrophizing as an action therapy for endometriosis.
Teresa Götz: Lot of good ideas to research.
Idhaliz Flores: Yes, that is the most important thing for me.
Also, now that we’ve been researching this disease here for 20 years, I’m trying to impact public policy. We are working with some legislators to come up with a law that will make it easier for patients to get all the treatment they need, and to protect them at the level of labor law.
There are issues with discrimination in the workplace because they have to miss so often. We are working with the Legislature here to promote this law. As you can see, I’m trying to touch on a lot of different fronts, but I’m not alone. I work with a group of people. I work with psychologists, physiologists, neuroscientists, and students. It’s a big group of people that I’m very fortunate to work with. The students in the medical school have been fantastic as well.
Teresa Götz: Endometriosis is a disease that needs a multidisciplinary team to work together.
Idhaliz Flores: I agree. It’s a complex disease. Its treatment must be multidisciplinary and the research as well.
Teresa Götz: What do you think about digital self-help? We have the Endo-App here. What do you think about various apps?
Idhaliz Flores: Very, very important. I have partnered. I’m trying to do some work also with an app called Sora based in the UK. We are trying to get more information. It’s useful in many ways. The patients can easily find some support right there conveniently right in their own time. Resources are easy to get to and accessible. It’s another way of gathering longitudinal real-time data that will help us in the future to do more science as discoveries into potential disease subtypes, for example, of what works for some patients. What makes it worse? I encourage patients to participate in research. I think it’s very important that we get to know what’s going on so we can then just be innovative about what we can offer in the future.
Teresa Götz: What do you think about digital self-help? We have the Endo-App here. What do you think about various apps?
Idhaliz Flores: Very, very important. I have partnered. I’m trying to do some work also with an app called Sora based in the UK. We are trying to get more information. It’s useful in many ways. The patients can easily find some support right there conveniently right in their own time. Resources are easy to get to and accessible. It’s another way of gathering longitudinal real-time data that will help us in the future to do more science as discoveries into potential disease subtypes, for example, of what works for some patients. What makes it worse? I encourage patients to participate in research. I think it’s very important that we get to know what’s going on so we can then just be innovative about what we can offer in the future.
Teresa Götz: Thank you very much. Now, I have my last question. Is there anything else you would like to share with those affected by endometriosis?
Idhaliz Flores: They’re not alone in this process. There’s a whole group of scientists we met in Scotland. There were over 1,000 of us. I could sense the enthusiasm, the passion of all these scientists working so hard to get to the bottom of what’s going on at the genetic level, at the cellular level, at the psychological level. Working together with patient groups that were present as well. Advocacy groups. The energy was tangible. Also, we do feel frustration sometimes that we cannot quickly offer a solution but think we’re making progress and hang in there, participate, and be vocal about the disease. Help us on social media to make the disease more visible and hopefully together we will bring some solutions soon.
Teresa Götz: Thank you very much. Now, I have my last question. Is there anything else you would like to share with those affected by endometriosis?
Idhaliz Flores: They’re not alone in this process. There’s a whole group of scientists we met in Scotland. There were over 1,000 of us. I could sense the enthusiasm, the passion of all these scientists working so hard to get to the bottom of what’s going on at the genetic level, at the cellular level, at the psychological level. Working together with patient groups that were present as well. Advocacy groups. The energy was tangible. Also, we do feel frustration sometimes that we cannot quickly offer a solution but think we’re making progress and hang in there, participate, and be vocal about the disease. Help us on social media to make the disease more visible and hopefully together we will bring some solutions soon.
Teresa Götz: That’s a very nice message for the endometriosis patients. Thank you very much. It was very interesting hearing about your research and your long experience with different aspects of the research.
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