Speaker 1: Welcome to AACE Podcasts. Thanks for tuning in as we elevate clinical endocrinology by taking deep dives into trends and topics that can help us improve our patient care and global health. Find the latest episodes on aace.com/podcasts. Now, let's meet the endocrine experts who will be talking with us today.

Sina Jasim, MD, MPH: Hi, welcome to AACE Podcasts. I'm Dr. Sina Jasim, the Editor-in-Chief of ACEE Clinical Case Report Journal and associate professor at Washington University in St. Louis, Missouri. Today we have the pleasure of hosting Dr. Reisman to discuss the reported case at ACCR, hematospermia in a transgender woman with evidence of endometrial tissue in the prostate. Dr. Tamar Reisman is the clinical endocrinologist at New York Presbyterian Weill Cornell Medical Center, where she serves as the clinical co-lead of the Gender-Affirming Care Program. Dr. Reisman, thank you for joining us today.

Tamar Reisman, MD: Thank you so much for having me. I'm very excited.

Sina Jasim, MD, MPH: Of course. We're happy to have you. Could you please tell us a little bit more about yourself and about your work?

Tamar Reisman, MD: Yeah. I am a clinical endocrinologist, but I have interest in transgender care and just more generally in endocrinology involving sex steroids, so PCOS, amenorrhea, transgender health, hypogonadism, all things sex steroid related.

Sina Jasim, MD, MPH: Oh, interesting. That's really nice, and we're happy to have you here. The reason we wanted to go over this case that you shared with your group, an interesting case in our journal at ACCR, and I wanted you to summarize the highlight of this case to our audience.

Tamar Reisman, MD: Yes. This is a case describing our lovely patient, a 35-year-old transgender woman who had been treated with gender-affirming hormones. That includes an injectable estrogen and a GNRH agonist for about a year. She initially presented with hematospermia. After an extensive workup, it was determined that she had a 1.7 centimeter prosthetic cyst. What's interesting about that is that the contents represent either a Müllerian cyst or endometrial tissue. This is, again, somebody who was assigned male at birth, treated with gender-affirming hormones, who after biopsy and microscopic evaluation was actually found to have some endometrial tissue present in her prostate.

Sina Jasim, MD, MPH: Interesting. When I was reading through the case, the conclusion of that case that occult endometriosis or ectopic epithelial tissue growth may occur in transgender women taking feminizing, gender-affirming hormone therapy. I understand not many endocrinologists see this as part of the routine practice and some endocrinologists might have interest in these cases, so is this something that endocrinologists need to be familiar with, do they need to screen for, and how when to suspect something like that?

Tamar Reisman, MD: Great question. Overall, Müllerian cysts exist in the general population. It's something that exists in cisgender men. The prevalence of it is pretty rare. We know from autopsy studies it's probably about 1% of the population. In a lot of cases we don't know about it because usually if it's there, it's sitting there, it doesn't bother anybody, but occasionally they grow so big that they cause pain. That's one reason we might find out about it. Another reason we might find out about it is in a case like this where it was actually communicating with a seminal vesicle and causing hematospermia, which was very alarming for the patient.

There probably isn't any indication for screening, but it brings up a lot of really, really interesting concepts. The main writer of this case was a medical student, and it was really interesting for the medical student because it brought up a lot of topics for a review that were really important, I think, as part of medical education. The first implication is... just in terms of gender-affirming care, I had my prior mentor, the head of the Center for Transgender Medicine and Surgery at Mount Sinai, Dr. Josh Safer, asked me one time, he said, what's the difference between patients who are transgender and patients who are intersex? The answer to that question is whether you find an anatomic condition that allows a patient to be labeled as intersex or not. For this patient in particular, it was really gender-affirming and exciting to have evidence of this endometrial tissue present. That's sort of concept number one.

In general, one of our questions is, did the exposure to estrogen precipitate the development of this tissue? It's not clear, but definitely, again, just how rare these things are in the general population, it doesn't seem to be a huge concern in terms of our gender-affirming therapy and the side effects of treatment. What's way more interesting and exciting is technically this is endometriosis. It's the presence of endometrial tissue, so the epithelium, the stroma, in a place where it's not supposed to be, so outside of the endometrial lining and myometrium. One huge question in the gynecology world is where does endometriosis come from? Why do patients develop endometriosis? There has been this theory that endometriosis was the result of retrograde periods, but that hasn't really been clarified. There are other theories at play for why endometriosis occurs.

We've always sort of suspected one of the proposed mechanisms for endometriosis is this induction theory. Something happens, maybe an embryologic development, who knows, or maybe there's exposure to inflammation and that results in endometriosis. Really recently, within the past couple of months, there was a really interesting paper where they linked a bacterial infection with endometriosis. One of the questions, again, is sort of how does this case play into the bigger question of how does endometriosis occur? This is not somebody who had a menstrual period, so retrograde flow is not an explanation for this patient. Could this one case play into this bigger question of this other condition that affects a lot of people?

The last question is just a reminder, again, to the medical student who was involved in the case and to all of us as endocrinologists, just the really interesting embryologic development, and jogging our memory of this embryologic development and what are the ways that changes in that development or differences in that development can lead to adult medical conditions? If everyone remembers, early in fetal development, we have the Müllerian duct and we have the Wolffian duct. In response to exposure to AMH, most people who are XY will have regression of that Müllerian duct, so that can be incomplete. Sometimes you can actually get a condition called persistent Müllerian duct syndrome, PMDS, where patients actually have the development of fallopian tubes, uterine tissue, the upper third of the vagina. That is a condition where you have the full development of the Müllerian structures, and that can sometimes present actually in adults. People who end up getting evaluated for infertility who basically find out that they had these organs present that maybe they weren't aware of their entire childhood.

You can have those more extreme cases, but then you can have these smaller cases where you have maybe failure of total regression of the Müllerian duct and you have these little cysts present. The other thing that can possibly happen is in the prostatic utricle, so that's sort of a remnant of the Müllerian duct. One of the questions we had was are there maybe some stem cells there or some other cells that can then differentiate after exposure to estrogen? It's really, really interesting.

Sina Jasim, MD, MPH: It is. I think the estrogen effect on that is probably one of the mechanisms, and it would be really fascinating if you see more cases like that maybe to create some sort of series or a theory generating research that could potentially look into these mechanisms. When I think of transgender care, and you do that more in a daily practice, what do you think sometimes some of the challenges or the barrier that you face when you care for a transgender population, what additional screening that you think should be probably advisable? We want to use this platform to educate clinicians who don't really commonly see these cases how to be better educated and informed about some of these situations that they want to look specifically for.

Tamar Reisman, MD: Right. The biggest issues that we face regarding transgender healthcare are mostly systemic issues, societal issues. We're in a period of extreme backlash, unfortunately, and that's quite scary for a lot of our patients, as historically transgender patients often don't have access to healthcare or aren't positively received by healthcare providers or have poor past experience with healthcare providers. A lot of what we do is just ensuring that patients have access to proper healthcare, proper screening. Again, this is a very specific case, a rare case, but common things, so how do we make sure that our patients who need mammograms have access to them? How do our patients who need cervical cancer screening get access to that? How do people get access to hormones they need for gender-affirming care and to the other services that they need? Those are sort of the bigger concerns that we have.

Sina Jasim, MD, MPH: Yes. No, absolutely, and I think part of the journal mission is sometimes to highlight some of these cases because it is geared toward endocrinologists in early career to help if someone saw an educational case or a rare case or a common case, but unique way of management is to share it with our audience so if they are in similar situation, they can always refer back saying, oh, I saw and I read a similar case. That's part of the mission of our journal. Dr. Reisman, are there any additional thoughts that you would like to share specifically regarding this case?

Tamar Reisman, MD: Additional thoughts? No, I just think, again, it's a really interesting look at the adult manifestations of this embryologic development. A lot of endocrinologists might not recognize this as being under the umbrella of endocrinology. That's a shame because hormonal management, even a lot of hormonal management of menstrual issues, these are all things that we are trained to handle really effectively, so we should be more empowered to take more of these cases, and we offer a really unique perspective with these kind of cases, these kind of reproductive cases that they might not be getting from their urologists, from their gynecologists. Again, this is absolutely under the umbrella of endocrinology.

Sina Jasim, MD, MPH: No, I totally agree with you. I'm happy that you said that. Oftentimes we give away these cases, and I think cases like hormonal changes in the productive system and amenorrhoea and PCOS and of course transgender care, and oftentimes that goes to be managed by people who probably are not endocrinologists. I think this is an opportunity to say yes, embrace those cases, and it should be part of the wider general endocrine practice.

Tamar Reisman, MD: There's just one more aspect of it that we didn't really touch upon, which is just the hematospermia aspect. In reviewing hematospermia, that is not uncommon. Oftentimes it is transient. There are a lot of things that can cause hematospermia, different infections, et cetera, so it's worth mentioning if it's not entirely clear that this patient went through a formal process where the more common causes of it were excluded. Also for the med student who's participating in this case, it was a nice review for her to recall the different etiologies and the workup process.

Sina Jasim, MD, MPH: This is all discussed in the case for the wider audience to refer to look at the case and review some of the workup that has been done. Dr. Reisman, I want to thank you for joining us today to share your expertise. To learn more about this case or other cases at ACCR or to submit your own interesting case or visual vignette, visit www.aaceclinicalcasereport.com. This is Sina Jasim. Have a wonderful day and thank you.

Tamar Reisman, MD: Thank you so much.

Speaker 1: Thanks for listening to another great AACE podcast. Join us for another episode at aace.com/podcasts and help us in our mission to elevate clinical endocrinology together. We are AACE.