The Division of Endocrinology, Diabetes and Bone Disease presents a Grand Rounds discussion by Tamar Reisman, MD. Dr. Reisman discusses the different stages of breast development from prenatal through puberty and beyond, breast development in special cases, the hormonal pathways to lactation, and endocrine-mediated processes. She also describes a case at Mount Sinai’s Center for Transgender Medicine and Surgery in which the team was able to induce functional lactation in a transgender patient.
So I'm sorry for the delay. You saw we had some usual I T issues or some regular I t issues. So I get the privilege of introducing Dr Reisman today. Um, you know, it trickles down. I guess enough people are gone, so eso But I get the privilege. And Dr Reisman, for those of you who don't know we recruited to Sinai about two years ago because she had an interest in Trans. We were getting her back to New York. She had trained, did college at N Y U. She went to med school over Rutgers across the way and then went out to California, where the weather is perfect and did med school. Excuse me. Did residency at U. C. L. A at USC and fellowship at you at U C L A Kept those backwards There s O and it's really a mystery to me why you are not still out there. I was, but nonetheless, we got her back. It's that little trans think that always the weather who knew? And she also takes an interest for those who who what may want to collaborate in bariatric and weight management. In any case, that means that suck up all her time, but turn things over to discussing cool endocrine with her talk about technology of the rest. Thank you so much. On. Thank you for having me, Andi. I promise I will keep breast related puns and jokes to the bare minimum throughout the next hour or so. So it's no look. Yeah. Okay, So, uh, we're humans and you might remember from biology class we are mammals. And, yes, we are, and a thermic vertebrates. But really, what makes us distinct and unique eyes that we have memory glands and that those memory glands produce milk, which is how we feed our young, um, both the developments of breasts on the process of lactation, our endocrine mediated processes. So today I wanted to talk a little bit about how that occurs in the pathways that lead to that and also to talk about a case that we had at the Center for Transgender Medicine and surgery downtown, Uh, in which we were able to induce functional lactation in one of our transgender patients. So just to break it down, eso I wanted to talk about the different stages of breast development. Uh, prenatally through infancy and beyond. I wanted to talk about breast development in some special cases. Um, then I wanted to switch gears a little bit. Talk about the hormonal pathways that lead delectation on sort of. There is a lead a little bit by ending with our case. So starting with fetal developments, so the earliest earliest breast development is actually hormone independent. Andi. It doesn't differ between the sexes, so we start developing memory specific progenitor progenitor cells around 4 to 6 weeks. Gestational e um, those cells proliferate, and they develop memory crests that you can see in Picture A. And those run essentially from the equivalent of the underarm to the groin area. Um, over the next couple of weeks to months, those memory crests regress on DWhite. Left is the typically paired memory buds, but when interesting uh, vestige of that development is that some of us actually have supernumerary nipples along that memory crest development by around the third trimester. That's when you really start seeing the rudimentary breast structure that that remains until puberty, which basically is, ah, small activist ducts, which is surrounded by connective tissue, of which this Troma what So after birth. Um, all of the estrogen that the fetus is exposed Thio by nature off the mom, passing it along drops. And that leads to some interesting hormonal, uh, developments. So the first development that occurs is something called many puberty that I'm not sure if the fellows are aware of which basically, um, that dropping of the estrogen causes the hypothalamic pituitary activation and, um, reproductive hormone levels that aren't seen again until puberty. It can also cause prolactin secretion, which leads Thio, the phenomenon of what's kind of cutely called, which is milk, which is neonatal milk secretion. Some of the data that I read said that, uh, this can occur in tow in up to 80% of new units. That sounds like insanely high number. But again, reporting what's out there in the literature Now, most of even this rudimentary new NATO breast tissue regresses, um, and that occurs in the period following mini puberty. So about six months, uh, on and then breast tissue is actually pretty, uh, pretty quiet, developmentally until puberty. So what happens at puberty for girls eso at around age 8.5 to 13. That's when Theo larky occurs. And how do we track breast developments? Uh, we do that with 10. Or staging, which I'm sure you recall from your pediatrics rotations. Um, and, uh, Tanner staging ranges from Tanner stage one, which is pre puberty, all all the way until Tanner stage five, which is adults breasts. And basically, uh, the larky clinically correlates with a tender stage two. So tender. Stage two is the earliest breast developments in Tanner Stage two. We see elevation of the breast and elevation of the Propel A, uh, tanner. Stage three. We get a little bit of enlargement of the breast tissue enlargement of the mound. Stage four. That's what we describe as the mound on the mound where the areola forms a secondary contour over the breast contour and then by Tanner, Stage five. The aerial contour sort of aggress is into the contour of the overall breast. This process in, uh, when it happens indigenously in girls takes about four years to occur on. By the way, each of these stages is radiological distinct. We can we can see way can see this histological e and radio graphically. Yeah. So what does a mature breast look like? Uh, mature is sort of in quotations, because what I mean is tender Stage five breasts but breast continue to change and develop both during pregnancy with lactation and then change again. Postmenopausal e Um, but the basic structure is this and this kind of goes from left to right. So we have our papillon, which eyes the outlet site for the ducks. There about 10 to 15 ducks, large ducks that drain into it. Those branch into what we call terminal doctor lobular units, which are smaller ducks surrounded by a cluster of Cassini. Um, surrounding those terminal ductile lobular units is the intra lobular strom A. That's connective tissue that helps support those structures. And then the yellow, uh, color sort of surrounding the whole breast. That's the inter lobular Strama, um, that provides shape instructor to the breast itself. Now, um, when we are when women are younger, um, that's Troma is pretty fibrous. And that strom A as we age gets replaced by fat, which helps explain why we make certain clinical decisions. So when there's a mass in a younger woman, that fibrous tissue is radio dense. And so mammograms are in a great, uh, diagnostic tool, but the fatty tissue is more Radio Lucent, and so mammograms progressively become a better technique for identifying masses, etcetera. So how do we end up with mature breasts? Uh, the answer is basically, and this is obviously really simplified estrogen. Um, estrogen is the primary hormonal influence for breast development. It's what helps stimulate duck growth. It's what helps stimulate fat deposition, um, in mice who are either genetically, uh, genetically not exposed to estrogen or for mice treated with tamoxifen. We see that that ductile growth that I described that doesn't happen, um, progesterone important, but not in early development. So later on, and we'll talk about this in more detail later, when people breastfeed, Progesterone plays a more key role in, uh in helping to differentiate that terminal ductile lobular development, Onda helps contribute to morphological changes that allow for lactation. Okay, in breast development, not in lactation. And again, I make a slight distinction on, and we'll talk about blacked ation more later. Prolactin does play a role on it, sort of acts like the right hand man for progesterone. So in mice that again, or knock out and don't have access to prolactin, we know that even in the presence of adequate progesterone, we don't see appropriate ductile formation on there a couple of ways that we see why that is, um it turns out that prolactin up regulates progesterone receptors in the breast and actually increases progesterone secretion by inhibiting its degradation. So when Josh and I are downtown on, we treat our patients with prospects hormones. We typically as a result of treatment, expect to see breast developments. Um, the regiments that we typically use thio help that breast development and all the other physical changes that we anticipate comes from a combined regimen. And I know that you've all been, uh, two prior talks where we talked about this in more detail. But essentially, we're using an Esther dial products, uh, in a number of different, uh, formulas with an anti androgen, which nine times out of tennis, burn elect own. And for those of you who have rotated through a clinic, you know, this is an issue that comes up time and time again, which is that our patients want progesterone. Um, they've read online. They have a friend who raved about it and said that it increased breast volume um so that sort of And the answer is no. We don't give progesterone to increase breast size. Which leads us to sort of the question that everybody wants to know which is the million dollar question. Which is Why do some people have bigger breasts than others? Right. Um, it's certainly a question that's on our patients minds. And the answer is Strama. And the problem is, we don't really know why some people have a lot more of it than others. Um, but we do know that there's basically very, very if essentially zero evidence that progesterone helps to increase it. Andi, the mawr data that we have looking at things like estrogen levels, estrogen, formulations, age and other. Basically any factor you can think of that could help increase that volume. Hasn't really shown any. Um, uh hasn't been really compelling that it helps with size either. So histological e When you look at the breast tissue of transgender women, it's indistinguishable from CIS gender. Women s O. I am not a histology gist, but I'm told that this slide shows terminal ductile. Uh, lobular units, um, and more than that for transgender women who are treated with estrogen. There's something called, uh, pseudo lactation all change, which essentially means that the La Buell's have the appearance of CIS gender women who are pregnant. Now that actually is different from the histological appearance of gynecomastia, which is breast enlargement in mostly puberty boys. So it turns out this is actually something that's incredibly common in puberty. Um, they say 40% of boys have it. Uh, they say it's probably did estrogen dominance. That's one of those like keywords that I see over and over again, without any sort of understanding as to what that means or who might be susceptible. Definitely. We know in certain cases, gynecomastia can be a telltale sign for problems with hypogonadism or other hormonal abnormalities, which is sort of its own talk in and of itself. Obviously, uh, that guy to capacity appearance can be made worse when our patients are overweight. Um, but the good news is it most pew brittle boys. That sort of results by itself. Although it could be pretty distressing for a lot of patients while they have it. Okay, So moving on in pregnancy, there are a number of morphological changes that helped prepare the breast for lactation. We see cell proliferation and differentiation. We see the replacement of Strom A with Mawr, glandular tissue and more terminal doctoral lobular units on. Even before pregnancies over around the third trimester, we start to see those ass and I fill with cholesterol, which is the earliest milk product that's made now in lactation. Prolactin is the star. We know that this is the principle hormone for synthesis of milk protein. But while patients are pregnant, we don't We don't fully see way. Don't see it. Achieving its full effect on estrogen sort of puts the brakes on that. So it both helps it along and also puts the brakes on it. Estrogen, actually, a, uh induces the differentiation of laughter troves. It suppresses dopamine activity. Dopamine secretion. Excuse me. Um, beyond those two, there are a number of other hormones that seem to be implicated on when they're missing. There seems to be some issues with lactation, but the exact role hasn't fully been elucidated. Now there are other hormones that play a role. You may have heard of human placental oxygen. Um, that's sort of a member of the proactive family. It's secreted by, uh it secreted by the end of gestation, about 30 times the concentration of prolactin eso You know, it becomes a player just by nature of how much it is by the end of pregnancy. But in terms of functionality, it's probably interchangeable with other hormones. And, of course, and I'm sorry because I couldn't help myself. But oxytocin, which helps with milk letdown and don't let you take a minute to appreciate all the splendor of the Internet. Okay, so what happened at Patrician? So the first milk product that's made is kill Ostrom eso. It's a little bit thicker, and it's yellow. It's used in a filic and pro tenacious on that comes for about four days or so on that offers a ton of passive immunity for the infant later on. That's replaced by mature milk, which has fat lactose and protein on Ben again. So this is what's kind of interesting, and you see it again and again in the in. The literature is sort of these vague, uh, numbers that sounds super scientific, but then kind of make you scratch your head when you think about it, right? So I kept reading this, that 1 to 2 mL programs and brushed his breast tissue for day is ah, common, uh, production read for breast milk. Now let's think about that. So what does that mean? Um, as we sort of mentioned before the Strom A isn't active. That's not helping to produce the the breast milk on that's actually making up most of the volume of the breast. So that led Thio some myths that we used to think like, for example, that small breasted women have problems. Breastfeeding don't make enough milk, etcetera eso there again just to sort of reiterate there's zero evidence that that's the case. In most cases, uh, everyone has the terminal ductile lobular units that they need in order to produce milk effectively. Okay, so I'm gonna pause there and switch gears a little bit. Um, any questions? The scar? Yeah, e protecting developing breast growth. Because male side. Yeah, you lose your testosterone, and then you get developed some questions. Um, that's an interesting question. Eso I think, uh, that might be sort of where that catchphrase of estrogen dominance kind of comes in where there's some sort of interplay. Onda ratio becomes important. But again, I didn't That's actually, probably something I could have investigated a little bit more and included in our slides. That's interesting. Um, get back to you on that. Treating. Yeah. Who's rusty? You have absolutely on dso What's interesting? Histological e eyes eso in those cases. So specifically in cases of androgen deprivation therapy in prostate cancer, etcetera, histological e uh, that breast tissue looks more, is gynecomastia and doesn't really have this sort of ductile structure that you see in transgender breast tissue and insist gender women. But clinically, that's something that we're definitely aware of that what's that s Oh, yes. So there's there's definitely histological differences in terms of people with high estrogen levels versus versus those who have breast tissue enlargement for other reasons. Yep. Okay. Shit, please. Out which. Yeah, um, maybe prolactin related. But it's tough to say so usually the scenario that we see clinically eyes that, um you know, so people will come in with eso specifically sis males will come in with high prolactin levels and complain of gynecomastia and low libido and all these things. And then we find that they have sky high prolactin levels. Eso you know. Is it the prolactin itself, you know, I don't know, Dr. Safer might be any insight into specific libido and issues. Yeah, so yeah. E defer to the boss. I defer to the boss. Okay, Sort of the switch gears just a tiny bit. Onda talk about breast feeding itself and really zero in on that. So, in the basically, as long as we've had written recorded history, there has been mention of cooperative feeding. So basically, the idea of women breast feeding Children that they didn't personally carry to term and give birth to, um, he's actually some animals do it to eso these cute guys over here. Those are the dwarf. That's a dwarf mongoose on day, engaged in cooperative feeding to, um, now, historically, cooperative feeding was hugely hugely important for our survival. Um, during times when maternal mortality rates were sky high, there needed to be some mechanism Thio feed these kids and keep them alive. On board formula is a fairly recent invention. Um, now, today we're a little bit more suspicious of things like wet nurses and cooperative feeding were very acutely aware that pathogens can be transmitted in the breast milk. Um, but there's still some pretty compelling reasons why, uh, why we recommend breastfeeding in general. Obviously, there's certain cases where we absolutely forbid it. Right, Um so number one, the immune benefits We know that breast milk contains I g A on offers passive immunity Thio babies. Um, there are plenty of papers that go beyond that. Say that breastfeeding infants have a lower rate of things like road A virus, a titus media hospitalizations for lower respiratory infections on and on and on. I take them with a little bit of a grain of salt. Obviously, correlation is not causation. And there could be a lot of other reasons why babies that are breast fed tend to be a little bit healthier. Do better than other babies. Um, certainly we know that there are metabolic, uh, benefits for mom. Women who breastfeed burn a ton of calories, find it easier to lose weight. Postpartum babies that are breast fed are less likely to be obese again. I wonder, sort of about that relationship again. There might be a lot of compelling reasons why breast fed babies or healthier do better overall later on In life, there are psychosocial benefits. Eso mom and baby gets a bond? Um, certainly their economic benefits. So the one thing you can't argue breast milk is free formula costs money on Ben. There's another piece of it which we don't really talk about in medicine quite that much. But it is really important for our practice in transgender medicine, but also insists gender women as well, which is just the idea of self actualization. So for a lot of women, it's just important. It's important and it's a goal, and it's something that they achieved. Thio. So, um, there is a small body of literature that looks at inducing lactation, non properly meaning in women who have not undergone pregnancy on DPI. Probably the most common one that I've heard about and I spoke to a couple of lactation experts eyes this Newman Goldfarb Protocol, which you know all these things seem a little sketchy in our little D I Y. But basically the it makes sort of sense when you think about the hormonal pathways that we discussed, right, So basically what you're doing is you sort of increase estrogen progesterone, and in the meantime you increase prolactin. So in this protocol, they recommend taking down Paradorn about a little bit more in a second on. Then you also maybe increase prolactin secretion and oxytocin by pumping, you know, a lot on. Then you withdraw the estrogen and that allows for for milk flow. Okay, so again, so ah, lot of the protocols that I read mentioned the use of dumb Paradorn. Don Paradorn, you may not be familiar with it Is a dopamine agonist on? It's very similar to read gland in that it's used for nausea, vomiting and dyspepsia G I symptoms. But unlike regular and it doesn't cross the blood brain barrier. And so it doesn't result in a lot of the neurologic problems that we worry about with red land. Um, it is not FDA approved. Why is it not FDA approved? Because when it was used intravenously, uh, there were a couple of documented cases of cardiac arrhythmias and arrest. Um, but, um, now, even in Canada, um, it is on Lee. It's only labeled use is four g I symptoms. However, it has been documented as a very useful galactic dog, and it's kind of used off label worldwide for that purpose. So that leads us to our case, which waas a in which a transgender woman came to us, Uh, interested in potentially inducing lactation? Um, this is in the background of a really robust online community where basically for years, at this point, a lot of transgender women had written that they had successfully achieved that. But But like a lot of this stuff, uh, you know, there was a lot of, um, sort of here say a lot of chatter on the Internet and not a lot of academic documentation. Eso we tried it using some of the protocols that we had seen on. Basically, we documented our experience. So this is our story. Oh, great. Question s Oh, this is a Greek writer. Let me remember his name. Ceramist of a thesis. So he wrote ethicists. Sorry s o. He actually documented. Ah, Lot wrote ah lot about different O b g y n topics, but had a lot of advice to give on nursing as well on day. And, uh, and so wrote, you know, sort of gets honored here in this. Left for that purpose again. Sort of, uh, calling back to what I said earlier. Which is that the idea of cooperative feeding and and physicians being interested in, uh, in, uh, in improving lactation sort of is an ancient concept. Okay, So our patient was a 30 year old transgender woman. She was in a good baseline state of health, and she had a pregnant partner on. She was interested. She came to us interested in breastfeeding. She had been on hormone replacement therapy since 2011. And when I saw her for the first time, she was on Esther dial 2 mg p o b i. D. She was on spironolactone. 100 mg p o b i. D. On. Then. Interestingly, she was on progesterone, which again, we don't typically recommend that I think in this particular instance was advantageous because of all the the important role that progesterone plays in breastfeeding. So her past medical history was significant for insomnia and anxiety. Basically, your only medication besides hormones was a little bit of Ambien as needed. Her past surgical history was significant for coal suspected me. She hadn't had any gender affirming surgeries. She hadn't had breast augmentation. Um, and on initial exam, her, uh, her exam was essentially unremarkable. She had tanner stage five breast, which is important to note because I have read, You know, there is this idea in the transgender literature, um, that transgender women often undergo muted breast development with, uh, smaller breasts overall and oftentimes failed to reach attain our stage five. So that was not the case for this patient. Her initial labs. Her progesterone was 8.7. Her prolactin was 9.5 secs. Foreman binding globulin was 48 total. Testosterone was 2 56. So not quite a goal for us. Uh, in the transgender world and her estradiol was one night. So this patient in particular, uh, it was a little bit of an unusual case because her mother worked for Lilesa league and she had an aunt that lived in Canada, so as a breast, a breast feeding consultant. She actually had used prolactin, uh, and was very familiar with it. Andi, she had this access to this medication that again was is not FDA approved. Eso she started taking that 10 mg p o t i d. The normal, uh, dozing for G I problems is about 10 to 20 mg t i D or Q i d. On. She also started using a breast pump. Five minutes per breast. T i d. Um, At one month she came back, we increased. She increased the damn paradigm to 20 mg p o que i de so that's the maximum, uh, safely recommend safe recommendation in Canada for G I problems. She also increased the micro sized progesterone to 200 mg Pio daily Esther down to 8 mg Pio daily and increased use of the breast pump. Yeah. So basically what we had we were kind of feeling this out as we went and one of the things we were interested in potentially trying to do was to see if we could get the estradiol and progesterone levels to mimic, uh, pregnancy levels on bond. This is probably a better slide rather than going through it piece by piece. Um, these are all the visits where we saw her on by the Estrada. I'll protect and progesterone and testosterone levels. Unfortunately, we don't, uh we don't have a lot of data with the testosterone on DSM. Things were missing, but what you can see very clearly is that even with all that estradiol and progesterone and Don Paradorn, we didn't scratch the surface. So when you talk about Esther dial in the first trimester. I mean, you're talking about a nester dial level of hundreds to thousands. We even scratch the surface. Um, same thing with the progesterone. Um, so, unfortunately, we were sort of, you know, going into things blindly. Yeah, a in damn it. E wonder. That would be a really interesting study. I didn't come across it, but it would be interesting to see a retrospective. Study data is available in terms of blood. Yeah. Eso volume versus hormone concentration. Yeah, sure, but yeah, that's interesting. Yeah, s that? Even though I've been wrong? All Yeah. E yes. That is true. That's something I know now e a to this, and usually yes. Okay. News sources importance What was saluting the arms or in pregnancy or feeding issues? Josh is absolutely right. Yes. So that's something I know now, But not that, but is really sight. All right. Oh, spilling most ministry. All right? No. Yeah. So there's Yeah, trust that we wouldn't usually, except trans violence, which suggests that perhaps, uh, yes. Uh, the first one was too high. Um, submission. So in general estradiol, patches. Um, even in the highest dose, that's available. Don't at all me, uh, our, uh, like, let alone pregnancy levels. Even the the endocrine Society recommended goals. For some reason, that is not exactly clear to me. I can order a patient, 20 pills of extra after out per day if I If I want Thio, they really limit the patches. So I find it really hard logistically to get patients on more than one patch at the time. Um, but yeah, so, to your point, uh, patients are very, very obsessed with the idea of s Trone. There seems to be a really common idea in the Internet sphere among patients that if your restaurant is too high, that competes with Esther dialogue and sort of reduces feminization. Um, but yeah, we don't know where that comes from. Definitely. With coral estrogen. We'd expect to see estrogen levels being high, so yeah. Yes, I've seen. Yes. I don't wanna I mean, the numbers air really all over the place and based on not a lot, as far as I can tell, So I just didn't even put it. Yeah, so they're so I mean, there's some So, for example, like way know that people have, like, okay. Uh, pretty decent lactation with the Don Paradorn. Um, you know, if we get even a little bit elevated in the setting of some of these regimens Eso like one study that looked at Don Paradorn group versus placebo group with breast with a lactation saw that basically, there was adequate lactation when the proactive was over, like 2030 or so. But we know that, you know, Mawr expected numbers would be closer to 100 or even several 100,000, like in those ranges. But again, the numbers that I've seen are too scattered and, uh, seemingly unreliable to sort of report with any kind of confidence suit process is over. This astronomers upset, and he's still a person just like doing a, uh, a comfortable Yeah, the qualified black because yes. So So there's a lot of back up like you mentioned eso Definitely human placenta lacked a gin, even growth hormone in a pinch. Uh, and yes, eso There are other confounding factors. Yes. Although since we can increase it with medications and it is the number one player Um, yeah, we wanted to see sort of where we were a Yeah, right. Yeah, I understand. Please crest. So? So that leads us to So So just thio kind of give you a summary. So basically, the patients was born was breast fed exclusively for six weeks. Um, the those six weeks were great growth feeding bowel habits. Everything was okay. At six weeks, the patients ran into a volume problem on dso still continue to breastfeed. But I started supplementing with formula so that I Zant sticking your neck out at all. That's actually one of the number one questions we had. So, first of all, you know this patient pumped all day long? Um, chest wall stimulation, of course, increases prolactin levels on helps with oxytocin as well. Likely on may be the dump Cardoen, and sort of this question of it being sketchy. And how do we get it? And it's not FDA approved. Maybe that's completely relevant. And on just the pumping itself would have been sufficient. Um, definitely. And you can see this, Uh, very obviously, when you look at sort of the haphazard way where we sort of increase the dose and then we kind of waited to see what was going on, and we increase again. Um, definitely We have questions about what the optimal levels for our treatment should have been. And going back to the aural estradiol versus injections, patches, etcetera was our choice of formulation appropriate? Um, one of the questions we had was sort of what was going on with the Spurn Elect own was that safe? There is a little bit of literature that seems to imply that high testosterone level, uh, negatively impacts the ability to breastfeed eso. We made the decision to continue with the spironolactone. Um, the American Academy of Pediatrics says it's okay. Um, there does seem to be ah, little bit of spinal Acton, uh, byproducts sort of being secreted into the milk. By overall, the American Academy of Pediatrics says it's limited enough that they're not especially concerned with it. On Ben, one of the questions we had So after we withdrew quote unquote the West Road Island progesterone, the patient did take a 0.25 estradiol patch. She wasn't on no Esther dial. So one of the questions I have is basically was that enough? Thio negatively impact her breastfeeding and cause volume issues. Now, what's unfortunate? I mean, obviously, this is a very unique case, but unfortunately with an end of one, we don't know. Um, plenty of CIS gender. Women who undergo normal pregnancies and don't have any apparent pathology have breast feeding issues and volume issues as well, I've been told, and maybe you can help either agree to repeat this but that six weeks when you do when When people do run into breast volume issues, that's typically when it occurs. So So we definitely have a lot of questions about how we could have optimized our regimen. Department people. Yes. Yeah. She, uh, situation wasn't entirely clear. Eso basically on e. I wish. So I had, uh, maybe somebody point this out or I wish I had edited this When I When I wrote up the case report, I wrote that the patient the partner was uninterested in prosecuting on I sort of threw that in there, casually ended. Think much of it, the patient. Although she was anonymous and all the identifying markers were sort of removed, she was actually deeply, deeply hurt by the fact that that was in the report. She felt that she was identifiable and that her partner wasn't able to breastfeed. And that that statement sort of made the partner look bad. Like she wasn't interested and was callous. Something you care about the baby? Um, I don't know. The exact circumstances of the partner, Basically, the partner was not an option in terms of rescuing this child That was off the table for whatever reason. Um, so, yeah, it's complicated. Andi felt terribly that I had heard the patient. It didn't even occur to me. You know that that was something that, uh, but yeah. Anyway, eso just to kind of wrap things up. Eso communal feeding eyes. A very ancient concept for us and also occurs in other species. We do have plenty of documented cases of non purple induced lactation, insists gender women. Um so obviously we need more more patients in order to determine what the optimal regimen for transgender and just lactation is going forward. Um, but and this is sort of the key points. I think pre puberty breast tissue is similar across the sexes. Andi, what allows us develop breast? What allows us to lactate is purely hormonal. So there really isn't any reason why biological males couldn't breastfeed in the setting of ah appropriate hormonal milieu. So that's it, Um, Questions. Cooking? Yeah. Toward the end, you're giving us a viable. So what delivery you have given the partners H g big race. Oh, um uh, hcg Yes. I mean, so presumably, you know, in this patients with you know, uh, male reproductive anatomy that would increase testosterone, which we were trying Thio avoid with a spoon. Elected? Yeah, Exactly. Yeah. Thank you. Very, very enlightening discussion you mentioned there waas personal produce. Initially, I'm just curious. E I can find out for you. It's in the report. I wish. I wish I remember the exact. So basically one of the benefits of the breast pumping is that we were actually able to monitor, you know, pretty accurately, exactly. Um, but I can't recall off the top of my head, but it is in, um, in the case study so I could get those numbers. E don't remember. I would have to Look, I won't make it up possible. Um, I don't know that we tease that out. Uh huh. I'm not sure. So one of the biggest disappointments to me with this case and I have a couple of regrets, obviously eyes the fact that we weren't able to get breast milk testing, So I called a couple of labs. I was given the runaround and then just in sort of life intervened, and we missed. I missed the window. I am obviously hugely regretful of that. I would love to know what exactly was in that breast milk, Uh, both for nutritional reasons, but also for, uh, yeah, for safety reasons. Especially with the things burn elect own etcetera. But it didn't work out. Yes. Get down. I dropped the ball in in many ways, that all e e ideas? Okay, Hats okay? Sure. Yeah. This can systems. Yeah. Attention, Sure. Yeah. So that that was one of the more interesting things reading about the histology of breast is that, you know, again. And and I put this in quotes, you know, we talked about 10, or stage five is being mature breast, but breast histology. I mean, it keeps there are all these changes that happen in terms of this Troma, you know, depending on age, depending on the plantation status, depending on phase of the menstrual cycle, all these things really affect the histological. The histology and major major weighs on bond. Definitely. You know, there are ways that I'm sure, you know, that will eventually be exploited. Helpful in terms of cancer and other things. So lists name for that between question. Local proactive effects, Black breast, losing it different matter. It's I used yes to know the experiment, Adam. And what it does actually expressed. Relax, tag it, Um, I would I would read that stuff. I can't speak to any specific anything that I've seen. Thio, look into that. All right. Thank you. Thank you, Thank you.