Rhiannon: In the general population, it’s 1 in 6 couples are unable to conceive naturally within 12 months of trying, which gives them the official infertility label. Of those couples, when it comes to all those women, females in the relationship, when it comes to endometriosis, we’re looking at about 20% to 50% of those who present with infertility have endometriosis. It’s considered to be that 10% of the female population of reproductive age, although that is widely considered to be an underestimate of course, because women are so programmed to accept that menstrual pain is normal or common that if it doesn’t affect their chance of conception, many of them actually won’t look for a diagnosis.

Andrew: Right. So, why though, is this such a big issue? Certainly, there’s gotta be a player in this, and that is our burgeoning waistlines, but is that the only issue? It seems to go far more deeper than this.

Rhiannon: Yeah, it’s certainly not the only issue. And, you know, there are a whole cohort of very slim women with endometriosis who actually, when you read the literature, are considered to have a higher risk of endometriosis due to their higher estrogen exposures. But overall, the risk factors are considered to be heavily genetic, heavily epigenetic. And by that, we’re really probably talking about endocrine-disrupting chemical exposure in utero. Of course, there’s immunological factors for endometriosis autoimmune-type hyperimmune-vigilance. And there is also of course, microbiotic factors for endometriosis that we, perhaps as naturopaths, have accepted for quite a while, but from a literature perspective is really just…really opening up from an information perspective.

Andrew: Can we just cover off on that comment about autoimmune versus hyperimmune? It’s not autoimmune because there’s no self-tissue antigens and things like that, but it certainly seems to be driven by an immune dysfunction, is that correct?

Rhiannon: Yeah. Yeah, that’s right. The process by which the body identifies endometriosis tissue creates a hyperimmune response that creates inflammation in an attempt of course, in the body’s attempt to eradicate the tissue from the system, but it actually just makes it worse. So, it’s a self-fulfilling inflammation, if you like. And, you know, sometimes they say in the literature that endometriosis resembles a wound that never heals. The body treats it like a wound, but in the process of attacking it from an immune perspective, it actually just makes it worse. So, it’s very self-perpetuating.

Andrew: Now, that in itself is really interesting, because even though it’s a hyperimmune state, one would think that there would be excessive tissue destruction and hopefully resolution, but it doesn’t appear to be tissue destruction at all. It seems to be this, just this inflammatory cesspit of, you know, just boiling over all the time, going through a waxing and waning, depending on so many other factors, stress hormones and, you know, you were talking about endocrine disruptors, all these other sort of things happening. So, when we’re talking about a wound that doesn’t heal, we certainly are talking about lesions, but is there any, I don’t know what the word is, stromal destruction within the lesion?

Rhiannon: So, I think the key factor that differentiates endometriosis is that it’s estrogen-dependent, of course. So, it has this individual driver from an immune and wound perspective, very different to other tissue damage. And the endometriosis tissue, whilst of course, outside of the endometrium is reactive to cyclical estrogen and progesterone levels, it doesn’t have the capacity to shed with the end of the menstrual cycle like the endometrium does. So, to a degree, it bleeds into itself creating a more profuse and complex wound. This is particularly clear for the lesions on the ovaries that are called endometriomas, but sometimes called chocolate cysts, and they’re really just blood-filled cysts that continue to develop. And from a fertility perspective, they’re some of the most significant lesions of concern.

Andrew: Ah, okay. Now, forgive me, I’ve got this wrong, and this is probably to do with not fertility, but pain. My understanding was that it was the least…the smallest lesions could create the greatest amount of pain, and that sometimes the serious ones were the most painful. Is that correct or not?

Rhiannon: I am not sure about that. I mean, the deep infiltrating lesions that go all the way, obviously, into the bowel and the bladder for some women, can be and they become fibrotic, causing adhesions, certainly can all contribute to the significant pain, I believe. From a fertility perspective, however, they’re very significant, but they’re almost of less consideration than when we have ovarian involvement. That’s our most significant concern from a fertility perspective.

Andrew: Gotcha. Now, of course, from a patient perspective, a patient comes in to see you and all of them of course say, “Hi, I know I’ve got endo.” Not the case, right?

Rhiannon: No. No. No, I’ll just diagnose.

Andrew: So, what are the things that pique your interest to go, “Hang on, maybe we need to do some more investigation here?”

Rhiannon: So, certainly menstrual pain, obviously. Heavy menstrual bleeding, clotting as a character of the menstrual bleed, and spotting, and dysfunctional bleeding patterns outside of the menstrual cycle. They’re all very typical endometriosis symptoms. I do a lot of pathology testing, so I am looking for estrogen dominance in these patients that is an indicator. It’s a part of the puzzle, it’s certainly not definitive. If I’m really suspicious and the patient doesn’t yet have access to a definitive diagnosis, which is either an endo ultrasound, which gives fairly clear indications of Stage III and Stage IV endo, but is less clear regarding Stage I and Stage II. Or a laparoscopy for diagnosis, of course. That’s the key diagnostic tool. But outside of those, if I was to suspect and we didn’t have access to that level of medical care, I would potentially refer them for a CA-125 test, which is otherwise considered to be a marker of ovarian tumour. So, you have to be very cognizant around the alarm bells that you are eliciting when you refer a patient for that test, but there’s a consistency with a level of 30 on the CA-125 of about 60% or 65% for endometriosis prevalence. So, it just gives you another piece of that puzzle, if you like.

Andrew: Gotcha. Can I ask also about CEA, what is it? The carcinoembryonic antigen, is that correct, CEA?

Rhiannon: So, the CA-125, it’s the cancer antigen 125.

Andrew: Yeah, but there’s also a CEA, carcinoembryonic antigen, but I’m not sure if it’s got anything at all to do with endometriosis. I think it might be another pointer, hint at possible ovarian cancer risk. Certainly, not used as a screening…there’s a thing. But I’m wondering if there, you know, if maybe you have, you know, 5 tests and you did a CA-125, a CEA anti-Mullerian hormone. I’m not doing well with the pronunciation today. Do you get a satellite of tests and you go, “We need to do further investigation?” Is there any hint that you get there?

Rhiannon: So, I would be doing… The CA-125 would be the key one that I would be doing from a cancer antigen perspective. AMH really can vary significantly. It can be low in endometriosis, or it cannot be low in endometriosis. It’s certainly… And of course, there are other situations in which the AMH will be low and it’s not endometriosis. So, it’s not…you know, there is not a lot of pathology. I think the answer is that, is that useful for a diagnosis of endometriosis? It’s really just putting the whole clinical picture together with those couple of other insights, and then referring them off where needed for medical investigation and diagnosis.

Andrew: And you were saying about, was it an intravaginal ultrasound that you were talking about for Stage I and II?

Rhiannon: Yeah, that’s right. Yeah.

Andrew: Yeah, okay.

Rhiannon: So, it gives some insight.

Andrew: But the gold standard is really to see it on laparoscopic investigation. So, therefore, you have to have very good relations with extremely well-experienced practitioners, as in specialists, medical specialists. Do you always look for…I think it’s a CREI specialist, is that right, CREI, C-R-E-I?

Rhiannon: Yeah, that’s right. So, we do work predominantly with fertility specialists who are slightly different of course, to gynecologists.

Andrew: Of course.

Rhiannon: Because, you know, this isn’t about my overwhelming clinical experience with endometriosis, it’s not about endo management from a pain perspective, but it’s about getting these women pregnant. So, we’re more…

Andrew: Yeah, got it.

Rhiannon: …interested in intervention that is relevant at this moment for them to improve their fertility in the shortest amount of time possible, usually, of course.

Andrew: Gotcha. Okay. Now, obviously, when we’re talking about fertility, we’ve gotta consider things like egg quality and ovarian function, and then there’s the other player that nobody ever talks about, and that’s sperm quality. Can we go into this and just how important all of these interplay together?

Rhiannon: Yeah, absolutely. I think it’s really interesting actually that from an endometriosis perspective there are…it’s multifactorial in the way that it influences fertility. And I’d love to take you through the… I’ll put them into four separate groups. I’d love to take you through them. So, I think it helps practitioners to compartmentalize it a little bit to understand it. But one of the interesting things is that the high reactive oxygen species concentration in the female reproductive tract does actually compromise sperm quality. So, this is a slightly different take on sperm quality to that conversation that we usually have, of course. This is actually less about the blokes, and more about what actually happens in the female reproductive tract once the sperm is there. But it’s an interesting, poorly-recognized component of the impact of endometriosis on fertility.

Andrew: So, when we’re talking about an increased reactive oxygen species, did you say in the female reproductive tract? So, we’re talking in utero, along the fallopian tubes.

Rhiannon: Mm-hmm.

Andrew: Something’s causing that. How do you settle that down? Are we talking general anti-inflammatories? Are we talking, you know, the fish oils and things like that, herbs?

Rhiannon: Mm-hmm, yeah. So, yeah, it’s the key feature really of endometriosis. I think we think it about quite routinely in its mechanical sense. You have the lesions, non-patent fallopian tubes, tubal blockage, but really, it’s a highly-inflamed, highly-oxidative environment that is self-perpetuating, and of course, estrogen-driven. And so, the impacts on fertility are those obvious ones, which most people would think of, mechanical fallopian tube obstruction. And along with that, actually, it does affect egg, sperm, and embryo movement through the female reproductive tract, because the motility of the fallopian tubes is compromised by the elevated cytokine concentrations. But really, what we’re seeing a lot in the literature and clinically, this is very, very clear when you see young women whom are going through IVF because they have endometriosis and should not otherwise have significant egg quality issues, but their eggs are just sadly, very poor quality once they’re removed from the eggs and in the lab, it becomes very clear that their eggs are poor quality. It’s because of this highly oxidative area. So, high oxidization in the follicular fluid, and damage to the ovarian tissue itself due to the oxidization and the inflammation, and that self-perpetuating high estrogen. So, it actually potentially impacts the DNA normalcy in the eggs and compromises their viability. Women with endo have less eggs, poorer-quality eggs, and poorer-quality blastocysts or embryos, and poorer-quality pregnancy outcomes.

Andrew: Gotcha. Okay. So, now forgive my poor memory. I know I’m gonna get this wrong, but am I correct in thinking that some of Leah Hechtman’s work for her PhD was to do with follicular fluid? Is that right?

Rhiannon: Yes. Yeah, she talks about follicular fluid a lot. Yeah, there’s a lot of follicular fluid work in her literature. I think Leah’s… I’m not that familiar with it, but I think that Leah’s work was on PCOS…

Andrew: Right.

Rhiannon: …or [inaudible 00:18:23] in particular, rather than endo, yeah.

Andrew: Gotcha. Gotcha. Okay, so we are talking about an oxidative, forgive my poor vernacular here, but an oxidative stressful environment. It’s really badly worded.

Rhiannon: It’s fair.

Andrew: How do we intervene? Like, can we give direct things orally, you know, fish oil, curcumin, some hormonal-modulating herbs? Can we affect that local area not just transiently, but long term by the use of these oral agents? And 20 questions, how important are the foundations like diet, stress, sleep, love, the anti-aggravations to life? How important are these in getting a positive result and maintaining it?

Rhiannon: So…

Andrew: In 20 words or less. No, I’m kidding.

Rhiannon: I’m out. So, the very good news for naturopaths and for women, and for functional medicine doctors is that we have some really good recent literature on our side that shows really positive potential for some of our interventions for endometriosis, managing the inflammation and the oxidization, which can improve egg quality and implantation and early pregnancy outcomes for these patients. And probably the most recognized one in the literature at the moment is NAC, N-Acetylcysteine. Glutathione depletion is a really key feature of endometriosis, and we of course, have NAC as one of our most effective interventions to improve glutathione, along with selenium, and lipoic acid, and glycine, and phytonutrients, green tea, vitamin E. But in particular, NAC has been shown in the literature to reduce the size of lesions, significantly reduce pain associated with endometriosis. A key study in 2013, I think it was of Italian women showed a shrinking and resolution of endometriomas. But really importantly, half of the women in this study, in the three months that they were included in the study, removed themselves from the surgery waiting list that they were on for their laparoscopic surgery for their endometriosis pain management. So, it’s…

Andrew: Wow.

Rhiannon: …actually, a radically effective intervention. Small study.

Andrew: Wow.

Rhiannon: Yeah, 90, 95 participants. But compared to the control where one woman removed herself from the list, more than half of the women removed themselves for their surgery. Removed themselves from the list for their surgery, because their pain resolution was so good with NAC. And clinically, I’ve gotta say, since I’ve been using NAC, you know, which is basically since, you know, since about that time, 2014, ‘15 for endo, my clinical outcomes with endo have increased significantly, and not only of course, for pain, but really importantly for endometrioma-associated infertility, and in general for egg quality for women with endometriosis, especially those undergoing IVF. It’s a radically key intervention actually.

Andrew: Right. Okay, dose? How much per day?

Rhiannon: The dose in the study was 650 or 700 milligrams TDS. I use 1,000 BD…

Andrew: Oh, right.

Rhiannon: …or TDS.

Andrew: Right.

Rhiannon: So…

Andrew: Gotcha.

Rhiannon: Yeah. So, it’s about 2,000.

Andrew: This is so Australian, so blow the TDS, take it twice a day.

Rhiannon: Yeah. Compliance is key, I’ve realized.

Andrew: Don’t even bother doing TDS. That’s right, compliance. And the whole thing is there’s no point having a fantastic intervention if people won’t take it. So, that’s how… I’m a BD person, that’s it.

Rhiannon: Yeah.

Andrew: Okay, so NAC, oh gosh, where do we go from here? So, what about other phytonutrients and things that are designed… And I’m not a fan of this term, antioxidants, I’m not a fan of that term, but those things that help along inflammatory processes, how’s that?

Rhiannon: Yes, all of those.

Andrew: What else do you use? Yeah, let’s go into some of the herbs that you use.

Rhiannon: So, probably the key herbs really for endometriosis, turmeric is, you know, impossible to overlook, good old turmeric, both because it helps to optimize estrogen clearance, but also importantly, it’s you know, one of the most powerful anti-inflammatories that we have of course. And it’s important to understand that the normal, the endometrium in women with endometriosis. So, not the endometriosis outside of the uterus, but that endometrium itself is more inflamed and of course, dysbiotic than the endometrium of women who don’t have endometriosis, and this affects implantation, what we call endometrial receptivity, and increases the risk of early miscarriage or spontaneous abortion in that early window.

So, turmeric, you know, whilst usually we’re quite careful around using turmeric, especially in curcumin extract doses for implantation windows, I find it really beneficial for those women who have that inflamed endometrium to optimize endometrial receptivity and implantation. And then other phytonutrients, bromelain has been shown to be beneficial for endometriosis lesions. Resveratrol is a big one as well. And green tea is one that also can’t be overlooked. And they all have little estrogen clearance optimization, pathway optimization roles as well.

Andrew: Yeah, so this is something I was pulling out. You know, when you’re talking about NAC, then you talk about turmeric, not curcumin, but turmeric, the original use of which was as a cholagogue, you know, it’s sort of going along this estrogen-driven condition, which if you get rid of excess estrogen, maybe it might have some play on at least dampening, but not necessarily egg quality and things like that. That has also helped with, or is dependent on things like pollutants and genetics, and epigenetics and things like that. So, with regards to firstly, the turmeric, do you opt for one of the more bioavailable? It’s not bioavailable, it’s more absorption. But the more bioavailable curcumin products, or do you just use fluid extract of turmeric? Yes, of turmeric.

Rhiannon: Yeah, I definitely use the more bioavailable extracts. And there are those of course, that the… I understand that there are those that the research is heavily associated with. But also, turmeric extract stains everyone’s benches, and so they stop talking to you after a while. But even more importantly, I guess clinically the results are just so much obviously better with the extracts. It’s just…it’s hard to deny that it really does. You know, I love my old-school headless side, but at the same time you just can’t…you can’t argue with the science and with the clinical outcomes.

Andrew: Yeah. No, I take your point about the staining, but I’m reminded of a friend who she was in dire need, she had cancer, and she was using the supplements that were more concentrated as well, but she always included turmeric in her herbal formula. And her whimsical comment was that her tongue was always yellow, always, just constantly yellow. Okay, so let’s delve into more about the pollutants. Now, obviously these are not just far-ranging, they’re insidious and they’re ubiquitous throughout the community, the society. And they don’t just affect females, they affect males. So, how do we make sure that our gametes are pure?

Rhiannon: You and I spoke a little bit about this the last time we spoke, of course, because it’s such a large subject and so much so that we wrote a book on it, but really it… How convenient. But the challenge, of course, is identifying the endocrine-disrupting chemicals in your orbit, removing them as much as possible. Being, you know, unfortunately cognizant that it’s probably impossible to completely remove them from your life in this day and age. And also, I think being cognizant of the fact that you have to balance your stress with pragmatic expectations or, you know, as a practitioner, you have to balance that for patients. But it is undeniably influential. Now the mainstream literature is really…it’s just irrefutable in the mainstream literature that environmental chemicals are significantly affecting both male and female fertility. But in particular, you might have noticed a lot of talk about it in the literature, in mainstream media actually, recently, regarding male fertility, and these kind of doomsday articles about the species becoming infertile because sperm counts will be 0 in 30 years. It’s not actually how the science works and that won’t be the case, but certainly male fertility is significantly affected by these endocrine-disrupting chemicals and dropping at a measurable rate every single year. It’s pretty crazy.

Andrew: Thank goodness we got rid of tight jeans, that’s all I can say.

Rhiannon: Good to know. There are still some tight jeans in Melbourne.

Andrew: I was looking at some pictures of Bon Scott the other day from ABC. But anyway, it wasn’t a good look.

Rhiannon: I think they had looks back then, Andrew.

Andrew: Now, obviously, the hallmark of endometriosis is pain. How do we effectively manage that? We’ve spoken about curcumin. Do you use any of these nutraceuticals like DIM for pain? Do you use herbs like corydalis, California poppy? Like, tell me how you manage this, and how do you individualize it depending on how a woman is presenting?

Rhiannon: I always joke with the practitioners that I mentor who bring me endometriosis patients when the patients are seeing them for endo management and not for fertility, but this is why I work in fertility, because it’s much easier just to focus on getting them pregnant and not to have to put in place protocols that will maintain their pain for the next 20 or 30 years. It’s a really hard job. Some women, when they respond to NAC and estrogen clearance…so if they have ovarian involvement, overwhelmingly, I would see an 80% or 90% improvement in pain in about 3 cycles with a combination of NAC and broccoli extract. Radically effective and difficult to take for the rest of your life, I think, but most women will realize that they need to come back on to it if they take a few months off and their pain returns.

For others, unfortunately, it’s not so straightforward. Of course, some patients will get benefits with turmeric, with corydalis, with California poppy, with PEA, although I don’t… Honestly, clinically I haven’t found that that useful for endo pain. With DIM. Certainly, obviously, dietary change is key for some women. I think clinically… I think as clinicians, sometimes we can exaggerate the benefit of dietary change. And even dare I say, going back to what you were talking about before, you know, stress, love, these things are all very important, but endometriosis is so insidious and so embedded for some women, that really very little helps for pain management. And it is entirely pragmatic for some that medical intervention is indicated to just get them to a position where we are better able to manage the inflammation, better able to manage the oxidization, and therefore better able to manage the pain for them.

Andrew: Gotcha. Now, results. Now, you are obviously extremely well-known for your results, but let’s go into those a little bit. And also, can we go through a few safety issues? What should we be aware not to do? That was really bad syntax. What should be aware of not to do? And what sort of red flags do we have to look out for to go, “This is something more sinister than what I think it might be?”

Rhiannon: The sinister thing is a very good question, and I would say that that is why as a rule, we really prefer to work collaboratively with our patients’ medical care providers to make sure that no red flags are missed. And you know, we’re lucky/it’s a result of the hard work that we’ve put in over the years that we have strong collaborative relationships with fertility specialists and some just endometriosis specialists in Melbourne. I do think what I would have to say, I guess from a clinical perspective about herbal medicine and endometriosis is, I see a lot of patients who have seen other naturopaths who have been given hormonally-promoting herbs and have found that their endo gets much worse, so heavier bleeding, more pain. And that’s because if you look at the mechanism of action of these herbs that contain, for example, steroidal saponins, it’s estrogen-promoting. And I think it can be difficult to differentiate with maybe some of the monographs that are built on traditional explanations when not to use these estrogen-promoting herbs with patients that have estrogen issues.

But for endometriosis, I think it’s important that you fully understand the condition, the presentation of the individual, and that you have assessed them from a pathology perspective, and you know what their hormones are doing before you go in and do anything that might actually promote the ovaries to produce more estrogen. Really, the whole idea is to optimize estrogen clearance rather than increase estrogen.

Andrew: Yep. So, we start with good old fibre, exercise, sleep, lots of water. Do you tend to choose different fibres, like, you know, let’s say a partially hydrolyzed guar gum over a psyllium or anything else? I’ve just chosen two, forgive me.

Rhiannon: So, oh, I’ve forgotten the name off the top of my head, but the glucomannan.

Andrew: I’d like to do this.

Rhiannon: Glucomannan. Yes. Thanks. Glucomannan is a fibre that is…

Andrew: Glucomannan.

Rhiannon: …particularly beneficial for estrogen clearance. It’s in a number of formulas, or you can buy it directly. You can access it directly. So, that’s particularly good for estrogen clearance, but you just can’t get… You just can’t beat broccoli extract for estrogen clearance. Yeah, and calcium D-glucarate if you’re gonna go down a non-herbal pathway. But yes, digestion, obviously there’s a strong IBS component to a lot of endometriosis presentations, and that’s partially of course, because of the significant dysbiotic microbiome association with the gut and the endometrium in endometriosis, but also just that inflammation, of course, in the bowel can create constipation. I always say that you’ll never get improvement in women’s menstrual pain if you haven’t sorted out your constipation.

Andrew: Gotcha. And obviously, we don’t wanna mention brands, but if you’re looking at a broccoli sprout extract, you want high glucoraphanin from a very high myrosinase content, correct?

Rhiannon: Mm-hmm, correct.

Andrew: Not mentioning any names, Christine. Anyway…

Rhiannon: Not mentioning any names. We wouldn’t do that ever.

Andrew: Now, Rhiannon, I have to ask this question of you. You weren’t always an expert. You started off as a budding young practitioner with starry eyes going, “I wanna help people.” How did you become the expert that you are? You said that you wrote a book, so can we talk about that book and what that might offer younger practitioners who wanna learn more? What’s in the book?

Rhiannon: So, the book is, it’s myself and four of my Fertile Ground colleagues. I definitely cannot take all of the credit at all. And in fact, Gina Fox and Charmaine Dennis deserve most of the credit, and Tina Jenkins. I just stand up and talk about it. However, you know, I think that the key answer to the first part of your question is mentoring. I’m a big believer in mentoring. I’ve always had mentors and, you know, I’ve been mentoring with Rachel Arthur, not about fertility, she repeatedly says that she doesn’t mentor in, but all the other things that allow me to deal with everything else going on with these patients. And mentors in fertility, including my colleagues at Fertile Ground. And, you know, now we, you know, being able to offer mentoring to practitioners who are less experienced or just wanting to specialize continues, I guess, to build my appreciation for the benefits of mentoring.

I think it gives us that confidence when we’re sitting one-on-one with patients, and we may have never seen a condition before, to be able to say, “We see this in clinical practice. This is the way we understand it.” To confidently say that. To not sit there feeling like you’re making something up or illegitimate in your position, but to, you know, really stand on the shoulders of, you know, the giants that you have learned from and contributing to going forward. So yeah, we’re really big believers in that.

The book was written for patients. It’s a clinical guide for patients, but we have a lot of practitioners who have read it and find it beneficial for their own understanding of the importance of preconception care, and certainly then use it for their patients. And, you know, we all acknowledge the benefit of the authorship of Francesca Naish and Ruth Trickey, who before us were so important in building our understanding in this area.

Andrew: Absolutely. So, Ruth Trickey’s book, Lara Briden, Leah Hechtman, yourself, these are for seminal texts, which any young naturopath on their journey to specialize in women’s health and perhaps fertility, you should be getting these as an absolute foundation for anything to grow from. But Rhiannon, I thank you so much for sharing your obvious wealth of expertise. But it’s your care, it’s your care of these, not just women, but couples who come through your door and they’re searching, and they’re frustrated, and they’re crying, and they’re in pain, and you help them to have a family. Thank you so much for joining us today on “Wellness by Designs” and for sharing your expertise. I really appreciate it.

Rhiannon: Thank you, Andrew. And how lucky are we in this profession to have this role in people’s lives. It’s such an honour.

Andrew: Well said, so well said. Now, thank you obviously, for joining us today. Hope this has been of benefit for you, not just now, but for your career into the future. Now, remember that you can find all the show notes and all of the other podcasts on designsforhealth.com.au. I’m Andrew Whitfield-Cook. This is “Wellness by Designs.”