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The Emerging Biomarkers for PCOS and Fertility with Leah Hechtman

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Emerging Biomarkers for PCOS and Fertility with Leah Hechtman

Is polycystic ovarian syndrome being over-diagnosed?

Today we are joined by Leah Hechtman to share some insight into new biomarkers with a stronger association to ovarian function that are now in early stages of research, and so far the results look promising. Both from a diagnostic perspective, but also for predicting fertility outcomes, these new biomarkers could mean less fear and uncertainty about having a family, but also, potentially less intrusive medical interventions in the long term.

Leah will be presenting on the topic of Optimising Fertility for the PCOS patient, at the forthcoming ATMS PCOS Symposium in Sydney in September 2018. For clinician's working in the areas of women's health, you do not want to miss this outstanding educational opportunity.

Covered in this episode:

[00:51] Welcoming back Leah Hechtman
[01:27] What is the true incidence of PCOS in Australia?
[04:00] New biomarkers for PCOS
[09:23] What is BMP15 and GDF9?
[10:20] Can we prevent overdiagnosis now?
[11:36] Can we rely on classic physical manifestations?
[13:35] Ovarian reserve: is it clinically relevant?
[14:49] Can genetic testing be of value?
[19:07] The trans-generational issues of environmental toxins
[27:54] Valuable herbs and nutrients for PCOS?
[34:45] What to expect from the ATMS PCOS Symposium
[37:03] Leah's PhD progress


Andrew: This is FX Medicine, I'm Andrew Whitfield-Cook. Joining us on the line today is Leah Hechtman, who's an ultimately experienced and respected clinician who specialises in fertility, pregnancy, and reproductive health for men and women.

She's completed extensive advanced training and is a university lecturer, keynote speaker, author, and educator to her peers. Leah is currently completing her PhD through the School of Women's and Children's Health, Faculty of Medicine at the University of New South Wales in Sydney. 
Welcome back to FX Medicine, Leah. How are you? 
Leah: I'm well, Andrew. Thanks for having me.
Andrew: Today we're going to be talking about predicting fertility in polycystic ovarian syndrome, something you'll be speaking at the ATMS symposium later on this year in Australia.

But just as a review, can you take us through a little bit about polycystic ovarian syndrome? I guess especially in Australia. What's the purported incidence and what are the diagnostic issues that are facing it?
Leah: Absolutely. So, at the moment, I think that statistics, we're looking at about 1 in 10 women. But we're in a situation where it's been extremely over-diagnosed.

So we have used three different criteria to make the diagnosis of PCOS: the Rotterdam, Androgen Excess society, and NIH. And the problem is is that all three of them are fairly dated. The Rotterdam criteria is the only one that's had amendments to it and has been looked at a little bit more extensively, but you still have way too many women out there that are diagnosed as having the syndrome when they just have multiple cysts on their ovaries.

Andrew: Right.

Leah: Or they have multiple follicles, really. You know, their antral follicle count is excessive. 
And I was speaking to a colleague of mine the other day. And the new technology in all the sonography units now, they've had to change the criteria, but the diagnostics haven't caught up. So all the new ultrasound units can actually detect follicle counts, you know, in the 30s and it's completely normal. And they're now saying that PCOS is really only if you're using the latest technology and your AFC is more than 25 per ovary. Which means that we've been diagnosing all these women when it's more than 10 per ovary and they haven't actually changed the criteria even though they've got new technology.

Andrew: Right, right. So we're able to see more, and we're still diagnosing as if we couldn't see more.
Leah: Exactly, exactly. So you’ve got, you know, statistics is saying it's 1 in 10. I think that's a lot of rubbish. I don't think it's that high at all. Yes, I think... 
Andrew: Best guess probably.
Leah: Well, I think we're overlapping a lot of conditions, and you know that I'm a little bit interested in endometriosis.

Andrew: Yes.

Leah: I think that the incidence of endo is 1 in 10, and the incidence of endo with PCOS, I think we're probably looking at 1 in 15. And I think that PCOS, it depends...you know, how much of it is just...everyone's overweight and has a crap diet and all that, and how much of it is actually true syndrome? You know, where there's genetic markers that correlate with actually having an abnormality here. I think the latter is actually quite a small percentage. And I think the rest of it, you know...maybe if you look at true, true PCOS, I think we're probably looking at maybe 1 in 40 women.
Andrew: Right. So let's talk about these biomarkers then. What new biomarkers are available? You normally, you know, we'd look at even apple-shaped obesity with cardiovascular issues and excess androgens. Apple-shaped obesity is a load of rubbish. Because thin women can get polycystic ovarian syndrome I'm gathering. 
Leah: Absolutely. They can get on any of it. Yeah, absolutely.
Andrew: Yeah. So, what are the novel biomarkers? What should we be looking at? 
Leah: Well, okay, so the Rotterdam criteria, even as early as 2007...Professor Robert Norman, who's going to be speaking at the symposium, he's wonderful. And he released a paper where he actually said, "That's it. We can all use AMH as a diagnostic for PCOS." And that's fit with the research around where AMH was at the time.

So we're talking about anti-Müllerian hormone where the average assay cuts off at 30. And a woman that has an AMH greater than 30, you basically say she's got PCOS. Whether or not that's entirely true, that's part of what I'm doing in the PhD. If my supervisor's listening to this, then, yes, it is true. But if not, I'm not 100% sure!

But it's one of those situations where they're using AMH as a diagnostic now. So, basically they have a woman that comes in and you suspect that she has PCOS. Rather than getting down that slippery slide into, "Let's look at androgens and do quantification," and all sorts of different things, it's basically, "You just test her AMH. If it's greater than 30, she has PCOS."

I don't know that I entirely agree with it. But certainly if a woman presents and she's got an AMH of 157, yes, she's got PCOS.

Andrew: Right.
Leah: Remember AMH, it's basically the communication between the ovary and the brain. And so if the AMH is pumping and it's going at really, really high levels, the FSH is really non-functioning. So the anterior pituitary...you know, like, I always joke with patients, I say, "The PCOS woman, she's stuck in third gear." You know, first gear is the release of FSH. Second gear is the release of oestrogen by the ovary. Third gear is the release of LH by the anterior pituitary. When her AMH is that high, she's stuck in third gear. The FSH is just not secreting, and that's why her ratio is so distorted. 
You can use that as a diagnostic. You can do the FSH to LH ratio. So, in a situation where normal, healthy women it’s an FSH to LH of 2:1. If the LH is higher, then obviously you know that that's pretty much one of the criteria for PCO confirmation.

Otherwise, you're looking obviously at all your androgens and things like that, but the exciting stuff that I'm working with at the moment with part of the study is we're looking at these new novel biomarkers. So we're looking at BMP15 and GDF9. And what we're starting to see is...essentially we're looking at two main populations. We're looking at the polycystic ovarian syndrome women, and we're looking at the premature ovarian failure women, so both extremes. And we're seeing a direct correlation in the numbers of the BMP15 and the GDF9 that can certainly tell us what's actually happening in the ovary.

Because all these other markers are just telling us...you know, like, AMH is just telling us the antral follicle count essentially or the pre-antral follicle count. It’s giving us a snapshot as to what's happening there. But it's not telling us the quality. It's not telling us the ovarian function. And it fluctuates for many, many different reasons.

But the BMP15 and the GDF9, we're actually seeing very, very marked stability there, and it gives a really good assessment as to what's going on for the woman and actually what her fertility potential is. So it's pretty cool.
Andrew: GDF9, I'm imagining, is gonadotropin-something? BMP15...and also, are we looking at...do we need to be aware of cyclical changes here?
Leah: With respect to the BMP or the GDF9, or which part?
Andrew: With any of the biomarkers. You're talking about with anti-Müllerian hormone, the woman is stuck in third gear. But she's stuck in full gear all through her cycle, correct?
Leah: Well, AMH, when you look at...and we've got fairly good data now because we've been using the assay for a long time. We did have a glitch with the assay, and it's only in the last 5 years that I think we can trust the information because it was a stability problem. So anyone that had their AMH levels tested more than 5 years ago, there was 30% level of inaccuracy where it was...
Andrew: Wow, a false positive?
Leah: Yeah, and many women made very drastic fertility decisions where they were told that their AMH was 30% lower than what it really was. 
Andrew: Oh, lower, so a false negative?
Leah: False negative.
Andrew: Wow.
Leah: I still think of one patient where I counseled her around it, and she had a non-detected. And I still wonder to this day was it real or not? It's one of, you know, those patients that always sit on your shoulder. She's one of those.

Andrew: Yep, yeah.
Leah: Yeah, so it's a situation where AMH, they say now, is fairly stable throughout the whole cycle. But if you're on a contraceptive pill, it can lower it by as much as 30% to 40%. The accuracy is certainly better at the beginning of the cycle, so day 2, or day 3. And that certainly makes it much more predictable and certainly all the other hormones you do it on day 2 or day 3.

Whereas the new markers, we're finding that there's no change within the cycle. There's no fluctuation. But there's fairly good accuracy that the number that it produces can give you a really good indication as to what's actually going on.
Andrew: So BMP15, bone morphogenetic protein, is that right? 
Leah: Mm-hmm.
Andrew: Okay. Take us through what this is, what's its relevance?
Leah: So basically what...this is really, really very new research. So it's certainly not an assay that anyone can request from a pathology lab. We're in the early research stages.

Andrew: Yep.

Leah: But what we're doing this year are two molecules that we know that is secreted by the ovary. So, the AMH itself is not secreted by the ovary, it's secreted by the pre-antral follicle. So we don't necessarily get an accurate picture as to what's going on versus now with this we can actually see this is what the ovary is secreting and when the levels are dwindling. It can give us a better idea as to what's actually going on inside. 
Andrew: And GDF9. Now I said gonadotropin, it's wrong.
Leah: No, not gonadotropin.
Andrew: Growth/differentiation factor.
Leah: They're all growth hormones basically.
Andrew: Yep.
Leah: Yeah. And they are secreted by other tissues in the body, but there is a heavy concentration in the ovary.
 Andrew: Okay. So, you say that these are heavily in the research domain at the moment. What do practitioners do now particularly to, you know, thwart overdiagnosing polycystic ovarian syndrome? What should we be looking at? 
Leah: I think it's a really good point. At the moment, I think, you know, I'm highlighting the research because we know where medicine is going. We know the direction, and we know that we'll get more accurate information.

But certainly at the moment, I think it's important to...when a person's sitting in front of you, look over what has been tested, what time of the cycle it's been tested, and use your clinical judgment to actually work out, is this actually an overdiagnosis, a misdiagnosis, or a true diagnosis? And if it is a true diagnosis, then... I mean Lara did that wonderful talk, and she's going to be talking at the conference as well. You know, you can classify the type of PCOS and then be much more strategic with your treatment.

But, you know, so many times women walk in my room and I'm just like, "You don't have PCOS. What's going on here?" You know, and they're like, "No, no, no. Blah, blah, blah." And, they’re put on metformin. Some of them are pushed into ovarian drilling. Some of them are put on antidepressants. Like, there's a whole host of different medical interventions that they're moved towards, and they have the fear of God in them that they have to be on the pill, and they have to be on metformin, because otherwise they'll never going to have a baby. But they never actually had PCOS in the first place.
Andrew: When we're looking at the physical characteristics that patients present with, we know that apple-shaped obesity, that's out. That may be important in some, but it's certainly not in all. Can we rely on any physical characteristic like, say, for instance, hirsutism? Can we rely on any one sort of thing to point us, or at least to alert us to go there's something else going on here? 
Leah: Look, I think if you have a woman in front of you with hirsutism, with acne, with weight gain that's really stubborn, with an absence of periods, you know, with blood sugar irregularities. They're forming a picture that, yes, is suggesting that PCOS is there and then you can look into it a bit more deeply.

And you certainly weren't saying this, but to suggest that every woman that has hirsutism has PCOS is so simplistic. And I actually find it quite racist. Like, I have a lot of women that present, that have various upbringings and ethnicities that increase their facial hair growth, but they have nothing to do with PCOS.

Andrew: Got you.

Leah: Or high-androgen for that matter. So, I think that it's just important to really look at it carefully.
And definitely, you know, the apple-shaped woman idea is out, so is the obese woman out, and so is the very thin woman out, you know? Any woman of any shape can get it. And I do think that, you know, there's a lot of positive theories from the various body shapes.

Like, Prof. John Eden's theory, which I've really leaned into a lot over the years. His idea that women who are very thin and when they go into a famine state that they can still ovulate. That supports why they could essentially have PCOS.

The women where they're very overweight, a lot of Joe Pizzorno's theories around heavy metal exposure and environmental pollutants. He really believe that PCOS is just environmental aspects. And you know, we're writing the PCOS chapter for the 5th edition of his text book at the moment, and he said, "No, no. We just focus on environmental." I'm like, "Joe, no, we can't just focus on environmental. There's other aspects," but it could theoretically be that, and we might find that out to be the case.
Andrew: What about things like with regards to polycystic ovarian syndrome and fertility issues, which is obviously why many women start to investigate this as a possible diagnosis? What about ovarian reserve?
Leah: Mm-hmm. I think the biggest thing that has always been a real “aha” moment for me, is that you have the classic PCOS woman with a high AMH, if we believe entirely that that's exactly what that is.

Andrew: Yeah.

Leah: She has a drop-off of eggs. And the thing is that the PCOS woman is often miscounseled, and she's often lulled in a false sense of security of, "I have really high AMH. Time won't run out on me." But what we understand now is that she still has a blueprint for when menopause will happen.

Andrew: Yep.

Leah: And her menopausal age isn't usually any later than a woman without PCOS. It's just that she has this high AMH, this high-follicle response, but then she's still classically going through menopause at the same age. 
So the woman with an AMH of 120 at 42 thinks she's fine. But she's not. And that's something that I think, as clinicians, we need to be quite careful around and we need to counsel our patients around because too many doctors are saying to them, "Your AMH is fine. Don't worry about it."
Andrew: The age of genetics is upon us, and genetic testing is now available. Do you find any link here with things like COMT or methylation. Do you find any pictures evolving? 
Leah: I do see lots of different patterns with it. I definitely see a lot of, I just call them, ‘glitches’ in like the transsulfuration pathway and glutathione production and all of the liver metabolism of all the hormones. I find that that doesn't work very well and lots of issues in all of the genes around that.

I do tend to see an undermethylation picture more prevalent. So a SAMe production decline and obviously a SAM:SAH ratio issue that grows with it. And so then typically the COMT gene precedes all of that. Definitely methylation. I mean it's one of those ones in methylation that we all prescribe B vitamins for God knows how long, and now we're just much more specific with it. And I think that's always going to be the case. If you get someone's B vitamin status right and the more genetic information you have, the more specific it can be, the more you're going to help every problem.

But definitely, you know, tidying up methylation reduces inflammation, and we know that PCOS is an inflammatory condition.
Andrew: Going back to the days when we didn't even consider genetic SNPs, we didn't think about them. Have you ever looked at a comparison of patients, let's say, 10, 15 years ago compared to now? And the supplements that were available back then, versus the supplements that are available now, have you ever thought, or has anything twigged in your mind about, "Mm, I saw some similarities there," or, "Gee, I'm seeing some vast differences in treatment outcomes with regards to the newer, available..."? Let's call them active B vitamins. 
Leah: I'm seeing genetic differences. I'm seeing differences...there's a few reasons for it. I always think that, "God, if I could treat the people I treated 20 years ago, they'd be so much better." But, you know, we treat the people at the right time and all that good stuff.
Andrew: It's all you've got to work with, yeah.
Leah: Yeah, it's what you got to work with. But there's still be those patients that miggle in the back of your mind that you didn't quite nail or that you didn't help the way that you wanted to. And I think if I could treat them now, God, I'd make much so much more difference.

But, I can't get over the speed of my results now by having the genetic information and the methylation information, with outcome. You know, patients that may have taken 6 or 9 months to get pregnant can now taking 3 months. That's a huge difference in time, and it's also lowered incidence of miscarriage. Like, PCOS women, for example, really high incidence of miscarriage because their eggs are so much older and all that sort of stuff.

Andrew: Yep.

Leah: And so you know, you could get them pregnant, but you maybe couldn't shorten their cycle to less than 6 weeks, say 15 years ago. Whereas now I can get their cycle under 3 weeks no problem, and so the incidence of miscarriage is dropped off.
So, there's huge differences in treatment outcome. I think it's incredibly powerful and I'm really excited to see what's going to happen in the next 5 or 10 years. But then I think treatment responses are going to improve even more so. We’re just getting much more individualised and specialised, and I think that naturopathic treatment really leaps ahead of where the diagnostics are. In that sense where PCOS, I think, is still too simplified in the mainstream community.
Andrew: You love using traditional Chinese medicine especially in herbs in your treatment. Do you ever find that the TCM treatments have an explanation with today's modern understanding of SNPs genetics and that sort of thing? Or do you just think, "Oh, no, it was the energetic"? You have to look at it in an energetic way. 
Leah: No, I do. I really do. And I do find that I can use the energetics of herbs or any of my other treatments, homeopathics, anything like that, and they'll give me answers that connect and correlate with the genetic information really well. And I think it's just getting much more individualised and specific about things.

And I think when you dig really deep into traditional Chinese medicine and you go beyond. You know, the initial level of information you really get into the spiritual stuff, that's where you can start to get some really fascinating outcomes in treatment, and that certainly has a correlation and you can match the types of people with the types of genetic profiling as well. 
Andrew: You mentioned before about writing a chapter with Joe Pizzorno in The Textbook of Natural Medicine regarding environmental issues. And, I think I agree with you to put it all in one basket might be a little bit of a strong opinion, but certainly it's got to be playing an important part, yes, with polycystic ovarian syndrome?
Leah: Absolutely. Yeah, absolutely. Look, I mean the research that Joe is doing...and I mean he's pretty much dedicated his life to this now. And I mean hats off to him. What he’s found is just alarming, and I think that all of his research around heavy metal exposure, environmental pollutants, all those sorts of substances and what we're actually doing with our environmental exposure I think is having a huge impact on fertility, and we've seeing that. But certainly with the incidence of PCOS.

And, he looks at it and simplifies it and goes, "Okay, women, weight, sugars, PCOS, yep, that's going to be environmental." And, pretty much it is. Let's be honest. I mean if you can get all these women to lose weight, if they are overweight, if you can normalise their sugar receptors and get rid of the arsenic or the cadmium, or whatever it might be. You do have a much more stabilising effect. 
But, I think one thing that we have to factor in with the environmental aspect is the tri-generational impact. And I think that, when you look at some of that genetic research that's come out looking at what your maternal grandma did and how that influences your reproductive fitness, that's where we're seeing huge information coming out right now about PCOS incidence.
So, yeah, I don't know if listeners are aware of...it's probably one of the biggest studies was the Dutch famine study. Where they did three generations of women, and they looked at women who were going through World War II through famine and how they lost their fertility when they had gone through all the starvation. They then regained it after the war. Then their daughters had significant difficulty with breastfeeding, and their granddaughters had significant difficulty with fertility. But they’ve kept going looking at that information, and they're now seeing the PCOS incidence increasing in the fourth generation. 
Andrew: Wow, so it's a quad-generational, not a tri-generational.
Leah: Yeah, no longer just tri. They're now thinking quad. So, whatever is going through the maternal line through environmental exposure... I mean that was specifically looking at starvation and famine. But I'm a bit nervous about what's going to happen to our daughters? We know what's happening to our sons from an environmental perspective with all the sperm count reduction. But perhaps this is the environmental translation in women. The equivalent of the sperm count reduction, we're having the polycystic ovarian syndrome.
Essentially it's making women not have periods and not be fertile. And potentially that's what it's actually doing, and is it that it's environmental exposure that they've had or is it multi-generational? And I think it's a bit of both.
Andrew: Are we seeing any of these correlations with male to females with regards to any of these reproductive-type issues? In males, sperm’s going down. There's several theories still floating around about, is it population density? Which I wonder about if.. how you could explain that one. But then you've got pollutants and things like that. Like, has anybody thrown any research into looking at males versus females and the fertility impacts? 
Leah: I’ve seen some… I'm not sure if I'm answering your question so jump in if I'm not, but I have seen some research correlating the incidence of male fertility parameters in their semen and having daughters with PCOS. And so what Dad as exposed to and how that creates the daughters and how it influences her. I definitely have been seeing that. That's starting to come out.

There's lots of stuff that they're correlating that way. But did I misunderstand your question?
Andrew: So that's not a trigenerational female-female-female or quad-generational. We're talking male to female issues here then...
Leah: Male to female.
Andrew: ...transference? 
Leah: And then, yeah, it’s definitive what's on the X chromosome. It's new research so it's early days. I've only seen a handful of papers, but I'm obviously quite abreast of PCOS stuff at the moment. But it's quite fascinating. It's very scary but it's quite fascinating. And they're specifically looking at what's happening with the daughters. And there were some suggestions of, you know, “is what our men are doing actually making our women infertile?” Well, their daughters infertile.
Andrew: Okay, so that does lend back to a xenoestrogen-type theory, doesn't it? Or let's say a persistent organochlorine pollutant?
Leah: Yes, because the theory was always that the women were the ones that could have a generational impact because they're born with their eggs, you know, and the children are in their eggs and all that sort of stuff. Whereas with men, because they're generating new sperm but they're obviously realising more the damage to the testes. And then how that's impacting things and whether or not they're actually not passing it down every 72 to 76 days.
Andrew: Can you rescue the sperm or are we talking about damage to the actual Sertoli cells?
Leah: They're not sure now. 
Andrew: Oh, my God.
Leah: They're not sure. Yeah, I think we can rescue the sperm because I see it clinically all the time. But I do know that there are certainly men that you can't rescue it because, you know, perhaps they have a genetic mutation or they have something high-order that has influenced their testicular development, which then can lean back to their mother but that's another story. But, they're finding that the damage to the Sertoli cells and the recovery of the sperm production is potentially not as great as it could be.

I think the environmental aspects we need to be very, very conscious around, and I don't think that we have enough of an idea as to what is going to happen. I mean if I just think about my short career in the sense of in the last 20 yeas and whatever, what have I seen? I'm pretty scared, and I'm quite nervous about my kids, what's going to happen to them?
But the diagnostics around PCOS, yes, it's been overdiagnosed but I do think it has to be increasing. Like, bringing it back to PCOS for a second. It has to be increasing and I think that some of the environmental impacts has to be a variable there.  
Andrew: I'm sorry to keep harping on about...
Leah: No, it's fine.
Andrew: ...sperm quality but, like, I know that I can ask you. The old theory of population density may be affecting a pheromone production or something like that that may be affecting fertility in that way. Is there any basis to this? Is there any juice to that theory or have we really moved on from that?
Leah: I don't think there's enough substantiated evidence to it. Nothing that I’ve seen that’s significantly conclusive, and it certainly doesn't correlate with male quality of life studies or anything like that that I've seen. Do you know what I mean?
Andrew: Yeah.
Leah: I don't think that we're seeing...like, we don't even have enough proof around andropause, do you know what I mean? To then be suggesting that the pheromone production, like all that sort of stuff, is changed as well.
Andrew: When we're discussing your talk that you're going to be given at the ATMS symposium in September; “Predicting fertility with polycystic ovarian syndrome”, what are the important factors looking at the prediction of fertility? 
Leah: I think it goes back to what we were talking about earlier about having appropriate diagnoses and appropriate facts, and really making sure that women are aware that they don't have these extra 5 or 10 years that we used to believe. And then making sure that they have a really thorough work-up. They'd know that it is PCOS if it is. I mean so many times someone walks in and it’s high prolactin levels and they just haven’t been properly assessed. Or something like that. And then if it is, then working and navigating through the right treatment. 
And I think as well with prediction of fertility, it's remembering that the goal is about normalising and stabilising the cycle, not just getting them pregnant. Because the PCOS woman has a much higher incidence of miscarriage, even late miscarriage. You know, at 16 to 18 weeks, she also has a higher incidence of stillbirth. She's got all sorts of other complications: high-risk of gestational diabetes, preeclampsia, etc. etc. 
So, it's about making sure that it's not just about getting her pregnant, it's about her understanding what her true fertility is, what her true diagnosis is so that you can be strategic with treatment. And then recognising that the more individualised the treatment, the faster the results now, like we were discussing earlier. And realistically most PCOS women, you should be able to get their cycles sorted, and pregnant, and everything within the 6 months easily. And if you're not, then you've missed something.

So, I think it's overly generous to continue to treat them how we may have in the past, and I don't think PCOS women should be waiting a year or anything like that anymore.

Andrew: I don't want to get into the situation of, you know, seeming to be protocol-driven because I hate that word.
Leah: Of course.
Andrew: But, do you find any, let's say, particularly valuable herbs or nutrients? And what's their place in therapy with polycystic ovarian syndrome?
Leah: Probably the number one nutrient is zinc. And at the right dose. And zinc comes across with all of the types of PCOS. So even if it's adrenal or if it's metabolic or whatever, zinc will regulate and normalise almost all of those pathways. And it's about the form of zinc that you're using, the dose that you're using, and the frequency that you're using. And I do think that we're all very zinc-phobic. I do know that, with PCOS women, you do need to push the dose up quite high. Monitor them of course and, you know, continue to test their plasma zinc, and serum copper, and do all the ratios and whatever. But you do need to make sure that the zinc status is optimised and maintained. 
And there are definitely women where their zinc is extremely low in pregnancy, and their copper's extremely high. So you're going to need to monitor them in the pregnancy. And, you know, just the gestational diabetes component that's common in a PCOS woman, when she's pregnant, is usually normalised if you get her zinc and copper sorted.

Andrew: Right.

Leah: You don't have to jump into alpha-lipoic, and chromium, and all the other bits and pieces. So, for me, zinc is a fundamental. And then if you go into any of the SNPs, we know zinc is such a normalising and regulating nutrient. 
Magnesium, it's pretty much, of course, for everybody but certainly for the PCOS women for many different reasons. But again it crosses over into all of the different etiologies. Methylation cofactors, B vitamins, all of that sort of stuff absolutely has to be sorted and addressed. And then I tend to find that it gets much more specific.

So then you're looking at, you know, in situations, there might be the need for chromium, there might be the need for inositol. There might be the need for numerous herbs: cinnamon, gymnema, those sorts of things. Or it might be all adrenally related. It's just very independent. But every single PCOS woman will get zinc, all the methylation stuff sorted and all of the magnesium.
Andrew: And you mentioned, for instance, before a zinc to copper ratio, like, do you use zinc as an antagonist or do you tend to sort of look at zinc for its effect on hormones like for instance 5 alpha-reductase?
Leah: Well, it depends on what's going on. So if the copper is through the roof even before they've conceived, you know, like, they've been on the pill for a very long time and they need to get all that copper out of the body, then obviously I need to sort all that out first. And I don't want to get copper toxicity. And, you know, you just dance that walk quite gently with molybdenum and right doses of zinc and everything like that.

But then the zinc, depending on the presentation on where it's needed, absolutely be using it in quite high doses. It tends to normalise everything.
Andrew: And any caveats with that? Like, for instance, there's that 150-milligram sort of warning dose with regards to causing a copper deficiency long-term and potentially leading into cardiomyopathy but that’s… 
Leah: Look, I don't think most people need 150-milligrams of zinc. I think it's more that they need the right form. And explore the delivery methods of the zinc. But too many people are just still using, you know, amino-acid chelate form or citrate form and not getting anywhere.

And I do think that, you know, the deeper we dive into the SNP world, we will find some zinc receptor SNPs that will elucidate some of this for us. And I certainly see a correlation with vitamin A SNPs. You know, like some of my patients will have, like...there's the three main SNPs where there's the abnormalities. And, for example, I've got one woman and she’s homozygous for all three and because her vitamin A SNPs are so deranged, her zinc is always stuffed.

Andrew: Right.
Leah: So, I think it's about trying to understand what's going on inside. But I’ve certainly had many, many people over the years where it was just the form. You know, like they've come to me from other clinicians, been on 120 milligrams of zinc a day, and their plasma zinc is still 6. And then you just change the form and they're sorted.
Andrew: What about TCM herbs?
Leah: Again, it's very much about trying to ascertain what's going on for them. So the PCOS woman, if you look at it through the energetic lens, I tend to find they're quite cold. You know, their ovaries are freezing. There's an enormous amount of scar tissue on them from all of the follicles leaving the scars essentially. I get them doing ovarian massage with rose oil or geranium oil. Occasionally I get to mix some cinnamon into it if they're like really cold, and then I use Chinese herbal formulas to warm them up.
So, you know, a lot of our Western herbs in Chinese context can be beautiful. You know, cinnamons, and turmeric, and all that sort of stuff. But, you're really wanting to warm them, and I find that that's usually the most effective. And then adding adrenal herbs is indicated or blood-sugar-regulating herbs is indicated as well.
Andrew: Yeah. Forgive me if this is ignorant of TCM, but it is the TCM way of looking at cold dissimilar from how we would look at cold thermically in Western medicine. Like, for instance, is exercise going to help in the energetics of the presentation?
Leah: There's two parts for that. So the TCM language and the thermal language is a little bit different, but it's more just a type of cold that you're dealing with in the TCM language.

So, I mean is it a cold because it's stagnant and it's, you know, just blood not moving around the body properly type of cold, or is it a cold because it's damp? You know, there's various types of cold, and it's trying to work out what that is and then specify how you treat it. 
But exercise in a PCOS woman is actually quite interesting. So when you look at it through a research lens, everyone always says to the PCOS woman, “go exercise, you'll fix your PCOS.” They don't look at the body shape of the woman, and they don't factor in her stress levels or anything like that.

But we know that the overweight cortisol-driven PCOS type of woman, if you tell her to exercise, it makes it worse. So you don't have her pumping weights at the gym, and you don't have her trying to run and do bootcamp at 5am in the morning. You don't have her do anything like that. You have her doing yoga, and stretching, and moving her body, and improving the blood flow and her body, but essentially not getting her heart rate up very high.

Andrew: Right.
Leah: Whereas the thin woman with PCOS, she might be cold because she needs more body fat. So again you don't want to get her aerobic capacity up too high. But you still want her to be exercising for blood to move around the body. And you just do that in conjunction with saturated fat intake.

And I’m doing a lot of… you know, with the thin PCOS, I'm doing a lot of dermal application. You know, getting them to lather themselves in cocoa butter and shea butter and stuff like that. Because they don't want to eat that much and then that's actually improving just their natural production of oestrogens and progesterones and stuff like that.
Andrew: What will people be learning more about, about the practical things that they can implement, by attending the ATMS symposium in September
Leah: I think the symposium, anyone that went to the endometriosis one will attest that it was amazing.
Andrew: Incredible.
Leah: And I think probably one of the best things about the symposium is that you've got five really experienced clinicians and researchers there.

So you've got Prof. Norman who is...anyone that is in the reproductive world knows Prof. Norman, knows his position in fertility society, in the preconception unit of the Fertility Society of Australia. So he's very open-minded to complementary medicine, done enormous research in PCOS itself. He's headed the Adelaide research institute, the Robinson Research Institute. He's phenomenal in how he works.

You know, then we've got the exercise physiologist professor. I don't know him well. That's going to be really fascinating to understand his take on exercise. Lara will be there, Lara Briden, and her podcast was wonderful. Lara's take on things, she's just so wonderful at organising information and making it translatable for the clinician to go, "Oh, I can just copy this, it's fine."

Caroline is an acupuncturist. She's a researcher at UWS as well...sorry, it's now called Western Sydney as well, through NICM, and she's brilliant. I mean she's a GP, acupuncturist, and she's so...
Andrew: She's lovely.
Leah: ...grounded. Yeah, she's just wonderful and she's so, so knowledgeable. So she'll bring Chinese medicine in a way that is very accessible for anyone in the medical community. It's very interesting for me. Some people might not like it but we'll see.
Andrew: I know people will be taking away some, "oh, my God" moments. You always do that.
Leah: I hope so.
Andrew: So, obviously we need to attend. How can people find out more about when it is, where it is, and how can they register?
Leah: The wonderful Alex Middleton has put this one together again and if you just jump online to atms.com.au. And just I think there's an events tab or something like that on their website.

Andrew: Yep.

Leah: It's going to be held in Sydney at UTS at this amazing function centre on Sunday, 16th of September. And it'll be a big day. I think it starts from 8 in the morning, so there'll be lots and lots of information. 
 Andrew: Yep, one last question. I have to ask, Leah, how is your PhD going? Tell me a little bit more about that.
Leah: Look it’s, I always say to people that the PhD is what I do for me. You know, like, there are many things that we do in life, and the PhD I'm purely doing just because I love it.

It's a lot of work but it's so rewarding. Look, anyone that is considering doing a PhD, I really say go for it, because it's such a wonderful way to challenge yourself and to get a lot of knowledge. And it immerses you in all the different worlds, and it gives you confidence in ways that you didn't actually anticipate you could acquire. 
But, you know, content-wise, it's exciting. I mean I'm working with a phenomenal faculty, a phenomenal research group where they've identified these ovarian biomarkers. They haven't been actually bought by any company yet so we're purely research phase, and it's exciting. You know, like, every day we're learning something else, and the driver for why I did the PhD is being answered every day. You know, the “I never wanna have that woman again in my clinic where she's there and I tell her I can't help her with fertility.” And I think we're getting a lot more answers so that we can educate and empower women so that they can make decisions around their fertility. So, I'm loving it. It's good. 
Andrew: Leah Hechtman, there are many reasons that I admire you, not the least of which is the utmost responsibility you hold of treating your patients and always looking out for their wellbeing. Indeed, you speak about those patients who are sitting on your shoulder. That responsibility doesn't end with you treating them. You still carry the responsibility of those treatment failures, and that's what drives you to be able to, you know, delve further and bring some more answers. And indeed I've got to say bringing scientific validation to natural medicines.

I can't thank you enough. Our listeners, I'm sure, if ever they've read any chapters of any of the books, indeed your book itself, will know what a dedicated and caring professional you are. Thank you so much for joining us on FX Medicine today.
Leah: Thank you so much, Andrew. I really appreciate the opportunity. 
Andrew: This is FX Medicine. I'm Andrew Whitfield-Cook.

Additional Resources

Leah Hechtman
RACGP: Rotterdam Criteria for PCOS
NIH: Diagnostic Criteria for PCOS
Androgen Excess and PCOS Society
Prof. Robert Norman
Assoc. Prof. John Eden
The Textbook of Natural Medicine

Research explored in this episode

Hart R, Doherty D, Norman RJ, et al. Serum antimullerian hormone (AMH) levels are elevated in adolescent girls with polycystic ovaries and the polycystic ovarian syndrome (PCOS). Fertil Steril. 2010 Aug;94(3):1118-21

Monica D. Nye, Rebecca C. Fry, Cathrine Hoyo, et al. Investigating Epigenetic Effects of Prenatal Exposure to Toxic Metals in Newborns: Challenges and Benefits. Med Epigenet. 2014; 2(1): 53–59. 

Other podcasts with Leah include:


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