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PMDD: Debunked and demystified with Lisa Costa-Bir and Sandra Villella

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PMDD: Debunked and demystified with Lisa Costa-Bir and Sandra Villella

Join Naturopath Sandra Villela and our Ambassador Lisa Costa-Bir as they discuss and dispel some of the myths around Premenstrual Dysphoric Disorder (PMDD), a condition that affects and estimated three to eight percent of women. PMDD, both a gynaecological and mental health disorder is an under-recognised disorder that is riddled with misconceptions around the role of excess oestrogen.

Together, Sandra and Lisa discuss the latest research including PMDD sufferers' sensitivity to normal hormone fluctuations and the important role of progesterone the relationship with neuroactive steroids like pregnenolone, oestradiol, progesterone, and corticosteroids. The roles of allopregnanolone and serotonin in PMDD are discussed, as well as prescribing solutions including saffron, vitamin B6 (including dosages to prevent peripheral neuropathy) and vitex, and protocols to boost clinicians prescribing confidence. The conversation is rounded off by nutritional strategies and light therapy's serotonin-boosting potential shown to be beneficial for PMDD symptom management. 

Covered in this episode

[00:44] Welcoming Sandra Villella
[02:05] Prevalence and diagnosis criteria of PMDD
[05:34] Changing the naturopathic approaches to PMDD
[09:13] Hormones as neuroactive steroids
[13:48] Allopregnanolone
[16:37] Serotonin and saffron
[21:11] Calcium
[25:02] Vitex
[30:25] Surgical option: bilateral oophorectomy
[32:59] Mental health concerns for women with PMDD
[36:57] Considering a patient’s history of trauma
[39:04] Dietary recommendations and strategies
[42:02] Light therapy
[44:14] Summarising today’s key takeaways and thanking Sandra

Key takeaways 

  • PMDD is a gynaecological and mental health disorder that is often under recognised or misdiagnosed as PMS or bipolar however there is specific DSM-5 (Diagnostic and Statistical Manual of Mental Disorders) criteria to aid with differentiating PMDD from either syndrome or disease. Patients need to meet 5 of 11 symptom from criteria A of the DSM which helps differentiate PMDD from other conditions. 
  • The changes in levels of allopregnanolone, a metabolite of pregnenolone, during the luteal phase triggers PMDD. 
  • PMDD does not stem from oestrogen excess, but the condition arises due to altered interactions between steroid hormones and neurotransmitters – particularly GABA with allopregnanolone and oestrogen, with serotonin. 
  • Neuroactive steroids (pregnenolone, progesterone, oestradiol, and corticosteroids) produced in the endocrine system, not only act to regulate the menstrual cycle but can bind to various neurotransmitter receptors such as GABA where some women have an altered response to the fluctuations in neuroactive steroid binding leading to PMDD. 
    • Oestrogen clearance or progesterone (and derivatives of) excess can lead to detrimental outcomes. 
    • Focus on targeting neurotransmitter receptor responsiveness . 
  • Major stressors or trauma must be considered during case taking as this influences PMDD. There’s no need to delve into the details of a person's trauma, but knowing this helps guide the use of appropriate therapeutics like adaptogens. Refer where required. 
  • Saffron can be a useful acute herb especially if patients are already on an SSRI. It can also be used throughout the cycle. 
  • B6 is a first line nutrient (50-100mg/d) to consider for its role as a cofactor in neurotransmitter synthesis. Doses of 200mg/d should be carefully considered for risk of peripheral neuropathy. 
  • Calcium (500mg/day up to 1000mg/d) has been studied for effectiveness in PMS and depressive symptoms. Calcium levels also have a cyclical fashion that follows oestrogen which is a contributing factor to PMDD due to calcium’s relationship with neurotransmitters. Combined with B6 they are a powerful PMDD management tool. 
  • Vitex should be highly considered for its effect on the HPO axis and activity on oestrogen receptors. Best used as a standardised extract, as close to Day 1 of the cycle and dosed throughout with some symptoms to push through (cyclical mastalgia, headache) before considering non-use. 

Resources discussed and further

Website: Sandra Villella
Website: Jean Hailes
Clinical tool: DSM-5 Classification (American Psychiatric Association)
Guidelines: Royal College of Obstetricians and Gynaecologists 2017 guidelines - Management of premenstrual syndrome. (BJOG, 2017)
Research: 'The effect of bright light therapy on depression associated with premenstrual dysphoric disorder' (Am J Obstet Gynecol, 2005)
Research: 'Plasma melatonin circadian rhythms during the menstrual cycle and after light therapy in premenstrual dysphoric disorder and normal control subjects' (J Biol Rhythms, 1997)
Research: Effect of calcium on premenstrual syndrome: A double-blind randomized clinical trial (Obstet Gynecol Sci, 2017)


Lisa: Hi, I'm Lisa Costa-Bir, and welcome to fx Medicine where we bring you the latest in evidence-based integrative, functional, and complementary medicine. 

fx Medicine acknowledges the traditional custodians of country throughout Australia where we live and work and their connections to land, sea, and community. We pay our respects to the elders past and present and extend that respect to all Aboriginal and Torres Strait Islander peoples today. 

With us today is naturopath Sandra Villella. Sandra has been in practice for almost three decades and runs a busy practice in Melbourne. Sandra has a particular interest in women's health and is also a consultant naturopath and clinical leader for Jean Hailes Australia's leading women's health organisation, a position she has held since 1999. 

Welcome to fx Medicine, Sandra. Thank you so much for being here today.

Sandra: Thank you, Lisa, it's a real pleasure to be able to talk about something that I feel quite strongly about. And I know you and I have spoken about there's a bit of misinformation around this topic. So I'm really pleased to be sitting here and nutting it out with you.

Lisa: Oh, me too. And I've been counting down the days for us to have this chat. And really bring awareness to what premenstrual dysphoric disorder is all about. And I'm going to call it PMDD from now on, because it is a bit of a mouthful.

Sandra: Of course.

Lisa: So if we look at the stats, PMDD is incredibly prevalent. Three to 8% of women worldwide have it, including me. So I'm very excited to chat about it. But it's also very under-recognised. And because it's under-recognised, I feel like a lot of women go undiagnosed, or they’re misdiagnosed with bipolar or PMS. 

So maybe you could start by telling us what PMDD actually is, and differentiating between PMS and PMDD. Because they get lumped together a lot, even in the research. So tell us how they're different, I guess.
Sandra: I guess I have a bit of a biased approach, because I actually see so many women with PMDD. And I get lots of referrals, particularly from the GPs, at my work at Jean Hailes. And also the stats that you were talking about in terms of the percentage, if you look at what happens to women, you know, you think about that three to eight percent (3-8%) of women, roughly what it works out to be is one week per cycle, which they would experience about 8.6 years cumulative years of symptoms.

Lisa: Oh my gosh.

Sandra: And so that's really similar to what someone with recurrent major depressive disorder would experience across their lifetime. So it really does have quite an impact. And I see a little bit of emerging distinction between PMS and PMDD. But as most people would know, the PMDD does have a DSM-5 criteria. And so it's like has a psychological criteria. And there's four categories.

Lisa: That's right.

Sandra: And particularly the women need to have at least four of the section of number eight, which is kind of looking at a lot of the anxiety symptoms, you know, marked depressed, fever moods, marked anxiety, effective liability, persistent and marked anger. I'll just lists these and you can decide to keep them or not. Decreased interest in usual activities. And I think that's a key one. So work, school, friends, and hobbies.

Lisa: Yeah.

Sandra: And a subjective sense of difficulty in concentrating. Lethargy, easy fatigability, or marked lack of energy, marked change in appetite, overeating, or specific food cravings, hypersomnia, or insomnia. And a subjective sense of being overwhelmed or out of control. 

Other physical symptoms, you know, such as the breast tenderness, swelling, headaches, joint or muscle pain, and the sensation of bloating or weight gain. So they need to have at least five of those 11 symptoms. And then there's criterion B, and C. But I think the distinction is if the person feels like it significantly interferes with their ability to be social in terms of occupational and their interactions, their sexual interactions, their scholastic functioning. I think that's the big distinction.

Lisa: Yeah, I've had a partner say to me previously, "It's like a Jekyll and Hyde change. You're totally nice and normal and then you turn into this other person, and I've never seen anyone kind of flip so quickly."

Sandra: Yes.

Lisa: I've had patients say to me...like I've had a patient that constantly lost her job, because she just morphed into this other person after ovulation and was really difficult to deal with. So it's, you're completely right, it’s that really marked change.

Sandra: It might be it. And I think the thing to acknowledge about that is these people feel out of control.

Lisa: Yes. Definitely.

Sandra: It really means, they can't do anything about it. It feels really like something kind of takes over. And are going to talk about the understanding that, we going to get an understanding of why. And so yes, it is disruptive.

Lisa: Yeah, a lot of people feel like it's very overwhelming. It's like this there's a flip that gets switched. 

Okay, so you mentioned that it fits into that DSM-5 criteria. And I know that in 2022, it was also classified as a gynaecological disease. So we're seeing this kind of marrying between female repro and depressive disorders. How do we view this naturopathically?

Sandra: Well, I don't think we've done this very well in the past. And I think that's what I really like to highlight in this discussion, is that previously, we would I think, traditionally, and like for 30 years, we've kind of looked at this PMS as being an oestrogen dominance condition.

Lisa: Yes.

Sandra: And that is my real bugbear, I absolutely hate it. And I've done talks on trying to just try to debunk the myth.

Lisa: Yeah.

Sandra: But it is just worrying and what we know about the aetiology of PMDD, it's an interaction between the steroidal and you know, there's gonadal and neurotransmitters, so it fits in both. And then, look, in Melbourne, we have a whole unit at the Alfred where it's dedicated to mood and hormones. And so well, it is a gynaecological and really a mental health disorder as well.

Lisa: Yeah, I guess that's the real beauty, right, of what naturopathy does. I think sometimes we like to compartmentalise conditions into systems. But it's a really beautiful depiction of the synergy between systems and how one system always affects another.

Sandra: The beauty of it is as naturopaths, we have fantastic tools to be able to deal with this. But one of the things that I'm really keen to do and my understanding changed, after the new guidelines came out in 2017. And these 2017, there was these guidelines that came out from the Royal College of Obstetricians and Gynaecologists it's a great big, fat paper, but it talks about the new theories. And so I presented at the NHAA International Conference, I think, in 2019, or 20. And this has opened up a really good discussion, a lot of my colleagues who are really respected who do a lot of work with reproductive health and women's health. We had great conversations about this. You know, I know I was hoping to change the way we think about this. And I'm not saying I'm the full, or I'm the one who did it. But I know my colleagues in Melbourne kind of thought, "Okay, we need to look at this differently."

Lisa: Yeah.

Sandra: And we do have these great tools, but now it's how we look at it. So I think, rather than looking at the hormones, because all the research is showing, there are normal levels of hormones, all of the hormones. So oestrogen, progesterone, the metabolite of progesterone, which is really interesting, along with pregnenolone, which I'm sure we'll talk about.

Lisa: Definitely.

Sandra: All novel levels, whether you've got PMS, PMDD, or you're asymptomatic. It's the altered response and the sub-optimal response at the level of the neurotransmitters, particularly GABA, with the allopregnanolone, and progesterone, and the relationship between oestrogen and serotonin. And so I think that's the key thing. And so what we want to do is we target those we can do stuff with all of those, we can modulate these neurotransmitters. And one of the things I'd love to...I don't know whether anyone's looked at this, but I wonder whether there's some of the ways that our beautiful medicines work is it's working on the plasticity of those receptors to respond better.

Lisa: Yeah.

Sandra: Because when research has been done to look at altering the metabolism of these hormones, it doesn't make a difference.

Lisa: Yeah.

Sandra: So it's really looking at the level of the, you know, we've got great medicines to work at the level of these neurotransmitters.

Lisa: Definitely. So let's chat more about what you've said. Because we've from what I've understood is that it's not an excess of oestrogen, we don't need to clear excess oestrogen, our oestrogen isn't the ‘bad guy.’

Sandra: No.

Lisa: Progesterone isn't necessarily the ‘good guy’ that we want to increase because that can cause problems too.

Sandra: Yes.

Lisa: It's more that there's a sensitivity these women have a sensitivity to normal fluctuations that are occurring between the hormones and there's a flow on action to the neurotransmitters in the brain, particularly.

Sandra: You know, I actually find that's really difficult but sometimes it's... with my students, it’s a really difficult concept to understand. And I think the whole idea about oestrogen excess, as you know I hate it, I use a different terminology like oestrogen dependent. This is not oestrogen dependent or excessive condition.

Lisa: Absolutely.

Sandra: And so there are times when oestrogen clearance is highly appropriate if you're dealing with an oestrogen dependent condition like endometriosis or gynaecological cancers. But here, particularly if we do that, it can worsen symptoms. And if I give an example, particularly of a peri-menopausal woman, who already a bit more sensitivity to the decline in the oestrogen, now I am talking about a decline in oestrogen, that normal endogenous decline in their premenstrual phase with some of these women in their 40s will get PMS if we can just determine just classic PMDD. Because I really wanted to introduce this peri-menopausal PMS. They get these nights sweats, low mood, hot flushes, headaches in that phase, you go in and do oestrogen clearance, you are worsening their clinical outcome.

Lisa: Exactly. Yeah. A pet peeve of mine too.

So these hormones, in terms of how they work in the brain, they're actually called neuroactive steroids, right?

Sandra: Yes.

Lisa: I think a lot of the time when we're at uni, and a lot of the general public just think that the hormones are there to kind of give us a period and that's all they do.

Sandra: Yeah.

Lisa: But they were actually made in the brain from cholesterol, right?

Sandra: Yes.

Lisa: And that's in part how they work in terms of their behaviour and mood effects. And what we see in PMDD, there's receptors, right?

Sandra: Yes.

Lisa: For hormones.

Sandra: Yes, I love that you brought that up. There's neuroactive steroids, or NS we can call them. And they are, you know, they're producing endocrine tissue or brain and they interact with these neuron receptors, like GABA. And look, I don't claim to know the specifics of the different receptors, but it goes into the specifics of which GABA receptors. And then these neuroactive steroids are pregnenolone, progesterone, oestradiol, and also corticosteroids. And the interesting thing is progesterone and allopregnanolone, which is a metabolite, normally, they actually work to make you relax.

Lisa: Yeah.

Sandra: They modulate GABA. But somehow they have this paradoxical effect in women with PMDD. Or sometimes they talk about whether it's the drop that might be triggering it.
So the problem is, is we don't know. So if you come in and try and increase the progesterone metabolism, or increase progesterone levels, generally, and this woman is sensitive, then again, we could get the wrong outcome.

Lisa: Yeah, that's actually happened to me. I was actually prescribed pregnenolone and I literally cannot describe how bad it was. It was like a manic psychotic episode.

Sandra: Yes. Yes. Absolutely.

Lisa: I think it's really important to bring that up.

Sandra: Yeah, and there's two points that I'd like to make about that, like in terms of how we treat allopathic ally, but also if we look at the current theories of what this is, it's still it says, you know, if you look at PMS and PMDD, there is uncertainty around the aetiology, but it revolves around the ovarian hormone cycle. And the two theories are that some women are sensitive to progesterone and the progestins.

Now, again, if you're sensitive to these progestins, and endogenous progesterone, you get put on the pill, you’re going to be sensitive to those progestins. The newer generation progestins in the pill, you might be better at, and possibly progesterone, like in terms of the progesterone now that's prescribed as a body, identical, bioidentical, or body identical, you might get response. But it will often worsen if you're already sensitive, you could be sensitive to these exogenous as well.

Lisa: Yeah.

Sandra: And then the other one we talked about where there's this interaction, or responsiveness of the neurotransmitters, serotonin and GABA that are responsive to oestrogen, or the progesterone, or the allopregnanolone, respectively. So, these neuroactive steroid hormones are really working and changing the metabolism of those hormones isn't the way to go, but maybe working out how we can target the neurotransmitters particularly, and the receptors.

Lisa: Yeah. So you've mentioned allopregnanolone. And I think, again, we hear a lot about progesterone. We hear a lot about oestrogen, but we never hear about allopregnanolone.

Sandra: I know.

Lisa: And I came across it a couple, oh, maybe four or five years ago, not a couple and it was reading an Instagram post on allopregnanolone. That actually alerted to me to the fact that, "Okay, I think this is actually what's going on with me and this is why...

Sandra: Yeah.

Lisa: the standard basics in magnesium just is doing nothing." So can you tell us about allopregnanolone?

Sandra: Yeah, look, the more I read about it, the more I find it intriguing. So it's synthesised from progesterone, there's a couple of steps that do it. And there's some theory about women might be having a higher expression of one of the enzymes. But there's no direct evidence today that women with PMDD have any alteration in their enzymatic pathway from progesterone to allopregnanolone.

So, you know, traditionally, we might have wanted to improve progesterone. And certainly you want to think, "Oh, should we improve that pathway," because no evidence that it does? And so what the research looks at it's not likely the absolute level of this allopregnanolone. But certainly, it's very important, but changes in its levels across the luteal phase that trigger PMDD.

Lisa: Yeah, that's right. And so when the woman is sensitive, as you said, she's getting those symptoms off aggression, and anxiety, or depression. But I think something important to note is this isn't only happening in the luteal phase, right?

Sandra: Yes. Yes.

Lisa: If it's...

Sandra: And I think that's the distinction... when we talk about premenstrual syndrome, and PMDD it could be a lot of symptoms. But it's when it occurs, it's not how much or the level of urge, or the degree of it, it's the fact that it has to be in that luteal phase and should resolve within the first few days of the cycle.

Lisa: Yeah.

Sandra: Which if you've got. And that if we need to make that distinction because sometimes women are getting an exacerbation of an underlying condition.

Lisa: Yes.

Sandra: So if you've got anxiety all the time, you might get an exacerbation of this. But it's interesting, one of the things that I'm really interested in, and I don't think we have the answer to it seems to be these...plasticity of these GABA receptors, or their subunits in response to these neuroactive steroids. A fluctuation that may be the key aspect of PMD pathophysiology. And I don't think...at this time we've got limited animal research. And I wonder, and there will be people out there smarter than me, that might say that actually, some of the nutrients we're using, are actually working on that plasticity of the receptors.

Lisa: Yeah. Yeah.

Sandra: And I think that's still to come.

Lisa: Oh, I'm dying to talk more about that. But I'm just going store that away for one sec, and then come back to it.

Sandra: I can kind of expand on that [inaudible 00:17:28] in you know, in 10 years time, we might know more about it.

Lisa: So we've talked about allopregnanolone. And really it is the main kind of metabolite that is involved with PMDD. But so is serotonin right?

Sandra: Yes.

Lisa: We know that women are often prescribed SSRIs for management of PMDD. And they're one of the first line treatments, but what's going on with serotonin and PMDD?

Sandra: Well, that's interesting. So the serotonin oestrogen relationship is more distinct.

Lisa: Yeah.

Sandra: And I was just reading before trying to get my understanding around how the SSRIs work, and some work better than others.

Lisa: Yes.

Sandra: And certainly in the guidelines, they give specifics in terms of and when we talk about the allopathic interventions. And I think then they talk about how maybe they then have an impact on GABA, because the serotonin we always think about is the happy hormone, and I kind of focus on that one a lot more and target that serotonin sparing, particularly with the low mood...

Lisa: Yeah.

Sandra: ...that will occur with that. And that you do an endogenous drop, a normal endogenous drop of oestrogen just beforehand, and that's often the low mood is just prior to period. Do you notice that like, you know, you get all that the agitation...

Lisa: Yes. Definitely.

Sandra: ...and immediately you're on the mood.

Lisa: But I see it. A lot of my patients say to me, it's literally...they feel amazing at ovulation and it's literally...

Sandra: Yeah.

Lisa: ...straight after that drop in oestrogen that they notice...

Sandra: Yes.

Lisa: Oh, oh, now it started then it kind of levels out, and then again, at a second drop in the mid-luteal things really kind of they run into problems. Yeah.

Sandra: And again, we don't want our practitioners to work on the oestrogen levels there.

Lisa: No.

Sandra: Although, you know, in terms...but again it's how it then has this conversation with serotonin. Professor Jayashri Kulkarni, who heads up MAPrc at the Alfred, she's got great stuff about how oestrogen works on serotonin and, you know, I think also we dem... as naturopaths traditionally we demonise oestrogen. Oestrogen rocks, you know?

Lisa: Yeah.

Sandra: It does have an impact on our brain. So I'm really interested in some of the serotonin-sparing herbs for PMS and my key one, and I know you like this one too, is if we can bring in any saffron.

Lisa: I love it.

Sandra: And I do tend to use that more than then I do with St. John's Wort and because often a lot of the people I'm seeing are already on an SSRI. And so saffron you can use but you can't use St. John's Wort. So the SSRI give them some relief, but not complete relief.

Lisa: Yeah, I think it's something like 40% of women don't respond to SSRIs. I mean, and that's a huge percentage that do obviously but sometimes. Yeah, there's a whole lot more we can do. Yeah, I love saffron. So it sounds like you do that throughout the cycle?

Sandra: Yeah, I do. Look, it's interesting. When you at the allopathic treatment, they sometimes just use cyclical SSRIs. And then if it's not... that doesn't improve, then I'll use it, I'll increase the dose orI'll use it throughout the whole cycle.

Lisa: Yeah.

Sandra: But I tend to use if I'm...I'm just thinking about what I would use, I would often use saffron throughout the cycle. But given that the SSRIs might work, but that they just work in that luteal phase. And I don't know the pharmacokinetics of how quickly the saffron works.

Lisa: Yeah, I found that literally I could just do it in one shot. And I will notice a difference straightaway. Yeah, so I think it's working pretty quickly.

Sandra: Yes.

Lisa: But I mean, I'm lucky when I'm doing the liquids, my patients get it throughout the month.

Sandra: Yes, yes, I do. Look, sometimes I will alter, I will alter the dose. If we look at the guidelines, it's one of the things about the guidelines that I talk about, and I'll put a reference in is I had about two or three pages. Now this is back in 2017, of the research of the nature of the complementary medicines and therapies. So it actually gave a literature review. And some of them were kind of a bit novel. But in the guidelines, in that first line of intervention, basics is talked about as first line. So it says exercise, cognitive behavioural therapy basics. And interestingly, arguably, there's insufficient evidence about what basics does, but we know as practitioners, how might it work? You know, it has a role to play in the synthesis of GABA and serotonin, it tends to be a precursor for those. And it's kind of like we have to be careful with the doses. That's too much...

Lisa: What sort of dose do you tend to do?

Sandra: Yeah, really interesting. So I kind of look at levels between a baseline 50 to 100. And never any more than 200 because there are cases of peripheral neuropathy. And I might increase it in that luteal phase, but no more than 200.

What sort of doses are you using with B6?

Lisa: Well, I don't use B6.

Sandra: At all?

Lisa: No. I feel like I only use calcium... is my number one.

Sandra: I love to talk about that. Yeah.

Lisa: Yeah. And yeah, I feel like my patients have really tried magnesium. And that's not to say it hasn't helped but it just hasn't been enough. So I use calcium, magnesium, [vitamin] D. And I feel like calcium is the VIP when it comes to PMDD, does it work so well?

Sandra: Do you know what? I'm like yes. And interestingly, naturopaths love magnesium, there's limited evidence for like clinic limited scientific evidence of magnesium. But clinically, I feel like it works. But in fact, arguably one of the best levels of evidence we have for the management of PMS and PMDD is calcium.

Lisa: Yeah.

Sandra: So originally in 2009 when they came in, it's really high doses, 500 milligrams BD of calcium carbonate, so we're not going to use calcium carbonate, we'll use beta-forms. And then later on, there was a study looking at 500 milligrams daily reduced PMS, and one of the things particularly it was the depression.

Lisa: Yes.

Sandra: That was useful. And so I think a lot of naturopaths forget about calcium.

Lisa: Yeah.

Sandra: And so I do the use of both together.

Lisa: Yeah, I found some really interesting research with calcium. And you might already know this, but I was shocked that calcium follows a similar pattern to oestrogen in the body. So when...

Sandra: Oh.

Lisa: Yeah, so women with PMDD show these alterations in cyclical calcium homeostasis, and it's because they're so sensitive. What we know oestrogen kind of modulates calcium anyway in the body. And so when...

Sandra: Yes.

Lisa: ...oestrogen withdraws, we see a drop in calcium as well. So calcium is responsible for essentially neurotransmission and release of monoamines, like serotonin and dopamine.

Sandra: Oh, yes. Oh.

Lisa: So when we have this dysregulation of calcium in the luteal phase, basically those calcium channel gates don't open properly. And we see this neuronal dysfunction and this probably, I don't know if it's no release, but impaired release of serotonin and dopamine.

Sandra: Oh, that's fantastic.

Lisa: Yeah. Which drives a lot of this mood stuff.

Sandra: Yeah, and I think it's really hard to find evidence on RBC you have with calcium, and I think I searched and searched. And I've often said, "Look, I don't know why it works." And I think I found something. Some reference to how it might have been working with schizophrenia like this is one line.

Lisa: Yes. Yeah.

Sandra: But yes, it is. I think it's under-utilised in this area...

Lisa: Yeah.

Sandra: And probably has yet one of the best levels of evidence.

Lisa: Yeah. And then if you look at the signs of low calcium, the mood deficiency symptoms, it's actually mania, irritability, hostility...

Sandra: Oh, yes.

Lisa: ...aggression, which is very similar to the PMDD.

Sandra: Yes.

Lisa: So I think, probably like a lot of women in their menstrual cycle, I feel really good in that follicular phase, and I don't take any of my supplements, and then...

Sandra: Yes.

Lisa: I go. "Oh, oh, I'm starting to..." that person chewing next to me is really irritating me. I can hear that person breathing, and I'm filled with rage. And as soon as I take the calcium, everything feels calmer. It's still that those feelings are still there. But instead of them being an 11, out of 10, there might be like a 3 or 4 out of 10. They're not as...

Sandra: That's great.

Lisa: ...overwhelming and unmanageable.

Sandra: I really appreciate you sharing your experience too. And I think the listeners will benefit from it having, as from a practitioner point of view, and from a patient point of view. But look and also, how many of your patients do you feel like you're getting adequate calcium in their diet?

Lisa: Oh, I mean, hardly any.

Sandra: How many out there?

Lisa: Yeah, this is the thing. Yeah.

Sandra: Yeah. Particularly with you know, sort of any sort of dairy exclusion, I know dairy is not the only answer, or certainly with diets that have gotten exclusions, it's quite difficult to achieve.

Lisa: Yeah. So do you have any other favourite supplements?

Sandra: Yes. So, I’d love to talk about Vitex.

Lisa: I actually said to you, “Would you like to about Vitex?”

Sandra: I know. Look, I'm one of these practitioners, so many students and practitioners are scared of Vitex. I'm not. And, first of all, I really don't think we know how it works.

Lisa: Yeah, I was going say, how does it work?

Sandra: But we do have the evidence that it works.

Lisa: Okay.

Sandra: Standardised extracts of Vitex agnus-castus do work. And I think as naturopaths we think that it has something to do with the hypothalamic-pituitary-ovarian axis, but it is also working on oestrogen receptors, it probably has a direct action on oestrogen. I think the thing that I'd like to tap into a bit more and I don't claim to understand is because it works on dopamine., somehow that maybe how it's working for the mood aspects.

Lisa: Interesting. Because I feel like there's a real art to prescribing Vitex. And tell us more.

Sandra: Well, you know what? I think I'm just gung-ho with it, like I just think you know what happens is sometimes I'm not using it and do all the neurotransmitter stuff and use the nervines and the B6 and magnesium, calcium and then I think “Do you know what? I really need to use some vitex with this patient.” And it works...

Lisa: Have you ever had a patient where it makes... I guess where I'm worried is I've taken it and I just felt terrible, worse mood. So now I'm always cautious. I'm scared. But have you ever had a patient where you've given it and you've gone "Oh, oh," or they've come back and said, "Oh, I felt terrible?"

Sandra: Oh, that's interesting. Usually no. And like I've got really trusted colleagues, who have got all these rules about using it and don’t use it without testing. I'm not a big tester. I don't do lots of testing. I don't feel like you need to have any. And certainly because we know that hormone levels aren't relevant with this anyway. I usually warn people, I'll say to patients, "We need to do this for three months."

Lisa: Yeah.

Sandra: And I always say for some reason, the first period is often more painful if they do have dysmenorrhea. I don't know why. And sometimes in that first month, there's a worsening of cyclical mastalgia. And I just say, "Hang in there," and there's a small handful of people who will get headaches and I like usually ask them to persist because it usually goes away. And there's probably a minority of other people that I won't continue Vitex with. So it's funny, I've got this thing, you know, “to Vitex or not to Vitex? And other things you know. And there's very few times that I wouldn't use Vitex, but it's not always my go to, but I've used it for years, you know, 30 years, and I still don't think we know how it definitely works.

Lisa: Yeah, that's right. I love that you were talking about that it may work on oestrogen receptors, because I've never heard that. And we always just hear that it's, well, we know that it helps to decrease prolactin...

Sandra: Yes.

Lisa: We know that it can increase LH but a lot of people kind of say it's progesteronegenic, and I think that's because of what it does with prolactin. But I've never heard about that oestrogen aspect before.

Sandra: No. And like I kind of ignore that a little bit. Because we always think that what does it do? Is it I think what it will do is we'll facilitate or help with ovulation. And we know that with our fertility patients that has an impact on doing that.

Lisa: Yeah.

Sandra: And so it's also good for the peri-menopausal, premenstrual woman who might have irregular cycles. But I think the other thing is, is some really dumb things out there about how people use it only, you know, only the cyclical phase… traditionally every day.

Lisa: Yeah.

Sandra: If you're starting it in the luteal phase, you've missed it, because it's got to work on that ovarian follicle development, that follicular phase. But I think it has a use, it's not always the way to go. And of course, you can't use it if someone's already on an oral contraceptive pill.

Lisa: Okay, so if you were going to give Vitex you would give it all month.

Sandra: All month.

Lisa: And do you suggest starting it on day one of the cycle?

Sandra: Always. Yeah, quite as close to day one, if you've got someone who's a bit oligomenorrhea, you know, just kind of risk and say look, "It might mean that the period comes earlier or later." But yes, I do day one. And the other thing is I think particularly young practitioners or you know, early out, they'll think that they only need to take it for three to six months, and that's it. A lot of people just need to be on it for a long time. Years.

Lisa: Wow. Okay. Yes.

Sandra: So I'm not scared of doing that. Usually the first 17 years of my practice, I worked with Ruth Trickey, and she used to say, "Generally there's little sign if you've been on it for too long, the cycle starts to get longer, it stretches out and then you can have a little break." I've got another colleague who stops it for a few months and then starts back on. I just, unless there's a reason to stop it, I just keep going.

Lisa: Yeah, and to be honest, I think with conditions like these, I don't know if PMDD kind of ever completely goes away. Do you know what I mean?

Sandra: Yes.

Lisa: Until you maybe like menopausal, so it's more about...

Sandra: It's a really good point.

Lisa: ...just continuous use to really minimise symptoms and make everything more bearable, but it's very unusual for me and my experience for it to completely go away.

Sandra: It's fine.

Lisa: Yeah.

Sandra: It's a management strategy, an ongoing management strategy. And really, unless you have an oophorectomy and/or until menopause. And then of course, you might... the women with PMDD are more likely, unfortunately, to have low mood at menopause.

Lisa: Oh, no.

Sandra: Yes. But we don't know, because there's no way of predicting.

Lisa: Can we go to what you were just talking about before about the partial hysterectomy because I'm on a Facebook group for women with PMDD.

Sandra: Yes.

Lisa: And because I feel like generally, my symptoms are quite well managed, like now definitely with what we do naturopathically. I am always very shocked to see some of the posts that are being written and you've got young women, that are really struggling and I'll talk about that in a sec. But there are some women that are opting to have a partial hysterectomy because their mood symptoms are so bad. So can you run us through some of the allopathic...

Sandra: Yes, I can. Look, it's in the guidelines, it's the fourth line of intervention where you've got this surgical treatment, so it's an oophorectomy, a bilateral oophorectomy. I think the uterus is usually left. Because that's where it's coming from, the ovaries. It's not the uterus. 

And I've had one patient who had that done last year and she was on medication, and she was knocking at the door of menopause and was kind like, you know, "Can you hang in there?" and she opted for that, and it has made a difference. But of course, now she's got menopausal symptoms, but they are far more manageable.

Lisa: Yeah.

Sandra: Yes, so it does. It's concerning that on that Facebook page, there are young sufferers of PMDD opting for that, because there is so many things that can be done before that.

Lisa: Yeah. I find all the things naturopaths and holistic nutritionists recommend extremely helpful. But I do know, in some other countries, they do offer allopregnanolone blockers.

Sandra: Yes.

Lisa: And which I find really interesting, because the research suggests that reduces mood symptoms by sometimes up to 75%.

Sandra: Oh, they're usually blocking the allopregnanolone.

Lisa: Yeah, they don't offer that here.

Sandra: Oh.

Lisa: Yeah, but they don't have those meds here, but I kind of thought that was really interesting. Yeah.

Sandra: Look, the third line of treatment, they use it the GnRH analogs, so they basically put you into a biochemical menopause. And then they do a bit of add-back hormone therapy, so they'll use like oestradiol and progesterone. So they'll use like an oestradiol patch, so body identical oestradiol, and then they'll use a gel, and then they'll use the micronised progesterone. 

But again, look, if you're sensitive to these hormonal changes...

Lisa: That's what I was thinking.

Sandra: ...you are going to be sensitive to the exogenous as well. But you know, to those people, I would say, at least before you have a surgery, try what it's like at a biochemical level, like at least go on the Zoladex, or whatever it is to see...

Lisa: Yeah.

Sandra: ...if you starved those oestrogen hormones.

Lisa: Yeah.

Sandra: It's pretty extreme.

Lisa: Yeah, it is. I want to just run back on something you were talking about before, and that is your patient that had had, you know, some pretty severe depression, it would seem. And definitely when a lot of my clients come to see me there, the main kind of driver for them coming is that they're experiencing these extremes in mood and they've sometimes got small children and partners. And there's this real shame and self-loathing that comes with their behaviour, and the way that they behave towards their loved ones, but also just this very strong depression. And we know from the research, the menstrual cycle has been found to be a trigger, increasing risk of suicide in women who are more hormone sensitive, meta analysis shows this.

And in the last, I think, couple of years, there's been at least three meta analyses that show that women with PMDD should be considered a high-risk group for suicidality. In fact, I think in one survey was like 30% of women had reported attempts to end their own life. 

So do you think then, as practitioners, we really, we should be doing DASS and working in line with a psychologist or is that something you... I mean, I know, you do...

Sandra: That's a really good question. Look, I'm quite privileged, most of the patients I'm seeing are co-managed by a GP, usually at Jean Hailes, we share patients, so we can actually share the files. Certainly most people will definitely be encouraging to see a psychologist for cognitive behavioural therapy, and I know you want to talk a bit about trauma or whether it's trauma-based therapy.

Lisa: I do. Yeah.

Sandra: And I think the idea of some sort of prom so we can go look at what's happening even with you know, the old menstrual cycle, or using an app that looks at what's happening. And the idea of the DASS. Yes, I guess to differentiate between if it is cyclically or is it generalised anxiety disorder? Is this person a depression risk?

Lisa: Yeah. I often find, yeah, that I've been referred like the patient's been seeing a psychologist and it's a psychologist that's actually picked up.

Sandra: Yes. Yes. Absolutely.

Lisa: "Hey, this is a cyclical thing. Let's see, a referral to the naturopath, there's some assistance there." But some patients yeah, they've heard a podcast or something like that, and they're not under the care of a psychologist and I just find that working together with one we just get so much better results. You know?

Sandra: Yes. Look, you raised the point about you know, listening to a podcast and unfortunately there is a lot of misinformation, and I have a real bugbear with when patients come in and they're taking hormone-balancing formulations that they've got from the internet, and it's kind of a one size fits all, put everything all in together. And some things might be okay, but it cannot hormone balance. It's not about that.

So I had a patient who had gone on, because they think it's an oestrogen excess, and gone on those formulas that really deplete oestrogen and just have really bad symptoms.

Lisa: Yeah.

Sandra: So I think we're privileged to work with these patients. And you've really again, like we are naturopaths. It's individualised care.

Lisa: Yes.

Sandra: And I think it also brings in the other thing that we think about naturopathically, we've talked a lot about this hypothalamic-pituitary-ovarian axis, but the HPA axis, we do know that, certainly, if these GABA receptors fail to respond appropriately to these fluctuating allopregnanolone. You've got over across the menstrual cycle, it follows that these GABA receptors exert poor control over the HPA axis in PMDD, as well.

Lisa: That's right.

Sandra: So there's this overlap. So it might be that the poor GABA regulation of the HPA Axis may be reflected in this increased stress sensitivity in women with PMDD. So in that luteal phase, of course, we've got to look at everything else, what's happening in their life? Are they having a poor diet? Are they really stressed?

Lisa: Yeah.

Sandra: So it's not just working on those, of course, we're going to be using our adaptogens. And...

Lisa: My favourite. Yeah, so going back to... I mean, I feel like the adaptogens are really king here and they really make a difference.

Sandra: Yes.

Lisa: And, as you've said, women with PMDD experience this heightened stress reactivity and the week or two before their period, things that wouldn't normally stress them out, they have this amplified reaction to it. And I think that's to do with the allopregnanolone because normally, apparently, it helps with stress modulation, but it's not doing what it's supposed to. So it's not making us feel sedate and relaxed, it's doing the opposite.

So coming back to that trauma, I find it really, really interesting with a lot of my patients is that there is a trauma history. And I know trauma is kind of a buzzword at the moment and it's overused and misused a lot. But the research does show that women with PMDD often - not always - but there is often a history of trauma, and more so than women without. And I think that's an important consideration for practitioners to remember to be asking, “Have you experienced any big stressors in life?” And again, it's coming back to that HPT, HPO, HPA axis. Yeah.

Sandra: And Lisa, I love that you use the words, have you experienced any big stresses, because even talking about trauma, you know, we have to have that trauma-informed way of speaking. And I think the other thing is that we need to be respectful. It is not necessarily asking the patient to recount the trauma. You know, I have long-standing patients who might have had PTSD, Post Traumatic Stress Disorder, way back before it was more common. And to this day, I don't know what the cause of that was, because I don't need to know. I just need to know how it impacts the patient. And then I can do something about it.

Lisa: Exactly.

Sandra: She doesn't have to rehash that trauma, she can do that in a safe place. And that might be with you, or it might be with another practitioner, or it might be with her psychologist, but it's really important that yes, we ask if there's been big stressors. And how it impacts them. And that will help the way I think we shape our treatment.

Lisa: Absolutely. Because I think sometimes practitioners feel like "I don't know how to deal with that, if they do say something,” and then it is about staying within our scope, but also completely being aware that these things do impact the client's presenting complaint.

Okay. So what about diet? Do you do anything special there?

Sandra: Yeah, look, first line of naturopathic therapeutic therapeutic order: institute a more healthful regime, like, you know, remove the obstacles to cure. There's a lot of people not eating well.

Look, in terms of research, one of the things that's clear is alcohol any more than one standard drink a day is considered an increased risk. Interestingly, coffee, even up to I think three cor four cups of coffee a day has not been shown to have any impact, but I don’t…

Lisa: Oh, great. I love it.

Sandra: I know. But I sort of still think, you know, from a naturopathic point of view, what's it doing to the nervous system? And look, I think in moderation, I do like coffee, and I'm not an anti-coffee, but I think if we are having three coffees or four coffees a day and not eating well.

Lisa: Definitely.

Sandra: But in terms of diet, you know, I kind of look at it and I'd be interested in your comments about making sure they've got the right macro-nutrients, particularly protein, and adequate amounts of carbohydrate, you know, good carbohydrates. And the carbohydrate picture is, interestingly there seems to be... there's a big nurses study done on quite a lot of women that didn't seem to have any impact on carbohydrates, but you know, low carbs, high carbs, I think you certainly want to be getting rid of the refined carbohydrates. But often there's room for movement with diet. Absolutely.

Lisa: I often find women are skimping a little bit on the carbohydrates and whole-food carbohydrates are something I really recommend to my patients in their luteal phase. Because I find that often because they're getting these wild cravings, and I think that's in part due to that withdrawal of serotonin which can help to kind of govern satiety, when they feel like they're getting the cravings that like "I can't eat," and so they deprive and then then they binge.

Sandra: Yes.

Lisa: I think if, you know, they just focus on just eating normally, which I know is hard sometimes, then everything is going to be a lot better. I also feel like something I recommend a lot is just prepping a lot more in the follicular phase, so that you have food ready for that luteal phase, when you know you're just not going to be motivated, the energy's going to be lower. So then if you've got the food in the freezer or the fridge, you're less likely to be calling for the Uber Eats and the DoorDash.

Sandra: And that's in line with, you know, first line of intervention should be planning. So you know, planning that sort of thing. And also planning like, you know, you're not going to host family Christmas of 50 people that happens to be in your premenstrual phase. No.

Lisa: Yes.

Sandra: Give it to the sister-in-law this year. You know, it's kind of like, planning is really important. And I think some people are in really high-powered jobs. And I always say, if you're the CEO of this company don't have your board meeting scheduled at that time. The planning is really important.

Lisa: Yeah. 

Sandra: It’s interesting about that carbohydrates prime instantly that you said, you know, like if you usually have a canned fish and salad at lunchtime, throw in some brown rice or red rice or some sweet potato.

Lisa: Potatoes.

Sandra: Good healthy carbohydrates. So then you're not raiding the biscuit barrel...

Lisa: Yeah, absolutely.

Sandra: ...in about two hours later.

Lisa: Okay, last question for you. What about light therapy?

Sandra: Yes, I've haven't heard about one, Lisa.

Lisa: Okay, I'm really big on it, it is one of my favourite recommendations for everyone, but especially for women with PMDD. So there's been a couple of very small studies where they expose women to light and essentially this could be natural light, there would be nothing wrong with, I usually say, "Go to the beach "or "Just go outside on your verandah and get some natural light." It's better early in the morning. But when light hits our eye, it actually transmits to the brain and we get a release of serotonin. So what they've done in these clinical trials is they've given women a light, a light that emits a specific frequency of the light. And so they're exposed to the bright light and this actually increases their serotonin. And they've only done this in the luteal phase in women with PMDD, but they experienced an improvement in their mood. So we know generally, light therapy helps with just regular old depression and seasonal depression.

Sandra: Yes.

Lisa: So they found that the same thing is great for women with PMDD. So natural light therapy is something I recommend to all my patients, because, I mean, it's good for everyone, but especially good for anyone with a mood disorder.

Sandra: Absolutely. And I like that, you know, sometimes I feel like I'm quite, you know, when we talk so technically and whatnot about all of these, it's really important to think about naturopathic principles where, you know, basically get into nature, with you know, level two, in terms of stimulating that healing process, and how do we do that? Get into nature. 

And I love that there's more of this awareness of these kinds of green psychology. And so, that's an interesting point. I wonder then, Lisa, if there seems to be a worsening of the PMDD in winter compared to...?

Lisa: Yeah, I think so. I do know that plasma melatonin has been shown to be delayed in the luteal phase of women with PMDD. So if we think about that serotonin-melatonin kind of relationship, and it's probably something to do with that too, but I definitely find I can speak for myself here, definitely worse mood and motivation in winter than in summer.

Sandra: Yes. Interesting. That's a good one.

Lisa: Well, thank you so much. I've learned so much and I'm sure our listeners have just gotten so many gems from you. Key points today that I've taken away are probably the big one is good old Vitex. I'm going give it a second chance.

Sandra: I just scared you.

Lisa: I'm going to see how I go and report back to you vitex for management of PMDD symptoms, giving it first thing in the morning and all through the cycle. 

The second one I really have to highlight is both our favourites is the calcium and dosage between 500 to 1000. Also, do you do that throughout the cycle or just luteal phase?

Sandra: I do it throughout the cycle.

Lisa: Okay.

Sandra: And I keep it more to the 500 and especially as they get older because unfortunately, they talk about higher doses in susceptible women might be increasing the risk of cardiovascular disease, but I think in our '20s and '30s, we're okay with those higher doses.

Lisa: Yeah. Fantastic. So calcium, game changer, I think for a lot of women with PMDD. And then I think the big thing is just re-emphasising that oestrogen is not the bad guy. And not at all. And it's very, very important for everyone, but especially when with PMDD and we don't want to clear it out. It's more that PMDD has to do with that…

Sandra: Yes. Lots of it. The abnormal...

Lisa: …abnormal reaction to the fluctuations in hormones, and that flow actually to the neurotransmitters

Sandra: And I know you've just done a summary but we really need to say that because we're working at GABA, how many beautiful herbs we got that modulate GABA?

Lisa: Yes.

Sandra: That is going to be really important for that agitation and irritation.

Lisa: Yeah, chamomile.

Sandra: You know, we've got documentation that, you know, Melissa, Withania, and Melissa has had some trialling done on it, but your favourite GABA modulating herbs for that agitation, irritation, and, you know, anger kind of symptoms are really important too.

Lisa: Ah, so many gems. Thank you.

Sandra: So many gems. Oh, it's been lovely. I look forward to part two of this, Lisa.

Lisa: Yes, definitely. Definitely, Sandra. Thank you.

Sandra: All right. My pleasure. Thank you very much for sharing your knowledge too. It's been great.

Lisa: Oh, thanks. 

Thank you, everyone for listening today. Don't forget, you can find all our show notes, transcripts, and other resources from today's episode on the fx Medicine website. I'm Lisa Costa-Bir and thanks for joining us. We'll see you next time.


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