Speaker 1Hello and welcome. My name is Dr. Ashley Broomfield and this is the GP Show. Thank you for joining me today for a discussion about the work that we do and the people that we care for. Before we begin, I would like to acknowledge the traditional owners of the lands from which I am podcasting from, the Goombangia people, and pay my deepest respects to their elders past, present and emerging. I would like to acknowledge their continuing connection to land, sea and sky and pay particular homage to the work that the community is doing to revive and restore Goombangia language, culture and wisdom in these lands. Today's guest is Professor Jayashree Kulkarni, one of Australia's leading psychiatrists and researchers specialising in women's mental health. She's the Director of the Monash Alfred Psychiatry Research Centre and Professor of Psychiatry, at Monash University. Professor Kulkarni's work focuses on mood disorders across the female lifespan, with particular attention to the role of hormonal changes in conditions such as perimenopausal depression and premenstrual dysphoric disorder. Her research has contributed to a growing body of evidence examining how biological, psychological and social factors intersect in women's health. This conversation today was recorded together with our recent episode on perimenopause. episode on perimenopause as part of the same sitting with Professor Kulkarni. So it flows As part of the program, we're going to be talking about the role of women in menopause. on directly from that one and I'd really recommend going back and listening to it first if you haven't already as it's kind of like a pre-listening requisite. Today we're narrowing in on the premenstrual dysphoric disorder, PMDD, what actually distinguishes it from common premenstrual syndromes, and the emerging research of influence of trauma on gene expression as well as an approach to treatment. Professor Kulkarni's focus in both conversations is on the underlying hormonal mechanism and why, in her opinion, hormonal treatment is important consideration in management. This is a slightly shorter conversation than usual, so let's get into it. we're talking about this idea that during a woman's life when there's changes in the cyclical hormones that there's an impact on the brain and for some women presenting to our practice that impact is quite significant and so we have these periods of time we spoke about in our last episode the perimenopause postnatal and then also just in general if someone's got a natural cycle in their cycling that there could be a premenstrual dysphoric disorder happening how is PMDD different to the changes that some women might experience throughout their cycle
Speaker 2so um it's a confusing area because there's all these different terminologies there's pms and there's pme it's a premenstrual syndrome premenstrual syndrome usually refers to the physical symptoms that many many women experience related to the day before or of the day of the means first day of menstruation and usually it's the bloating headaches just feeling a bit yuck in terms of crankiness and so on it's mild i mean i'm not i'm not diminishing that it's it's not good um but it usually isn't life-altering and that's pms and it does affect about 80 percent of reproductive age women. This is the hot water bottle and chocolate craving, you know, and some analgesia for dysmenorrhea in the first couple of days. That's PMS. That's not what I see. So I'm seeing women with PMDD, premenstrual dysphoric disorder, and it's a major depression so again you know I always find it annoying that terms used to describe women's pain are sort of demeaningly less so dysphoria dysphoria is just this mild sadness when your football team loses it's not descriptive of this major depression that occurs for some women and again the percentages of women who experience it depends on what you read some of the figures say it's between 12 and 15 percent and other of the reproductive age population other studies say it's only three or five percent so who knows but there is no doubt that there is a subsection of women who are in their reproductive phase of life who every so often cyclically develop a full-on tearfulness rage can be brain fog some anxiety and panic exactly what i described for menopause but it comes on for it comes on suddenly and it offsets suddenly as well usually with bleeding but it doesn't necessarily have to coincide with that textbook picture of the 28 day cycle and ovulation at day 14 of which i've only ever seen you know a handful of women
Speaker 1yeah yeah and and often in in in some of this population there is a bit of a regularity in in the cycle as well so and you
Speaker 2throw in if the woman is on some um psychotropic then already she's got uh aberrations in the cycle as well so what i look for is the sudden onset and so many times women say oh this happens to me every two months or it happens every three weeks or you know like it doesn't have to be the 28 day thing um and you look for the sudden onset for those symptoms uh that come on and that also then get better um but when you look at it stand back and look at it this is still at least a week to 10 days maybe out of every four weeks or five weeks or six weeks for the whole reproductive time which is from possibly from age 15 right through to age 45 that's a lot of time that she's spending struggling and suffering and feeling dreadful and possibly not functioning
Speaker 1yeah well it's it's roughly about 30 to 40 percent of the time isn't it yep so it's not persistent that's sort of the difference it's not persistent over time it's very clearly on and off and as you said in our previous discussion could potentially be misdiagnosed as a as a bipolar affective disorder or that sort of cyclical mood change
Speaker 2yeah or worse she's putting it on um you know there's that that sort of comment is is not unusual so the invalidation that many women describe um is unfortunate but it does happen so um the other thing that's really important here with pmdd to understand is that um dubay d-u-b-e-y and colleagues in 2021 have done work isolating a pmdd gene so the gene is an estrogen modulating gene it's called the e2 esc comb of zest gene fabulous name and um this gene is apparently present in about 50% of women, all women, but it obviously is not expressed in a large percentage of women. So the question was, why is it expressed in some? And it's trauma that makes the expression of this gene. So many times I've seen women who did not have PMDD when they became when they menstruated from menarche onwards but they develop pmdd after they had a rough child birth that was the trauma the trauma of childbirth and then bang after they've stopped breastfeeding and all the rest of it and the cycle re-establishes they have this pmdd um so it's it's again tied up with there is a genetic finding but it may not be expressed uh does it's not expressed in in a lot of women so there's protective factors and then there are the other factors that make it um that make the pmdd establish as a condition it's interesting
Speaker 1as you you say that because it's something that i noticed in in clinical practice for a certain proportion of people who are experiencing significant postnatal anxiety or postnatal depression was that there was something about the birth process or nurturing their newborn that sort of brought up the memories of what had happened to them in early lives or experiences in early lives that prior to the onset of those particular changes was less apparent to them at the time and then led to having more awareness and an impact on them in their lives I'm not sure if that's part of what you're describing there or not
Speaker 2I'm sure it is the but again i would say we can view things through a biopsychosocial lens and often that what you've described is the is the psychology of um the childbirth and what's happened for her uh any abandonment stuff that's happened will come back again but there is another biology aspect of it which is you know post natally especially if she's breastfeeding the cns estradiol levels are dropping because prolactin is an antagonist for estrogen and so that's why she's not menstruating when she's breastfeeding and so on and so on but we know from the neuroscience discoveries that in fact estradiol is a neuroprotective steroid so if you lose the levels of neuroprotection then repressed issues may come back up whereas before you kind of used the hormonal ones as a weighted blanket on those memories and uh that allowed you to function so many times people have hypothesized about you know the the role of of these hormones in the brain that as a species we're meant to reproduce because otherwise the species dies out and so there's a priority to reproduce so maybe in order to get on with it finding a mate reproducing is a biological drive and so there's a priority to reproduce so maybe in order to get on with it finding a mate reproducing the estrogen neuroprotection kicks in to enable that this is all very speculative yeah yeah we're
Speaker 1in we're in an evidence-free zone here in this discussion army yeah this sort of but the
Speaker 2prolactin antagonism in terms of breastfeeding we know is a thing because yeah in the hypoestrogenic state the hypoestrogenic state so you see that when women drop the night feeds for example that that all of a sudden feel better um and especially the women who are breastfeeding who have said i had brain fog and then when i start to have periods wow i'm back i can think um so there's a whole way again evidence of what is going on in the brain with these particular uh neurosteroids the hormones so
Speaker 1with pmdd how is that different or similar to managing someone in the perimenopause yeah
Speaker 2i don't think it is that different um so again the concept is that it's the fluctuations the drop in estradiol and and the changes in progesterone across the cycle in the hormone sensitive woman that then triggers the depressive and brain fog and anxiety symptoms so again using common sense we can manipulate the cycle we can wipe out the symptoms so in this instance um again you've got a woman who's of reproductive age so contraception might be a critical issue for her so using a mood neutral pill and i like in my clinic we use the normogestrol and estradiol combo um but in other places people have found that treating pmdd with a standard 50 microgram transdermal estradiol patch plus 100 milligrams prometrium at night um does the job beautifully as well and in fact does it better because you've got more estradiol um with the patch
Speaker 1and so that would only be available if they had another form of contraception that they were using you
Speaker 2do have to have that contraceptive discussion um but it's interesting that none of the guidelines again talk about hormone therapy as primary treatment no
Speaker 1it's ssri and actually cyclical ssri which i always find really odd because i don't know if this is if if this is a thing but i went if you're using an ssri for a short period of time for only part of the month it takes a certain period of time for the onset and offset of the ssri so i don't understand how that actually works i
Speaker 2agree with you i mean it's a it's it's it's an interesting area that again i think got missed by people who are allowed to prescribe medications it got taken up by psychologists who first of all you know kept talking about cbt and and other things and i'm sure there's there's there is room obviously for psychotherapies very important we all do supportive psychotherapy every time you meet with a patient that's pretty much what you're doing but in this instance the biology got left behind there is just some areas of women's mental health where biology is just not thought about particularly neurobiology it's as if it's too scary to go into and to apply it you know even perinatal psychiatrists are very much about the psychotherapeutic interactions and and the dynamic relationships and so on and there's a lot of psychologists who work in that area that's great but there's also a brain here and the brain biology needs to be attended to same dynamic is happening in the um in the in the in the pmdd area and it's really worrying because um again i think the other part about why ssris are used first line is the sense of suicidality is is a feature of this because anytime there is severe depression you've got to think suicide and so people freaked out when patients talk about suicide and it's like oh we better get the antidepressants in there otherwise we're negligent well no get the treatment in there that's going to best stop this cyclical depression um would be the way to treat the suicidality as well but we do have to think about that and so many times the guidelines will kind of skirt around the issues of hormone therapy and go straight to ssris so it's not common sense again it's it's uh it's i don't know medico-legal defensive practice or a practice that is not about people who are familiar with using the hormones so this is the other
Speaker 1thing so the silos in medicine and yeah
Speaker 2getting stay in your lane it's a psychiatrist i've been told this stay in your lane what's my lane well you can use antidepressants and you can use antipsychotics and you can use mood stabilizers but don't deviate from that lane you know well hang on i trained as a doctor i did stuff in general medicine am i just not allowed to apply that to the individual i'm seeing
Speaker 1in front of me i guess what we're touching on here though is this historical lack of research into um how women's reproductive cycle and and the impact of trauma yes of women yes has affected mental health absolutely i think
Speaker 2for women's mental health the two pillar the two pillars that are big causalities for mental disorders is trauma and hormones they're interrelated so they're not separate platforms and often both are ignored um in psychiatric circles
Speaker 1well yeah i mean a complex trauma as a diagnosis isn't in the dsm you know it is now in the icd but it's not in the dsm and we sort of talked about in in the last or the earlier part of our discussion about the link between trauma and hormones and i think that's a really important thing and that's why we're talking about the link between trauma and hormones and i think that's a really important complex trauma and the hbaa and hbg access um so it is a really interesting sort of emerging field of medicine that it's um i'm really glad that there's people like you in the world doing some of the research and the work and demonstrating it and um but we we do see that my understanding in in very a lot of other parts of medicine where we're not considering how the hormonal cycle actually impacts blood pressure treatment there's a whole whole sort of dearth around what does the the endocrine system actually you know do in when we're looking at the interactions of all of the medications that we
Speaker 2use i'm actually always surprised by the lack of brain endocrinology it's it's like endocrinology or endocrinologist uh you know very talented people who work really well with diabetes with thyroid conditions and with the rare things like pheochromocytomas and so on but there's this whole brain um area and you know again if we look at the hpg axis two parts of that are in the brain and that by the way they keep cycling after the gonads have waved goodbye um there's still uh links between the pheochromocytomas and pheochromocytomas of course there is um and so it it's a real specialty in itself which would be uh well worth either the physicians picking it up or the psychiatrists picking it up and perhaps doing it together would be really good and that's where a lot of my research has been in psychoneuroendocrinology i think this whole thing is is really a problem because of the individual silos that we practice in like you know me being told to stay in my psychiatric lane it doesn't help the woman who's sitting in this is where GPs have this big advantage and disadvantage you've got everything and you're allowed to work with everything but the problem is you're never remunerated properly for the short times that you're allowed to spend you don't know how you do it my hat goes off to you all the time
Speaker 1and emerging fields is tricky as well because you know we sort of need the support of guidelines and you know peer acceptance and all that sort of stuff as well but
Speaker 2some of the guidelines and make no sense because they're not actually based on you know what people are clinically seeing I think we've got to bring back the the respect for clinical wisdom and clinical evidence as well you know it isn't all about experience even it's not all about the RCT I mean sure you're going to have some of them but what happened to the old-fashioned doctors who would actually practice the art of medicine because that's important
Speaker 1you yeah and you know the art of medicine is also important when working with a population that's experienced significant distress in in their lives as you say so if we roll it sort of back to this idea do we have some evidence that treating PMDD hormonally
Speaker 2works yes good I mean simple answer yes and intuitively a lot of patients who haven't got the severe life-threatening symptoms are not going to be able to do that so I think it's important to be able to do that and you know if you can get them early which is where you are you would have that opportunity you're basically just putting them on the pill I mean you must do that for women all the time who it's not a it's not a serious thing to do which is why I can't understand why it that you would go to an antidepressant that has so many more side effects and it makes withdrawal from the site from the antidepressant difficult you know the pill people can take on and off and it's under her control your control to make sure that the rest of her health is good but we have many options so I don't understand why we don't have guidelines that say hey try the hormone strategy first because it's common
Speaker 1sense so what about for the women who aren't keen to try hormonal treatments what are their options
Speaker 2sure so again it depends on we talk about hormonal treatment as if it's one thing and again the person who's had a bad experience with one pill or two types of pill it's worth saying you know try if you tried the one that we're talking about if she says oh yeah I tried that one and it didn't suit me either then I'm more likely to try a modified MHT format by using a 50 microgram well it's not even modified it's a standard MHT format and then talk about barrier contraception to make sure that there's no accidents as well and talk about the follow-up cervix screening breast ultrasound to do that screening because she's too young to have radiation with a mammogram but she can have a breast ultrasound and breast self-examination many women say I don't know what I'm feeling there are lumps and bumps there so let's just go with the breast ultrasound and do that that's pretty much what I do if there is a lot of other stuff going on then obviously we're going to work in complex therapy as in trauma therapy modalities as well if she needs to we can do a combination with an antidepressant plus hormone therapy there's no reason you can't combine the two that usually takes us to where it's at what I really want to prevent though is young women having their ovaries and uterus ripped out because this is a brain condition it's not a end organ solution so that's sad I have seen 22 year olds with total hysterectomy oophorectomy in a attempt to cure PMDD gosh
Speaker 1that sounds like a remnant of the hysteria age
Speaker 2wandering womb etc yeah that's sad it does happen though it's still happening the other sort of levels of treatment involve uh chemical menopause so there are some of the um hypothalamic drugs that can shut down I did see
Speaker 1that and then I wondered wouldn't that cause like this massive drop in then the estrogen which would drive some kind of what we're talking about in our earlier discussion this massive shift in
Speaker 2estrogen so what used to happen is in the clinic that did that they would do awful things like say let's just shut down the whole HPG axis by using zolidex or something and then come back in three months and we'll think about replacement well that was just a disaster because exactly that happened and she would often just go into a free fall depression nowadays it's much more likely that people doing that will say will go immediately into advec estradiol and so then come back when you've got estradiol on board and then we'll add in the prometrium usually okay so you use it in
Speaker 1conjunction with replacement at the same time so
Speaker 2what you're doing is you're losing the fluctuations in the cycle because now you've got an artificial situation where she's not cycling because you've shut that down and you're adding back uh estradiol and uh progesterone progesterone um it's drastic and it's also it works in some people as a last resort i wouldn't be doing that myself this is when i work with the gynecologists who are doing that but i think that's better than the surgical options which really scare me surgery for pathology we all agree that's different you know that is a different thing um but surgery to remove the end organs to treat pmdd is ridiculous because pmdd is a brain condition
Speaker 1and from what i'm sort of hearing you talk about you know the focus of prevention would be your early life experiences really yep
Speaker 2if everybody had a lovely nurturing easy childhood there may not be the need for as much psychiatry and psychology but
Speaker 1yeah exactly you know i concur with that um my bias and my experience in clinical practices is similar to you i think that a lot of the things that i come across in the medical practice are in practice would be solved by a nurturing and loving early life so i mean
Speaker 2there are conditions like schizophrenia that we know are brain conditions and that the genetics of the genetics of schizophrenia is a bit more established and so on so we do know that there are those illnesses however when you get to talking about depression anxiety cptsd substance abuse even some of the ocd some of the eating disorders they're all they have a portion that are trauma responses maladaptive responses but they're trauma responses so what
Speaker 1is what would be the value then of of providing a trauma response in this population particularly phase one safety and stabilization
Speaker 2fabulous i think i've you know read some studies also where um the sad situation of women who were raped to go to emergency department uh get a their estrogen um you know they were given the emergency contraceptive pill but in fact that was also helping their cns because it's it's helping to decrease the level of acute ptsd at the same time they're getting the trauma therapy starting right there um in in the absolute heat of the crisis with better results yeah and the
Speaker 1surgical assault services are sort of trained in that sort of first aid around supporting that particular
Speaker 2person yeah wish it hadn't happened at all yes that is another domain not doctor's domain you can advocate for it but how are we going to get now
Speaker 1i know that we've reached to our time and i just just want to thank you so much for spending the time with me to explore all of this i'm sure we could talk for hours and hours and hours on end and i could have a hundred more questions for you and we could go on a lot of deep dives but i really appreciate your time and like we said in the previous episode um people can find more information on the her center website yes and there are any specific pmdd resources for
Speaker 2clinicians i wrote in the uh australian what's it osdoc i wrote a how to treat pmdd article it might be a little old no it's not that old but i've written a how to treat pmdd how to treat cptsd and how to treat perimenopausal depression the perimenopausal one is probably the oldest but the other two are not that old but i specifically wrote it in osdoc because you and your gp colleagues are absolutely the the front liners who have the best chance to really get great outcomes um by the time people get to me it's also already a little bit later in the whole story and things have been lost so um i take my hat off to our gps because they are just brilliant in the work they can do and do as well so keep on keeping on well thank
Speaker 1you and thank you for your contribution to psychiatry for women thank you this brings us to the end of the supplementary episode on pmdd we'll put some links in the show notes in relation to her article on how to treat pmdd as well as a link to the green top guidelines for a gp update on available menopausal hormonal treatment and contraceptive options our episode fast facts in sexual and reproductive health with dr sarah whitburn is a great companion listen to thank you so much for listening to the gp show you
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