Welcome to PsychEd, the psychiatry podcast for medical learners, by medical learners. This episode covers reproductive psychiatry with Dr. Tuong Vi Nguyen, Assistant Professor, Department of Psychiatry, Faculty of Medicine and Health Sciences, McGill University and Scientist, RI-MUHC, Brain Repair and Integrative Neuroscience (BRaIN) Program, Centre for Outcomes Research and Evaluation.

The learning objectives for this episode are as follows:

By the end of this episode, you should be able to…

Define the field of reproductive psychiatry
Discuss the possible neurobiological pathways impacting mood and cognition during the reproductive cycle of women.
Discuss the influence of sociocultural gender roles on psychopathology.
List the DSM-V diagnostic criteria of premenstrual dysphoric disorder.
Recall the epidemiology of premenstrual dysphoric disorder.
Describe the steps in the diagnostic evaluation for premenstrual dysphoric disorder.
List lifestyle and psychopharmacologic interventions for premenstrual dysphoric disorder.
Discuss common mental health concerns during the perimenopausal period.

Guest: Dr. Tuong Vi Nguyen

Hosts: Nima Nahiddi (PGY4), Audrey Le (PGY1), and Arielle Geist (PGY2)

Audio editing by: Audrey Le

Show notes by: Arielle Geist

Interview content:

Introduction - 00:00
Learning objectives - 01:00
Defining the field of perinatal psychiatry - 01:50
Discussing neurobiological pathways impacting mood and cognition during the reproductive cycle - 02:47
The influence of sociocultural gender roles on psychopathology -05:28
DSM-V criteria of premenstrual dysphoric disorder - 11:18
Epidemiology of premenstrual dysphoric disorder - 13:40
Diagnostic evaluation of premenstrual dysphoric disorder - 14:38
Management of premenstrual dysphoric disorder
- Pharmacologic - 17:45
- Lifestyle - 24:15
Perimenopausal period - 24:45
Closing comments - 31:39

Resources:

Brzezinski, A., Brzezinski-Sinai, N.A., & Seeman, M.V. (2017). Treating schizophrenia during menopause. Menopause, 24(5), 582-588. doi: 10.1097/GME.0000000000000772.
Epperson, C.N., Steiner, M., Hartlage, A., Eriksson, E., Schmidt, P.J., Jones, I., & Yonkers, K.A. (2012). Premenstrual dysphoric disorder: evidence for a new category for DSM-5. The American Journal of Psychiatry, 169(5), 465-475. DOI: 10.1176/appi.ajp.2012.11081302
Marsh, W.K., Gershenson, B., & Rothschild, A.J. (2015). Symptom severity of bipolar disorder during the menopausal transition. International Journal of Bipolar Disorders, 3(1), 35. DOI: 10.1186/s40345-015-0035-z
Soares, C.N., Almeida, O.P., Joffe, H., & Cohen, L.S. (2001). Efficacy of estradiol for the treatment of depressive disorders in perimenopausal women a double-blind, randomized, placebo-controlled trial. Archives of General Psychiatry, 58(6), 529-534. doi:10.1001/archpsyc.58.6.529
Weber, M.T., Maki, P.M., & McDermott, M.P. (2013). Cognition and mood in perimenopause: A systematic review and meta-analysis. The Journal of Steroid Biochemistry and Molecular Biology, 142, 90-98. https://doi.org/10.1016/j.jsbmb.2013.06.001

References:

Kornstein S.G., & Clayton, A.H. (2004). Sex differenes in neuroendocrine and neurotransmitter systems. In Women’s mental health: A comprehensive textbook (pp.3-30). Guilford Press.
Chrisler, J. C., & Johnston-Robledo, I. (2002). Raging hormones?: Feminist perspectives on premenstrual syndrome and postpartum depression. In M. Ballou & L. S. Brown (Eds.), Rethinking mental health and disorder: Feminist perspectives (pp. 174–197). Guilford Press.
American Psychiatric Association. (2013). Depressive disorders. In Diagnostic and statistical manual of mental disorders (5th ed.). https://doi.org/10.1176/appi.books.9780890425596.

CPA Note: The views expressed in this podcast do not necessarily reflect those of the Canadian Psychiatric Association.

For more PsychEd, follow us on Twitter (@psychedpodcast), Facebook (PsychEd Podcast), and Instagram (@psyched.podcast). You can provide feedback by email at psychedpodcast@gmail.com. For more information, visit our website at psychedpodcast.org.

PsychEd_Ep_45_-_Reproductive_Psychiatry_with_Dr._Tuong_Vi_Nguyen.mp3: Audio automatically transcribed by Sonix

PsychEd_Ep_45_-_Reproductive_Psychiatry_with_Dr._Tuong_Vi_Nguyen.mp3: this mp3 audio file was automatically transcribed by Sonix with the best speech-to-text algorithms. This transcript may contain errors.

Nima Nahiddi:
Welcome to PsychEd, the Psychiatry Podcast for Medical Learners by Medical Learners. In this episode, we'll be exploring the psychiatric aspects of reproductive mental health. I'm Dr. Nima Nahiddi, a fourth year resident at McGill University. And I'm joined by Arielle Geist, a second year resident at the University of Toronto, and Audrey Le, a first year resident at McGill University.

Arielle Geist:
Hi, everyone.

Audrey Le:
Hi, everyone.

Nima Nahiddi:
We're really grateful to have our guests, Dr. Nguyen, this week to share her expertise. Dr. Nguyen, if you could, please introduce yourself.

Dr. Nguyen:
Sure. So I'm a reproductive psychiatrist at McGill University Health Centre.

Nima Nahiddi:
For this episode. Our learning objectives are the following to define the field of reproductive psychiatry to discuss the possible neurobiological pathways impacting mood and cognition during the reproductive cycle of women, to discuss the influence of sociocultural gender roles on psychopathology, to list the DSM five diagnostic criteria of Premenstrual Dysphoric Disorder. To recall the Epidemiology of Premenstrual Dysphoric Disorder. To describe the steps in the diagnostic evaluation of Premenstrual Dysphoric Disorder. To list lifestyle and psycho pharmacological interventions for Premenstrual Dysphoric disorder and to discuss common mental health concerns during the perimenopausal period.

Arielle Geist:
So I'll start with the first question today. So before diving in today's discussion, could you briefly explain the clinical scope of reproductive psychiatry and what your work entails? Exactly.

Dr. Nguyen:
So reproductive psychiatry is really about all of the mental health changes that occur in a woman's lifetime during reproductive periods, typically around puberty. You start to see changes related to hormones and you can see a significant proportion of women who start to have premenstrual syndrome, 70 to 80% with a smaller proportion that go on to the premenstrual dysphoric disorder. Another stage of life when you have these hormonal fluctuations is, of course, the pregnancy and postpartum period. And then finally you have the perimenopausal period. And there has been talk amongst us, reproductive psychiatrist that psychiatry should also include hormonal changes for men. But we'll see maybe in in ten years. For now, it's pretty focused on women's mental health.

Arielle Geist:
Mm hmm. Since you mentioned hormones, my next question was, how do these hormones, especially in the field of reproductive psychiatry, where the focus is on mostly estrogen and progesterone, how do those hormones modulate mood and the neurobiological pathways that are involved in regulating mood?

Dr. Nguyen:
There's no simple answer for that. I think that when you think about hormones and women hormones, you have to think about the fact that there are classes rather than just thinking about estradiol and progesterone. It's really all of the steroid hormones are linked together. And you can have up to 54 metabolites, maybe more, maybe more metabolites could be discovered. And then you have these three or even four classes. I don't know if you're aware, but it all starts with cholesterol. And then you have one branch that go on to be corticosteroids. You have one branch that go on to be the estrogens, but then you have tons of different types of estrogens, including 17 beta estradiol, the most famous one. And then you have the progesterone progestogen basically progesterone alone and all of these related hormones. And then you also have the androgens like DHEA and testosterone. So all of these hormones change cyclically throughout the menstrual cycle and then very drastically during pregnancy and the postpartum period and of course the perimenopausal period in terms of how they affect neurotransmitters, I would say again, no easy answer, but just in a very broad way, in simplified way, the estrogens tend to regulate serotonin. Well, all of the all of the neurotransmitters, it's really like they're really almost like dirty medications. So they will affect serotonin and norepinephrine, dopamine in different ways. Progestogen also and estrogen suppression tend to have opposite effects. So for example, estrogen tends to be more stimulating to, for example, up the serotonin, serotonin tone and also androgenetic tone. And then progestogen tend to act again, not all of them, but most of them act through the GABA receptor and then they will lead to inhibition or kind of downregulation of the HPA axis, for example. So the kind so more a bit more like benzos androgens, there's a lot of research that remains to be done on androgens, which are really not well studied. But the typical effect is really in terms of activity, mood, lability, competitiveness, things like that.

Arielle Geist:
Thank you. I think you really were able to simplify something that that seems very complicated to. I think many trainees. Next, because of the way that we formulate things in psychiatry, going with the biopsychosocial model, I wanted.

Arielle Geist:
To step away.

Arielle Geist:
From the biological aspects of reproductive mental health for a second and take some time to explore its social aspect. So my next question was about how do you feel that social and cultural type of gender norms affect clinical presentations of this field? For example, how the way that it might affect the experience that mothers who have postpartum depression have?

Dr. Nguyen:
I think there are still many unanswered questions regarding that. And one of the key aspects of the literature is that we still don't know enough about the social determinants of health for perinatal depression. I hope that beyond post-partum depression, we'll start to talk about perinatal mental health disorders. I think PPD has become very famous. Postpartum depression has been recognized by and large by the mainstream media. But then oftentimes we miss the anxiety disorders that present during the period of period the post-traumatic stress disorders, OCD, which is its own different beast as well. And so I think that, yes, there's a lot of advantages to to have more recognition and awareness, awareness of depression. But we must I think it would be more helpful for women if we use a broader term, perinatal mental health disorders. And I think that in the past decade or so, more and more women are delaying fertility or delaying reproduction to further career or other interests that they may have. And so more and more women will have unfortunately, more and more couples will have infertility and fertility problems. And then that kind of opens the door to a whole other area of mental challenges, which is all of the mood fluctuations related to hormonal treatments, IVF IUI, and in addition to the psychological issues of repeated miscarriages and pregnancy complications. So I think in terms of in terms of that social aspects of mainstream recognition and awareness, we've done a lot, but there's still there's still a lot of work to do because some women will still come to me and say, well, I have suffered for two years because I had no idea.

Dr. Nguyen:
I thought they were suffering from postpartum anxiety, let's say, and then not want to present to not want to discuss it with their doctor because it's they felt they were obviously not depressed. So I think that's that's one aspect. I think the other aspect socially that is that is important to mention is that unfortunately, we're still, despite the fact that Hillary Clinton said several years ago that women's rights are human rights or human rights or women's rights, something like that. I don't know if I'm quoting her properly, but I still think that we are struggling to we are struggling to kind of have the political recognition that we that we need. And this is at all levels. Just to give you an example, all of the reproductive psychiatrists currently working in Quebec have really struggled to implement to have even a prenatal clinic. This in the in face of the fact that we know now that maybe one in three women around the period may have a significant period of mental health disorder with all of the uncertainties surrounding COVID, with the fact that most of the child care burden and house chore burden still falls on the woman at home, and that several of them have out of work because of that. Even so, we're still really struggling to establish these these clinics. And there's actually just one, I would say, clinic in the Quebec province that offers psychological help, an experienced nurse and a psychiatrist. Then the rest of us are basically perinatal and reproductive psychiatrists that are working with little support.

Arielle Geist:
Mm hmm. Thank you for all of that wise insight. I have one last question about the social aspect that I think you kind of touched on to. So when I was reading on the literature leading up to doing this episode, some of it suggested that premenstrual syndrome and postpartum depression and such are quite seem to be a bit more culture bound because there is some literature out there that suggests that it's less prevalent outside of Western countries. So I was just wondering if you had any comments to make in terms of how those differences might be explained by cultural norms or whether that even is true, whether or not we do see it pretty prevalent in in all cultures?

Dr. Nguyen:
Yeah, No, no, absolutely. I wanted to mention that too. So it's again, an example of of perhaps some of the biases that are in some of the controversy that always surround women's mental health in terms of of how long it took for the premenstrual dysphoric disorder to make it into the official category of the diagnosis instead of being relegated to the culture bound syndromes. I would say all of the evidence up to now point towards the fact that there are similar percentages, proportions of women suffering from PMDD across all across all cultures, across all ethnicities. And so I would say if you have a multiple choice question, I would say that PMDD is not the culturally bound syndrome. And it it really does seem that there is an overlap between the women who suffer from PMDD and the women who may have bad reactions like disinhibition and aggression with alcohol. So there seems to be something surrounding maybe men alone and the GABA receptor, but there's several biological and particular genetic contributions to this to this illness.

Audrey Le:
Thank you for answering all of those questions. We're going to move a little bit now into premenstrual dysphoric disorder. So this is a depressive disorder that's linked to the menstrual cycle with symptoms presenting in the week before the onset of menses. Before we dive into this further, it might be helpful for our listeners to briefly talk about the DSM criteria for premenstrual dysphoric disorder to get a better understanding of what this looks like. So before asking further questions, I'm just going to run through the DSM criteria for premenstrual dysphoric disorder. So A, in the majority of menstrual cycles, at least five symptoms must be present in the final week before the onset of menses start to improve within a few days after the onset of menses and become minimal or absent in the week post menses, criteria B one or more of the following symptoms must be present, and these include effective lability, irritability or anger or increased interpersonal conflicts, depressed mood, feelings of hopelessness or self deprecating thoughts and anxiety, tension and or feelings of being keyed up or on edge. Criteria C, one or more of the following symptoms must additionally be present to reach a total of five symptoms when combined with the symptoms and criteria B above.

Audrey Le:
These include decreased interest and interest in usual activities, subjective difficulty in concentration, lethargy, easy fatiguability or marked lack of energy, marked change in appetite, overeating or specific food cravings, hypersomnia or insomnia, a sense of being overwhelmed or out of control. And lastly, physical symptoms such as breast tenderness or swelling, joint or muscle pain, a sensation of being bloated or weight gain. Of note, the symptoms I mentioned must have been met for most menstrual cycles that occurred in the preceding years. And the rest of the criteria after this include D causes significant distress or interference with daily activities or relationships. E The disturbance is not an exacerbation of the symptoms of another disorder such as MDD, panic disorder, PDD, or personality disorder. F Criterion A should be confirmed by prospective daily readings during at least two symptomatic cycles, which we'll talk about more detail later in the episode and G. The symptoms are not attributable to a substance medication or another medical condition. So now that I've gone through the diagnostic criteria of premenstrual dysphoric disorder, let's talk about the epidemiology. How prevalent is this disorder and how does it evolve across the lifespan?

Dr. Nguyen:
So in terms of the last estimates, they go between two, it's 2 to 8%. I think if you define it very rigorously with a two month perspective ratings, which not all women are willing or able to complete, then it maybe is 2 to 5% and that is compared to the 70 to 80% of women who have premenstrual syndrome.

Audrey Le:
Thank you. And and how does this tend to evolve across the lifespan?

Dr. Nguyen:
So typically, PMDD, unfortunately, tends to get worse with the years, particularly after having had children, that we we still don't know what exactly in terms of hormonal mechanisms that's due to. But that has definitely been documented in terms of it's getting worse over time.

Arielle Geist:
And again, thinking about premenstrual dysphoric disorder, what's the differential diagnosis that you think about when you're seeing a patient?

Dr. Nguyen:
Oh, you have to think about all of the gynaecological endometriosis, for example, PID (pelvic inflammatory disease), ovarian cysts or ovarian torsions. There's a lot of different gynaecological conditions that you have to think about. I am actually of the school of thought that I don't. I think that disorders can be co-morbid. And so even though I know that in the DSM, it says it cannot be the exacerbation of another condition. We know from family studies that, for example, MDD and PMDD coexist in these families. And so you will have several women who suffer from both. And so then it's really difficult to disentangle. Is it just an exacerbation of MDD or PMDD and MD together? So for me, it's not kind of hard exclusion criteria per se.

Nima Nahiddi:
I was just wondering how realistic or easy do you find it is for people to do the prospective charts for the two months? Is that something that if you will have resources or with your smartphone, that is very doable.

Dr. Nguyen:
It is doable. I just find that this is this goes back to the social determinants of health, I guess, but it's just very special to me that it's the only disorder which you require. Two months perspective ratings for all of the other disorders are not it's not that hard to to meet the criteria, basically. And I think that for some of our some of our population it is quite difficult. You know, like you have three children, you're trying to get diagnosed with PMDD, you just don't have the time. So it can be challenging for some people. So at least we have the option of being of giving a PMDD provisional diagnosis until the person kind of hands in the two months perspective readings. But typically I really try to encourage them to do it either like you said, on the smartphone or some people just like hard paper copy. So it's it's doable. But I think maybe in ten years there may be changes again to that specific criteria.

Audrey Le:
And thinking of those rating scales. What are some rating scales that are typically used in diagnosing premenstrual dysphoric disorder that you use?

Dr. Nguyen:
They're quite widely available now, particularly given that a lot of women are trying to track their fertility. So you just there are several apps like Overview and several other new apps as well. It's called Fertility. I don't remember, but there are several for both iPhones and Google Samsung phones now. And even if you just do, you don't even have to download an app. You can just do a Google search and you'll see like all of these paper forms, you just have to make sure that the big categories, like the effect of symptoms, cognitive symptoms, physical symptoms are all properly listed, but they're widely available and free.

Nima Nahiddi:
Now that we've reviewed the diagnosis of premenstrual dysphoric disorder, what is your approach to the treatment once you've diagnosed someone?

Dr. Nguyen:
It really depends on the patient. I think most of I think most of reproductive psychiatry is. There's a lot of joint decision because it's such a it's such a personal decision. For example, for PMDD, it depends whether the woman is willing to consider contraception, in which case you could try something like Yasmin for three cycles with four days off. It's important to mention, though, because I see this very commonly, is that you cannot just throw any oral contraceptive pill at PMDD and hope that it works. Several pills, particularly the ones that have more androgen potency, actually can make PMDD worse. One common culprit is alesse, for example, which is quite commonly prescribed. So even though if alesse has very low levels of hormones and so some GP's or some other health care practitioners may think that this is going to be helpful for someone who's suffering from PMDD. It actually is not about the levels of hormones but about the potency and which direction, which of the different classes of the steroid hormones that I mentioned earlier, which the oral contraceptive is offering. And the other thing that people often forget is that you have to prescribe it really three cycles and four days off, which is not the typical regimen for oral contraceptive pills. Usually it's like three weeks on and then you have like a week of sugar pills or placebo pills. But you need to do this to disrupt the cycle and to help in terms of the PMDD symptoms. Another aspect I would say is some women actually come to me already on SSRI, And then I think in that case, it's easy to consider, okay, why don't you try to increase your SSRI during your luteal period? And so the week before menses, this is depending on their perspective tracking this.

Dr. Nguyen:
This can be useful in terms of knowing. Does the woman start to have symptoms right after ovulation, which some women do, unfortunately. So they have like a full two weeks of symptoms that then only start to improve slightly when menses start. Some women only have like three days of symptoms before their period occurs. And so depending on the timing that you can tell them to increase, bump it up a little bit. For example, if the person is on escitalopram, they could go up to 25 or 30 just for that period. What's important to remember is that the mechanism through which the SSRI work for PMDD is not the same as how it works for depression, for depression and anxiety. You have all of these changes at the synapse or occurring the changes in auto receptors 5HT1A But for PMDD, it's really thought to occur through a disruption in the way that the hormones are being metabolized. So again, because there's this communication between the serotonin and just overall neurotransmitter systems and the hormones, basically the if you administer SSRIs or an increased dose of SSRI during this period of time, perhaps it's changing how fast the hormones are being self-rated or converted to different metabolites in a way that then helps women. So there's still a lot of research, kind of more fundamental research that needs to be done in terms of how that occurs. Exactly. But there are now several studies showing that the SSRI are quite effective for PMDD when administered in this fashion.

Nima Nahiddi:
So to clarify for pharmacological treatments, there's oral contraceptive pill and SSRI. And so can you explain in which situation would you choose one or the other or would you recommend one or the other?

Dr. Nguyen:
I think I've touched a bit on that in terms of, you know, depending on the on the patient perspective and what they what they want to priorities. Some women may be in the midst of trying to conceive and so the Yasmin wouldn't be the right choice for them. Some women might have a family or personal history of stroke, pulmonary embolism, deep vein thrombosis and other and have other risk factors such as being over 35 years old and smoking, etc. And in that case, Yasmin and Yaz, that whole category of oral contraceptives actually are associated with an increased risk of stroke and deep vein thrombosis, etc. So there are some exclusions in some cases where I tend to shy away from the Yasmin or Yaz, oftentimes. Also, it may be easier for women who are already on SSRI to just continue on and just change their dosages that way. And then it's less stressful for them in terms of changing medications. I just want to mention also that if SSRI and oral contraceptives don't work, then you can help. GNRH agonist or antagonists are kind of like basically surgical or medical menopause. So this is really a last resort, though. And I would say 70 to 90% of women actually respond to Yasmin or SSRI. And in terms of the study. It does seem that the contraceptives have a slightly higher rate of success. It may be 80 to 90% versus the SSRIs, which are more like 70 to 80%. So like a highly treatable condition.

Nima Nahiddi:
You had mentioned that we should avoid certain contraceptives like Alesse, What is the specific reason why you would avoid that? Just to clarify.

Dr. Nguyen:
So some contraceptives have more androgen activity like you remember, Like the difference, like there's androgen activity, progestogen activity and estrogen activity. So each pill actually has different balances or mixes of of that similar to, I guess, the antidepressants in the different neurotransmitters. So if you have one that acts more on androgen and not so much on the drospirenone or basically it's the metabolite that is in the progesterone category that is part of Yasmin and Yaz, then it's not going to be effective. So some some contraceptives will just be neutral. It will neither help nor worsen the PMDD and then some others will make it worse if they have the wrong mix, if they have too much androgen activity, for example. And then that's why we think that it's Yasmin or Yaz, that has that is efficacious because of that drospirenone metabolite specific to those medications.

Nima Nahiddi:
Thank you so much for clarifying that. Are there any lifestyle interventions that can help with the treatment of PMDD?

Dr. Nguyen:
Unfortunately, there's very weak evidence to support that. Some women will say, I've tried calcium, I've tried B vitamins, I've tried exercise. And I'm not saying like in lots of cases, add on CBT, add on light therapy even could help. There's a lot of different conditions, but it's just that the the evidence behind those complementary therapies is still quite weak.

Nima Nahiddi:
So I'd like to finish our discussion by going to another topic. Mental health concerns during the perimenopausal period. Can you clarify? First, the definition of perimenopausal?

Dr. Nguyen:
Perimenopausal is again, difficult to define because you have so you have menopause, which is one year after the cessation of the complete cessation of menses. So you can basically only define menopause retrospectively because you never know if you're going to have another period at perimenopause. In most of the studies are is thought to represent the whole period of when the ovaries or the follicles are starting to decline up until menopause, which is one year after the last period. And then you have early perimenopause and you have late perimenopause. I feel like for your learning, you don't need to know all the details of that, but just know that the changes of hormones are different in early versus late perimenopause. Menopause in early perimenopause, you can see a lot of erratic changes in estradiol and other hormones, too. I don't want to get too much into the complexities of that. And in the late period menopause, that's when you start to see a profile that is more similar to menopause. So a lot of ups and downs and fluctuations throughout that whole period. And just to mention that some women can start to enter the early menopause around age 40, 45 years old. So it can be quite much earlier than than some of us would expect.

Nima Nahiddi:
And what are some mental health concerns that arise during this time period?

Dr. Nguyen:
It's typically anxiety and depression, but you will also see exacerbations of schizophrenia and exacerbations of bipolar disorder, for example. So again, if you have a patient with bipolar disorder or schizophrenia and suddenly you have treatment resistance, you have to think about asking those questions about the menstrual, the menstrual history and reproductive history in terms of the more common disorders like anxiety and depression. And so what we see is that these perimenopausal mental disorders tend to be more persistent and more comorbid. So instead of just seeing a classical picture of depression, you will see a lot of anxiety, kind of depression with anxious features, difficult to treat, a lot of insomnia. And sometimes the women will describe it as the worst, the worst mental breakdown that she's had during her entire life and accompanied accompanying these mental symptoms. You have, of course, the physical symptoms also. So the hot flashes, the vaginal dryness, there's a lot of discomfort physically that occurred during this time as well.

Nima Nahiddi:
Can you speak about the incidence of depression specifically in the perimenopausal period and perhaps what effect estrogen has in the treatment of depression?

Dr. Nguyen:
I think other than the fact that the depression is often comorbid with anxiety in terms of presentation, I don't see any remarkable features of the depressive symptoms that are different from an MDD at another period of life. It's possible, though, that in terms of psychological and social contexts it's even harder because it's like a woman ageing, her children leaving. There's a lot of life changes also that are different from other periods of life in terms of the hormonal treatment. So I mean, we do consider transdermal estradiol as one of the useful add ons to antidepressant treatment. I don't tend because I'm not a gynaecologist, I don't tend to start with the transdermal estradiol, Some gynaecologists will, and I guess it's for them to comment on how the how they think, how they consider it first line versus second line. For me, I consider it more second line because there are several antidepressants. All of the antidepressant categories have been shown to be effective for perimenopausal depression and anxiety. Maybe with the SNRIs being a little bit more effective, we think because of all of the hypothalamic changes and dysfunction in the noradrenergic nucleus in the hypothalamus that happened with hot flashes. And that may also be may also cause some of the mood fluctuations that occurred during this period. So perhaps a SNRI a little bit more effective, but SSRI is also effective. Mirtazapine is also effective. I wouldn't go so much with bupropion though, because it's too activating and it can increase the anxiety that is often comorbid with perimenopausal depression.

Dr. Nguyen:
And then if that doesn't work, then you can consider something like transdermal estradiol. I think Raloxifene at some point was also discussed. It tends not to be very effective, maybe mildly effective sometimes a bit like how we use Pregabalin for for GAD like it can be effective, but oftentimes more like an ad as an add on. It actually has been studied in schizophrenia. I don't know if you're aware, but in terms of schizophrenia for cognitive and effective symptoms of schizophrenia and Raloxifene, which is a selective receptor modulator, seems to be effective for those symptoms in schizophrenia. And so that's why sometimes we also use it for perimenopausal depression. If someone, for example, has contraindications to transdermal estradiol, I always make sure to have a family doctor or a gynaecologist who is my partner in prescribing these medications. Typically, I've had no issues with people kind of collaborating and getting back to me quickly. And usually it's like at least it takes six weeks of transdermal estradiol and sometimes a bit more six weeks to six months. I would say after that I would be reluctant to continue to prescribe unless I have like an ultrasound or a really good follow up by the the other either family doctor or gynaecologist to make sure that endometrial thickness is not has not change, etc..

Nima Nahiddi:
And these other side effects that you've spoken about, like hot flashes that occur during menopause, do you find that these contribute to having increased mental health concerns?

Dr. Nguyen:
So just like the co-morbidity between PMDD and MDD, sometimes it's hard to disentangle. However, all of the prospective studies have shown that even when you control for hot flashes and all of the physical symptoms of menopause, you still have a peak. So the mental health symptoms do seem to be independent, although of course, the worse, the more anxious you are, the more you can suffer from hot flashes also. So so so there's a bidirectional kind of exacerbation that can occur. But even in a woman who would have very little physical symptoms of perimenopause, you can still have an increased risk of perimenopausal depression, anxiety, as well as exacerbations of bipolar disorder and schizophrenia.

Nima Nahiddi:
Thank you so much for that overview of reproductive mental health. Before we leave, do you have any specific clinical pearls you'd like to leave our listeners with?

Dr. Nguyen:
Oh, I would say I mean, I hope that everyone who listens to this podcast will remember to ask about menstrual history, because that's what I kept repeating throughout the podcast and then strong sexual history. I think these are really key and this is something that we often as psychiatrists feel uncomfortable to talk about and at any life stage, as you can see. So even a woman who comes to you 55 years old. So I have to ask about reproductive history, sexual history as well.

Nima Nahiddi:
Thank you so much, Dr. Nguyen.

Dr. Nguyen:
You're welcome.

Arielle Geist:
Site is a resident driven initiative led by residents at the University of Toronto. We are affiliated with the Department of Psychiatry at the University of Toronto, as well as the Canadian Psychiatric Association. The views endorsed in this episode are not intended to represent the views of either organization. This episode is produced by Dr. Nima Nahiddi, Dr. Arielle Geist, Dr. Audrey Le and Dr. Rebecca Marsh. The episode was hosted by Dr. Nima Nahiddi, Dr. Arielle Geist and Dr. Audrey Le. The audio editing was done by Dr. Audrey Le and the show notes were done by Dr. Arielle Geist. Our theme song is Working Solutions by All Live Music, and a special thanks to the incredible guests we had today, Dr. Nguyen, for serving as our expert for this episode. You can contact us at psychedpodcast@gmail.com or visit us at psychedpodcast.org. Thank you so much for listening.

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