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Puder:
All right, welcome back to the podcast. I am joined by Dr. Bergink. She is an expert in all things women’s mental health and was on a prior episode on postpartum psychosis [see episode 280]. She is coming on today to talk about menopause [and perimenopause]. We are going to be trying to go through some commonly asked questions and maybe some myths that I found on the internet and seeing what kind of truth we can give to an audience that is often barraged by falsities. So welcome to the podcast.
Bergink:
Yes, very happy to be here. Yeah. There's lots of information out there, but also as you say, some myths and it's difficult for women, for patients, to navigate that landscape, right?
Perimenopause, Anxiety, Panic Attacks, and Mood Changes (00:48)
Puder:
Yeah. I think the first topic we'll talk about is can perimenopause or menopause cause anxiety or panic attacks?
Bergink:
Yes, the short answer is yes. So most women go through perimenopause without anxiety and depression, but there is an increased risk both for first-onset anxiety disorders or depression, or it's often, of course, a mixture of both. As well as women who had this in the past—depression, anxiety—are at high risk. They are at higher risk at any time in their lives, right? But then specifically in perimenopause. So that is actually the period before the last menstruation. So I think that's the first myth that menopause, after the last menstrual period, is the risk period, but it's actually the years before in most women, starting at the end of their 40s, basically. And what we know now is that the risk might be specifically high for women with bipolar disorder for having mood instability.
[Clarification: Psychiatric vulnerability appears to increase during the menopausal transition, particularly in the years surrounding the final menstrual period, with risk generally declining after menopause. Shitomi-Jones et al. (2024) found that new psychiatric diagnoses increased by approximately 50% during the four years surrounding the final menstrual period before returning toward baseline afterward. Similarly, Cohen et al. (2006) reported first-onset depressive symptoms in 32.5% of women entering perimenopause, compared with 20% of women who remained premenopausal. Shitomi-Jones et al. (2024) found that first-onset mania approximately doubled during perimenopause (RR = 2.12), whereas rates of first-onset schizophrenia-spectrum disorders did not increase.
Clinically, the more informative screening question may therefore be not simply, “Is she menopausal?” but rather, “Is she in the menopausal transition?” The timing matters: psychiatric vulnerability appears to be concentrated around the transition itself rather than uniformly throughout postmenopause.]
Bergink:
So among all psychiatric disorders, those women have specific sensitivity maybe for those hormone fluctuations.
Puder:
Okay. And, so one of the myths that I found was that new midlife anxiety is always caused by low estrogen.
Bergink:
Yes. That's a great myth. I mean, when we were nine, estrogen was low and it was not a period of high anxiety, right? So it's mainly the fluctuation in hormones that causes mood symptoms, if any. Again, many women go through perimenopause not having depression and anxiety. I think we shouldn't dramatize it too much. And it's not a matter of low estrogen, but some women are vulnerable to the fluctuations. I wish it was as simple as low estrogen, right? Because hormonal therapy, such as an estrogen patch, is not a magical bullet. Some women might help a bit with their sleep, with their mood symptoms, but it's not a matter of fixing low estrogen.
Hot Flashes, Sleep, and Mental Health During Perimenopause (03:21)
Puder:
Yes. Also, how do you differentiate between hot flashes, which themselves can mimic anxiety, sweating, racing heart, rapid breathing, and anxiety itself?
Bergink:
Wow, that's a very difficult question. Really, on two levels, as an expert, but also personally, I have to be honest with you. So, just to give some personal background, I did not have a psychiatric history until perimenopause, in which, for the first time, I had quite severe panic attacks and those started as hot flashes. So, well, at least my body couldn't differentiate between the two, you know, both a gynecologist and a psychiatrist ask like, "Yeah, but are these hot flashes or is it a panic attack?" And I answered, “Yes.” All that I know is that I feel very hot, that my heart is racing, and then I start panicking, even though I somehow know that this is a panic attack or a hot flash. So I think that's difficult to differentiate for those women who have anxiety.
Bergink:
But having said that, that is, of course, not everyone has hot flashes during perimenopause, but I think most women do, and the severity is a norm variable. Those are worse during perimenopause, and after post-menopause they're a bit less. But they're worse during perimenopause. And there is a huge variety in the severity of these symptoms. And, most women do not have what I had, a panic attack coupled with a hot flash. But that happens, women other than myself also feel anxious or not. But in any case, if it occurs during the night, then it can be a major sleep disruptor, which in itself, we know, is a risk factor for all kinds of psychiatric misery, basically.
[Clarification: Vasomotor symptoms can persist considerably longer than is often assumed. Avis et al. (2015) reported a median total duration of 7.4 years, including a median of 4.5 years after the final menstrual period. Gold et al. (2000) found that vasomotor symptoms remained common among postmenopausal women.
These symptoms also have important psychiatric implications. Nighttime vasomotor symptoms can disrupt sleep, and persistent sleep disturbance may further contribute to psychiatric vulnerability. Importantly, this creates an opportunity for nonhormonal behavioral intervention. McCurry et al. (2016) found that 70% of women receiving telephone-based CBT-I reached the non-insomnia range, compared with 24% receiving menopause education. And a 2024 Lancet review by Brown and colleagues (2024) notes that cognitive behavioral therapy can help with sleep disturbance and the burden of vasomotor symptoms.]
Bergink:
If you don't sleep well, then you're more vulnerable. And that makes it sometimes, I think, also for us as psychiatrists, a bit difficult to differentiate what is what, right? Is it sleep disturbances? Is this caused by perimenopause? Is it part of the symptomatology of a depression, for example? So, it's a mixture of symptoms. But I think for psychiatrists, it is already major if people think about women in their 40s or, you know, beginning 50s, that this all plays a role and really ask about it. You know, “How is your cycle? Are you using contraceptives, or Mirena IUD, or hormonal therapy?” You know, “Is your cycle regular or not? Do you have hot flashes? Do you have other perimenopausal symptoms?”
Bergink:
So when we try to diagnose anxiety, depression, we also need to ask about those symptoms.
Puder:
What was most helpful for you when you sought help? What was helpful from the professionals that you saw and what do you feel comfortable sharing?
Bergink:
Yes, I'm totally comfortable sharing. And I saw lovely professionals, but they….
Bergink:
Don't know either, in a way, right? So, I first saw a gynecologist and she put me on hormonal therapy and at that time that was oral hormonal therapy and that made my mood worse. That happens sometimes in women, right? There are also women who are sensitive. For example, Mirena IUD or contraceptives, that is associated with depression, so that wasn't so helpful. And then I got hormonal therapy, a patch, and that was helpful for perimenopausal symptoms such hot flashes and feeling stiff in the morning and all kinds of other symptoms. But my anxiety responded well to an SSRI. So for me, the hormonal therapy was not solving the panic attacks.
Hormone Therapy: Benefits, Risks, and Common Myths (08:19)
Puder:
Okay. Yes, that’s actually, one of the myths I found on Reddit, was that HRT [hormone replacement therapy] fixes anxiety within the first 24 hours. For almost everyone.
Bergink:
Yes, that would be lovely.
Bergink:
Yes, I know. As I said, it's not the magical bullet. I think over the past decades, you know, we went from a phase where the recommendation was to most women, everyone should go on hormonal therapy because it might be, it keeps you young and it might give cardiovascular protection. And then we had these women's health initiative studies coming out saying, "Okay, no, it increases risk for breast cancer and even dementia. And, no one should be on hormonal therapy." And it turned out, there was a lot to say about these studies, that this alarming message was really not justified, right? That these risks were overestimated, that it was investigated in older women and younger women, with different forms of hormonal therapy.
[Clarification: Manson et al. (2013) demonstrated a clear age gradient in the absolute risks associated with menopausal hormone therapy. With estrogen plus progestin, there were 12 additional adverse events per 10,000 women per year among women ages 50–59, compared with 38 additional events among those ages 70–79. With estrogen alone, women ages 50–59 experienced 19 fewer adverse events per 10,000 women per year. Although the increased breast cancer risk associated with combined estrogen-progestin therapy is clinically meaningful, the absolute increase is relatively small.
For healthy women younger than 60 or within 10 years of menopause onset, the overall benefit-risk profile of hormone therapy is generally favorable when there are appropriate indications and no contraindications. The key is not to avoid hormone therapy because of risk, but to identify the appropriate patient through careful consideration of age, timing, medical history, treatment indication, and individualized risk factors.]
Bergink:
Yes. And now we're in this age in which we see both. Calls for overtreatment, like, “Yeah, it helps everyone and it keeps you young, and happy, and healthy and all women should use it.” And yet, at the same time, we also see that not that many women use it. In the end, there might be a group of women who have really severe perimenopausal symptoms and who could really benefit from hormonal therapy and not get it. So we see now we have a mix, but the nuance has been gone a bit out of the debate.
Puder:
There's another myth that if the hormone therapy does not fix anxiety, the dose must be simply increased.
Bergink:
Yes, I think the dose finding is a bit challenging. It's a bit of trial and error, but you start with the lower dose. But you're so right. It's not that it’s immediately going to fix it. I have to say there are women who have a whole broad variety of symptoms and who start hormonal therapy and describe it as a game changer, right? Like, okay, this really worked well for me. But that is on an individual basis. Yes, we know from studies that it sometimes can help to prevent depression or it can do something for sleep and depressive symptoms. But we also know that for major depression or a more severe anxiety disorder, it still needs to be treated by us as psychiatrists, just in the same way as we do at other times.
Bergink:
But I think, for some women, it's worth trying. Again, because there are women who describe, “I feel really much better after hormonal therapy.”
Puder:
Right. I think one of the recurring myths is [that] anxiety medication and psychotherapy to treat anxiety during this time period doesn't work because it's a hormonal issue. And one of the studies I saw, Brown [et al.] (2024), is that CBT (cognitive behavioral therapy) actually does help with sleep disturbance [and] vasomotor symptoms. So even therapy is helpful. Any thoughts on that?
Bergink:
Yes, absolutely. Therapy is very helpful. And CBT-I [cognitive behavioral therapy for insomnia] is a short therapy. It works well and, and people should try it because it also teaches you not to focus too much on your sleep, right? Paradoxically. And, I think that really helps and that is part of it. Also accepting that sleep might not be that ideal in that period and creating the right circumstances that you actually can get some sleep. So, CBT-I works really well. At the same time, and we know this for therapy at other times as well, most people do not get it, right? Because they think it's difficult to access or, you know, are not motivated to do it.
Puder:
What other medical problems can sometimes mimic or be similar and should be ruled out? Like, things like thyroid disease, cardiac symptoms, maybe even…?
Bergink:
Yes. I think thyroid disease is a problem, which occurs mainly in women, right? So that plays a major role during this age and needs to be excluded, because that further complicates it. And cardiovascular symptomatology is important as well and I think that needs to be ruled out. Of course, if there are palpitations or someone is anxious that there is an underlying medical condition that needs to be ruled out, especially in this period. And that's, by the way, also another reason to treat depression in perimenopause, because we know that there's also a risk factor for adverse cardiovascular outcomes in women later in life. So, that is a reason to treat it. But yeah, I struggle sometimes with seeing women, and I also had that question myself, what do you start first, right?
Hormone Therapy vs. Antidepressants: What Should You Treat First? (14:07)
Bergink:
So if you, let's say, you have severe symptoms, if it's sleep and cognitive behavioral therapy works, that's beautiful. But if that is not sufficient, should you first try hormonal therapy? If you can, if you don't have a clotting disorder or an increased breast cancer risk. Or should you try, start an SSRI?
Puder:
And what do you think?
Bergink:
I think it's important not to do both at the same time.
Puder:
Okay. That's fair.
Bergink:
Because then you don't know what is working. And the problem is, we know for our medication, as psychiatrists, that it takes weeks to work and to get a good idea if this is helpful or not, right? For SSRIs we need so long. But for hormonal therapy, it's even worse, right? It's sometimes months. You want to evaluate what it does. So it takes some time. At the same time, in terms of side effects, SSRIs, most of them come with some side effects, which are also especially problematic during this phase of life, such as weight gain or lack of libido, which is a major symptom of perimenopause. So, I think that is also a reason, if it's mainly driven by sleep loss and vasomotor symptoms and perimenopausal symptoms, to first see what happens if you start hormonal therapy.
Bergink:
And then see what is left of symptoms. But having said this, of course, if someone has a more severe depression or a more severe anxiety disorder, we should treat that because we know that needs treatment. So it is really dependent on the severity of the symptoms.
Puder:
Yes. And I think as a clinician, you should get kind of, like, baseline libido, and so you can re-ask and see if there are changes. If there are changes, maybe it is the medication and if it is, some people have worse issues than other people. If they have worse issues, then you could consider a different medication or a different treatment.
Libido, Testosterone, and Hormonal Sensitivity During Menopause (16:37)
Bergink:
Well, I like the concept, baseline libido, but, you know, in women, sometimes that is a bit challenging as well, right? Because that can also be variable with the cycle.
Puder:
Yes. We could ask in, like, the last three months. You could ask questions around how high the different aspects of libido are, so that you know if you're adding an SSRI, and is the SSRI causing the issue or is the issue there beforehand? That's all I'm saying.
Bergink:
No, and that's absolutely true because we also have these patients who actually have more libido, right? Because their depression was causing this. So then we should ask also, in times when they felt well, when their mood is well, and then that is the baseline. And I think that is very important. And especially because there's now also a lot of information about testosterone, right? That this would be a fix for women, and that women should be using it in addition to estrogen. And progesterone, because women with a uterus should use progesterone, as well that they should also start on testosterone.
Puder:
Testosterone. What do you think about that?
Bergink:
Yes. Again, I think for some…. The evidence is not there, right? I think it's a myth that women lack testosterone, right? That needs to be fixed. Because actually, if you look at women after menopause, their ratio of estrogen and testosterone is higher postmenopausal. So, I think it's a myth that everyone should be using testosterone and that they're more energetic and their libido is great and they feel amazing. Because, especially in higher doses, it also comes with some side effects, like excessive hair growth or other testosterone-related side effects. So I think that it should be cautiously used. But I have to say, if low libido is not caused by depression and sex life is not improved by estrogen patch or vaginal estrogen, then for some women, it can really help.
[Clarification: After menopause, total estradiol decreases much more than testosterone, which declines only gradually with age. So the ratio of testosterone to estrogen rises, not estrogen to testosterone (Burger et al., 2000). The 2019 Global Consensus supports testosterone only for postmenopausal women with low sexual desire disorder (HSDD), not for energy, mood, or general well-being (Davis et al., 2019).]
Bergink:
And, I think that it is frustrating that we do not know beforehand that this field also is so much trial and error. And we also know that someone's past history, reproductive past history, can give a clue, right? If someone had postpartum depression or someone had really bad PMS, premenstrual symptoms, and that person might be vulnerable for hormone fluctuation. That person might be vulnerable during perimenopause. And we know this is true, that especially women who were vulnerable for those hormone changes. There are some studies suggesting that there is a mood disorder subtype, consisting of women vulnerable for those hormone fluctuations (Schmidt et al., 2015) . But it's very unpredictable. There are many women, fortunately, who have gone through postpartum depression and their perimenopause is not bad at all.
[Clarification: In a double-blind estradiol withdrawal trial, Schmidt et al., (2015) reported that depressive symptoms recurred in 5 of 14 women with past perimenopausal depression switched to placebo, while women without that history stayed well, supporting a subgroup that is sensitive to changes in estradiol.]
Bergink:
And, you know, I'm the example of the other way around. I didn't see that coming. I did not have postpartum depression, nor premenstrual dysphoric disorder (PMDD). And I really struggled through perimenopause. Still do. So, yes, I think it's really unpredictable in a way. And, therefore, very interesting.
Puder:
Yes.
Bergink:
And I wanted to say because women have that question a lot as well, what contraceptives to use. Because that is associated with anxiety, depression as well. So there are really women who are on contraceptives and stop and feel better. Same for the Mirena IUD, that is associated, as contraception, that is really associated with also having the onset of depression. But we do not know for the patient in front of us if this holds true for this person, right? So the only way to figure that out is sometimes to remove the IUD or stop the oral contraceptives and see if someone feels better. But then, you also have the problem like, "Yeah, but what about birth control?"
Puder:
What would be other options, right? Is that what you're saying?
Bergink:
Yes. The other options are not always great, right?
Puder:
Oh, in outpatient practice, we try one thing at a time and see if it makes them worse or better. Or when we're getting the history as a psychiatrist, it's like, "When did you start a new medication? When did you get your IUD placed? When did you get your oral contraception? When did you start these different things? And did that timing fall in line with the worsening of symptoms?"
Bergink:
Yes. Absolutely. And I don't know about you, but when I was in my training, during residency, I didn't learn that as part of the things. We learned to ask for psychiatric symptoms, right? Depression, anxiety, psychosis, mania, and then all kinds of somatic symptoms. But part of that was not like, “Do you have symptoms associated with your cycle? Do you feel worse before your menstruation? Are you using contraceptives? Did you notice a worsening in mood? And for women in perimenopause, I never learned that. So I think it's a really important thing to think about because, again, for some women, relatively simple interventions can make a major change in how they feel.
Bergink:
And especially in perimenopause, I think it's also good to know that the [time period varies greatly]. For some women, it takes a year, for others, maybe 10 years, but somehow this period will end. And that is good for women to know that, you know, that it's only a period [of time] they go through, you know, comparable to puberty, but someday, it will end. At least for me, on a personal level, that gives me hope.
Surgical Menopause, Bipolar Disorder, and Psychiatric Risk (23:33)
Puder:
What I've seen a lot in my practice, women that have total hysterectomies, have their ovaries taken out, and overnight they immediately develop mood-type symptoms. Any thoughts on that population specifically?
Bergink:
Absolutely. I mean, that's quite dramatic for women to enter menopause at a younger age and also so acutely. So we do know that that is, and I'm so happy that you bring that up, that it is even a higher risk period for having mood symptoms if it's so abrupt than natural perimenopause. And I think there's also a shift. I mean, for some women, they don't have a choice, right? They might have cancer or they might have a serious underlying reason to get their ovaries removed or to go through surgical menopause. But in history, so many women get an oophorectomy or hysterectomy without clear reasons other than having some gynecological symptoms or even, back in the day, emotional symptoms, as that would cure it.
Bergink:
And I think nowadays, more and more it becomes obvious that it comes at a high cost. If it's really needed, you should do it. Again, if you have a serious medical disease or cancer, or there is a reason, but I, at least, see a shift in that happening less often. And I think, especially at the younger age, we know then I would not wait and see how you feel during this period, but start hormonal therapy right away. So, I don't know if the patients you treated were on hormonal therapy, or they first felt worse and then saw you.
Puder:
They first felt worse and they went from doctor to doctor. I mean, this one person, in particular, not only had mood issues, but had burning mouth syndrome. I ran for 10 years, I ran a program that was an IOP (intensive outpatient program) partial program for people with physical issues and psychiatric issues. So it's kinda like people that had more psychosomatic stuff.
Puder:
I mean, more kind of odd symptoms that normally we wouldn't see even like burning mouth syndrome. But I put her on estrogen and progesterone, and it made the biggest difference. But then I couldn't find an outpatient OBGYN that wanted to refill it because they were afraid to refill it, because….
Puder:
Of old evidence, you know, like, from that old study you said. But I was like, I looked at the risk factors. I looked at all of the risk things. I put it before her, and the burning mouth was like, she was like, "I'm going to kill myself because this is that bad." That's how bad it was. And yet these doctors wouldn't refill it because she was like… Because of what? You know?
Bergink:
And now you say it, I also have patients who have, you know, some issues with finding a healthcare provider for hormonal therapy, so I prescribe it. But it is a bit of discussion among psychiatrists, whether we should be the ones prescribing it. So do you do it? Do you prescribe hormonal therapy? Are you comfortable prescribing patches or oral micronize progesterone, or you never do it?
Puder:
Sometimes, if the OB wants to do it, I'll let them do it. Sometimes, I'll do topical testosterone as well, because it helps with some people. Just, it's not the first line. Injections of testosterone, for some men who are low, I obviously measure their levels, and then measure….
Bergink:
Oh, for men, you prescribe it, not for women?
Puder:
For men and women. As kind of like an adjunct. For some, it's made all the difference. For some it's disappointing. It doesn't do anything. And for some, it's for sarcopenia, if they have really low muscle mass (Huang et al., 2014). As a way of helping them get back on track after a severe medical illness. Remember, I saw a lot of people with medical illnesses and like….
Bergink:
Right, right.
Puder:
For them, sarcopenia, in and out of the hospital, it's like they're just fighting against this thing. And so I get creative and sometimes they're already on an antidepressant, you know, it's like what, what else can you do at this point?
Bergink:
No, I agree with you. It's worth trying because there are patients, as you say, for which it is a game changer, whether it's hormonal therapy with estrogen, or whether it's low, low testosterone. It's not for everyone, but sometimes it can help. So if we do this cautiously, and start not too high, right, I think we, as psychiatrists, can also do it, if comfortable. I discussed it with the gynecologists in our hospital and they say, "Yeah, sure, you can do it." But the other way around holds true, as well. That I tell them that they, for example, can prescribe an SSRI during pregnancy if someone is really not well and has a major depression and they also have a preference that, you know, psychiatrists do it. So I think the patients get the best care if either the care is coordinated or providers feel comfortable to prescribe both.
Puder:
So it's like, if I'm going to monitor someone very closely and watch symptoms very closely week-to-week, or every other week, you know, an OBGYN might be seeing them once every three months. That's the pace, or that they may even be able to just get them in at that pace. That's the only pace they'll be able to get them in. So maybe I start something and then I ask them, "Hey, we're at a stable dose, you're doing well. Can you see if your OBGYN would continue to fill this?"
Bergink:
Yes, that's hugely helpful. And well, a question I struggled with is for bipolar women and they ask me about this, right? So should women who had had a postpartum psychosis in the past, as in groups of women with high vulnerability for endocrine transitions, should they start it as a preventative? So before any symptoms occur, should…? I know that some patients, also women in bipolar patient organizations say, "I didn't even want to wait until I had the first symptoms of perimenopause. I was so anxious of getting depression again, or hypomania, or destabilizing that I chose to start hormonal therapy as prevention quite early in the game." So I don't know what to recommend, right? If we should first see how it goes, or some high-risk groups, already start, you see what I mean, as prevention?
Bergink:
Yes. So not as treatment of perimenopausal symptoms.
Puder:
The only sort of thing that I would kind of question on that is, during the post-birth period, there's a lot of things, not just the hormone issues, right? So it's inflammation, and then you had the immune suppression, now the immune overactivation. So is it just the hormonal issue? Is it a multiplicity of issues, right? And so, because our understanding of it is multifactorial, does that change how you might approach this question with the patient?
Bergink:
Yes, that's true. So, after childbirth, it can be multifactorial, but the endocrine glands play a role. And there is some evidence, there is a new UK Biobank study, or not that new, it's last year or so, showing that for bipolar disorder, it has a bit of a peak, but it's not enough evidence to start treating as prevention (Shitomi-Jones et al., 2024). But yeah, I don't know. I also really understand those women I spoke to who have bipolar disorder who said, “I started early, right away when I had the first symptoms or when my cycle started to be irregular a bit.” Because that's the other difficult thing, at least for childbirth, that's a very clear event when that happens and the weeks after. But perimenopause is so blurry and vague. It's the cycle starting [to become] irregular and then there are women who had an irregular cycle to start with, or as I said before, women were using Mirena IUD, so they hardly have any menstrual bleeding, and there are women on atypical antipsychotics that might mess up the prolactin and their cycle.
Bergink:
So it's sometimes a bit difficult to determine where someone is, if that makes sense.
Puder:
Right. Yes. I don't like to leave people with high prolactin from Risperdal. That would be one thing that I think I would, if someone did have, if they were messed up in their cycle from…. Because…. Is that what you're thinking? Like the prolactin goes up with….
Bergink:
Yes, yes. I mean, for women, some antipsychotics are more risky in that respect than others, right? So I think we should think about it; and because all [medications] have side effects, we should weigh those side effects.
Perimenopausal Depression: Can Estrogen Help? (32:59)
Puder:
Okay, let's move on to can menopause [and/or perimenopause] cause depression? And so I think we answered this to some degree, but let me…. Maybe I'll just read some of the myths that I found. And this is mostly on places like Reddit.
Bergink:
Oh, wow. Yes, yes, please do.
Puder:
So myth, depression during perimenopause is only a hormone problem. Low mood proves estrogen deficiency. HRT cures all perimenopause depression. If depression persists despite HRT, the person is using the wrong dose rather than having another condition. Depression automatically disappears once periods stop. So those are all the different opinions that people professed emphatically on Reddit.
Bergink:
I have also heard some women call themselves perimenopause survivors. Well, that is, that sounds severe, right? Like I said, so many have perimenopause without…. The majority of us, you know, are doing just fine. But, yes, I think if the depression is severe enough, then hormonal therapy probably is not going to make women feel better, in most women. So they need to treat their depression or severe anxiety disorder, as well. And, now we're talking only about the biology, but let's not forget that it's also, you know, getting older comes also with all kinds of, and this is your specialty, physical problems, and other disorders. And this phase in life, also, for women who have children, they leave the house. It's not an easy period to transition and children being in their puberty themselves, or being older.
Bergink:
For some women without children, they might struggle also with aging, for that reason, as in not having children. So both ways, it's a difficult period. And then there are the problems people are having with their parents; and either losing them or them going... And at the same time, men and women often being at the top of their career, as in being in a position that they work hard, and I think all these things together also form the baseline, and that holds true for men and women, and then women on top of that might have all these perimenopausal symptoms which also I hear a lot from, I don't know if you hear about it, but from men, that they struggle as well with the perimenopause of their wives, because some women really get irritable, right?
Bergink:
As in, very irritable. So I think that is also good to realize that is a symptom that is highly variable over time, but what many women describe is that it is strange and that it gets better over time. But, we know that this period not only comes with depression, but also sometimes dysphoric depression or irritability, or almost more of a mixed state, as in feeling agitated and restless. So not the classical melancholic depression, as being low. But more something that women also describe as having before their menstruation, being really dysphoric and irritable, and sometimes even suicidal, right? We know that both suicides and homicides peak in these days before the cycle. So, yes, I think it makes it difficult.
Bergink:
Also for women themselves, of course. They really struggle with this low mood, but I also hear a lot of women struggling with irritability and anger.
Puder:
Yes. I won't ask you if that was something you experienced or….
Bergink:
Myself. Oh, yes, absolutely. Yes. Yes. I experienced…. Well, not so…. As I said, not so much PMS, but just anger. More irritability and impatience. And I never was the most patient person on earth, and that got worse to the level that it's like, “Okay, now you're so impatient, that's just unbearable.” Also for myself. So yes, of course, that is a reason to try what helps for that. And also, it's good to know that some of these symptoms pass naturally, right? So yes, I think that's good to know. As in the irritability and the sleep issues. That just makes a difference postmenopausal.
Puder:
What do you think about estrogen, you know, [that] it isn't FDA approved for mood in post-menopause? Do you think it's just not effective for depression, specifically in menopausal women, or is it perimenopausal women? Is it another option? What's your perspective?
Bergink:
I think perimenopause. Perimenopausal. That is, yes, I think that is what most [of the] evidence is pointing [to], that it can do [the] most in perimenopause. But that….
Puder:
Yes, there's one...
Bergink:
And not so much, like, having being low on, on your hormones and estrogen. Again, women had that before puberty as well, right? That was, being low estrogen is not, in itself, a risk for low moods. And, as far as I know, there is not good evidence for older women, being postmenopausal and then starting hormonal therapy, that being beneficial for depression. I think those longitudinal studies showing benefits, also in prevention of depressive symptomatology, especially in perimenopause.
[Clarification: This defines a hormone-sensitive subtype identifiable from history alone: prior PPD, prior PMDD, prior perimenopausal depression. For that subgroup, the treatment logic is endocrine, not serotonergic. Estrogen is the most evidence-backed intervention. De Novaes Soares et al. (2001) reported remission in 68% of perimenopausal women treated with transdermal estradiol, compared with 20% receiving placebo. Gordon et al. (2018) found that transdermal estradiol combined with intermittent progesterone reduced the development of clinically significant depressive symptoms from 32% to 17% over 12 months, suggesting a potential preventive effect. Supporting a role for estradiol in women with a history of perimenopausal depression, Schmidt et al. (2015) found that women with prior perimenopausal depression experienced recurrence of depressive symptoms when estradiol was withdrawn and replaced with placebo, whereas women without such a history did not.]
Bergink:
But yeah, it's a bit difficult to investigate because again, what I said, the duration of perimenopause is so variable, right? Can be one year, can be 10 years. So, and then to do any study and follow up with women, so many years. Ideally, you want to know how they are before, during, and after. Well, that's a bit more simple during childbirth, for example. The field I worked in. We know, you know, the pregnancy, the childbirth, you know how many weeks postpartum you are. So from a research perspective, that is challenging. And if we look at big databases, then you can, of course, look at all those women who use hormonal therapy and the kind of psychiatric disorders and see what the association is. But it doesn't say much about causality because then you will find that women on hormonal therapy have more often depression, anxiety, but that is maybe because they started because they had these mood symptoms.
Bergink:
You see what I mean?
Puder:
Yes. Yes, this is the difficulty of looking at a study that's not a randomized controlled trial. It's like, okay, are they putting women who have more depression or anxiety on hormonal therapy? Yes, of course they are. You know? And so is the depression or anxiety completely treated compared to the general population? So, maybe they still have some signs and symptoms and…. Or, in these big studies, like what they can see is an ICD-10 code in the chart. They can see [this], but they can't necessarily see what their current level of depression or anxiety is.
Bergink:
Yes. Yes, that's true. And those studies really are measuring ICD codes, which is, in a way, the tip of the iceberg, of course, of depression and anxiety. On the other hand, you know, depressive and anxiety symptoms, we do not want to treat everyone with depressive and anxiety symptoms. That just doesn't make sense. We also know that, especially among older women, the use of SSRIs is sky-high. I think it's almost one out of five women being on an SSRI, right? So really, for me, as a researcher, but also as a woman, it's really questionable whether that is justified because we also know that many of these medications, in many women it's either they're not that effective or it's a placebo effect, right? If you start at the lowest point and you feel better over time.
[Clarification: About 1 in 5 US women aged 60 and over took any antidepressant in 2015 to 2018, not SSRIs alone (24.3% of women 60+, 17.7% of all women 18+; Brody & Gu, 2020). Across 522 trials, all 21 antidepressants studied outperformed placebo for acute major depression, though the average benefit is modest (Cipriani et al., 2018). Some analyses find the advantage over placebo is larger in more severe depression (Fournier et al., 2010; Kirsch et al., 2008), while others find little effect of severity (Furukawa et al., 2018). Severity should be assessed before choosing treatment; milder symptoms often respond to therapy, sleep improvement, and watchful waiting.]
Bergink:
So yeah, I don't know. We want to have a nuanced message out. Yes, sure, treat depression if it's severe, or anxiety disorder, but not immediately. In a way, because some of those perimenopausal symptoms may pass or will get way better once you start hormonal therapy. That might be a very first step, a good first step. If your symptoms are not severe, then you might want to start there. But, I have to say, it helped me a lot going through this myself and also struggling with, “Is this perimenopause? Is this anxiety?” You see what I mean? It's interesting.
Menopause Brain Fog, Memory, ADHD, and Cognitive Changes (42:25)
Puder:
Okay, here's another big question that's kind of out there, online. Is menopause brain fog an early sign of dementia?
Bergink:
Yes, that's one of my big anxieties as well, by the way. No, of course not. And we should reassure all our patients that it's a very normal, physiological event, and it's very normal, and it doesn't mean that you're getting Alzheimer's. At the same time, I've also read those studies that those women with the most severe vasomotor symptoms are at a bit increased risk for dementia later in life. But I think, if I look, for me personally, it would have helped me if I knew better that that was happening to me, that brain fog, because I had that. And that also increased anxiety at some point, that you can't find a word. You're in a meeting, and especially, you know, sometimes we do a lot on Zoom meetings. You're in a Zoom meeting and you want to say something, everyone's looking at you, and you just cannot find the word.
Bergink:
That is really anxiety provoking. So for me personally, it would've helped if I had known this early in life, that that would happen to me. I never thought about that. I didn't see it coming. I could always totally rely on my memory, one thing. And in an ideal world, it would be ideal if we would all be a bit more mild to ourselves and just comment on it, like, "Oh, I have some brain fog, and that's happening to me now." And I think that would be huge if women felt comfortable enough to bring that up and then other people would not respond as in, "Oh, that is weird." You see what I mean?
Puder:
"In one study of 16,000 women, forgetfulness complaints rose from 31%, before menopause, to 44% in early perimenopause, then stayed at 41% after perimenopause. [Gold et al., 2000, SWAN cross-sectional survey of about 16,000 US women aged 40 to 55: forgetfulness was reported by 31.2% premenopausal, 44.0% early perimenopausal, 44.8% late perimenopausal, and 42.0% postmenopausal women (Table 2). These are self-reported complaints, not test scores.] And then they showed that the testing of learning memory during perimenopause was a little bit impaired, but actually recovered in menopause. [This finding is from a separate SWAN study, not the survey above: Greendale et al. (2009) followed 2,362 women with repeated cognitive tests. The normal improvement that comes from retaking the tests stalled during perimenopause and returned after menopause.]"
Bergink:
Post-Menopause.
Puder:
Yes. Post-menopause, yes. Yes. After menopause.
Bergink:
Yes, yes, that's hopeful, right? It's the same with the pregnancy/postpartum dementia, that will pass as well. Because if you just look at cognitive functioning in the third trimester of pregnancy and postpartum, that's really bad. That's making women anxious as well, you know? They have this baby, they go back to work, they're like, "Oh my God, I'm totally incapable." And then that bounces back. So it's good to know that that happens in perimenopause as well. But the difficult thing is, especially if perimenopause, just as in my case, I'm in and out for, I don't know what, eight years, like an insane amount of time. So, at the same time, we age, right? So not sure if it bounced back to the level we were before, because everyone, men and women, have some... Yeah, we have to live with that, that our cognitive peak is in our 30s. Even if you are past it.
[Clarification: Different cognitive abilities peak at different ages. Processing speed peaks around the late teens to early 20s, working memory and some memory skills around the 30s, and vocabulary and accumulated knowledge into the 60s and 70s (Hartshorne & Germine, 2015). Midlife memory changes during perimenopause appear largely temporary: in the SWAN cohort, learning stalled during perimenopause and rebounded after menopause (Greendale et al., 2009).]
Bergink:
And from then, onwards, we're going slowly down to who knows? But, yes. For me, talking about it, weirdly enough, is a bit anxiety reducing, as in saying, "Okay, you know, I can't remember, but that is brain fog.” I think that's just helpful if people talk about it and then it becomes more normal.
Puder:
Yes. I'm glad this is anxiety reducing to talk about it today. Is that what you're saying? Today, specifically?
Bergink:
Yes, for me, it is. I'm not sure if you saw it, but I even saw, there is this man working for television, and he's presenting, and as he is presenting, he's having a panic attack. I'll show you the link. And then he says, "Oh, what is happening to me now is that I'm having a panic attack." And the people around him say, "Okay, just stay calm, breathe." And he's like, "Okay, I'm over it." And, you know, when I watched this that was also really liberating for me. It's like, “Wow, this is next level,” right? Because I think part of the anxiety, at the moment, is that you feel like, “I'm not functional. I'm not doing well. I'm crazy.”
Bergink:
“What will other people think?” You kind of take that away if you address it yourself. If you're comfortable enough to say, “Okay, this is what I have. It's not that serious. It will pass. It doesn't make me less of a professional.” You see what I mean? So, yeah, I think it's important.
Puder:
The meaning we attach to things and the shame we attach to it make it worse, right? And this is where this becomes a little bit of a behavioral exposure event to lessen the thing that you're anxious about. Or it's like when we have anxiety, avoidance is not a good long-term strategy for overcoming the anxiety. We have to expose ourselves to the thing that we fear, progressively, over time, in a way that is not overwhelming or traumatic, but then it can improve.
Bergink:
Yes, and it takes time. I mean, I think if you just have it, then it takes time, but in time, if you can learn, and we know this from not only anxiety, but I think from other psychiatric disorders, as well, that it really helps some people or patients to talk openly about it and for sure it helps others. So, yes, on a personal level, it helps for my own perimenopausal symptoms and anxiety to talk about it, and hopefully it helps for others a bit, as well as learning that can happen, that it's treatable, it will pass, and yes, part of it, as you say, it sometimes is what it is, right? And it's not completely gone, but you make sure that your life is not impacted that much.
Bergink:
Because that is the avoidance. Sometimes the anxiety is not a problem, but some women even quit their job in perimenopause because they feel so non-functional. And having brain fog and the symptoms and….
Bergink:
I think that's a loss for everyone, right? Because those are experienced people in the workforce. And also, I have to say I understand it. You know, it also crossed my mind, of course, if you have many symptoms that you think, "Okay, you know what? I call it a day. I stopped doing what I'm doing.” But I think, in the end, that's not the best way to go.
Puder:
I think a lot of patients, the more the anxiety [they have] that their cognition is worse than it actually is. You know, I always tell my patients with the anxiety and the depression, and then they have the cognition issues, and they're anxious about, "Oh, gosh, am I…? Do I have dementia?" It's like usually the dementia patients are the ones who are confabulating and not worried about their memory. You know, “Are you having any memory decline?” “Oh, absolutely not, doctor. Why would I have memory decline?”
Bergink:
Yes. That's true. But that's maybe also later. No, but it's true. And also, it's often not so much a memory problem as it is an attention or concentration problem.
Puder:
Attention and concentration?
Bergink:
And I think that is underestimated, as well. Because we know also from perimenopause that also women who already had ADHD (attention-deficit hyperactivity disorder), or are on the spectrum, because some have those traits, that those traits also specifically peak in perimenopause [anecdotally]. So then it's not the cognitive deficit, as in, not having access to your memory, or storing things, but it's purely sitting down and getting work done and concentrating on the thing you're doing instead of being distracted by all the things happening around you. Because that is what I heard from women as well, right? They're easily [distracted]. They could work in a bit of a noisy room. Now, they just cannot stand noise anymore, which doesn't go well with kids in their puberty, or it has to be calm.
Bergink:
And so they're more sensitive for those things, and that causes the feeling of cognitive deficit, while it's actually more of an attention and concentration problem. I don't know if you recognize that.
Puder:
Yes. So how do you treat the attention-concentration problem in perimenopausal women?
Bergink:
Well, that's a good one. If anyone knows…. I don't know. What I do myself is that the things that need the most concentration and attention, I do them in the morning.
Puder:
Oh, okay.
Bergink:
And early in the afternoon and not late afternoon or in the evening. Whereas, back in the day, I could also be fully concentrated at 11:00 PM and write something beautifully. And that's not going to happen anymore. What people, in general, say, “Be mild to yourself. Get some more rest. Make sure that you don't multitask at work, because if you have to multitask and constantly shift focus, then it's harder to get things done. But having said this, sometimes that doesn't work because some women just have a job that is quite hectic. And, you have to face the circumstances you're in. So then, it's really about, I think it already helps a lot if you're mild to yourself.
Bergink:
If you notice that if you cannot do it, that you think, "Okay, then I'll try tomorrow or I will do it in the morning." But, do you have solutions for how to treat these ADHD-type of symptoms?
Puder:
I think your points are well received. I mean, if you can optimize sleep, if you can optimize exercise, look at what they're eating. If they're eating a huge meal midday, that might not be the best for focusing later in the day. And so, simple things like that is where I would go first. And then, secondarily, are they scheduling the highest energy tasks in the morning? Because I think that's everyone. I have to do that too, you know? Or if they have a history of ADHD, is that being treated or do they have ADHD? You know, do they need testing or is it obvious? If it's obvious, then go over the risks and benefits of different medication classes for it.
Bergink:
That's true because there are some women who, ADHD traditionally, being underdiagnosed in some women a bit. And they enter perimenopause, their ADHD symptoms get worse, maybe over the threshold that it becomes clinically significant. At the same time, it might be that their children have been diagnosed with ADHD and then they start wondering about themselves. I don't know if you recognize that, but I had quite a few patients like, “Oh, maybe I am the one. We know that it's highly genetic, so maybe I carry one of those risk genes and maybe I have some of these symptoms myself.” So yes, and I think it's good too, as you say, it's good to know because ultimately, if you have other symptoms as well, then you might lean more into medication that is also better for ADHD or you could also try using ADHD medication.
Bergink:
But I have to say, I do not have a lot of experience with starting this first time in perimenopause, in women with those symptoms.
Bergink:
That's good to know. So I don't know.
Puder:
Yes, it's not a normal thing that I've done either, but, you know, we're presenting a scenario that we're trying to figure out what we do under this given scenario here.
Bergink:
Yes.
Puder:
Okay. So, wow, I think we covered a lot. I think people's brains might be saturated at this point.
Puder:
Any other sort of final reflections on perimenopause, treatment, things you would want clinicians to know?
Bergink:
Yes. Clinicians, to know and ask about it. And women going through it, it will pass. And there are good options out there.
Puder:
Awesome. Well, we will leave it there for today. Thank you so much for coming on. I feel like there's a lot to take away, and I'll put some links to articles you recommend so people can continue learning. And we'll leave it there for today.
Bergink:
Thank you so much.
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