0:03 [music] Welcome to the Stanford Women's Health podcast series. I'm Dr. Sharon Hung, director of women's health for the primary care and population health department at Stanford. From debunking myths to exploring the latest research, we will delve into the world of women's health with leading experts in the field. Today we'll be talking about insomnia across a woman's lifespan. And here with me I have Dr. Mera Zayn. She completed her medical degree at McGill University in her psychiatry residency at NYU where she developed and led programs in integrative behavioral health and collaborative care models and also completed a year-long training specifically in women's mental health. Dr. Dr. Zayn then completed her consult
0:49 liaison fellowship at Stanford where she now serves as the psychiatric director for integrative behavioral health for Stanford's primary care clinics. She also works with consult liaison psychiatry supervising fellows in the psychosomatic medicine clinic and teaches residents and fellows in women's mental health as well. Thank you for being here Dr. Zayn. >> It's a pleasure to be here. So insomnia is a very common problem for everyone but more women are more likely to experience insomnia in part due to the hormonal fluctuations during our lifespan. So we'll spend the first half of our conversation on insomnia manage during pregnancy and the second half on pmenopausal related insomnia. So jumping right in to insomnia during pregnancy. Insomnia affects a third of pregnant
1:34 women. What are the main drivers of insomnia across the trimesters and how does it affect mood disorders and pregnancy outcomes? >> Yeah, absolutely. So when we think by trimester and we think first trimester, that is where you have a rapid increase in estradiol and progesterone as well as other hormonal changes. And with that rapid change, you can see a lot of sleep disruption due to the complex interactions of estrogen and progesterone with various sleep architecture and sleep functions in our brain. Um, other aspects from the first trimester rate, nausea becomes a really big factor that can keep women up at night and just the significant changes happening in their bodies can lead to discomfort. When we move on to second trimester, we actually see general
2:20 reports of improved sleep compared to first trimester. If you have persisting nausea, that can be an issue. And then once you get towards the second half of your second trimester, you might start to have um fetal movement, right? In which case that can be interruptive, especially right when it's happening frequently at nighttime. You also start having more of the physical changes that lead to discomfort. So growing belly leading to just discomfort with sleeping uh higher rates of gird that can happen as well of reflux and then right leg cramping that can happen. You really see also the changes in iron and folate metabolism that can lead to anemia that start progressing more during that time as well as drops in vitamin D. So all of those factors can lead to sleep disruption and then in third trimester
3:07 all of those really ramp up. So reflex becomes much higher. you start having nocturnal uterine contractions because oxytocin peaks at night. So you get those more frequently in the evening, much more fetal movement um as well as just like the leg cramping, the discomfort from as your size is getting larger and larger. When we think about impacts on mood um and and outcomes there, one of the biggest things is that poor sleep, especially if you've got severe insomnia throughout, can lead to higher risk for parartum and postpartum depression. higher risk of parartum and postpartum anxiety and then if people have pre-existing psychiatric conditions it also can worsen those. Um another thing to note is that sleep disordered breathing especially obstructive sleep
3:54 apnnea um had often goes undiagnosed in women who are pregnant. There was one study that showed that less than 10% of women um who ended up being diagnosed later with OA was actually asked about sleep and sleep disordered breathing by their OBGYNS or primary care docs. so underdiagnosed and can have impacts on both maternal and fetal health in periodum and postpartum. >> Thank you for walking through all those changes. I don't think I slept well during any trimester. So, >> me neither. I think postpartum also ends up being underrecognized because you have hormonal changes and then just sleep changes right from as your baby is going through different stages. Postpartum also huge impact, >> right? And then as with many other medical conditions, we start by counseling on lifestyle modifications.
4:40 What changes or modifications would you recommend to patients to improve sleep duration and quality? I think this is where right sleep hygiene which we talk about a lot right and primary care docs and objal about a lot becomes really important. So thinking about right maintaining consistent sleep schedule um for pregnant women who are already told to limit caffeine intake this becomes dually important. um avoiding nocturnal eating, right? Avoiding your artificial light exposure close to bedtime and then having relaxing bedtime routines all become really really important. Um and it's been shown that sleep hygiene practices can be effective for women throughout all stages of pregnancy. I would also say regular physical activity um can be really really useful. So there
5:26 have been studies looking at right aerobic exercise looking at yoga you know different types of exercise can all help improve sleep quality. >> Does it matter what time of day people exercise in terms of impacting their sleep? >> It's a good question. I think the evidence is inconsistent with that for I think it's more some people find that if they do it close to bedtime it makes them more awake. Some people report that that actually helps them sleep better. So I think whatever time works and can actually like fit into your schedule consistently. >> Okay, great. And we have cognitive behavioral therapy for insomnia. CBTI is the first line treatment option for insomnia in general and of course during pregnancy. What is the evidence for CBTI on sleep outcomes? And how do you
6:12 explain what CBTI is to your patients? >> Yeah, great question. So, CBTI for um cognitive behavioral therapy for insomnia is recommended across the board by the American Academy of Sleep Medicine, including for parartum and permenopausal patients. Um, and there are there's been randomized control trials and meta analyses that show that CBTI has meaningful improvements in sleep outcome. So including sleep quality um sleep latency wake after sleep onset um and that's also with patients with comorbid psychiatric and medical conditions and patients with insomnia and then there is a robust evidence for parardon patients to utilize um par CBTI as well. Now I'll
6:59 explain to patients that CBTI it tends to have multiple components. So, sleep hygiene tends to be built into CBTI as part of it. Other things that they might do is helping with right how much time you're actually staying in bed if you're not right awake or if excuse me if you're not sleeping. Um, and so that can help in terms of right adjusting that. And then the h the cognitive and behavioral aspects of it will include kind of exercises on like refocusing sleep and what is your brain doing. A lot of people have trouble like turning their brain off at nighttime. And so helping to think about cognitive strategies as well as the behavioral strategies of getting out of bed when you're not able to fall asleep after a certain period of time, not engaging
7:47 with bright light activities. What are relaxation techniques that you can use to help with sleep? >> I think patients often come in and ask for medications right away. And obviously we should be recommending CBTI first. And I think the other thing is patients don't realize that in studies these medications only help increase sleep duration by like 10 to 20 minutes. It's not magical. Do we know how much improvement we can see with sleep duration in terms of CBTI? Um so CBTI has shown to for and it's variable for it hasn't been shown specifically for women who are parartum. Um but evidence has shown between I'd say like 40 minutes to a couple hours.
8:32 Um so that can be so I think it has more robust data consistently on just improved sleep latency um and sleep maintenance versus medications. >> So that's great to know that CBTI is so much more effective than medications and but I find that one-on-one CBTI can be really limited in terms of access. Is there data to support either digital formats like online or through an app as well as group formats for CBTI? >> Yes, there's good data for both of them. Um particularly when we're looking at general population. So if there there's been multiple randomized control trials and meta analyses that show that group CBTI can provide reductions in insomnia severity, improvements in sleep latency, improvements in wake after sleep onset.
9:19 Um, and group CBTI also has been shown to be effective with patients with comorbid depression or other mental health conditions. And so it is definitely if that's more accessible for patients something that they can do. There have only been a couple small studies that have looked at parartum populations specifically, but both of those did show that group CBTI was effective. There haven't been trials kind of onetoone showing uh individual versus group. So we can't really count on like if one is superior versus the other. One to one definitely is more of the gold standard. Um moving on to digital CBTI, there's actually a good growing body of evidence looking at its use both in the general population and in pregnant women specifically. There was a large random randomized control
10:05 trial in pregnant patients that showed that digital CBTI produced greater reduction in insomnia severity and global sleep quality and perceived sleep quality versus standard care um right in a primary care or OB/GYN office. And there were effects that were maintained at followup um during the study. There was also a decrease in depressive and anxiety symptoms during that trial with lower incidence of postpartum depression versus the standard of care patients. Um there was another randomized control trial in pregnancy that showed that c that digital CBTI led to faster and higher rates of insomnia remission compared to control. So definitely a lot of good data there um for using digital CBTI apps when you can't access other
10:52 things. That's really reassuring that there is data to support the use of digital CBTI both in the general population as well as helping with sleep and mood disorders during pregnancy. And what resources would you recommend for providers and patients for them to help find CBTI whether that be a group, individual or digital format? Yeah. So I think always if there's something that's available within right your local um right center if you are at Stanford for example and you refer to like sleep medicine um but oftentimes right access can be an issue in those cases in which case you have to learn look externally into the community. Um there's a few different resources that that both providers and patients can look at. One would be provider directories. So, the
11:39 Society of Sleep Behavioral Medicine um has searches for credentialed behavioral sleep medicine providers and you can look and filter specifically for CBTI. Um the University of Pennsylvania, which is like a good training site for CBTI if anyone's looking to actually get training. Um they maintain an international directory of CBTI providers. And then the American Board of Sleep Medicine also has a list of clinicians who are certified in behavioral sleep medicine. in terms of those digital apps that we were talking about. So there's a free app called CBTI coach that you can get and download from the US departments of veterans affairs. So it will teach CBI CBTI strategies. It's not fancy but it is free and it can be used in complement with facetoface
12:25 therapy which is nice. Um there are a couple apps that do cost money although one of them can get reimbured depending on your insurance. That's Sleepio. Sleepio is an online evidence-based CBITI program that has a good growing body of evidence behind it. It's actually used in the UK like as part of the NHS as a prescription. Um, and it does contract with like different businesses and stuff as an actual like prescription that can be put in for sleep. Um, and then there's another program called Good Path which offers a digital multi-week CBTI program and that has coach supported lessons. So, it's not like fully digital the way that Sleepio is, but you do get connected with a coach via email, phone, or a video call, which is nice. Um, and then if people are more interested in like
13:10 educational pieces, you can go to Mayo Clinic's interactive skilluing module. It's a web-based module that teaches strategies um that are CBTI uh inspired to help with sleep. >> Wow. Thank you for sharing all those resources. We'll make sure to have the links in the description for the episode and pharmarmacothotherapy which I briefly mentioned in pregnancy is reserved for persistent insomnia after those lifestyle modifications you talked about about CBTI with of course careful risk benefit discussion. When would you consider short-term phicotherapy during pregnancy and which agents do you prefer in this population assuming they have no coexisting mood disorders? Yeah. So what I would say right which population as you described right someone who has
13:57 failed right other non-farmacological interventions whether it be they've tried it and they right are not it's still not helping enough or for people who due to various circumstances right can't access that type of therapy they or and they've tried lifestyle or their lives don't permit a lot of those lifestyle modifications right if we think about a lot of people who are more vulnerable who have or working right multiple jobs they don't have like that ability to to really adjust their lifestyle accordingly that's when I'll think about pharmarmacothotherapy also for people who do have actually depressive like depression and the sleep is making things worse and as you mentioned right having that risk benefit discussion can be really important I don't think most people realize the
14:43 significant risks that severe untreated insomnia can have on both mother and fetus And so it becomes an important discussion of like actually right I know you don't want to take medication but this is the evidence for right not treating your insomnia and what it might do. This is the evidence for what the medication might do. Um my go-to as a first line will be doxyamine um or unisome over the counter right it is actually combined and you and is recommended um for uh for nausea um during pregnancy. And so it's been part of several studies. It's been shown that it doesn't have congenital abnormalities first trimester that there's no evidence, right, showing that there's
15:30 significant changes in terms of right gestational growth, you know, or intrauterine growth restriction and no parartum complications in terms of like increased rates of C-sections or other complications during delivery. um it's then not recommended for breastfeeding, but I think from a parartum perspective, doxyamine can be really useful. Benadryl is the other one that tends to be recommended as first line, right? Both of those are going to be anti-histamines and how they're acting. Um and so those are the ones that I would recommend to women first line to see if that can be helpful for them. Are there any other prescription sleep medicines that you might consider if uh women don't do well on those medications?
16:16 So for some women we can consider lowd dose trazadone. Um but I would say that you want to again have that risk benefit discussion because then you're adding on something that is also serotoninally modulating. Now there's good safety profile for let's say SSRIs um but you know trazodone hasn't been studied as well but has been used safely in a number of women um but if they don't like antihistamines again is working mostly through antihistamine as well as through alpha activity um there is actual evidence and this can be very debated for using intermittently lowd dose benzodioipines and I would say particularly laorazzipam given its better metabolic profile Um I've also seen gabapentin used although that has
17:03 again not as great data. Um but what I would say with benzodioipines they get a bad w because there were earlier studies like with concerns for congenital abnormalities. Those studies have largely shown that the risk is not as high especially with something like larazzipam. Um, and then if it's used right in low doses and and hopefully sparingly that it actually doesn't have significant effects during pregnancy, it's mostly at the end of pregnancy where we're thinking about babies that are born with floppy baby syndrome where they are a little bit more flaccid and they can have decreased breathing and that's that is a risk that is there. Um, but this I would reserve laorazzipam for people who have are having a hard time sleeping and nothing else is working. That's interesting that laorazzipam may
17:50 be relatively safe option for refractory insomnia in pregnant women for the earlier parts of pregnancy. In that case, are the non-benzo hypnotics such as zulpedom an option for refractory insomnia during pregnancy? Yeah, it's it's a great question. So there is a lot more data accumulated for laurazzipam versus the z drugs and I guess out of all of them dopedm has the most data. Um, and then neither of them write first line. You can use Zulpadm let's say for refractory severe insomnia. But if I was going to choose one of them, I would choose larazzipm number one for better data. Number two, that sulpedm actually crosses the placenta pretty readily, more readily than laazzipam does. And so
18:36 both of them do have that risk in late pregnancy of neon of um of sedation and kind of and postpartum complications and potentially right having the infant needing more intensive support for resuscitation. But there are more cases of that with zulpadm in the literature and zulpidm also crosses into breast milk a lot more readily. So there's a higher percentage and from a safety perspective then during breastfeeding zulpadm isn't ideal. So what I would recommend is if you had to choose something for like severe refractory insomnia I would go with the larassa pamp over the zulpadm. Um the only caveat being like if someone like zulpadm is the only thing that's worked for them they're having severe insomnia you can consider it but I would say use
19:22 it sparingly if you can focus on CBTI and other interventions. Very interesting. And I find that pregnant women are understandably cautious about taking medications. But like you mentioned, it's important to educate women that untreated insomnia, untreated mood disorders are associated with significant maternal and fetal risks such as preterm birth, low birth weight, gestational hypertension, uh preeacclampsia, and other neurodedevelopmental outcomes. So if a pregnant patient has insomnia and a concurrent mood disorder, would you go through the same list of triing docyamine, dyenhydramine, or would your treatment plan be different? >> Yeah, I would say I would probably still go through the list and then see if they'd also be willing to take an SSRI.
20:10 The other thing that can be done is take an SSRI first and see if the sleep improves. Um because right a lot of sleep disorder d with you know comorbid mood disorders is due to the mood itself and so and we want to limit right multiple exposures if we can during pregnancy. So if someone can be started on an SSRI and improve with that then that would be the most ideal um and then if not then considering using one of right one of those first lines that I had mentioned. Um I would say what I thing I would want to add is some people would think oh can we use mtazipene or can we use peroxitine because those are both more sedating. Um peroxitine especially in first trimester we prefer not as a first line it does still have
20:58 some lingering questions around cardiac defects in first trimester. Um, and so we tend to try and go to with certuline first because it's the one that has by far the most evidence of a safety profile during pregnancy. Um, and then mortasipene can be used as a second line as well, but it comes with its own host of issues of right not only groggginess, but it it will lead to potential like increased weight gain and like just, you know, higher rates of gestational diabetes versus using a traditional SSRI. So many patients may think that supplements or something they can buy over the counter is safer for them than anything that we might prescribe. Um any thoughts on using things like melatonin or other over-the-counter sleep aids
21:45 during pregnancy? What I would say is that there's good evidence for the unisome as I mentioned and benadryil. So those I would say yes absolutely. Um, a lot of people will reach for melatonin, but interestingly, at least during pregnancy, there isn't a lot of good safety data. And so, the recommendation is if there is something doesn't have good safety data, don't use that, right? Because we can't predict. And in particular, melatonin as a hormone that is produced in the brain, having a fetus exposed to that as their brain is developing can potentially have impacts long term on their circadian rhythm and other sleep development. And so I'd actually recommend not doing melatonin during pregnancy. And same thing for other right like formulations that have a bunch of herbal remedies. We don't
22:32 have good safety data on what those do. And so the conservative and probably safest approach is to not be buying herbal remedies where we don't know what the data looks like for that in pregnancy because we can't confirm whether or not that's going to be safe. I would also say that I've met a lot of women who will use CBD gummies or smoke marijuana because they're like, well, it's natural and so, right, it's safe during pregnancy. There's also actually a large body of data that is emerging that shows that it has a lot of impacts on the fetus during development and then also on postpartum cognitive development. So, my general recommendation is if you're using that for sleep, let's, you know, talk to your provider about transitioning to something else ideally before you get pregnant.
23:17 Yeah, thank you for sharing that. So, I just want to put a plug in to primary care doctors to always ask about not only supplement use but herbal remedies because patients might not bring that up and personally I see a lot of liver damage from using, you know, some of these substances. But, you know, obviously, we also don't want them to negatively affect pregnancy outcomes. Well, thank you for going over your approach to insomnia as well as mood disorders during pregnancy. So we'll jump in now to talk about pmenopausal and menopausal related insomnia. Pmenopausal insomnia is very common affecting about half of women that go through this transitional period. Can you dive into our understanding of the key hormonal and neurobiological mechanisms underlying permenopausal menopausal insomnia?
24:03 >> What I would say is permenopausal and menopausal insomnia is even more complex than the perpartum one. Some of that is just due to aging, right? So independent of everything else going on with parmenopause and and menopause, studies have shown, right, that women and men, right, as they age will have more disrupted sleep architecture, changes in their melatonin production and just changes in their overall sleep quality as they get older. So there you've got that underlying impact. Then you've got changes in multiple hormones that are happening in pmenopause and menopause with right you have a lot of dysregulation in early pmenopause before you get just decline in estrogen and progesterone. You also get changes in FSH right where you get higher levels of
24:51 SF FSH during pmenopause. This interestingly studies have shown that it's the decreased estradiol and increased FSH so far that are more consistently associated with more frequent nocturnal awakenings and sleep fragmentation independent of basom motor symptoms independent of depressive symptoms. The data for progesterone decline is a little bit more messy. I would say it's it has less robust um association with sleep disruption than the other two. Right? So you can have direct effects of those changes in hormones and then you can have kind of indirect right because it can exacerbate basal motor symptoms. There have been interesting studies looking at actually the hypothalamic neurokin B dorphine neuron network that
25:36 are like integrating reproductive hormone signaling thermmorreulation circadian sleepwake regulation. And so there are estrogen sensitive um neurons that modulate G&RH and modulate um that hypothalamic system and interact with circuits that are controlling body temperature and sleep. And so right as estrogen starts going haywire and then starts declining you have significant changes there. Estrogen also has really complex interactions with the neurosircuitry around alertness and sleepiness. And so higher levels of estrogen will actually be more activating. So it's interesting, right? as you have decline, it doesn't actually lead people to be sleepier, but as
26:23 you're it's having disruption, then you're having all sorts of weird changes in adenosine and prostaglandin 2, which are somnogens that help push sleep drive um with the histamine, dopamine, serotonin syndromes that uh systems that help with alertness. Um as well as with orexin, which is connected to sleep circadian rhythm. Wow, that is much more complex than I thought it would be. So, we know that menopausal hormone therapy can improve vasom motor symptoms and if vasom motor symptoms are disrupting sleep that can obviously be helpful and I know you um just mentioned that the estrogen decline aside from affecting the vasom motor symptoms also affects difficulty sleeping. Do you think there's any
27:10 evidence for using MHT to help with insomnia treatment during this time? >> So what the evidence shows is if people have significant vasom motor symptoms and those vasom motor symptoms are impacting sleep then MHT can be helpful with sleep. So there have been a lot of studies that show that the MHT for those patients will improve of subjective sleep outcomes which is kind of first and foremost. Um the effect size is small um but it is there and it MHT has been shown to be most effective when people are having really significant phasomot symptoms and so for women without phasomot symptoms MHC has been shown to not improve sleep. So I wouldn't recommend it especially right
27:56 if you're using combined with the risks that you can have from MHT >> right and there are some contra indications to using estrogen generally we use the estradi patch such as estrogen dependent malignancy thrombomolic disease arterial disease that don't preclude the use of progesterone I know you mentioned earlier that progesterone decline doesn't seem to be play a big role in insomnia during this time but I'm just wondering since micronized progesterone in and it of itself has seditive properties. Do you see any role in using that alone for insomnia during this time period? >> Yeah, it's a great question. And so it's kind of strange because right the studies show that progesterone isn't necessarily linked with those sleep findings, but there are studies that have looked at micronized progesterone
28:41 and it does have evidence supporting its use for improving sleep quality in women with chronic insomnia during pmenopause and postmenopause. um and or menopause rather. And so there have been RCTs that have shown that if people are taking micronized progesterone, they will have improved subject subjective sleep. They also have improved sleep onset latency, better sleep efficiency. Um and it does have a favorable safety profile. So I would say yes, it's something that that can definitely be used in this population. Interesting. And in early menopause, we can't forget that women can still have children obviously at lower rates than when they're younger. Um, and so we often do use birth control in the age group of 40 to 55 if there's no other
29:27 contrations. Um, and we often use dresperanone containing birth control during this time period to help with the mood fluctuations that can occur due to the hormonal changes. Is there any evidence that using continuous birth control can be helpful for insomnia during pmenopause? >> Yeah, so I'd say not a lot of great evidence so far. Um but not a lot of studies. I've actually only seen a couple studies looking at um combined oral contraceptives that have drosparan specifically. In those studies, it did show that they might help decrease insomnia, but is this was in a general study that wasn't specific to per menopausal women. Um, and it was a small study with a lot of issues with it. And so, what I would say is there's not a
30:14 lot of good evidence yet. Um, and then if you look at the broader literature on combined oral contraceptives of various types, um, they don't find clinically relevant changes in sleep patterns. And some studies actually showed that it increased insomnia symptoms. And again, these are general studies, so they didn't differentiate between what kind of combined oral contraceptive. So, I would say there needs to be more data looking at specific subtypes of hormones that are being used in combined oral contraceptives to see if it could be useful for sleep. Okay. But it sounds like we at least have combined menopausal hormone therapy as an option if no contrrenications and vasom motor symptoms at night and possibly also the use of micronized progesterone alone to help with sleep during this period. >> Yep.
31:00 >> And the most common sleep disturbance during menopause is sleep maintenance insomnia where people have frequent awakenings and difficulty staying asleep along with uh CBTI and uh uh consideration of hormone therapy. What medications do you recommend during this time for sleep maintenance insomnia? >> For sleep maintenance, I would recommend either lowd dose docipin. Um, so that's the brand name sinoquin that's in like 1 to n milligrams. Um, you can also use liquid formulation of docipin if patients insurance does not authorize those lowd doxipins. Just to put that out there um but I would say lowd doxipin and it also has a good safety profile in older adults which is important. Um and then dual receptor ereexenin antagonists. Um so subreexent
31:48 has the most data in menopausal women and then lumbarexent is another one that's had more studies um in it. And so those have kind of the most robust data for sleep maintenance. And then prolonged released melatonin formulations or patches and pill forms of extended release melatonin. They have it has a smaller efficacy study. So, it could be used either as an adjunct or it can be useful if someone doesn't have significant symptoms of that sleep maintenance, but they and they want to try something that is what they find safer or more natural first. >> And by that, do you mean some overthe-c counter formulations or Romelion? So, so I So, Romelion is a melatonin agonist that works on M1 and M2
32:33 receptors. Um, and it doesn't have that same extended release. No, there are actually newer formulations of melatonin that are extended release ones. You can find both over-the-counter versions of that and there are prescription versions of extended release melatonin. >> Oh, okay. I haven't seen that yet. And what if uh someone also has sleep onset and sleep maintenance insomnia during menopause? Would your go-to medications be different? >> They would still be the same. What I would say is that you can also use Romelion as you just mentioned or melatonin um as an adjunct with the lowd dose doxipin or with the erexen antagonist if you need to if they are not going to sufficient but they do have they both have um data showing sleep maintenance
33:18 and sleep latency. Um so you can use the lowd dose oxipen and the ereexen antagonists for both of them. Most of my patients have tried some melatonin before they come and let me know about their difficulty sleeping and then they ask me about other supplements. How robust is the data we have on magnesium, eltheanine, etc. So I would say melatonin by far has the mo most robust and so if people are asking about natural supplements I would definitely go to melatonin first. Um, of other ones I would say eltheanine has some potential as does magnesium, but the evidence is overall like much lower quality. Um, magnesium it's mixed in terms of the evidence thus far that's been shown and a lot of that is due to
34:04 right you have it's not FDA regulated. So you have inconsistent formulations and types that can be hard to say. Um so I would say we don't have good quality evidence but there is some observational data that suggests um higher magnesium and better sleep outcomes. So if people want to try it I have certainly recommended it to people particularly for people who have like comorbid migraines because magnesium has great data for migraine prophylaxis um or if you know as kind of an easy thing to go through for muscle muscle tension to help think about relaxing. So, I'm always thinking about it in conjunction as opposed to like my first line as a go-to. Um, eltheanine, there was a 2025 systematic review and meta analysis that looked at 18 studies. And what that it found is that there were no
34:51 good studies looking at just atheanine. All of the studies had it in combination with a bunch of other things. And so, it might improve right on its own, but it's hard to know whether that was the elenine or that was other things. And so there we don't have good data telling people what the dose they should be taking if in it it in itself is efficacious versus it combined with a bunch of other types of supplements and um I would say things like muscle cramps are also very common for women as they age and like you mentioned migraines. Um is there a specific dose and formulation of magnesium that you would recommend? Yeah. So I would say magnesium depending on what formulation magnesium glycinate has better blood brain barrier penetration. So I would tend to recommend magnesium glycinate
35:38 first and I would recommend like 100 to 2 mill 200 milligrams to start. I know a lot of people like they'll go on Costco, they'll buy like the big magnesium oxide bottles. Those tend to need higher doses like 400 to 800 milligrams is the range for magnesium oxide. Um, and you can have a lot of GI effects from that. So, if you have constipation, magnesium oxide not a bad way to go. [laughter] Great tip to advise patients to look for magnesium glycinate 100 to 200 milligrams if they want to try all that for insomnia. So, if the patient has tried magnesium glycinate, long acting, over-the-counter melatonin, and they don't respond to the lowd dose doin prescription, I find that the most common patient request I receive is for Zulpa. What are your thoughts for its
36:24 use in pmenopause, menopause and beyond? >> Yeah, absolutely. So, Zulpadm is part of the clinical guidelines for the American Academy of Sleep Medicine. And so, it's something that you can use. Absolutely. Um and it does have um a couple placebo controlled randomized control trials in per menopausal and post-menopausal women showing that you know use over a 4-week period did right increase total sleep time reduce wake after sleep onset. Um and so in that regard it has good data especially when you're using it for short term. in the longer term, right, the concern for side effects, you know, such as, right, cognitive issues, especially as people are getting older, women will tend to have side effects at lower doses than men. Um, so can't
37:09 necessarily tolerate as high of a dose. And, you know, just thinking about, right, tolerance and other things. So, you can absolutely use it. Um I would say you know just being monitoring carefully using the most the lowest effective dose that you can absolutely pushing CBTI because it has such robust data in pmenopause and menopause and then thinking about right triing other medications if it might make sense as well. >> Right. And I think we really can't emphasize CBTI enough in this episode. I feel like patients never have never heard of it. So thank you for reminding us about emphasizing that and practicing in the Bay Area. I see that many of my patients are using wearables for health promotion. In the age of digital therapeutics, is there any data that sleep tracking with watches or rings can
37:57 ultimately improve sleep quality or duration? Good question. Not a lot of studies yet. Um, so it's like a really small evidence base. Um, there there have been studies that show it might um help with decreasing sleep latency and improving sleep quality subjectively. Um, but there was also a recent crossover randomized control trial that showed it improved perceived sleep quality, but not it didn't actually change any sort of somnographic information or change total sleep duration. Um, one of the more robust studies found that if it was used in conjunction with um kind of feedback and sleep education, that's where we'd there was the most benefit. It's hard to know how much was from the the wearable or not. Um there are a couple in there's
38:42 another interesting wearable that's come out recently that's actually a wearable for pmenopausal women that is cooling and so it'll kind of track changes in temperature um and then kind of to address phasom motor symptoms and has been shown in a very very small study to be helpful for sleep. So interesting innovations in that regard. >> Interesting. So it cools you down. >> Yeah, it's supposed to cool you down. Oh wow. Yeah. Speaking of that, then any other promising therapies whether they're wearable or medications or something else that for insomnia on the horizon that you know of? I would say most promising would be in the research realm of the erection antagonists and kind of looking at orexin one versus
39:28 orexin 2 antagonism and which one looks seems like can it can be more useful for sleep. Um there's also interesting studies happening looking at neurom modulation. And so looking at transmagnetic stimulation or other ways of doing neuro feedback and seeing how that can be helpful. There was one study that did um neuro feedback plus acupuncture and just look at how that improved and it had some improvements in sleep quality. So lots of burgeoning re research there in terms of like what sort of interventional techniques might be useful. Um and then I think more studies happening looking at complimentary since that is a very popular area. So looking at acupuncture, looking at different types of therapies that are non CBTI to see how robust they might be. Um and then there's always
40:15 interesting like apps or other things that are coming up. The one that I found most amusing is similar to the wearable. Someone created a cooling mattress um pad specifically for permenopausal women that will actually like track the heat of their body and can be adjusted to different temperatures automatically for that. >> Wow. Very exciting. And as we're wrapping up today, do you have any key takeaways about managing insomnia in women that you'd like to leave with us? >> Yeah. So, I would say for for providers listening, ask women of any age, always ask about sleep, ask about sleep quality, ask about right sleep quantity and help, you know, navigate with them, right? Possible, you know, things that could help with them. Um, and it's also
41:03 helpful to do a training in sleep hygiene and basic CBTI because it can be so hard to access. Um, and I would say ask about vasa motor symptoms for women starting at age 40, you know, minimum because a lot of women don't realize. I've had numerous patients that I've been consulted on in primary care where we've had a conversation and the primary care doc hadn't asked about basom motor symptoms and those were already having a significant impact and and intervening was really helpful. Um, for any patients that are, you know, people that are not providers that are listening, um, what I would say is super important to talk to your doctors about sleep if it's not working because sleep is so important
41:48 for our physical health, for our mental health. Particularly if you are a woman who is pregnant or going through pmenopause, you don't have to suffer. It's not an expected part of what's going on. It's not something that you just have to deal with. there are treatments and interventions that can be helpful and get improve your quality of life. >> Great. Thank you so much for emphasizing that. I think especially now that women are having um later childbearing years, they often go from the pregnancy sleep problems to having the young child and then kind of straight into pmenopause. Um and so all can be very challenging times and I appreciate you going through all the evidence um and studies behind the treatment recommendations that you made today. No, thank you so much for having me and always happy to help if there are
42:34 questions that come up about sleep and women's mental health. >> Thank you, Dr. Zane. >> Have a good day.
