Welcome to Everyday Wellness Podcast. I'm your host, nurse practitioner, Cynthia Thurlow. This podcast is designed to educate, empower, and inspire you to achieve your health and wellness goals. My goal and intent is to provide you with the best content and conversations from leaders in the health and wellness industry each week and impact over a million lives. this is the start of a new thursday series called the midlife minute that is really designed to address listeners questions in a little bit longer length of time and or deeper dive into topics ideally we're going to keep these podcasts under 20 minutes occasionally we make over to 30 but I'm trying to reinforce some key concepts and ensure that I'm addressing listeners questions in a way that's really helpful. So the questions that I will be addressing topics are going to be items that I'm being asked over and over and over again. I hope you enjoy this series. Please share with your friends. And as you know, you can always send your questions to support at Cynthia Thurlow.com. I appreciate each and every listener. We are back for this week's version of the Midlife Minute. And today I want to talk and unpack a really important topic, and that's mental health. I think that when we look at the statistics of women that experience an uptick in anxiety, depression, insomnia, and even suicidal ideation, it's important to bring greater awareness to this because I still feel like even in this day and age when we do a really good job of talking about mental health issues, there's still a tremendous amount of stigma, although there should not be. And so because I've been receiving a lot of questions around these topics, I thought it would be helpful to talk about the science, talk about why it's happening, and then bring greater awareness so that you as listeners can take this information and empower yourselves to demand better care, right? Hopefully most people listening have great conscientious, thoughtful, caring, compassionate providers. But unfortunately, I know from being in the healthcare space for over 25 years, that isn't always the case. So I hope that this information will be helpful and insightful. I really think about perimenopause and menopause as one of the most vulnerable periods in a woman's life. And that's just because we start to see women stating things like it's just stress. I'm just aging. I just push through when in fact it is these alterations in key hormones like serotonin, progesterone, even testosterone that can impact the way that we perceive the world and how we feel about ourselves. And so research from the study of the women's health across the nation, so this is the SWAN study, shows that women in perimenopause experience significantly higher rates of depressive symptoms and new onset anxiety compared to premenopausal women. So it's not a character flaw. It's not poor coping skills. It's physiology. It's neuroendocrinology. And as you've heard me talk about on the podcast before, it's not just about these hormones. We know that estrogen and progesterone fluctuations impact key neurotransmitters like serotonin, dopamine, even GABA, which vis-a-vis impacts our circadian biology. So that 24-hour clock that we have in our bodies can be adversely impacted by these changes as well, not to mention glucose regulation, which can make us tired, can make us cranky or even hangry. These are all really important for emotional stability. There was a 2025 systemic review looking at 19 different studies found that 84% of studies reported an association between the menopausal transition and increased suicide. I take that really seriously. One study showed that perimenopausal women were almost seven times more likely to report suicidal thoughts than pre or post menopausal women. And it has a lot to do with this kind of hormonal zone of chaos that's ongoing. We know that, as an example, estradiol can be 20 to 30 percent higher in perimenopause than at any other time in our lives. And while death by suicide is still rare, midlife women between the ages of 45 and 64 have the highest suicide mortality rates of any female age group in the U.S., around 8 to 10 deaths per 100,000 women. Why aren't we talking more about this? This is significant. and there are far too many women that are struggling. I'm getting goosebumps as I'm saying this. There are women suffering and this doesn't have to be the case. So why does this happen? Number one, it's the fluctuating hormones that I've kind of alluded to, estradiol, progesterone. It's changes in our sleep. It's vasomotor symptoms. A lot of people have such disruptive hot flashes that they can't sleep. They can't function. They're sweating at work. They're miserable. You see those memes that seem funny and kind of innocuous They not funny They not innocuous But it brings attention to the fact that there are women that have significant and prolonged experiences with hot flashes We're the sandwich generation. We are dealing with aging parents. We're dealing with older children. We might have more demands placed on us at work. We're more established there. Relationships can change with loved ones, not just friends or family, but even our significant in others. Underlying insulin resistance. So we know that women are much more prone of dealing with metabolic health issues at this stage of life. Thyroid changes. I can honestly tell you, I don't know one woman that I've worked with in the last year that has not had either a suboptimal thyroid or has had frank and overt hypothyroidism. Obviously, I wrote a whole book talking about the gut microbiome shifts, but that also changes. And then a history of trauma or prior mood disorders. Obviously, I'm not a trauma expert, but I'm someone that experienced significant childhood trauma, which has definitely impacted the person that I am today. I've been in therapy since my 20s. I jokingly tell my husband I'll probably be in therapy till the day I die. But there's always something that I'm working on. And I know so many of you have shared the same thing. And transparently, I will tell you that when I was hospitalized in 2019, something in me kind of snapped. I am not the same person I was before that hospitalization. Call it Pollyanna. As someone that worked in healthcare for many, many years, I never thought I would be so sick to need to be hospitalized. And it shifted something in me and really required me to show up differently in my personal life. By that, I mean a lot more therapy, kind of dealing with things that maybe I had suppressed or I had dissociated about my childhood, early adulthood and teenage years. And maybe one day I'll share more. But suffice it to say, perimenopause for me really has forced me to deal with my stuff. And for many of you, I know this has been the same case. Maybe you've subjugated things you experienced. Maybe it isn't until you go into perimenopause and menopause that you're forced to deal with some of your stuff. And when I say stuff, I mean, all of us have stuff. No one's perfect. Even if you grew up with a beaver cleaver existence, you probably have some things about your childhood, young adulthood that were beyond your control and happened to you for you. Okay. So getting back to perimenopause, I think of it as a neurological transition, just as much as a reproductive one. So not only are we losing a degree of fertility and we're changing everything. I mean, everything in our body is being recalibrated. It is a neurologic shift. And so I know Dr. Lisa Moscone, this is her area of expertise. When estrogen declines, it becomes erratic. The brain feels it first. And I've had many, many patients tell me that they knew they were in perimenopause by brain fog or just feeling like they're not as sharp cognitively, or it's the emotional things that we're talking about today. There are decades of neuroscience that shows that estrogen modulates serotonin synthesis and receptors GABA activity, our calming neurotransmitter that is intricately interwoven with progesterone, BDNF, so brain derived neurotrophic factor, which helps with brain resilience. It also helps us learn new things. This is where sometimes people will say it's like harder to commit things to memory. Sleep architecture, big, huge problem. Body temperature regulation, which explains like the hot flashes and the hippocampus is getting reset. And then glucose metabolism in the brain also changes. So it's no surprise that when estrogen is unstable, mood becomes unstable too. And I think for people that potentially have been poorly emotionally regulated their entire lives, maybe there's someone that's very emotionally labile, there's someone that wears their emotions on their sleeve, that might make it even harder for them to communicate and to navigate these changes. But the cool thing is there's empowering information that's out there. We know HRT can be helpful. And that's what I'm really going to focus in on right now. If you're a woman in midlife or beyond, you'll probably notice those changes in energy, strength and recovery just don't feel like they used to. And what's frustrating is that for many women, this happens even when you're eating well, lifting weights, prioritizing protein and doing all the right things. You're not lazy, you're not unmotivated, and you're not doing anything wrong. A big part of what's changing actually starts inside your cells. As we age, our mitochondria, the energy producing structures inside our cells become less efficient. And when mitochondrial function declines, it can show up as lower energy, slower recovery, reduced muscle strength, and feeling less resilient overall. This is a normal part of aging physiology, and it's one of the reasons midlife can feel so different. And that's why I've added MitoPure gummies from Timeline Nutrition into my daily routine. Mitopure is the only clinically proven form of urolithin A, a compound shown in human clinical trials to support mitochondrial renewal. In simple terms, it helps your cells do a better job of making energy. And when your cells have more energy, your body is able to support strength, endurance, and recovery as you age. What I appreciate most about Mitopure is that it's foundational, not flashy. This isn't a stimulant or a quick fix. It's a daily habit that supports how your body actually works at the cellular level. And the gummies make it easy They just two sugar gummies per day They vegan and cleanly formulated They independently tested and certified for quality And if supporting your energy muscle health and overall resilience as you move through perimenopause and menopause is important to you, MitoPure is worth considering. You want to go to TimelineNutrition.com slash Cynthia and use code Cynthia Thurlow for 20% off your order. Again, that's timeline.com slash Cynthia and use code Cynthia Thurlow for 20% off your Mitopure gummies. If you're in your 40s and 50s and feel like your body suddenly stop responding the way that it used to, you're not imagining it. Bloating, waking, sleep disruptions, food sensitivities, and unpredictable energy are incredibly common in perimenopause and menopause. But here's what most people aren't told. Your gut microbiome is changing right alongside your hormones, and those changes can influence everything from how you store fat to how well you sleep to how your body processes estrogen. That's exactly why I wrote my new book, The Menopause Gut. In this book, I walk you through the science of how the microbiome, metabolism, immune system, and hormones are all connected during midlife. But most importantly, I give you practical, realistic strategies you can start using right away without extreme diets or complicated protocols. You'll learn why the same diet that worked in your thirties may not work now, how your gut influences hot flashes, mood, and weight, the truth about fiber, protein, and blood sugar in midlife, and the daily habits that help your body feel safe, stable, and resilient. Again, if you're tired of blaming yourself for changes that are actually biological, this book will help you understand what's really happening and what to do about it. You can pre-order The Menopause Gut wherever books are sold. And when you do, be sure to check out the special pre-order bonuses I put together for you. Again, you can go to www.cynthiatherlo.com. You'll click on the banner. It'll take you to multiple options for where you can order The Menopause Gut in pre-sale. Hormone replacement therapy for mental health. Obviously, the foundational elements that we talk about lifestyle are still very important, But here's what the evidence shows. HRT can reduce depression and perimenopause. There's a landmark randomized controlled trial published in JAMA Psychiatry found that transdermal estradiol plus intermittent micronized progesterone reduced the risk of clinically significant depressive symptoms by 50% in perimenopausal women compared to placebo. That's quite significant, right? So I know that there's been this shift in talking about starting HRT earlier as opposed to later, like not waiting until you transition into menopause. That's why these conversations are important. And there are some people who might really benefit from starting and initiating it earlier, not just for all the other health benefits, but also for mental health. A review of controlled trials found that estrogen therapy improves psychological well-being, mood, and quality of life, particularly in perimenopause. and one trial showed that withdrawing estradiol led to a return of depressive symptoms whereas continuing estradiol again just as a reminder estradiol is the predominant form of estrogen our bodies make up until menopause suggesting a clear causal relationship and it some of the research that i looked at talked about early and abrupt menopause you know for people maybe that are whether it's premature ovarian they call it now insufficiency used to be called premature ovarian failure, that's menopause before the age of 40, early menopause before the age of 45, average age of menopause is 51. Those that are early or have an abrupt onset, like someone that's had a total abdominal hysterectomy where they remove the uterus and the ovaries, higher risk and greater benefit. There was a woman that shared with me when I was in London that she had premature ovarian insufficiency and her physician there got her started on hormone replacement therapy immediately. So bravo to the clinicians that know this and know how important it is for, especially for younger women that go into premature ovarian failure, sorry, insufficiency, I'm getting used to that new terminology, or early menopause, it's even more important that they're started on HRT. Studies show that women that have an early menopause, less than 40, surgical menopause, even chemo-induced menopause are at greater risk for depression and suicide because they're going longer without these hormones. HRT may be especially beneficial for these women because the drop in hormones is so much more sudden and severe. We know HRT helps improve sleep quality and improves mood. So if you sleep well, you're going to be in a better mood. That makes complete sense. When I don't sleep well, I'm not in a great mood. I mean, a one-time event is not a big deal, but imagine over the course of several years, you're consistently not getting good quality sleep. That can impact your mental health significantly. Poor sleep is one of the strongest predictors of mood decline. And we know that things like transdermal estradiol, so that skin absorbed estrogen improves night wakenings, hot flashes, sleep quality, and REM. And in many women, when sleep improves mood, emotional stability, and stress tolerance improve in parallel. So important to really understand that when I talk about sleeping foundational, it's because it impacts so many other things, including like appetite regulation, how well we control our glucose, our insulin, our ability to exercise, our ability to make good food choices. The other thing that I think is important is identifying that progestin is not the same as progesterone So some synthetic progestins can actually worsen mood So if you were recently put on a progestin IUD or you were started on MPA which is medroxyprogesterone acetate that may not have the same effects as oral micronized progesterone, which tends to have more of an upregulation and stimulation of that GABA, which is this main inhibitory neurotransmitter that our bodies make. So when we're talking about how to use HRT for mental health. These are things I think about use HRT early, the mood benefits of estrogen appear stronger and younger, perimenopausal and menopausal female. Obviously, we want, ideally, we want bioidentical estradiol. I feel like I'm making that sound redundant, but body identical, bioidentical is estradiol rather than older or high dose synthetic regimens, things like Premarin. I actually met someone recently who's on oral Premarin. And I was like, timeout, you're young. She's in her early 50s. I was like, why in the world is your provider prescribing Premarin? I mean, there are people that do well on oral estradiol, and that is superior to Premarin, which is like 40 different types of estrogen. And if you didn't know, Premarin is pregnant mare's urine. So that is from horses. Consider transdermal delivery. Some data suggests this route may be more effective for mood than oral estradiol, but again, it could be very bio-individual. tailored treatment to the individual. Like these are all notes I was making for myself. HRT seems especially useful in women with a history of perimenopausal mood symptoms or hormone sensitive women. If you had bad PMDD when you were still getting a menstrual cycle, if you had postpartum depression, you may be more sensitive to these alterations and hormones. That's not something that's intrinsically wrong with you. I wanna make that really clear. I'm just saying you may be someone that has to do a little bit more around supporting your mood as you make this transition into midlife. Combined with holistic care, so like sleep, lifestyle, mental health support, there's no shame in seeing a therapist, psychologist, psychiatrist, Reiki practitioner, whatever it is you need to do. HRT is not a magic bullet. It's not the one thing that's going to fix everything, but it definitely contributes. But it would go without saying for me to not mention the sleep, the stress management, the exercise, eating nutrient-dense whole foods, making sure you have loving relationships with friends and family. But what's interesting is the HRT does not guarantee mood improvement. Like, let me be very clear, not all studies show benefit. For instance, there's a 20-week trial of unopposed estrogen. So that means estrogen not in conjunction with progesterone found no statistically significant change in mood, cognition, or quality of life compared to placebo. The beneficial effect, again, seems stronger in perimenopause or early menopause, and it becomes less consistent if you've gone longer without hormones. I think it's important to note that the use of combined HRT may impact how you respond. And then the long-term risk and optimal duration remains debated. But I think right now, in talking to all the experts and researchers, we can remain on hormone replacement therapy lifelong, provided that we're not having any, you know, presumed contraindications. So to kind of wrap things up, you know, putting this all into practice, I think first and foremost, understand that our brain is recalibrating in midlife, our hormones are shifting, we all deserve support, screening is important. So if you were experiencing like persistent sadness, new onset anxiety, panic attacks, intrusive thoughts, hopelessness, sleep disruption, or thoughts of self harm, most importantly, if you're thinking about harming yourself or harming someone else, please get help. Please talk to your clinician. Obviously, I think I've done a really good job of having some of the leading voices in this space on the podcast, trying to frontline their work. There's so many good people doing good work that we just have to get you hooked up. If you're not already connected with someone that can help you, we definitely want to do that. And we want to think about HRT as a tool, but it must be personalized. So you could take 10 women and they might all have a slightly different approach. Again, start early. Transdermal estrogen seems to have the best research in terms of effectiveness. You want to pair it with oral micronized progesterone, and then add in the kind of sleep, nutrition, stress management, strength training, and mental health support. Too often women are told to tough it out. And I don't want to ever normalize anyone's suffering and to pretend everything is fine because in many instances, that's what we are conditioned to do as women. We are conditioned to just accept things as they are. So this is the end of the midlife minute for today, mental health version. Hopefully you found this helpful, beneficial. Please give me a post on what you are interested in me doing these little short little vignettes on. I was wonderfully overwhelmed on social media when I started asking like, what do you want to learn more about? What do you want to hear from me? What do you want me to share about my trajectory of the perimenopause to menopause transition? Because I'm just here to educate, inspire and empower for you to live your very best life. 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