Stacy London (00:00) I'm really interested in your sphere of genius, so to speak, because you're really talking about the brain in midlife. And you were talking a little bit about how, in your research, hot flashes, insomnia, and depression can be clustered together. I'm wondering why. Those things feel very separate, and yet how can they be attached to the same kind of mechanism in the body?

Dr. Hadine Joffe (00:26) That's a great question. These are the most common brain symptoms of midlife — of perimenopause, menopause, and postmenopause. The key thing is they don't always come together. Sometimes people can have hot flashes and that's it. Sometimes people can have mood problems without the hot flashes or insomnia. So it's not that people have to expect they'll have all three. However, it's common that they do occur together.

And the question you ask is why. Is it because something in the brain is directly triggering them to be connected, or is it because of this concept of the domino effect, where one thing leads to the other? I think the answer is both — the usual answer. So why would it be direct? There are brain mechanisms that trigger hot flashes — some of the mechanisms we understand with neurokinin B — that interconnect with the other parts of the brain that affect levels of arousal and alertness, and also stress and stress perception. These are areas of great interest to me and my team. So that would be what's happening in the brain that may be linking these symptoms. The other part, which is something I've done a lot of work on over the years, is how one symptom leads to the next.

Stacy London (01:52) Right. I was going to say, are we talking correlation or causality?

Dr. Hadine Joffe (01:56) We can say causality.

Stacy London (02:00) We can. Okay.

Dr. Hadine Joffe (02:02) The reason we can say causality is that in some of the work we do, we basically isolate one symptom. We take people and induce hot flashes in a very controlled way. They don't have anything else — they don't have sleep problems, they don't have mood problems. When we induce the hot flashes with a temporary medical menopause, two-thirds of people get them and one-third don't. Some get mild hot flashes and some get severe. We do this in men and in women, and it's all the same: two-thirds, one-third. So we now know that when we induce a temporary medical menopause, the people who don't get hot flashes don't get the sleep problems. Whereas in the people who do get hot flashes, we can see that their sleep, which was normal before, becomes problematic afterward in the typical pattern: interrupted, waking up repeatedly — that sleep fragmentation. So that's causally related, in this domino concept. The hot flashes emerge, then the sleep problems emerge, then the mood part.

Stacy London (03:21) In roughly two-thirds of people.

Dr. Hadine Joffe (03:25) Yes. And it's proportionate to how bad the nighttime hot flashes were.

Stacy London (03:30) That's what I was going to ask. Obviously there are variations in severity. And actually, lately they've been coming back, and I don't know why — I've had night sweats again, where I wake up and I'm soaking wet. My pajamas are soaking, or my sheets are soaking, and then I'm forced to get up. It's not like I just woke myself up and can go back to sleep. I can't sleep in that. So those kinds of sleep interruptions — I'm assuming the more severe the hot flash, the harder the sleeping becomes.

Dr. Hadine Joffe (04:05) Exactly. The more severe and the more frequent. Meaning if you have one and it's mild, versus two that are severe like what you're talking about — that's severe. We've done this with monitors that detect sweating, so we know exactly what's going on in the middle of the night, and also with EEG, where we're looking at real-time sleep activity based on the brain activity recording. So exactly what you reported is what we've observed. And I'll tell you, when we started doing this research, people said, "Why on earth would you do that? Isn't it obvious? Talk to anybody." And the answer is, at the time, the data were showing that it wasn't an issue.

Stacy London (04:56) Wow, really?

Dr. Hadine Joffe (04:58) With all my patients, it was obvious. So it was so important to validate what people experience, and what women in general experience. That was a major initiative. Now, it's not that people only get two hours of sleep. It's still a relatively small number of minutes of wakefulness. Obviously if you need to get up and change, that adds cumulative time, but most people fall back asleep relatively easily — we've looked at it, within a minute or two. So the issue is not that the total amount of wake time is so big. It's that it's repeated over and over and over.

Stacy London (05:44) And that there's that interruption.

Dr. Hadine Joffe (05:46) Right. It gets to this issue that we don't think of sleep interruption as being as problematic as reduced sleep time. But what our studies show is that even if you get eight hours of sleep — you let yourself sleep in to compensate for the fact that you're waking up all the time — it has all these problematic effects on mood, on alertness and cognitive alertness, and also on metabolism. We can talk about all those things as well.

Stacy London (06:22) Exactly. I was going to ask about each of these things. I'm curious, though: you talk about mood disruption. Have you noticed that there's a particular order? You have hot flashes, then sleep disruption, then you see mood disorders? Does it follow a pattern, or can these things happen in any order?

Dr. Hadine Joffe (06:53) I would say when people experience it, they often just come together, and the truth is people just feel overwhelmed. It's very hard to pin somebody down and ask what came first. Some people can really isolate and distinguish. Oftentimes they feel like they just came together. But from the scientific studies, we can see that it's this order: hot flashes, then sleep, then mood. Now again, the sleep problem is really common. If you look at a population of people with hot flashes, about two-thirds will have sleep problems. They're so intertwined just because people usually have both day and night hot flashes.

Stacy London (07:37) Right. And then how is it intertwined with the mood? Is it distinct?

Dr. Hadine Joffe (07:42) The mood is, fortunately, less common as an issue. People do have it. When it does occur, it tends to be mild. Obviously there are people who have more severe major depression, which we can talk about too. But for people who do get mood problems, it tends to be mild. I liken it to what we see with postpartum, where there's postpartum blues — this mild condition where people are crying but don't really know why. They don't feel in control of their mood state the way they normally would. It comes and goes and eventually settles. That is the more common pattern with this perimenopausal mood disturbance.

I'm not saying it's all about crying. It might just be not taking joy. And of course there are major issues with energy and concentration and a feeling of pleasure in activities — just feeling low and dull. When that mood state does happen, it's extremely common that there are both hot flashes and sleep interruption. That's a cluster. And again, that mild mood condition can be a spectrum, and it can come and go.

Stacy London (09:09) Maybe that's my next question: why is there such a spectrum? I know we talk about how there's no one menopause, because there's no one-size-fits-all. But are there any early indications of whether somebody is going to have more severe hot flashes or mood swings than somebody else?

Dr. Hadine Joffe (09:31) I wish we knew the answer to that. I really, really do. Because we would want to say to people, "Be prepared. You're the kind of person who should be prepared." And we don't want people to be afraid. We don't want to unnecessarily make people feel like every menopause experience is going to be like, as everybody calls it, the seven dwarfs — grumpy and irritable and these kinds of things.

Stacy London (09:54) Right. Grumpy, Sleepy.

Dr. Hadine Joffe (09:54) Because many people do extremely well and feel good and don't have a lot of problems, and their hot flashes aren't as bad as they could be. But for some people they're much, much worse.

Stacy London (10:07) One of the other reasons I was asking is because when you say we don't really have any way of knowing whether those symptoms are going to be severe — and when you talk about postpartum in the same way — all of the words you're using are really what I felt at the beginning of perimenopause. I felt that kind of blues, that low, "I don't know why I'm crying," and it got progressively worse. I'm much more open to talking about it now, but I didn't want to walk across the Brooklyn Bridge because I was actually afraid I might throw myself off of it.

When you get to that level of severity, and you have the hot flashes, and you're having this kind of sleep disruption, what is the first tack somebody should take? I realize that when we talk about symptoms, we're not trying to scare anybody. But the reason I feel so strongly about talking about some of the more severe aspects of this is that I felt like I got hit by a Mack truck, and there was no indication that anything like that could happen to me. So how do we walk the line? Sorry, I'm asking a lot of questions here — we'll take it a little at a time. But how do we manage this kind of almost major depressive disorder, as opposed to the blues? What do we manage first? And how do we talk to people about that without scaring them, but while preparing them for eventualities that could happen?

Dr. Hadine Joffe (11:49) Well, I'm sorry that happened to you. It gives me the chills, because it's a reminder that for some people it is very serious, very disruptive —

Stacy London (12:01) Brutal.

Dr. Hadine Joffe (12:02) — very frightening. So none of this messaging is meant to minimize the possibility that for some people it can be like that, just like postpartum depression can be very, very [inaudible].

We do know that some people are more likely to have mood problems — sometimes because they have a history of it, or because they tend to get a lot of hot flashes and a lot of insomnia. So there are some predictors, in some sense. We also know African American women are more likely to get hot flashes, more likely to have them for longer, and more likely to have some of these other issues with sleep. So there are some predictors. But obviously within that population there are people who do really well. There's such variability.

But your key question is what to do when you are experiencing mood symptoms at that more significant and serious level. The most important thing is to not go through this alone. Because when you go through it alone — like anybody — what goes through your head, how you process decisions and information, you may not always be able to sort through them at your best level.

Stacy London (13:27) Sure. You're not in your right mind. It's a little hard to pull yourself out of it.

Dr. Hadine Joffe (13:34) Right. It's not a time to make major decisions about things in your life — work, personal, and of course your health. This is where the people in your life who support you are key. Whether it's a partner, a family member, a spouse, a child, a parent, a sibling, a dear, dear friend, you want to connect with people who are part of your life in a regular way and help them understand that you are struggling. If somebody broke a leg, you wouldn't want to go through that alone either, and it would be normal to reach out and say, "I'm having pain here, I'm having pain there." It's in the brain, but we need to articulate it: "Mornings are hard," or "Alone time is hard." So of course you want to be able to engage people.

And this is someplace where you really do need treatment, when people are experiencing symptoms at the level you had. There are emergency services when things are emergent — whether it's an emergency room or suicide hotlines — that are available twenty-four seven, so that people are not alone in those most critical times, which might be in the middle of the night. It's also a time to talk to the clinician who works with you — whether it's a primary care doctor, a psychiatrist, or a therapist who is not a prescribing doctor — to be able to get treatment for a mood disorder. It's treatable.

Stacy London (15:15) Because I do find that lots of middle-aged women don't know what they're going through, and the first thing they're offered is an antidepressant. Rather than, "Hey, why don't we pull back? Are you menopausal? Could it be all these things?" We tend to go to "Let's throw a pill at it," like she's sad or whatever. Is there a way to distinguish between major depressive disorder and what we would call — let's just call them the menopausal blues for a second? Are they treated differently, or is it really this kind of spectrum you're talking about, where there are things we can do for each level of severity?

Dr. Hadine Joffe (15:57) You hit the nail on the head, which is that they are different. They're diagnostically different. For major depression, we have what's called the DSM, the Diagnostic and Statistical Manual. People have to meet certain kinds of symptom criteria that cluster together. Those symptoms have to occur for at least several weeks — they often occur longer — and interfere with function. And suicidal ideation is most commonly part of major depression. The blues would not really have that. So we can make the diagnosis, which is really critical, because the treatment approach differs. If it is major depression, the first-line recommended intervention is therapy and antidepressants. When it is the blues, the first line is going to be hormone therapy. So it really does matter.

Stacy London (16:59) It does matter, yes.

Dr. Hadine Joffe (17:00) And it's not that people couldn't take them together. Antidepressants are mostly serotonergic, and they can treat hot flashes, so they can be valuable for a range of symptoms. But the data on hormone therapy for major clinical depression are not as strong as the data for antidepressants. We've studied many antidepressants, and we and others have looked at hormone therapy. Some kinds of hormone therapy can work, especially when there are a lot of hot flashes, but there are also studies we've done that show it doesn't work. So it's not first line.

I always say to people, "If I'm going to a desert island with you and I can only take one pill" — well, first, you have to decide that it's a pill, because therapy is key. But if I can only take one pill and it's major depression, I'm going to take an antidepressant. I've seen many women who have been put on hormone therapy, their hot flashes are well controlled, and they get partial benefit for their mood. Then they think maybe this is good enough, and nobody reassesses: "Are you really back to where you should be? Are you really back to yourself?" Then we put them on an antidepressant and they do great. But they lost months of time.

Stacy London (18:26) Yeah.

Dr. Hadine Joffe (18:27) So we want to do the right thing. Sometimes the answer is an antidepressant, even though that's sometimes a hard message to get.

Stacy London (18:36) Sure, of course. But even the distinction you're making is one we weren't making before: that these are different kinds of depression, and they require different modes of treatment. Being able to be honest with your doctor about what you're feeling, and getting their feedback, is really essential as we move through the menopause conversation.

And I've got to tell you, I'm so fascinated now by the brain. I think of my brain as what I use for thought, and for feeling sad or happy, but I don't think of it as a thermostat regulator. I don't understand how hot flashes start in my brain. How can happy and sad and hot flashes all exist in there? How does that work?

Dr. Hadine Joffe (19:22) You have a big and very capable brain, and the brain does all of this. The brain regulates thirst. It regulates sleep. It regulates motor movement — do you want to move your arm, do you want to stand up? It does all of that. A tiny, tiny part of the brain called the hypothalamus is the part that controls all the core functions, like thirst, sleep, temperature regulation, sexual activity and drive, alertness — so many things. And in the hypothalamus are these neurons that have been recognized — the KNDy neurons and neurokinin B — which are the thermostat.

Stacy London (20:10) Mm.

Dr. Hadine Joffe (20:11) It's the thermostat, and it's in there. It's amazing, and it was discovered in the last fifteen years. We did not know the biology of hot flashes until the last ten to fifteen years, when it was figured out.

Stacy London (20:23) That's crazy. How long have women been around? I feel like we've been around a lot longer than ten to fifteen years. That we're just getting this information is fascinating to me, as we really start to look at female physiology and understand it from a deeper place. Is there a reason that the brain suddenly malfunctions when it comes to the thermostat? Is that due to estrogen loss, or is it much more complicated?

Dr. Hadine Joffe (21:03) There is a contribution of estrogen loss. But the brain has its own drive — a kind of chronological drive toward this. For some people it's a little earlier and for some a little later. These cells actually change in size; they get bigger. And it is part of a feedback loop with the ovaries and the estrogen that comes from the ovaries. But there's still so much science to figure out.

Stacy London (21:34) I was going to say: when perimenopause and menopause hit, how is that affecting the actual brain when it comes to deep, restorative sleep? Why do we start having these sleep malfunctions?

Dr. Hadine Joffe (21:53) The "why" question is like an existential question in some ways. What is this good for? Is there some evolutionary advantage? We can cogitate and theorize around that. There are studies in whales, for instance: some whales go through menopause and some don't, and the whale populations that go through menopause have longer lifespans for male and female offspring. That's part of the whole grandmother hypothesis — that if the grandmother stops reproducing, she's there to support all the generations. That's an amazing finding. So is there some evolutionary reason? I'm more on the science side. What are hot flashes for? Somebody said maybe they're a call to action — that reproductive potential is up against an end date.

Stacy London (22:59) Yes.

Dr. Hadine Joffe (23:00) But usually by the time people have hot flashes, their reproductive potential is pretty diminished, so it's not a last-call kind of thing.

Stacy London (23:09) Right. It's not a warning.

Dr. Hadine Joffe (23:11) But maybe it's helping people recognize — whether it's the hot flashes or, as you asked about, the sleep — that this is a different life stage. For the most part, women didn't live through menopause until a hundred or so years ago, so I don't think we have a lot of data on that. I do think there is a lot of suffering, and that people assume this is just aging. They tolerate a lot of discomfort and think it's just aging. And I always tell people, it's not. There are age-related changes in sleep — people tend to go to bed earlier and have more disrupted sleep. But this very distinctive pattern is hot flash–related for the most part — not entirely, it can be other things — and it's so treatable. It's really related to these endocrine, hormone changes, the biology. We've seen that it actually relates to the hormone changes themselves, even independent of hot flashes.

Stacy London (24:17) Wow. I'm so curious: is there a relationship between this kind of loss of sleep, the mood swings, and cardiovascular health long term?

Dr. Hadine Joffe (24:30) I didn't catch the last part.

Stacy London (24:32) Cardiovascular health long term. Is there a connection between this kind of sleep in particular — less about the hot flashes, more the interrupted sleep — and cardiovascular health as we age?

Dr. Hadine Joffe (24:47) The answer is yes. The nature of the sleep disturbance in perimenopause and postmenopause — this hot flash sleep problem, the interruption and fragmentation — is causally linked to risk for cardiovascular disease and also adverse metabolism. So the answer is yes. And once again, it gets to this point that we don't always see sleep interruption as a problem. We see short sleep as a problem. But I tell people: value and prioritize continuous sleep, and intervene to optimize it, because you will have better health. It does affect lipids. It does affect heart rate.

Of course, there are other changes with hormones going on at the same time, and we can see that the estrogen decline affects some of these things as well. But even when you take out the estrogen effects and look just at the sleep effects, having this interrupted sleep has clear downstream adverse effects on all of these parameters. We've shown this in a very experimental, controlled environment — all of these parameters that set us up for risk of heart disease later in life. And we know that women's heart disease risk is really accelerated around this time. People say it's a period of risk, but it's actually a period of opportunity: do the right thing, take care of your health, because you want to set yourself up for the best postmenopausal health, the optimal health span. That involves making sure your sleep is continuous, consolidated, and not interrupted.

Stacy London (26:45) Could we talk a little bit about poor sleep and weight gain? You touched on it before. How does broken sleep connect to belly fat and metabolic rate? Again, this is not to scare people. But if you don't understand that interrupted sleep, not just short sleep, has these long-term effects... Part of our podcast is really telling people, "Take the bull by the horns now. Here are the things you can do." Most people don't realize that poor sleep and metabolic rate are connected. What do we need to know about that connection?

Dr. Hadine Joffe (27:23) I love the way you're framing it: do something, because for many people this is the time to look at and take care of themselves. They've been taking care of other people. They're still prioritizing other people over themselves. But this should be a wake-up call: put your oxygen mask on first.

Stacy London (27:44) I matter.

Dr. Hadine Joffe (27:46) I matter, exactly. I matter and I take up space. And when I'm well, other people are well too. It's not only for other people, but for many people it's hard to recognize that taking care of themselves is good for taking care of all these other people they prioritize.

Stacy London (28:02) I feel like I did that my whole career in styling: if you look good, other people look good.

Dr. Hadine Joffe (28:08) Right, exactly. Thank you for that. So there are two core parts. Estrogen is going down, and we know that clearly leads to a propensity for weight gain, through all these appetite hormone changes, metabolism, exercise, and energy changes. That's a very powerful effect. And then, independent of that, we've shown these adverse effects of sleep interruption on some of these parameters — not all. The estrogen is changing, but the sleep does contribute adversely. And for most people, they're combined. When you combine the decline in estrogen with the sleep interruption, it leads to a propensity for weight gain and for heart disease, for sure. So just to say, there's a huge factor of estrogen decline in this, and the sleep keeps adding to it.

Stacy London (29:24) I really didn't know this, but oncology teams apparently often worry that intense sleep and mood issues cause women to stop taking anti-estrogen medications. How do reproductive psychiatrists partner with oncologists to keep patients more comfortable? My question is really about breast cancer patients who are undergoing endocrine therapies like tamoxifen or aromatase inhibitors and are often thrown into medical menopause. I'm curious, first, whether you see more severity with being thrown into medical menopause than with chronological menopause. And then, if patients stop taking those treatments, how do we build teams with oncologists and therapists?

Dr. Hadine Joffe (30:18) This is an area where I work clinically and also in my research, and I have a lot of compassion for these women. They're going through whatever they're going through in life, and then they get a breast cancer diagnosis. For most people it's what we call multimodal therapy: some combination of surgery, radiation, and chemo, and then these oral anti-estrogens plus other targeted therapies. It's a really complex treatment. Fortunately, it's hugely effective, so many people are very motivated to receive treatment, and they want to do everything they can to take it.

The oral treatments — tamoxifen, which is used mostly in premenopausal women, and aromatase inhibitors, which are used exclusively in postmenopausal women — are daily pills that people take for typically between five and ten years. They're used for people who have estrogen-sensitive, or ER-positive, breast cancer, which is about two-thirds, 60% or so. So not everybody is advised to take them, but if they are, that's taking a pill a day for a long time.

For some people, those pills are just fine. They don't have any concerns. They're so happy to be done with their chemo and their surgery and their radiation, because that was so hard. And of course now they have to process what they went through with the cancer diagnosis and treatment. For some people, the pills can cause hot flashes and sleep problems. The aromatase inhibitors cause a lot of joint pain as well, so that's a major problem for them, and they can cause other things too. When they do cause hot flashes, which then go along with all these other brain symptoms of menopause, some people say, "I can tolerate this," or "It's not too bad, it's mild" — just like a mild chronological menopause. For some people it's really problematic, and it has led to people stopping.

It's not everybody. Some people persevere and get treatment. That's the main thing: we can treat all these conditions. Obviously it's not always perfect; it's not 100% relief. But I always tell people we're taking mountain ranges and making molehills — much less severe, much milder, not as frequent, whatever the symptom is. That's a reasonable goal: to help people function better and feel better.

Stacy London (33:01) Yeah. Just to participate in your daily life. Once that's off the table, you really need a plan.

Dr. Hadine Joffe (33:08) Absolutely. Some oncologists are really, really wonderful with this, and for some oncologists it's just not their forte. They're focused on cancer-directed therapy. But most cancer settings have social workers and therapists involved, and some cancer settings have psychiatrists — we call them cancer psychiatrists, or psycho-oncology — who often specialize in managing some of these symptoms. Sometimes you go to community psychiatry, some primary care doctors are wonderful, and sometimes there's a survivorship program for people who are through the acute cancer treatment and need more symptom management. So it varies a lot by setting. But I tell people these are really manageable symptoms, meaning we have ways to support you through this course of treatment so you get to the other side. And you don't need them forever, although oftentimes people need them for the entire length of the oral anti-estrogen therapy because they're so symptomatic. But they do great with it.

Stacy London (34:19) Sure. And I think everybody needs to know the risk-benefit. I was talking about this yesterday with a group of women — we were discussing breast cancer — and this idea that you may want to go on hormones even though you have a risk of breast cancer. You should be informed about the choices you're making, and they should still be your choices to make.

I never think, "Those oncologists don't care about their patients." We understand oncology is about curing cancer, about getting rid of the disease in your body. All of these ancillary effects are things we're just starting to understand have a major impact. So when I hear you, I think it's important to recognize that these are things we should be sharing with all of our doctors, even if it's not their specialty. Maybe an oncologist says you need a psychopharmacologist or a therapist. There's some way for us as patients to be advocates that allows doctors to help us even more, and to lay out the scenarios: "Maybe you take hormones, maybe you don't. Here's what happens after chemotherapy." Just somebody to lead you through all the other things that happen aside from the cancer itself, because there are so many issues that don't get addressed when the number one priority is to kill the cancer. I always find these conversations so important and interesting, so people know: the more you ask, the more information you're going to get from a doctor or a therapist.

Dr. Hadine Joffe (35:59) Absolutely. And to add to that: not all information needs to come all at once. Right at the beginning of a diagnosis and treatment, people may need some information about what to expect — "If you do get these hot flashes, or if you do get major anxiety, we can help you. Come let us know." But sometimes people need that later and come back.

And to your advocacy point: ask questions, and don't just ask once. Obviously you don't have to ask every five minutes, but at a follow-up appointment you can say, "I'm now X months into treatment and I'd like to revisit this. I'm having this, I'm having that." Sometimes people are more ready to deal with things and think about them a little later, because it's such a multimodal, intensive time. I find people are often going through the motions: get up, go to this treatment, go to that treatment, get their family member where they need to be, do whatever they need to do for work. It's not that they aren't attentive to these things. They just push them aside sometimes, just to get through something that is so challenging, day after day after day.

Stacy London (37:19) Just to get through the day. That white-knuckling — we don't recommend white-knuckling to anybody.

Dr. Hadine Joffe (37:28) We don't. But sometimes people aren't fully ready. It's not that they're trying to white-knuckle it. It just takes so much of their attention, their emotional reserve, their ability to keep themselves together, just to get through the thing that's right in front of them. They're just not ready.

Stacy London (37:53) Right. They can't manage all of it. I completely understand.

Dr. Hadine Joffe (37:58) Not ready. But later on, they are. And later on they say, "My gosh, what just happened to me? How did I go through that?" And I see that women are strong.

Stacy London (38:11) Amen to that. Very, very strong. I'm curious: what are some of the more exciting non-hormonal treatments you're seeing, like NK3 receptor antagonists for hot flashes? If there's anything new that's being used and found to be healthy and sound, are there things women should be asking about in the doctor's office?

Dr. Hadine Joffe (38:36) In addition to hormones, for people who can take them and want to take them, there's an amazing range of treatments available now. It's so exciting. We should always have options for everybody; nobody should be told there's only one thing that works. As you mentioned, there are these new medications, NK3 antagonists. Two have been approved by the FDA over the last handful of years, so there are two options there for people.

Stacy London (39:04) And what are the names of them? Are you allowed to tell us?

Dr. Hadine Joffe (39:08) I'm going to let people look them up, because I don't want to be promoting anything.

Stacy London (39:10) That's totally fine.

Dr. Hadine Joffe (39:14) They've both been demonstrated to be hugely effective for hot flashes, which I like, because for people who say, "If I can't take hormones, then I don't have any options" — you do. These are fantastic treatments. One of them has stronger sleep benefits than the other, so that can be a difference. There's also monitoring — liver test monitoring — so it's not "take a pill and don't think about it." You have to go through some steps, but most people do really well with that. We also still use serotonin-based treatments — the quote-unquote antidepressants — for hot flashes, and they're actually really good.

Stacy London (39:55) Really?

Dr. Hadine Joffe (39:55) The criticism has been that they're not good enough. Okay, but I'll tell you, they're still good. Are they perfect? No. But we've also been able to show that they're within the range of benefit of low-dose hormones. So it's not like people are getting a bad deal if that's an option. Obviously you have to try.

Stacy London (40:15) What I was going to say is it really does sound like there's so much nuance here. We're still a little bit in the fog — no pun intended — and we're not completely clear on how all these systems work in female physiology. But the crux of this conversation has been that there's a spectrum of symptoms and a range of therapies that can be helpful. And this idea of "good" and "good enough" really requires knowledge and understanding, so that you're making the best decision for you. Is there anything you would say women should not consider anymore? Anything that's off the table in terms of these options and their risks and benefits?

Dr. Hadine Joffe (41:09) First, it doesn't have to be medication only. There are lifestyle and behavioral treatments that are really, really good. For sleep interruption, for instance, cognitive behavioral therapy for insomnia, or CBT-I, is the most effective treatment.

Stacy London (41:28) That's me.

Dr. Hadine Joffe (41:30) It's great. Once people have drunk that Kool-Aid, they think, "My gosh, I wish I'd known this earlier in life," because it's so effective. So that's great to hear.

Are there interventions people shouldn't do? I'll tell you one. We studied omega-3 for hot flashes as part of a large clinical trial network, and omega-3 was shown to be ineffective for hot flashes. Omega-3 is great for lots of other things — it's good for lots of blood vessel and heart conditions — and I don't mean to malign that intervention. But if somebody's going to spend all that money and prioritize omega-3 for hot flashes, I wouldn't go there. Sometimes people spend a lot of money on over-the-counter supplements, and there's a cost to that. There's a cost in money, but there's also a cost in time. They're trying something, they don't feel good, and whatever problems they had keep making them feel worse. Their health is worse. There are daytime consequences — work, relationships — because they don't feel good, they're not sleeping well, they're not exercising because they're not sleeping. So there's a time cost as well.

I think for some people, wonderful things work that we don't have data on. But I think people should stop and prioritize their health, and prioritize it now. Don't wait to put the oxygen mask on and see if you can just breathe the air for a little bit and hope you can use the oxygen later.

Stacy London (43:19) Right — now. And is there a particular age? It's so funny. I keep saying I wish I'd known in my forties, but I actually wish I'd known in my thirties. Even things like strength training — I had to start in my forties, instead of it being part and parcel of a workout that's good for women as they age. Not that you should have to be 25 and know the benefits of consistent good health. I struggle with that now. I see all these millennials starting to come to me and ask questions about menopause, and I'm like, you've got to get on it even earlier than this.

The way we teach women, "Okay, you're going to get your period, and here's what's going to happen" — we don't talk about menopause that way. And even hearing all the things you're talking about, there's real hope in care around this. I'm not even going to call it treatment; I'd just say care around this particular life stage. We have so many options — more choices than a lot of people realize. That's my number one takeaway from listening to you. And that these very disparate symptoms can all come from the same place, meaning that if you can grab hold of one, you might be able to get a handle on the others.

Dr. Hadine Joffe (44:40) I think there's so much reason to be optimistic, exactly as you said. I love the millennials for basically saying, "I matter, it matters. Why has nobody told me this?" This whole awareness campaign — I think millennials are really driving a lot of it, and I'm so grateful to them, because it's really changing the dialogue.

Stacy London (45:09) You have to include us, Dr. Joffe. You have to. Gen X — I'm sorry, I'm not giving the millennials the credit for the menopause revolution. It's ours.

Dr. Hadine Joffe (45:17) Okay, okay. Well, they are on our shoulders. And we are on the shoulders of the previous generation, the baby boomers.

Stacy London (45:24) Yes.

Dr. Hadine Joffe (45:25) It is absolutely true. I've been doing this research for 30 years. Nobody cared about menopause research.

Stacy London (45:33) And now you're a hero. You're a hero.

Dr. Hadine Joffe (45:35) And now I'm like, wow. Somebody said to me, "You're a pioneer," and I was like, "I guess." But people care, and it's wonderful. And I think millennials will talk about it at work. I hear men in that generation talking about it, because their colleagues, sisters, and spouses talk about it, which is great.

Stacy London (45:56) That's fair. I think millennial men are definitely on board.

Dr. Hadine Joffe (46:00) And then they'll talk to their kids differently about it. So, like you said, the preparedness for menarche that we have as a mission as a society is probably something we can expect will progress with menopause, too.

As for things you should have known in your twenties or thirties, one thing people maybe don't realize is bone health. The window for maximizing your bone health is really only through your mid-thirties. After that, you're maintaining. So that's the time for weight-bearing exercise and all the calcium and other nutrients you need to maximize your bone — vitamin D, of course, all these things. That should really be part of earlier education. Preparedness and anticipation, of course, but you need to do something about it to make sure that when you get beyond your mid-thirties, you've maximized your bone health. And I don't think anybody talks about that.

Stacy London (47:10) I don't think we talk about it enough. I was going to say, what's one thing we can leave our listeners with — or viewers, now that we're visual — that's really important to understand? If you're already perimenopausal and feeling completely overwhelmed, is there something you would say, "Stop in your tracks and do this right now"? That's very different from saying this is the kind of education we need to start in our twenties and thirties — start with bone health, then work our way into whatever female physiology system, cardiovascular, whatever that looks like as we get closer to menopause. But let's say somebody's perimenopausal, they don't know what's wrong, and they don't know what to do. What is the one thing you might say: start here?

Dr. Hadine Joffe (48:01) Start here: pick the problem that feels like it's the worst. I think people shut down because there are too many. I always say, let's start with one. Let's target the thing that's bothering you most. Sometimes some of the other things will settle down. Or once that main issue is really diminished, it becomes clearer how to tackle the others, and how to partner around supporting people through those things.

The main issue may be a relationship issue or a work issue that is so stressful it's making the intensity of the symptom experience worse. It's not causing the symptom, but it's making it so much worse — harder to bear, harder to tolerate. So the main issue may not be a symptom. It may be something that's driving a symptom, or driving the distress around tolerating a symptom. Or it may be the symptom itself. But choose one, and don't feel like you'll never get through it because there are too many things. Try to rank them and say, "If I could only choose the top three, they'd be in this order." Then approach whoever it is that way — a therapist, a clinician, a family member, or for some people their church or other religious community. Because sometimes people feel so overwhelmed that it's hard for others to know how to help. They're like, "My gosh, there are so many things going on. I can be there for you, I can support you, I can encourage you, but can we start with one thing?" Maybe the one thing is going on a walk one day.

Stacy London (49:41) Right. "Can you do the carpool on Thursdays?"

Dr. Hadine Joffe (49:47) Exactly. Or can you have a babysitter in the evening so you get your exercise time? Or community parenting, or sharing household chores, or not taking on extra work, or taking some time off work just to have the time, if need be. It really varies. And sometimes it is the symptoms — just start with the one that's distressing you the most.

Stacy London (50:17) I just love this whole conversation. It's all about "you matter." You matter. That makes me so happy.

Dr. Hadine Joffe (50:25) I really enjoy the way you're framing it, because it's true. It's empowerment. It's validation. I always tell people, yes, it's in your head — it's in your brain. These are real. These are not something you're making up. These are your everyday experiences, and they're part of your everyday health. And you matter, like you say. You don't have to white-knuckle it. You don't have to say, "It's just aging." People say, "I haven't slept well ever since I had my kids, and now the pets jump on my head, and my bed partner snores, so it's life." And I say, no, you matter. Right now, you can do something about some of these things. It's really a priority, and you need to make it a priority.

Stacy London (51:14) Dr. Joffe, thank you so much for your time. This was wonderful.

[End of interview]

‍