Bill Klaproth (Host): This is The Healing Podcast, brought to you by MarinHealth. I'm Bill Klaproth. And with me is Dr. Lizellen La Follette, OB-GYN physician at MarinHealth Women's Lifelong Health and Wellness, a UCSF Health Clinic, as we talk about perimenopause, what it is, how it affects your body and mind, and what can you do to feel your best during this transition. Dr. La Follette, welcome.

Dr. Lizellen La Follette: Thank you, Bill. And by the way, what a title, The Healing Podcast. You have a lot of work to do.

Host: That's right. But that's what we do here. We heal. We here at MarinHealth, that's our goal. And with people like you, we are doing that, Dr. La Follette. So, thank you so much for your time. We appreciate it. So, let's start out and set the stage here, Dr. La Follette. What exactly is perimenopause, and how is it different from menopause?

Dr. Lizellen La Follette: All right. Well, that's such a great question, Bill. I mean, this is the kind of things that we need sort of closer definitions because there's an awful lot of things out there that are circling around that everything is perimenopause and everything is menopause. So as a Menopause Society certified provider, and there's me and one other midwife in the system of MarinHealth that has got that degree, perimenopause is actually kind of a very wide range.

The Menopause Society feels that perimenopause, by definition of menstrual cycles—now we're not talking about mood and anxiety, which is really what is more to me the trump card of this—it is the following changes of menstrual cycle. Early perimenopause is within a seven-day change of cycle-to-cycle variation. So if your cycles are normally 28 days and if they all of a sudden are 21, that's considered to be early perimenopause. So, there is a definition in terms of a menstrual cycle. And then, late perimenopause is when you start to skip a cycle more than 30 days off. What's interesting about perimenopause is it actually can last through the irregular cycles and all the way past menopause. So, it's a quite a long time and it's really characterized by both menstrual cycle changes as well as other symptoms, which I think are a little bit more famous these days. And those are the things we're going to talk about down the line. But that's the definition.

Host: Yep. So, early perimenopause is when you're having a seven-day change. Late is when you start to skip a cycle. And how long can that generally last? Is it years or months?

Dr. Lizellen La Follette: Years. Usually, four to seven and sometimes 10. It can really last a long time. I mean, I think the biggest problem is when does it start?

Host: So, when does it typically start then?

Dr. Lizellen La Follette: Well, if you look at the average age of menopause at being 51 or 52 in this country, then perimenopause can start as early as mid-40s and go all the way till 55. So, it can be a nice 10-year zone in there. But many people can have symptoms that are earlier, and are not consistent. I think that one of the best things that the Menopause Society taught us long ago, which is that you can have more night sweats in perimenopause than you do in menopause. So, some of the hallmarks that were traditionally attributed only to menopause have now been sort of reallocated to perimenopause, which I think is really important, because we need to help people.

Host: So then, what are some of the most common signs and symptoms of perimenopause, and are there any unusual symptoms that tend to catch women off guard?

Dr. Lizellen La Follette: Yes. I would say perimenopause is a mood disturbance almost before it is a cycle disturbance. So typically, women will complain of heightened anxiety and of a vicissitude of moods unregulated by what they normally can do, more rage. So, there really are some variations in terms of mood that surprise many women in perimenopause.

There's a wonderful, board-certified psychiatrist as well as an OB-GYN by the name of Pauline Maki, M-A-K-I, in Chicago. And she talks about the brain changes with perimenopause with this up and down cyclicity and randomness of changes that are absolutely tied to hormonal changes along with mood.

So for many women, that's sort of the beginning, this sort of sense of dread when you wake up and this feeling as though, "What in the world's going on? I think I have everything under control. I know where my kids are, I know where my husband is, I know where my job is. What's going on?"

Host: I like how you put that. It's a mood disturbance before a cycle disturbance, and that is one of the early symptoms. So, a lot of symptoms can feel vague or easy to dismiss. "Eh, it's just a part of aging. Eh, I'm not going to worry about this." But how can someone tell if what they're experiencing is actually perimenopause?

Dr. Lizellen La Follette: Now, I will not spend much of this time talking about how women get dismissed in medicine, because I think luckily things are changing. But the reality is " Live with it" is not really a great answer in the Healing Podcast that you and I are now in the middle of.

Host: That is not good.

Dr. Lizellen La Follette: No. So, I would say that it really helps for a patient to keep track of what it is that seems unusual to her on the mood front, and then come in with a list of things that seem different, especially if it's accompanied with cycle changes, and then talk about the question about, "Okay, how do we diagnose this? Do we do hormones? Do we do birth control pills?" Certainly we do not blow it off. We listen and we figure out what's bothering women the worst, and we try to address that. So, there really is a science to this, but there's also a subjective analysis of what's different in your life that might make you think this could be going on.

Host: So, live with it is not a good plan.

Dr. Lizellen La Follette: No. That's never good choice.

Host: That's not good. Okay. Let me write that down. Live with it is not a good plan. But that's really smart. Come in with a list of symptoms and tell me what has changed in your life and what is bothering you

Dr. Lizellen La Follette: Let's talk it through and also this idea that maybe this is perimenopause, maybe this is a bunch of other things. But let's at least have a conversation in which you as the patient can come in and list things that seem odd to you in terms of how you react. I mean, it is clearly true that your high school kid should be cleaning up his or her room, and you've only told him 110 times. But now, there's a rage to it that really makes you wonder about who is that person. And so, those are really important things to bring in. I mean, obviously life stressors are contributing to this. But I need help to understand and to help you with a list of things that seem out of proportion with what the reaction should be.

Host: So, I am married to a woman of age, Dr. La Follette. So, mood changes, sleep problems, brain fog, weight changes. Why does perimenopause affect so many different parts of the body?

Dr. Lizellen La Follette: Well, if you think about the ovary as a reproductive organ. And most of us think of it as more than that, but that's sort of the way we've been, I would say, siloed. The reality is that what is happening is that cycles are not always ovulatory; and therefore, hormones are out of whack with a normal cycle. And those hormones have a direct neurologic effect. So, it's real, it's in your brain, and it is not made up. So, I think if we really pay attention to that connection of the ups and downs of hormonal fluxes related to cycle changes and associate that with also timing, then you have a better chance of trying to understand and to help women going forward.

Now, I have to say a little piece about weight gain. I don't think, and we know in the Menopause Society, that weight gain, despite it being blamed on perimenopause and menopause, it's clearly an association, but it may not be as strong an association as everybody wants to blame. Neither hormone replacement therapy nor the lack thereof necessarily contributes to weight gain.

But if you look at the change of hormones over time, weight can slowly be creeping up and all of a sudden you wake up and go, "What the heck is this 10 pounds hanging around my middle that I don't want?" So, I think we have to dissect this by symptom and by concern. And also for me, as a provider, I really want to know what's the thing that bugs you the most? What is it that really makes you feel as though you're not yourself? And that helps also to prioritize the next steps.

Host: Yes, and that's really important. So, let's talk about that. When should someone then talk to their doctor about symptoms and what does the evaluation process typically look like?

Dr. Lizellen La Follette: It really helps if the patient comes in with a list of things that seem out of whack, and even examples about why they got so mad about a certain thing. That's really a helpful thing to me. It's sort of like you feel as though you're reacting out of proportion with the insult, if you think of it that way.

So, there's a couple ways to do it. One is obviously looking at menstrual cycles and looking at the timing of these symptoms related to the menstrual cycles. The second is what has really been poo-pooed for a long time, which is hormonal checks. So, we can, in a very specific timing way, day two or day three of the menstrual cycle, do the brain to the ovary, FSH, so follicular stimulating hormone, and estradiol levels. And we can say, "Oh, look at that. You know, you're getting towards perimenopause because your FSH is above 15." Recognizing that every single cycle these numbers can completely change. So, the reason why providers have long resisted doing hormones and testing hormones is that that's a true for the cycle that you checked, and the next cycle may be totally different.

So, that's why there's so much variation. But sometimes it doesn't really take the hormonal question. It takes the, "All right, well, this could make a difference. Are you paying attention to when these symptoms are worse?" And I try to dissect people's understanding of their menstrual cycle and connecting the symptoms related to the timing of the menstrual cycle to help me figure out what do I add next.

Host: That's really interesting. You said you try to connect the symptoms to the cycle, and that really helps you pinpoint what's going on?

Dr. Lizellen La Follette: Yes. For example, in perimenopause, it's not unusual for people's cycles to shorten. They may not shorten by the full seven days yet and therefore, meet the criteria for early perimenopause, but they may change by four or five days. And so, I try to ask women, "All right. In the second half of your cycle, are you connecting how you're feeling your night sweats, your brain fog, and your mood to the second half of your cycle?" Because that's really where I would expect it to be and depending on the answers, then it helps you figure out what's the best approach.

So, I was trained by Wulf Utian, who started the Menopause Society after my residency at Case Western in Cleveland. And Wulf Utian was always very careful to talk about understanding the pieces of the reproductive puzzle that is changing around perimenopause and menopause. And so, he felt that you should always ask the question about cycle timing and mood and add back pieces first before you go to the full bore of hormone replacement therapy. And what do I mean by that? I mean that, for example, in the second half of the cycle for many women, which is basically after ovulation, they are more sleep-deprived, more moody, there's more weight gain, there's more water retention. That's usually where they will be able to tell and pinpoint for you where their mood disturbance is in early perimenopause and menopause in general, and perimenopause late or early particularly.

So then, the opportunity to add back in that timing a progesterone, which of course is so funny, because you look at all the cycles and you know the second half of the cycle is dominated by progesterone. But adding it back seems to restore sleep and tame the mood and do things that are really later on when you're in menopause sometimes feel completely contradictory to what this plan is. But in early perimenopause and perimenopause in general, progesterone in the second half of the cycle can help a lot. And all of a sudden, their cycle gets back to their normal 26 to 28 days, and they get a couple more years in which they're okay. You can also use a cyclic antidepressant, an SSRI just for the second half of their cycle, and that also is a mood stabilizer, which of course the psychiatrist always felt, "How could you possibly just do it cyclically?" It works fabulously because it's working on the other side of the hormonal receptors and can stabilize mood. But I am always very reluctant to talk about mood stabilizers when you know your hormones are changing, because that misses the point that this is a hormonal situation we're dealing with. And we have two or three ways to fix it, and I am not labeling you that you have a mood disorder or something like that.

And so, that's a little bit of a fine line to make sure that you walk with them and that you offer these solutions as you go, and that some of them may work and some of them may not, but it's not because we are ignoring what you're feeling and adding a label of a mood disorder to it.

Host: Yeah, that's great insight to what you look for. So, you're looking at cycle timing and mood to help you determine that approach. Is there a starting point of lifestyle changes or supplements you recommend as a starting point before you go on to further types of treatment options?

Dr. Lizellen La Follette: Well, I think that lifestyle is so important in this, right? So, this is always a typical very stressful lifetime moment if you think about it from the perspective of timing of where your family is typically—you know, your teenagers are giving you a hard time as it is, and you're somewhere between early mid-career to mid-career.

So, there's a lot of stressors that are on the outside. So, I always tell people you need to do the best to sleep, and we can help with that. Exercise. Obviously, quit smoking if you are smoking. Don't smoke other things, by the way. That's not going to help as a long-term solution. And watch alcohol. Those are the biggies. Now, I'm not even going to talk to you about recreational drugs, but those are obviously things that make things quite unstable, and that'll make things worse.

So, the usual lifestyle advice is sleep where your body can restore itself and heal itself through the night if you can get good sleep. Exercise because that allows your heart to get, in better shape and help you help your mood in general with getting your own endorphins going with a heart rate change. And then, moderation in everything, including in food, alcohol, and any other substances that are not native to you.

Host: So, that sounds like a great starting point for everybody. Quit smoking, make sure you're exercising, watch what you eat, sleep, watch your alcohol intake, all of those kinds of things. Then, for a woman needing additional support, can you quickly touch on supplements and then also touch on hormone replacement therapy?

Dr. Lizellen La Follette: There's an awful lot of people that are out there, talking about supplements that probably don't have a lot of use. For women, for bone, we need vitamin D. There's a really new article that suggests that to prevent Parkinson's, we probably all need to be taking a vitamin B, which is different than what we've heard before.

But as to what supplements are going to miraculously take you through this, yes, there are some plant-based phytoestrogens. But typically, those doses are minuscule compared to what you need. So, I would say in general, the supplement, despite multi-billion dollar supplement industry, there isn't a lot of credence to doing a lot of supplements to help you.

I mean, I do think women often, if they are not heard, will pivot to a different type of provider to be heard and to try to get some support, and I don't blame anybody for that. But my advice to that is find a better provider than it is to try a bunch of supplements that'll cost you a lot of money and may not make any difference.

That being said, let's talk about treatments, right? So, there's, three different sort of standard ways to do this. The first way is to say, "Okay, we can fake your cycles to get you to have a normal cycle and mask everything by putting you on a low-dose birth control pill, and that we can keep you on till 55 or so." Some people feel 52, some people feel 55. And that basically covers the vicissitude of moods and vicissitude of fluctuations of hormones by masking the whole thing. The problem with that is that the masking the whole thing doesn't always work because night sweats are not typically treated with non-bioidentical hormones as well as they are with bioidentical hormones.

And so, my pivot is, as I said before, it is twofold. One is adding back progesterone in the second half of the cycle and see if that stabilizes mood for the second half of the cycle in addition to the lifestyle changes of making sure exercise and watching alcohol in that second half of the cycle, which clearly will minimize the symptoms if you can adhere to that lifestyle change. And then, eventually add the full complement of hormone replacement therapy or menopause hormone therapy, which is typically a patch or a gel. Estradiol is the bioidentical molecule that we typically are using now transdermal because it's safer and you don't have a clotting risk. And although the patch shortage in the country, despite the FDA saying there's no shortage, is alive and well. So, you do have to wiggle around to figure out what pharmacy has what patch.

But there also are gels that also work. And then, natural progesterone at night to help you sleep. So, that's sort of my three-pronged attack, and I give everybody all those choices. And then if one doesn't work, then we pivot to the next. I mean, this is not a one-and-done situation. Everybody's different, and people respond differently to many different things. And our job as providers for women in this time is to try something, if it doesn't work, pivot to something else.

Host: Right. So, the three, we've got lifestyle changes and/or supplements, birth control, and then HRT. Would that be correct?

Dr. Lizellen La Follette: Right. Not too many supplements. Yes.

Host: Right. Well, you mentioned vitamin D and vitamin B as well. So, let's talk about HRT a little bit. I know it's been heavily criticized for years, and many women still feel nervous about it. Can you explain why HRT became so controversial and what we know about its safety today?

Dr. Lizellen La Follette: Yeah. So luckily, I've been in practice 35 years, so I've really gone through before and after the WHI study. But to summarize it in a sentence or two is the WHI study looked at synthetic estrogen Premarin and the synthetic progesterone Provera, and the average age of the patients were 63. And they were asking a question about does HRT, even though it was synthetic HRT, protect against heart disease? So, it was an interesting question because they used as an endpoint that if they saw more breast cancer, they would stop the study. And the study was done between probably '96 or '97 to 2001 or 2002 when it was stopped. They did probably 8,600 women in each group.

There was an interesting two things that happened to the group. Number one, the average age was 63, which is 15 years post-menopause and probably 20 years post-perimenopause, and certainly late to ask a question about a heart because the heart has been protected with hormones throughout women's lives, and they start to get into trouble 15 years after menopause, typically, unless there's a very strong family history.

So, they looked at, in my mind, the wrong age, they looked at the wrong sweet spot of timing, and they used the wrong molecules to replace. In fairness, that was what was available then, but we certainly haven't done it. So even when the study came out and it was stopped because they said there were more breast cancer cases in the women taking HRT than the women who were not, most of us looked at that literature to say, number one, you did not reach statistical significance in terms of the eight breast cancer cases, and there were only eight breast cancer cases that were different compared to the control group. So, why are you using that statistic to stop the study when it didn't reach statistical significance? So, that's the one question we all had. So number one, misinterpretation of the data.

The second was that the control group had actually been on HRT for the five years that in the old days was recommended to stay between menopause and five years after to take the lowest amount of hormones for the shortest amount of time was used to be the recommendation. And so many of those women to get into the control group had actually been on hormones before and stopped, which meant that the incidence in the control group of breast cancer was even lower than it would normally have been in a normal population.

So, you skewed the data in two different ways. There was less breast cancer because we know that. In women who start HRT around menopause, that there is a protective effect against breast cancer, but that if that sweet spot of timing within five or 10 years of menopause is lost, then you have the negative effect. And everybody only heard the negative effect.

So, 20 years went by in which actually there were many of us who continued to write for hormones because most of us gynecologists felt as though it was misinterpreted. And it was an example in which when you say the breast cancer risk was doubled in that group, you still didn't reach statistical significance, and twice a teeny number is still a teeny number.

And so, what did they find? They found less colon cancer in the women on HRT. They found less bone density loss and less hip fractures. So, there were some really good things that they were able to show. But in my mind, threw the baby out with the bathwater, in terms of saying it had a breast cancer association.

Now, we're still fighting that battle. It is pretty clear that women who are getting mammograms are still being told or being questioned or queried about HRT use despite our pivot to bioidentical hormones and to a lot of research going forward to say the sweet spot of timing of HRT is a protective effect against breast cancer rather than a negative one. And we need to get us all on the same plane to understand that we need to have one message. And the message has been quite confusing.

The other thing is that an awful lot of primary cares who are not OB-GYNs, many of them sort of grandfathered into the idea of hormones immediately stopped without actually being, I would say, as circumspect of the literature as the gynecologists were. And that meant for a whole generation of women, HRT was not offered or was, even worse, withdrawn. So, we are fighting that battle. I think the communication, luckily, in social media as well as many of us who have been trying to get our voices heard, to counter that information are finally getting heard. But it was a great disservice to women and the country and the world, for that matter.

Host: Yeah. Yeah. Well, people gravitate to negative messages, and those things do seem to stick. But like you said, there was a misinterpretation of the data. there was skewed data in the first place. People only heard the negative effect. You said the messaging, everybody needs to be on the same page, and it's not right now. It's kind of a patchwork, and primary care physicians didn't help when they just stopped and didn't really understand the full benefits of HRT and, fully understanding the results. So, a lot of things there, but glad to hear that that perception is slowly turning. So, that is good news.

Dr. Lizellen La Follette: It wasn't their fault. They were basically going by the news outlets and the big headlines of, you know, it causes breast cancer. So, I'm not blaming anybody of being cautious. What I'm blaming people of is not reading the literature critically and disregarding what is in the media compared to the literature. And maybe that's our best take-home, that with AI and with all of the opportunities that we have to be able to understand literature, let us try to be a little bit more circumspect on conclusions that are broadcast in the media rather than the real data.

Host: Yep. Great point and clarification on that. So, thank you for saying that, Dr. La Follette. So for listeners in this stage of life, can you boil this down for us? What's the most important message you want women to know about perimenopause and getting support?

Dr. Lizellen La Follette: I think the most important message is keep a diary, bring the diary to the office, speak to your provider about what you're feeling, and develop a plan together on how you're going to address it.

Host: I like that. Keep a diary, bring it to the office, go through it, and then discuss how you're going to work through this plan together. Dr. La Follette, always great to have you on. Thank you for this awesome information that you always bring to us. Thank you again for your time.

Dr. Lizellen La Follette: It's always a pleasure. And after all, you do have the Healing Podcast, we darn well be healing.

Host: That is our is our mission. And with people like you, we're getting there. Thank you, Dr. La Follette. We appreciate it.

Dr. Lizellen La Follette: I hope so.

Host: And once again, that is Dr. Lizellen La Follette. And for more information, just go to mymarinhealth.org/womenslifelonghealth. And if you enjoyed this podcast, please share it on your social channels and check out the entire podcast library for topics of interest to you.

It is The Healing Podcast, by the way. So, get it out there. Share it, please. I'm Bill Klaproth, and this is The Healing Podcast brought to you by MarinHealth. Thanks for listening.