1st Las Vegas Conference on
Integrating Therapy for Women
Las Vegas � May 19-21, 2004
Menopause � An Overview
Diana Schwarzbein, MD (WMS24-001)
MODERATOR: I'd like to welcome you all and thank you for choosing this conference, �Integrating Therapy for Women: The Science, The Heart, and the Soul.� My name is Peter Vegso, and I'm president of U.S. Journal Training, the company that's hosting this particular event. We're very pleased to have Diana Schwarzbein as the program chair for today. Diana is a physician; she's an endocrinologist. I think the material she's presenting is absolutely fascinating, and I think it's a different approach as opposed to a lot of what you hear in terms of the fad diets. I think she's very honestly trying to bring this back to some logical rationale in terms of how do we approach our health and how do we get our health back and maintain it and enjoy our lives. So I'm very pleased and proud that Diana could join us. So here's Diana!
SCHWARZBEIN: Good morning. Today is going to be a day filled with a lot of different lectures. I'm going to be giving four different lectures, and before I start the first lecture on menopause, I want to say a couple of things on the two lectures I'm going to give, one on stress and one on aging. You really should choose one or the other and pretty much not come to both. I mean, there are little differences in both, but over all, the overlap � the physiology, the biochemistry that goes along with stress � is pretty much the same as aging, so you would do better going to another one of the workshops because we've got some really great things planned today. I'd really advise that.
If you after this talk on menopause, which is an overview, if you're really interested in how it all works, then I would advocate coming to my menopause workshop where I'm going to get down to the nitty-gritty and explain how to do hormone replacement therapy, which I'm not going to be doing in this talk.
Anyway, today I'm going to present �Menopause: An Overview,� if you will. I think it's really important that we start off by understanding the differences between men and women. This is one of my favorite slides, I have to say. And for the men out there, don't get offended. It's just more of the complexities of hormone replacement therapy in women and how it's a lot more complicated than just giving back testosterone.
So we usually, at least I do, I like to start off with definitions; and it's really important to understand that menopause literally means �no more menses,� right? No more bleeding. No more menstrual cycle. But if we look at it from a working terminology, then the gynecologists are a little late because they say, do you know what? Let's wait until a woman has stopped having all of her periods for a year. So if you go 11 months and 29 days and you get a period, you're no longer in menopause, if you will, and you have to wait the next year for them to say, �Now you're in menopause and we'll do something about it!�
Now, I'm exaggerating a little bit but not a lot. I've had many women come to see me in the last 15 years as I've been doing hormone replacement therapy, and they have not been getting hormones because their doctor's saying, �Oh, you should wait until you go into menopause.� That's really late. The symptoms of menopause start a lot earlier than that.
Another way to define menopause is through the chemicals themselves. Chemically, what we're looking for is low estradiol levels, low progesterone levels, and high FSH levels. FSH is a pituitary hormone. It's a signal for the egg to grow; and when estradiol goes low, FSH goes high. So you can start in somebody who has irregular periods in the perimenopausal years. You can start looking for high FSH levels to start making that diagnosis early.
Emotionally, you have a lot of problems. There are a lot of issues that we'll get into. Hormonally, you get a lot of symptoms as the hormones are jumping up and down or when they go completely down. Physiologically, you get a loss of function, you get a loss of structure, you get more degenerative diseases of aging, and actually even increased risks of death and dying.
Now, what about the psychological symptoms? I put those first because of the group I'm talking to. Depression is big, but it's not going to be depression where somebody's been depressed all their life and now they're in menopause and we're going to say, �Oh, your depression is due to menopause.� These are people who come in who are not depressed but all of the sudden start getting hormonal changes and get depression or anxiety from their hormonal changes. Then when you give hormone replacement therapy back, you can solve that issue completely. That becomes a non-issue anymore; that's what I'm talking about.
There's emotionability issues as your hormones are jumping all around. You get moody; women get irritable. This is a lot of times when women leave their husbands, and I know it sounds kind of funny, but it's really a serious issue because the man starts saying, �This isn't the woman I married. What happened to the woman that I married?� Women lose their ability to cope. They get overwhelmed very easily. You get a lot of irrational thinking and a lot of irrational behavior going on. So it's important that we recognize this because, again, what I've seen is so many women coming to see me who've never had a hot flash but had all of these kinds of different psychological symptoms. So they weren't put on hormone replacement therapy because they were told that this had nothing to do with it since they didn't have any hot flashes. Well, you don't have to have a hot flash; these can be your only symptoms. So we really want to start defining what it means to be symptomatic in menopause.
There's obviously the physical symptoms that most people are aware of: the hot flashes, the night sweats. Disrupted sleep is a really important component. I call it the �Two-to-Four Club� � women waking up between two and four in the morning and can't get back to sleep. I used to stay that I was going to do a TV program at that time explaining menopause. That's a good idea, right? With all of the other things that I'm doing, but I will get there! Also, waking up at night to urinate. That is not a normal thing. I don't care how much water you drink, you really shouldn't be getting up at night to urinate; and if you're doing that, there might be a hormonal problem going on.
Heart racing. We get palpitations. Women have been so frightened they think they're having a heart attack. It can be such a big �thunk,� turnover, palpitations. It's very scary. But you know, interestingly enough, this is not a heart attack, and as scary as it is, it isn't physiologically harmful to the women. So it's enough that she'll wake up with nightmares screaming from it. You'll have to calm her down and basically let her know that we can do hormone replacement therapy and it will calm down the heart, but it is not harming you.
Dry skin, itchy skin, those are things that we see. Vaginal dryness, that women really understand. Increased urinary track infections occur. Increased yeast and vaginal yeast infections are occurring at this time. And again, it's not just menopause; it could be the perimenopausal years. Decreased sex drive. Again, the loss of hormones, especially for women, the loss of estradiol � that's the human estrogen � that's the most important hormone for a women's sex drive. For men, it's testosterone. So for women, if you're going through menopause and you're losing your sex drive, the first hormone to get back is estradiol. If that doesn't work, then the second hormone is progesterone. If that doesn't work, then we look at testosterone because in women, that is not our primary sex hormone. However, you can take testosterone and get a great sex drive from it; it just happens to be more of a male sex drive than a female sex drive. So there are a lot of women going out there getting testosterone, which, by the way, as an androgen increases the risk of heart disease. So we don't really want to treat a symptom, right? We want to treat a physiology.
Fatigue, very big in menopause. Loss of stamina. Weight gain around the mid-section. You know, women have a waistline because of our estrogen, and that's an important concept. Men don't have a waist, right? We don't see men curving in; they are straight. That's androgen production. So the difference between estrogens and androgens is estrogens give you a waistline; androgens make you straight up and down. So when we start losing our hormones � estradiol starts to go down � you start to get thick around the waistline. That's one of the main complaints that women have.
Hair loss � you get thinning on your head, you lose underarm hair, you might lose pubic hair, but you start to get hair in weird places, right? It's like it starts changing. It starts growing on the chin, the upper lip, the chest, sometimes the upper back, inside of the leg. So you start getting androgen pattern, right? Male-pattern hair growth, and basically male-pattern hair loss. That's part of the problem.
Headaches, that's also very big at this time in life. Estradiol plays a very important role in serotonin production; and when serotonin is low or fluctuating widely, you can get migraine headaches, so we see that a lot.
Pain at the bottom of the feet. This is the one that I heard early on, and I was just kind of surprised. Women would say they'd get out of bed, they'd step down, and they'd go �Wow! That was a shooting pain,� and they can't even stand on their feet. We found out that that's a low estrogen symptom.
Joint and muscle aches and pains, including arthritis. So there are a lot of things, and I haven't even listed them all. I've also had patients come in with all of their little nuances. �Oh, my left big toe aches or throbs. Is that hormonal?� I go, �I don't know, but let's give you hormones and see if it goes away.� That's how you can tell. So a lot of people will come in with these really strange things. I'll always say, �Okay, put that aside. That's not one of the known symptoms; but if it goes away with hormones, then we know it's your individual problem.� Another individual one I've seen is a lot of breast itching. That was another one.
What about the loss of function? Well, women can multitask because of estrogens. I hate to say this to the men again out there, but this is a scientific fact. Testosterone is a very focused type of hormone where you finish one task before you go onto the next; estrogens are multitasking types of hormones where you can juggle a bunch of different things at the same time. So women start to go into menopause and lose their ability to do more than one thing.
Decreased memory and concentration. Again, a serotonin issue there as well as other neurotransmitter problems. Estradiol itself is a neurotransmitter. It also becomes estrogen catecholamines, which are neurotransmitters. You do a lot of word searching of nouns. And you can even see this before menopause in women who are cycling right before their periods, especially when hormone levels are starting to go down, and they'll have a day or two of noun searching: �Where is my...key?� You know, �Where are my keys,� they can't even say �keys.�
Decreased stamina...Loss of sense of one's self. This is the scariest one to me, the fact that women will come to tell me they no longer recognize themselves. They don't even know who they are. The person they used to be before they lost their hormones is not the person they are now. So a lot of times with hormone replacement therapy what I'm waiting for is for a woman to say, �I'm back!� and then I know I have her balanced. So it's a very important one to look at.
Loss of zest for life. Same idea.
Overwhelms easily by daily tasks. So there's a lot of overlay here with psychological and loss of function.
And then weakness. Again, more injuries occur, you don't heal as well, you're not as strong. Things like that occur in women when they lose their sex hormones. But the real reason that I as an endocrinologist focus on hormone replacement therapy in menopause is not the symptoms, though that's really important. It really is the fact that the loss of hormones increase the risk of these diseases...degenerative aging. So there's more cardiovascular disease, so that means more heart attacks and strokes, more Alzheimer's, depression, osteoarthritis, osteoporosis, Type II diabetes, high blood pressure, increased cancer rates, and increased death rates. There is a 40 percent overall total mortality that goes up from the loss of sex hormones.
So if we look at a woman's fertility cycle as far as overall when we start off before we're in puberty, in pre-puberty we have very low estradiol and progesterone and we're doing okay. We're growing in pre-puberty, and the hormone levels are flat at that time. Then in puberty, that's the beginning of the whole thing turning on for us. And it really is in puberty and when you get to your peak levels that you get your full brain function. Your brain does not completely develop into an adult brain without the sex hormones, and that's an important concept. But anyway, in puberty you get the beginning of increases of these hormones, but you usually will have these cycles that are called anovulatory cycles that I'll be explaining a little bit later on.
Then you have peak hormone levels when you're the healthiest and the most fertile. And then peri-menopause where you start to have the decreases in these hormones, and then menopause when they go flat line again. So it's kind of interesting to look at it in this way and realize that what goes up, must come down.
So when we start off in pre-puberty, it matches the hormone levels of menopause. And puberty matches peri-menopause, and then the peak hormone levels are up there by themselves. Again, it's very important to understand the cycle that we go through. So it's not okay to lose our hormones. We're going to get in trouble when that happens. We want to be at the peak levels. That has a lot to do with the fact that health follows fertility. So in pre-puberty, you have an increased risk of infections. In puberty, you start to be able to fight off infections better but you're still at risk. It's really only at your peak levels that a woman is her healthiest. We are not worried about breast cancer in women in their peak hormone years. We're not worried about cardiovascular disease in these women. We're not worried about Alzheimer's or strokes. So this is not when we're worried, and yet what we're worried about is giving women back their hormones when they lose it, right? It's kind of ironic.
Peri-menopause, you start to lose your hormones and things start getting out of balance again, and you get more susceptible to infections. So another thing I should have brought up is increased susceptibility to colds, upper-respiratory infections, and pneumonia. We see that a lot in women going into menopause. And then in menopause, again, more increase of susceptibility to infections. So I think it's important to understand that your hormones really help to keep you healthy.
Now, as I'm talking about these sex hormones, I hope you're not thinking they're the most important hormones of your body. We're talking about whenever there is a hormone system that goes down or is lost, then that hormone becomes very important to the organism. But it's not going to be that every problem that you have is related to your sex hormones.
So what about aging and menopause? Now I bring these questions up because it's things that I've had to talk to with my patients when they're coming through my office. It is natural. I was talking about this last night; it's natural to age; it's natural to die. In the aging process, you lose your hormones. So that is part of the natural process. But it also is, if you will, the beginning of the end. If you start to lose your hormones, you're not in your peak years. You're starting on the slippery slope on the other side, and it's a reality that we need to face. We can either say, �Okay, that's a problem,� or �It's normal and that's not an issue for us.� But I keep hearing about this passage that this is just one of our normal passages of life, and I'm thinking not really; you really shouldn't be alive to go through this passage. You should have died when you were more susceptible to infections in the peri-menopausal years. But you now live in shelters, and there are immunizations and there are antibiotics and there is food all year �round. So it isn't anymore survival of the fittest; it's going to be the survival of everybody.
So menopause means you're one step closer to dying. I like being blunt, so here we have it. So we either are going to fight it or accept it, right? And again, if you accept it, that's all right, but we have to make a choice, and it has to be an informed choice. So there is no wrong answer to this. It's up to the individual woman to make her choices. The only way I think that someone can make an informed choice is to understand what her choices are, and I think that's what's up to all of us here to help women understand.
So if you are going to accept that this is normal, then you need to make some lifestyle changes to make this passage easier for you. But for those who want to fight menopause to the end, then there's a thing called bio-identical hormone replacement therapy that I'll be talking about. I really believe, and maybe this is my own political statement saying don't make it political, but that each group should leave the other alone. I can't tell you how many times I've had women who've been seeing me for five years on hormone replacement therapy, they feel great � their health is wonderful, their cholesterol levels are normal, their blood pressure is normal, etc., etc., and then their friends who have all of these kinds of problems and are on all kinds of medication are saying, �Why are you taking those hormones? You know it's going to cause you to die.� So they keep hearing this from all of the other peer-pressure groups, and it's getting all muddled. So I really think it's important that everybody makes their choice because they're being educated.
Okay, what are some of the myths that I've heard over the years? Again, that it's normal to go into menopause so nothing should be done about it . Now again, I kind of said it is normal to go into menopause, but what I meant by that is this: If you really think about nature and the animal kingdom, there is no animal model of menopause. You don't see menopausal lionesses out there, just so you know. Just kind of get that idea. We have domesticated menopause in our animals, right? We castrate them, and then they live with us. The same thing for women, then: This is domesticated menopause. If we were to live out in the wild, we would not survive. We're the weakest at that point in time. We're not going to run as fast. How many of you still run as fast as when you were in your thirties? It doesn't happen anymore, so you're going to be the one that's going to be preyed upon.
The treatment for menopause is for symptoms only. Again, if you're not having hot flashes, then I don't need to be on hormones. I think that came about because when we first started doing hormone replacement therapy, we used a drug called Premarin, which is still on the market today unfortunately. But Premarin is a drug and it's not a hormone. So initially it was not advocated for hormone replacement therapy. It was advocated for the treatment of the symptoms of menopause, and I think that's how this whole thing got propelled into thinking we should only use hormones for symptoms.
You will get over it or through it. I've had many people come to see me who have osteoporosis, have bad cholesterol levels, Type II diabetes; and when I start talking to them about menopause, they say, �Oh, stop right there! I'm already through my menopause, so we don't have to talk about that. We don't have to deal with that,� and I'm going �Wow! This is an interesting concept.� You lose your hormones; and in the process of losing them, you can call that process �going through menopause,� but for the rest of your life in post-menopause you don't make your hormones again, and a lot of women think that they do. So that's one of the things that I've been hearing over the last few years.
The other myth is that plenty of women do well without hormone replacement therapy. I'm sorry, I don't see that. I see depression, I see osteoporosis, I see heart disease, I see strokes, Alzheimer's, etc. Again, it might be we're not having hot flash problems, things like that. The other thing I see, because initially when I first started doing this work back in 1993, I really did think there were two separate classes of women: those that would do all right and those who would do well. It wasn't until women who hadn't been on hormones for five or ten years who came in to see me would be saying, �Gee, the only reason I'm here is because I've had bone loss, and I've heard you can help grow bones back with hormone replacement therapy. You've done that with my friend So-and-so, so I'm here for that. But I just want you to know that I'm fine. I have no problems. No energy problems, no mood problems, no memory problems.� And then I would get this woman balanced, and do you know what she'd say to me? �Oh, my God! I didn't know how bad I was feeling.� So I think what happens is if you lose your hormones very slowly, you get these changes in your body that are so gradual that you don't even know how bad you're feeling because you don't even remember how good you're supposed to feel, and that's really what I've been seeing for the last ten years.
And then, again, there is a lot of misunderstanding that sex hormones are not just for sex. So a lot of women are telling me, �Oh, I don't need my sex hormones. My husband died,� or �We're not having sex,� or �We're just holding hands,� or cuddling or whatever it is. So it's really important to understand that sex hormones help other hormones in your body work well, too. So it's the interplay between the other hormones in the body that's the real important process here.
So the truth is it is normal to age and die; and as you age, you lose the ability to make your hormones so that you stop functioning well. When you lose your sex hormones, it disrupts other hormone systems. And menopause is a time of rapid aging. So again, a woman can enter menopause pretty healthy at age 50. Within ten years, we can see a woman who's depressed with osteoporosis and heart disease. It doesn't take that long to see what will happen when you lose a hormone, but it is longer than what would happen if you would lose a major hormone. And again, I think that that's where some of the controversy arises from, the fact that when you lose estradiol you don't keel over and die. Because if you did, we'd say, �Oh, my goodness! Give that woman estradiol.�
Because if you lose a major hormone like cortisol or insulin or adrenaline, you are really sick. Then we go about doing hormone replacement therapy and we say, �You absolutely don't have a choice. We're not going to give you a choice. You have to be on these hormones,� and yet these minor hormones play a role in regulating those major hormones; they just don't make you keel over. Again, that's for me where I think all of this miscommunication about hormone replacement therapy has come in. Anytime you lose a hormone, it doesn't matter what the hormone is, there are going to be consequences; and in some cases with the minor hormones, it just takes longer for those to show up.
All right. So again if you talk about aging, it is the inability of your body to rebuild itself. And when you talk about hormonal aging, you have to realize that hormones help you either build or use. In the case of estradiol, if you think about bones, for instance, what do estrogens do for bones? Your bones are constantly turning over. It's normal for them to do that; that's how they repair themselves and stay strong. Estradiol works on the side that regulates the osteoclasts. Those are the cells that start breaking bone down and chew it up, if you will, like Pac-man. So if you lose estradiol, you lose the brakes on that and you get accelerated breakdown of bone. Then you have the inability to rebuild it back because progesterone is one of the hormones that helps you rebuild your hormones. So you're breaking down your bones faster and you can't build them as well as you used to, and the net result is bone loss. You see rapid bone loss occurring in the first ten years because it's also associated with changes in adrenaline and cortisol, which I'll talk about.
So the critics are saying don't take hormones at all and you should tough it out. That's what I keep hearing, especially from one surgeon who claims to be against breast cancer. And just so you know, there haven't been any studies showing that cycling hormone replacement therapy increases your risk of breast cancer. Just talk about hormones and cancer and scare everybody, and so women are being told, �You need to tough it out. Once the symptoms go away, you'll be fine.� It's not the way to go.
So what is the solution of these critics? What do I hear them saying? What they're saying is when you get all of the complications, take the drugs � instead of preventing them, right? Or if you get a fracture, you'll have surgery for that. If you have plaque in the arteries, maybe we'll put in stints. Or, again, this is the time in life where you're losing hormones, and they'll tell you to slow way down. So these are the solutions, and I'm going to put a question mark there because you can probably already tell by this talk I'm pretty biased on hormone replacement therapy. But I'm trying to give you two sides to the story. I don't know if I'm succeeding.
But, the wise woman of the tribe...what we do know about estradiol is it's an important neurotransmitter. It also helps serotonin. The more you do, the more serotonin you need in order to do things. So you can become the wise woman of the tribe and do less, sit in the middle of the village, let people come to you, and give that minimum output. I know that that sounds facetious, but I am being serious about that. If you truly believe in nature and to do things naturally, that's one of the things you're going to have to do.
On the other hand, some other solutions and the ones that I ascribe to more would be to take hormone replacement therapy in such a way as to mimic normal physiology. If we know that peak hormone levels is a time when a woman is at her healthiest, then we want to go back and mimic that.
Drugs are not natural; and at least if you take bio-identical hormone replacement therapy, at least you're giving something back that your body used to make. That's the definition. So the ice-flow theory really is if you don't want to take hormone replacement therapy because you do believe in the natural process of aging and dying, which is fine, and you know that once you've had your heart attack you're not going to pick up the phone and call 911 and be rescued, then you really shouldn't take hormone replacement therapy. That's your philosophy; and therefore hormone replacement therapy, which is anti-aging and will help prevent a heart attack, and yes, I'm going to say that again even though we're going to talk about the Women's Health Initiative and the HER Study, but we do know that bio-identical hormones can do that. You really shouldn't take HRT because it's going to slow down the aging process, and that might change your philosophy. So you remember the women of the tribe when they'd start to get old, then they would feel it, then they would go off to die in the wilderness. That's how it would work, right? Again, if you're one of these women, I applaud you. I'm totally afraid of death and dying, so you'll see me going kicking and screaming along the way.
But again, as I pointed out a little bit earlier, there is no animal model of menopause. When we're in our peri-menopausal years, we're weaker already and slower and we get more infections and things like that, so we'd be most likely the ones that would be eaten. And there's nothing wrong with that, okay? Nothing wrong with being natural; you just have to understand what you're choosing to do. That's really where I'm coming from.
But here's me, kicking and screaming. I do want to live as long as I can, and I want to live as healthy as I can. It's not all about longevity; it's also about quality of life for me. I want my brain to be functioning. That's probably the most important thing that has always been for me on the top of the list. My memory, concentration, focus, mood, and intellect � ability to choose the words I want to say � is really, really something I want to keep. Along with that, I do want to be healthy. I don't want to have heart disease and cancers and all of that good stuff. If you want to ascribe to the kicking and screaming route, then you want to take hormone replacement therapy correctly.
So let's talk a little bit about women in general and what's happening. I always call this a reality check. We really are changing the normal course, if you will, of fertility for women. I mean, what are we doing? If a woman can't get pregnant on her own, we're giving her fertility drugs or giving her donor eggs. We're doing everything we can to keep women having children because � and again, it's almost going to sound like I'm sexist � but physiologically, it's better for a woman to have her babies when she's younger. As we get older, because of hormone changes that occur in the body, you're more at risk for gestational diabetes, you're more at risk for hypertension, you're more at risk for cholesterol abnormalities, excessive weight gain, strokes occur, breast cancer that occurs during pregnancy. So the older women are, unfortunately, because of the changes in physiology, we are seeing more risks. But what we're starting to see, though, is women want to make choices. We want to have our careers, and then we want to have our children. I just saw something in the newspaper this morning saying I think it was in 1993, 10 percent of women between the ages of 40 and 44 didn't have children, didn't want them; and now it's up to 18 percent. So some women are making these types of choices to change over, and that's all well and fine, too, but I really do, especially when people come to talk to me about fertility and what is normal, before the age of 35, and even 35 is getting a little bit close to the line of when you're going to start having problems with fertility. Now, there are always exceptions to the rule. We know all about women the 50-year-old woman having twins and all of that good stuff, but it's just talking about the population and what we need to know.
So women really can't do it all. When you can do it all, it's when you have your peak hormone levels, and then after that it gets a little bit more overwhelming because estradiol is one of the hormones that helps you cope.
So what's going on now with menopause is not only are we having our kids later in life, but we're going into menopause earlier than we used to. It used to be that a woman would go into menopause 60, 65; so ten years later at 70, 75, when a woman was older and had more of the degenerative diseases of aging, I think that's a little bit more acceptable than going into menopause at 45 or 50 and ending up at 55 or 50 with these health problems, which, again, is what we're seeing, right?
When we start talking about the statistics of increased heart disease and increased stroke and increased cancers, we're not saying in 80-year-olds, in 90-year-olds, in 100-year-olds; we're saying in younger individuals. We're seeing more heart disease in 40-year-olds, in 50-year-olds, in 60-year-olds than ever before. We're now seeing � and this is kind of deviating from the subject � but we're seeing Type II diabetes, which always used to be an adult-onset disease, in teenagers. The youngest person to be diagnosed with Type II diabetes, five years old, and this little girl was five years old and looked like she was 15, that's how big she was. So there's a problem going on here.
So what do we think now the cause of all of this is? It's not really known, but it's probably related to poor nutrition, toxins in the environment, and other lifestyle problems. Again, it's not well studied, so I can't give you all of the answers, but it's certainly food for thought.
Okay, so the theory then is that if you lose your sex hormones and that causes you to age faster, then by replacing them, we should be able to slow down the aging, right? And decrease the degenerative disease of aging. That's what I'm saying to you today, right? That's the whole premise. Let's give back bio-identical hormones so we can stop this aging and prevent things.
So how did we test the theory? Well, as always we start with mice, right? And you have a handout, a little one-page clipping on this. Anyway, what we did was remove the ovaries and the uterus from mice, so they had a total hysterectomy and bilateral ovaries removed. Then we gave the treatment group bio-identical estradiol � the same estradiol that mice make and the same estradiol that women make. Then we gave the other group nothing; they were the control group. Guess what? The mice who got their bio-identical hormones back had a lower risk for heart disease, and I don't know if you know about vasodilatation and your response to your vessels in relation to heart disease, but there is a substance called nitric oxide that helps you vasodilate that the produces, and estradiol helps the body respond to nitric oxide. That's why the loss of estrogen causes vasoconstriction in women. But anyway getting back, the hormone was able to bring back that same property. We saw it in one group and not the other.
So what did we do with that information? We went running with it. We started off by just saying great, that means hormones are good for the heart; we're going to give hormones. So Premarin was started on women. Now Premarin is not a hormone. There are very strict rules on what a hormone is. It is, if you will, a hormone-like drug, if you want to, but semantics are very important. So basically what you want to do is you want to replace...instead of replacing the missing hormones with drugs, we want to replace them hormones, which we'll talk about. But what we did is we gave Premarin, and then we added Provera somewhere along the way, and we prescribed them incorrectly. But we didn't test anything; we just did it, and the testing actually was done on the uterus. We kept trying to figure out how much Provera, in what amounts on a daily basis, can we give to a woman when we give her Premarin to decrease her risk of uterine cancer? Because what was found was that if you gave unopposed Premarin that there was a slight increase in the risk of uterine cancer, and everybody panicked over that. Instead of going back and again looking at normal physiology and what that would mean, we started doing this continuous combined therapy, and they just kept looking at the uterine lining as though that was the most important organ in a woman's body. Right? Let's preserve the uterus over all else and never looked at what that would do to breast cancer, what would that do to Alzheimer's disease, what would that do to cardiovascular problems? They didn't look at that until the Women's Health Initiative Study.
So what they did is then they did the Women's Health Initiative Study, and you heard all of this two years ago and it came out in all of the papers across the United States basically saying, �Hormones are bad for you. Don't take them. They don't help you with anything.� Right? That was the clue there. But really all they were trying to do at that point is make women more afraid of hormone replacement therapy because semantically we have regained hormones back. The studies on mice were done with hormones; the experiment on humans were done on drugs, but the drugs failed. We could have told you so, right?
Okay, so who wins here? The pharmaceutical industry wins when that happens. And again, I don't want to be cynical and I don't want to have a conspiracy theory going on all of the time, but I have a feeling that behind some of this misinformation are a lot of companies who don't want you to understand how it works.
So what about the pharmacology? Again, what happens if I have headaches from menopause and I don't want to take hormone replacement therapy because I'm afraid of it? Great, I'll just buy more analgesics, right? Or maybe we'll put more people on serotonin reuptake inhibitor drugs that help with headaches, or other different types of drugs like Depakote or something. Or high blood pressure, and then we're going to put people on calcium channel blockers, right? Antigens and receptor blockers, diuretics, beta-blockers, things like that. And then with cholesterol levels, everyone should be on estatin, right? And yet the number one cause for women to have high cholesterol � high bad cholesterol and low good cholesterol � the loss of estradiol. I can't tell you how many women have come to me, and you can see the progression. They have their levels throughout their years that are being tracked. All of the sudden they go into menopause, boom! cholesterol goes up. Instead of getting put on hormone replacement therapy, they're being put on [statin] drugs. That's amazing to me, amazing, because that's a really easy fix.
Depression, anxiety, then we're taking antidepressants, antianxieties for sleep disorders, we're giving people sleeping bills, or, again, medications � arthritis, antiinflammatory medications. Think of some of these over-the-counter drugs that are just out...the statistics on the consumption of these medications are outrageous. They're just so high, because again, everybody's so afraid of a hormone, but as soon as they get a symptom, they're running off to take a drug for it without thinking about what does that mean for the physiology.
So if I have clogged arteries because I didn't take hormone replacement therapy, bypass, that sounds natural to me. You know, let's go ripping open the chest and take veins from the legs and bypass. Believe me, I am for these therapies, but not because women are told not to take hormones. I think that's a very important concept. So there are a lot of things that you can do drug-wise that you want to go back and try to figure out what is the problem with the physiology here? These things don't just happen; there are issues going on that we need to figure out. And of course, in Alzheimer's disease besides some of these new designer drugs that help with memory, there is nothing you can to do stop the progression. This is a progressive disease, except for hormone replacement therapy before it happens, and I think that's important.
All right, what about the Women's Health Initiative? I Xeroxed the first couple of pages of it for you so anybody who's interested can always go look up the rest of it. This is the one that came out on the Prempro Study, and basically the Women's Health Initiative focused on �defining the risks and benefits of strategies that could potentially reduce the incidence of heart disease, breast and colo-rectal cancer, and fractures in post-menopausal women.� That's a direct paragraph in that section that I gave you.
Now, why would we need to focus on the risks and strategies of heart disease, breast cancer, colo-rectal cancer, and fractures as far as osteoporosis if they didn't occur already? So basically they're acknowledging that as you go into menopause and you lose your hormones, you have higher risk for disease. So then what they decided was they said okay, we're going to be the first randomized study to assess whether estrogen plus progestin � and this is the Prempro Study � has a good or bad effect on coronary heart disease. This was going to be their predominant end point, to say, �As soon as we can figure that out, we're going to stop the study.� But their predominant endpoint as far as a problem would be if breast cancer was worse in the women who took the therapy versus placebo.
Now I'm sort of switching over to the HERS Trial, which was the Heart and Estrogen Replacement Study, because the HERS Trial was one of the first trials, again, done on Premarin and Provera that showed that if you give Prempro to women who already have coronary artery disease, you actually make them worse in the first year. And again, you probably heard something about that also, that hormone replacement therapy worsen heart disease, but this was in a secondary prevention study � in other words, women that already have the disease, can we now give them hormones and make them better? And what they showed was when they gave them hormones, they made them worse and not better. That was secondary study. So the Women's Health Initiative was the first study that was going to be a primary prevention study. We were going to check to see if we give hormones to healthy women, can we decrease the risk of them getting heart disease? See the difference there?
But anyway, the HERS Trial, when those studies came out, a lot of people went back to their own past studies and started looking at it and realized well, yeah, we also have studies showing that if you give Prempro in this matter and you already have heart disease, it makes matters worse.
In the WHI � in the Women's Health Initiative � they enrolled 161,809 women. Now not everybody was in the hormone replacement therapy trials, so there were other trials going on on vitamin D and osteoporosis and other things...Alzheimer's disease. But these women's ages ranged from 50 to 79, and there were two trials of hormone replacement use. There was the Prempro arm of the study where women got Premarin and Provera if they did still have a uterus, and there was the Premarin Trial if they had a hysterectomy, and then there was an observational study where, again, they got placebo, and then there are still the other trials going on with the Alzheimer's and the bone risk. What they found is that when they gave Prempro to women who were healthy � these are women who don't have coronary heart disease, who don't have breast cancer � that when they assessed � and how they did it is they had initially 8,506 women were assigned the Prempro and only 7,968 were able to be assessed at the end of the study, which was about a 5.5 year study, and the other group received placebo. So they were matching, but this who they checked, and the conclusion was that overall health risks exceeded the benefits from the use of the combined Estrogen/Progestin Trial, so that if you took Prempro and compared that to women who took nothing, that the group who took Prempro was worse off in colo-rectal cancer, breast cancer, and heart disease, strokes, and blood clots. That was the group that was presented, and you heard all of that in 2002.
So they basically said that �the risk-benefit profile found in this trial is not consistent with the requirements for a viable intervention for a primary prevention of chronic diseases, and the results indicate that this regimen should not be initiated or continued for primary prevention of coronary artery disease.� That's when a couple of years ago we had to start telling our patients we're sorry, hormone replacement therapy doesn't help heart disease, which is not really true. It's Premarin and Provera don't help heart disease. And then one of the conclusions in the WHI, they basically stated that basically what we're saying is conjugated estrogens or Premarin at a level of .625 milligrams in combination with medroxyprogesterone acetate, or Provera, at 2.5 milligrams on a daily basis is the trial, and that shouldn't be used. But we can't say anything about any other types of hormones, we can't say anything else about any other doses of hormones, and this was in the same paper at the end and it was their conclusion.
Now what did we hear in the newspapers? Just the opposite, right? �Oh, my God! Extrapolate this to every kind of hormone, any way you want to use it, and the results are going to end up being the same.� And yet in this very same paper they actually said that this is not a true statement. But that's when all of the sudden two years ago all I heard about was women all across the country stopping their hormone replacement therapy, and not stopping it on their own; stopping it because their doctor told them about it. So a combined effort here.
So the conclusions for them � and this was the American Medical Association � basically said on the basis of the HERS Trial and other secondary prevention studies, that they would then recommend that you can't say hormone replacement therapy for secondary prevention of heart disease, which makes sense because all of the Prempro studies showed that it would worsen it. And then with the Premarin arm, and that just finished about six months ago. How many of you realize that the Premarin arm of the study ended early? Just a few. It wasn't even publicized. Do you know how the Prempro study was all over everything, it was national news and you heard it on every talk show, every news station? The Premarin Study just fizzled out; they didn't even make a splash. But basically they stopped it because what they found after about six and a half years, do you remember what I told you they wanted to find out if Premarin would help against coronary artery disease? They found that it wouldn't. Not that it increased risks of other diseases., but that it would not decrease the risk of primary coronary artery disease, and that was basically their endpoint. That was why this study was done. So that's why this study was stopped early.
Now, if you think about Premarin for a moment, Premarin is a combination of about twenty-plus different chemicals that come from pregnant mares' urine � it comes from horses. What they've also discovered, and this is interesting reading letters back and forth from the Whitehurst Company and from the FDA, that Premarin not only has these estrogens in it, but when it metabolizes in your body, it metabolizes into stronger estrogens, which is, by the way, just the opposite of what happens with all hormones in your body. Hormones usually metabolize into weaker estrogens once they're used, and then your body disposes of them; but Premarin, the drug, becomes a strong estrogen, and then it stays in the body for a week or two...or three or four...versus hormones. They have very short half-lives of hours. So there's big differences between Premarin and estradiol.
The interesting thing was that with the Premarin group that we could have told you that because Premarin is not an antioxidant � you know, I told you about the nitric oxide � does not improve nitric oxide production in the body. It doesn't prevent your platelets from clotting, that Premarin shouldn't improve the risk for coronary artery disease. It shouldn't; it doesn't have any of the properties of estradiol, which is a vasodilator, keeps your platelets from clotting, helps with the nitric oxide vasodilatation part of the whole thing. Then they found out that Premarin has some testosterone in it and that Premarin has some progestins in it. So it's not even a true estrogen. Remember earlier on I told you that antigens increase the risk of coronary artery disease? So now we have a drug that we're calling an estrogen, giving it in a primary prevention study as an estrogen; it doesn't have the properties of estradiol, which we know can prevent coronary artery disease in mice. And then when the study says �it doesn't prevent,� then we're telling every woman and every doctor, �You're not allowed to tell your patients anymore that hormones are good for the heart.� So that's kind of where we are with that.
Really, this is the question. We're talking about hormone replacement therapy, and, again, we talked about the choices earlier. Don't take hormone replacement therapy, and then you work on your lifestyle changes. That's fine. Take it, but take it correctly � and you still have to work on your lifestyle habits even if you take it � but don't take it incorrectly. I think if we learned anything from these studies is that if you take a hormone incorrectly or you take a drug instead of a hormone, you're going to cause more harm than good.
Again, I kind of alluded to the fact that when I give hormone replacement therapy to women, it's not for symptoms; it's because of its effects on the other hormone systems of the body that cause more problems than the loss of estrogen does. So when you lose estradiol, what you need to know the connection is that adrenaline and cortisol levels go up. I write �initially rise� because after a while your body can't keep putting out that amount of adrenaline and cortisol, and you burn out the adrenal glands, if you will.
These are the major breakdown hormones of the body. So when adrenaline and cortisol go high, you're going to start losing tissues. And again, this is where we see some of that fast bone loss that we see in the first ten years. But the other thing you need to realize is that when adrenaline and cortisol go high, that's a natural trigger, or signal if you will, for the secretion of another hormone called insulin. And when insulin levels are staying high, then you're starting to become at higher risk for what we call the �metabolic syndrome� � you've heard that terminology that's coming out now � so the loss of sex hormones increases the risk for the metabolic syndrome, and that's the connection. All of my work on menopause started in Type II diabetic women. I was able to show clinically that when we gave hormone replacement therapy correctly, we were making our patients more insulin sensitive, and I think that's a very important concept.
In general for me, the treatment of menopause means calming down the stress hormones of the body; that's what I'm trying to do. So when you do have high adrenaline and high cortisol, then basically this is where you're getting a lot of the symptoms, right? High adrenaline and cortisol, you get heart palpitations, you can't sleep at night, this is where you're starting to urinate at night, you get the hot flashes, the night sweats, it's from this change.
So if you're a woman going into menopause and you're not getting this type of change, there are two reasons for that. One is going to be that you're losing your hormones very slowly and you still have some estrogen on board that's keeping this at bay. The other is that you might already have a problem with your adrenal glands and that they already are burned out. I'm using the term �adrenal gland burnout� very loosely, but now in the endocrine literature we actually are using that terminology. So this is not Addison's Disease; this is the loss of the ability of the adrenal glands as the reserve to put out as much stress hormones as you need to deal with a certain situation. Then, of course, we know that high insulin levels lead to cardiovascular diseases and diabetes and the metabolic syndrome.
What are lifestyle habits that will make this transition worse for a woman? All of the same habits that will raise adrenaline and cortisol, right? If the loss of estradiol already raises adrenaline and cortisol as the main event, if you will, then anything that a woman does that's above and beyond that. This is additive, right? This is cumulative. So if I lose estradiol and I skip a meal, if I lose estradiol and I drink alcohol, these are things that will raise adrenaline and cortisol even higher for that woman and make her more systematic. So skipping meals, dieting, eliminating food groups, not sleeping, excessive stresses, ingesting alcohol, caffeine, sugars, smoking, too much stimulating cardiovascular exercises. These are things that raise the cortisol and adrenaline; and again, if I don't have estradiol on board, it's additive and it's going to make all of the diseases and symptoms worse. So when I work with hormone replacement therapy, it's not just, �Here, just take a hormone,� it's �Let's work on your lifestyle at the same time.�
If women want to be treated without taking hormones, then really what they need to realize is they're going to have to change their lifestyle. And, again, there is no issue with that as far as you're not making the wrong decision unless you don't change your lifestyle. You can't run around being busy, being crazy, trying to do everything you want to do with a loss of estradiol. That just raises adrenaline and cortisol even higher than it would be, and you're going to end up with more diseases sooner than later. Oh, and I didn't say it earlier, but I will say this: The insulin-associated cancers are breast cancer, prostate cancer, and colon cancer. Obviously for women there is no prostate cancer, but what we are seeing, and again, it was just shown in the Women's Health Initiative Study that we're seeing more breast and colon cancer, right? When women go into menopause because insulin levels are going higher at that time. So women have to rest more. I think that goes without saying because, again, if I'm going to be missing a hormone that helps me do more and now it's gone and I'm breaking down at a faster rate, then I need to rest to help myself rebuild.
Because there are sleep issues with the loss of hormones, and if women don't want to take hormone replacement therapy, then we try to use supplements. Tryptophan becomes 5-hydroxytryptophan, becomes serotonin, becomes melatonin � the sleep hormone. Better to give tryptophan or 5-hydroxytryptophan, add a little bit of calcium and magnesium to that and some B vitamins to help that conversion happen, and B-6, because if you have the ability to make a hormone, and melatonin is a hormone, then you want to try to make that hormone. If you start taking melatonin � this is why I advocate not having patients take melatonin � then your body starts making less of that hormone. So the more you take melatonin, the more you can get yourself into more sleep depravation and more problems with sleep. Now, if somebody has jet lag and wants to use melatonin for a few days to get themselves back on track, that's not what I'm talking about. I'm talking about the chronic use of melatonin for sleep that we see all of the time.
Plus, there are feedback loops. Serotonin becoming melatonin. When you take melatonin, you don't block serotonin becoming melatonin; you block 5HTP becoming serotonin. That's where the block occurs, the feedback loop. So you're going to cause more depression by taking chronic melatonin, and that's another reason not to do that.
Now, here's a good one: What happens when women go into menopause? They start to gain weight, right? Because high cortisol and high insulin cause you to gain weight around your mid-section. Also, the other reason is the fact that when women lose their estrogens, they still have androgen production. You still have testosterone; you don't lose testosterone like you lose estrogen. You lose that later. So testosterone thickens a woman's waist also. So they have all of these things that are doing that. But one of the hormones that can be made in the fat cells is E-1, which is known as estrone, which is different than E-2 or estradiol. Estradiol is made in the ovaries; estrone is made in the adrenal glands and the fat cells. So you have more estrone estrogen production. E-1 and E-2 are interchangeable, too, so the body that can convert some E-1 into estradiol. So one of the things that you have to realize is that if you're going to go into menopause and do it naturally, you need to gain weight so you keep some estrogen on board. That is one of the reasons the body is doing that. It's trying to keep you having weight. And if you ever asked anyone who's not on hormone replacement therapy who's gained the weight, how hard is this to take off? The body does not want to get rid of the fat weight because getting rid of the fat weight means getting rid of the estrogen, and then you start to break down again faster. So it is a compensatory mechanism to gain weight; and if you want to do it naturally, you have to gain the weight. It's very important.
In other words, in Europe, you know, they keep talking about it, �Look at all of the Italian women who go into menopause. They're doing really well and they're not taking hormone replacement therapy.� What do they look like? So they've got the big round waist...all of the thickening around the waistline. And again, I'm not saying there's anything wrong with that because here we're so fashion conscious about what should a woman look like, but they're not running around trying to diet after that, right? They're not going, �Oh, now I'm not going to eat because I've gained weight around my mid-section.� These women continue to eat, and that's one of the reasons they do so well.
And then you want to eat balanced meals with plenty of vegetables and healthy fats and all sorts of vegetables and real carbohydrates and proteins, and I think that goes without saying. The reason I say stay away from soy products does not mean stay away from�okay? It's the products that we're worried about because there have been studies showing that if you take too many of the soy isoflavinoids that you can end up with probably breast cancer; you definitely will have thyroid issues from taking these things. And yes, the isoflavones will help with the symptoms, but this is not hormone replacement therapy. You're not going to take a plant chemical in place of your estradiol and think it's going to reduce your risk of heart disease. It's not going to happen. And, of course, you don't want to be on alcohol and caffeine and sugar and nicotine; but ironically when you don't have estradiol, guess what you crave? So there's a problem here.
One of the most important things to note, and especially if you do any work with addictions in your patients, is that the loss of estradiol really gives women alcohol cravings. That's a huge one. So if you have somebody who's in menopause and can't get off of alcohol, you really again should be considering hormone replacement therapy done correctly in these individuals to help them come off alcohol.
In the rules of hormone replacement therapy, if you will, if we're going to talk about taking hormone replacement therapy, I truly believe there's only one way of doing this correctly, and that's my way...no, just kidding! What I started to do when I started looking at hormone replacement therapy and menopause because I hate to admit this, but in the nine years of medical training I had, I had two sentences on hormone replacement therapy and menopause. �If a woman has her uterus, give her Prempro; if she's had a hysterectomy, give her Premarin.� That was it. And when I went to ask my professors, �How come you're not teaching us more about hormone replacement therapy and menopause?� the answer was, �Oh, the gynecologists do this. Diana, no one is going to come to you for hormone replacement therapy,� and I went, �Great! One less thing I have to learn.� Of course, that certainly changed the first year I was out in practice, right? I started getting women to see me saying, �Do you know what? I've been to this gynecologist and that gynecologist, and I've gotten no relief. I know that something's wrong. They keep telling me it's all in my head. They want to give me antidepressants; I can feel it's a hormone imbalance.�
And what did they do? They went to some dictionary and looked up what study of medicine studies hormones, and that's how they tracked me down. �You're an endocrinologist; you should know what to do.� You know, it's kind of interesting because I didn't know what to do � not in that situation. But what I decided to do was when I looked at it, I was going to go back and look at how did I replace insulin? That's a hormone. What are the rules that I followed as an endocrinologist to give back insulin to Type I diabetics? How do I replace thyroid hormone? How do I replace cortisol when somebody does have Addison's disease? So I kind of went back to the basics of endocrinology, and that's where these four rules come from, if you will. I'll try to simplify it.
Rule No. 1 it was very obvious that you don't ever want somebody to take a hormone that they still have, right? That sounds very obvious, and yet I'll tell you every day patients come to see me who've been put on thyroid for all of the wrong reasons. They're taking over-the-counter DHEA, they're rubbing on progesterone cream when they shouldn't be on it. So as simple as it sounds, this rule is broken every single day, and it is harmful. You're harming patients when you put them on a hormone that they can still make because there is a lot of feedback regulation between hormone systems. So it's only okay to start giving a hormone back when it's missing. Again, if you catch somebody in an early true Hashimoto's thyroiditis, which is an autoimmune disorder of the thyroid gland, no, you don't have to wait until their TSH is 20 or 30 before you replace them. You can start replacing them with the knowledge that they're going to keep getting worse and worse anyway, so that's okay to do. So again, we're not going to be waiting.
And the same thing for menopause, right? We know when a woman starts going into menopause, hormone levels are not going to get better; they're just going to get worse. So you can start earlier than later, but you do need to make the diagnosis that a hormone is missing. That's Rule No. 1.
Once you do, then you can go onto the other rules. So Rule No. 2 is whatever that missing hormone is, you want to go back and take the bio-identical form of that hormone. So what did I say earlier? Estradiol is made in the ovaries. Not estrone, not estriol, which we'll talk about in the workshop today, but estradiol. Not conjugated estrogens that you find in Premarin, but estradiol. So we want to go back and say, �Oh, guess what! This is such a novel concept. You lose estradiol; we're going to give it back,� versus what we've been doing for the last 30 or 40 years: �Oh, you lost estradiol? Hey! Let's take Premarin.� It doesn't work that way.
The same thing for progesterone. Here's a good one on progesterone, and something that I've seen a lot in the last ten years. Progesterone is also called medroxyprogesterone acetate, right? So it has progesterone in its name. So so many people think because it's called medroxyprogesterone acetate that it is progesterone, but it's not. We do not have the enzymes to break down the medroxy group from the progesterone. You can break down the acetate group; you can take that off; but you can't take the medroxy group off the progesterone. So it changes the whole property of that hormone, and, again, it becomes now a drug instead of a hormone. What they've done when they've studied medroxyprogesterone acetate, its properties are more like testosterone than like progesterone. So surprise, surprise that Provera has been shown to increase the risk of heart disease and strokes, right? It shouldn't be a surprise; that's the properties of that drug, and it's well known. It was also studied in the Peppy Trial that that came up too. So there's a lot of different studies that we've done,, even the study of the drug itself. So I like to say do you know what? Let's stop studying things. How about if we just look at this from the physiology viewpoint? What do we know about these hormones and their properties and not just blindly give people drugs and then decide 30 years later we're going to test it and see what's going on. That makes a lot of money for the pharmaceutical industry, and that's where the misinformation comes from. This is a billion-dollar industry...a multi-billion-dollar industry.
All right, so you want to take the bio-identical form. And for testosterone, you give real bio-identical testosterone, not methyltestosterone. Oh, I didn't tell you my progesterone story; let me go back for a moment.
With progesterone, I would have patients come in to see me; and because they were on Provera, they would come with their lab work for progesterone. Now let me just tell you that you can't measure progesterone levels on Provera, but you can order them. They can be done; they're just not accurate. So I'd have a lot of patients coming in with their levels and telling me how their doctor would get their level � and by the way, it's falsely low every time you look at it; Provera blocks progesterone in the body, so the levels would always be low � and the doctor would get this low progesterone level and up the Provera, and the woman would get more symptomatic, and they would come back in and get another level, and they would up the Provera. This would go on for quite a while until they realized, �Wow! Do you know what? This doctor doesn't know what they're doing,� and then seek other care. But so you know, you have to know what the drug is, can you measure it or not measure it, what does it mean when you do or don't. All right, so we're going to take bio-identical form.
The other thing about testosterone, in 1996 I went to Hawaii and took a course that the Mayo Clinic gave for endocrinology since I needed some CME credits, and I thought Hawaii's not a bad place to go, right? Who's going to go to Rochester, Minnesota? And they knew that, too; that's why they took us to Hawaii. But I was so thrilled because I had already been doing bio-identical hormone replacement therapy for about seven years at the time, and I was kind of sitting there with my arms crossed in the back listening to the male menopause lecture, and lo and behold, they started talking about bio-identical testosterone, that they had studied this in men and realized that for men they needed to be on bio-identical testosterone because the drug methyltestosterone was harmful. It really was important that when we did hormone replacement therapy, we give bio-identical hormones back. So I was all excited going, �Oh, my gosh! Tuesday was male menopause; Thursday is female menopause.� So on Thursday, I'm all excited now. Now I'm sitting in the front row. So on Thursday, I'm all excited. Now I'm going, �All right! You guys are up on track. This is going to be really exciting. I'll share my stuff with you and then I'll hear what you have to say because you're the Mayo Clinic,� and guess what they talked about? Prempro. They didn't know anything about bio-identical hormones for females in 1997. And yet, �Where am I going? What are you guys? Aren't you in the same building?�
And then for women they were still saying medroxyprogesterone, which is not a bio-identical form of testosterone. So even the male research on bio-identical testosterone didn't get put into the female research. That's when I realized that the left hand didn't know what the right hand was doing. Anyway, you want to give bio-identical hormones, again, because you want to have the same properties that you've lost, right?
The third is you want to mimic normal physiology as much as possible, and this is a very important concept, which I'll show you a little bit about. All hormones work by binding to their receptor sites, if you will. And then when they bind to their receptor sites, they set up a whole chain of reactions, and those reactions lead to other receptor sites for different hormones.
So for instance, estradiol when it binds to its receptors activates a chain of events that produces progesterone receptors. So estradiol activates progesterone. On the other hand, progesterone when it binds to its receptors sets off a whole chain of reactions that decreases the estradiol receptors. So that's the communication. Estradiol enhances progesterone, but progesterone blocks estradiol.
So if you go back to the Prempro study where you're saying Premarin versus Provera, they still bind to the estrogen receptors and the progesterone receptors; they just have other properties to them that change the physiology. Then what we see is that all progestins are antiestrogens, right? That's what they do; they block the action of estrogen. So if we go back to the group of placebo � in other words, women in menopause not taking any hormone replacement therapy � and then you look at the women Prempro, what can you say about the women on Prempro? That their total estrogen effect � the effect of the hormone in the body � is lower than women who don't take anything because whatever little estrogen left in a post-menopausal woman, if she doesn't take anything, it's still active. But if we give her Prempro � because remember, the Provera is so much stronger than the estrogen plus it's double the dose at least and we're blocking all of the estrogen � we were seeing that again the risk of heart disease, the risk of clots, the risk of stroke, the risk of Alzheimer's goes up in post-menopausal women not on anything, and now you add Prempro and the risks are higher than nothing.
I'm going to conclude, and yet this is not how it's concluded because, again, from a science viewpoint I know this to be true, that it's because of the blocking of the estradiol that we're seeing the increased problems. And again, that's in relationship to when I block estradiol, adrenaline, cortisol, and insulin go higher, and I have measured that in my patients and seen that to be true every single time.
So you want to mimic normal, which means cycling the hormones off of each other. You never want to give daily high doses of progesterone to block your daily low doses of estradiol. You just don't want to do that. So unfortunately, when you do hormone replacement � I say unfortunately because as a woman, who wants their period again after it stopped? � but you do get menstrual cycles again in women, and that's when you know that you have enough estradiol on board to prevent the degenerative diseases of aging, and that's a very important concept.
And then you track the effects, and the effects are going to be what's the rate of bone loss, what's my cholesterol levels doing, of course, all of the symptoms � are you sleeping well, what's your mood, what's your energy. I've had people call me in the middle of the night � this was early on before I explained it to them in the office � �Oh, my God! I feel so fertile. We're having sex. Can I get pregnant?� No, you're mimicking the cycle, but you're not getting the egg back. I just want to point that out. So if you ever counsel anybody, you can let them know ahead of time that no, this is not going to give them back fertility, but women feel very fertile again on cycling hormone replacement therapy.
So you're going to mimic normal; and the good news is that when you take hormone replacement therapy, you cope with stress better. So now we're talking about the lifestyle changes, right? We're saying do better with your stress management, do better with your sleep, get off of toxic chemicals, and all of that good stuff. What you'll find is that with hormones on board, it's easier for women to follow good advice and healthy lifestyle choices because cravings are gone, sleep is easy to achieve; you know, things will happen. And if they decide to do stimulating exercise, at least the estradiol will blunt some of the cortisol adrenaline response that comes from doing that type of exercise. So, again, it's easier to change lifestyle with hormones on board than it is without.
We're going to end with kind of just looking at the normal menstrual cycle. What I want � and this is very important � is to show you that estradiol and progesterone, we're going to talk about mimicking normal. So the first half of the cycle, the blue up there is estradiol, and at the beginning over here we've got let's say Day 1, at the end over there we've got Day 28, and then it cycles back to Day 1 again. That's kind of what the menstrual cycle does. So in the beginning you have an egg growing, and the egg is what's responsible for making the hormones. So that's called the follicular phase as the egg is growing making estradiol. Estradiol levels peak around Day 12, 13, 14 in the individual; then they drop for about 12 hours, and then you enter into the luteal phase where you have the egg is left � I'm not going to get into details here; I'm going to do this in the workshop if you're interested, but just to give you a really quick overview � and then you have the egg sack that's left behind, and that forms the corpus luteum, and that's where you start to make a lot of progesterone. And since the pathway to estradiol production involves progesterone, you'll get a peak also again in the second phase with estradiol. That will be maintained for a couple of weeks as the corpus luteum continues to make these hormones. But if you don't fertilize and plant the egg and the egg doesn't start making its own hormones, then the corpus luteum dies after 14 days � that's it's lifespan � hormone levels drop, you get a period, and the whole thing starts again. That's normal physiology of this hormone system.
So this is what menopause looks like. It really is flat lined. You lose your estradiol and you lose your progesterone. I drew progesterone above estradiol to make a point that other places in the body that make progesterone such as the adrenal glands keep functioning. So really estradiol levels are the ones that really go to zero; and as long as your adrenal glands are still functioning, you'll make some progesterone.
This is what continuous combined therapy looks like, where you're going to have a continuous amount of higher levels of progesterone blocking the estrogen all of the time. Again, this is the Prempro Study � Women's Health Initiative � the HER Study showing that this is harmful. No one should be on this type of hormone replacement therapy in my opinion. Therefore, this is what it looks like to mimic normal as much as possible. Because we're not worried about fertility and the ups and downs of estradiol are signals for fertility, we can flat line estradiol, if you will. If you take enough estradiol every day, the same dose, and usually twice a day because this is a hormone and hormones have very short half-lives so they're not in the body for very long times, you get a line that you do every day. And you don't stop. It used to be thought Days 1 through 25 we'll give you Premarin, and then maybe days 15 to 25 they'll give you Provera, and then for the five days that you'll stop. Premarin and Provera are drugs with long half-lives, so the idea of stopping for five days is to let that drug clear out of the system. But with hormones, you don't stop. You continue the estradiol all of the time. You've got to start somewhere. This is Day 1. So you don't do it a calendar day. You don't say this is the calendar day of the month. Whenever you start hormones, we're going to call that Day 1, and then you cycle with that. Then you start adding progesterone.
The reason I put that dashed line there on estradiol is the estradiol level does not change on progesterone. It's the effect of that hormone that gets modulated. It's important to know that. And when you do hormone levels, because people have asked me about accuracy in hormone replacement levels, then what you're looking for is you're going to test way over here. When you test over here to look at the estradiol effect, you look at a hormone called FSH. You can look at your estradiol levels to determine what kind of changes you need to make, but it's the FSH � the follicle stimulating hormones from the pituitary � that determines that. Again, I'm going to get into greater detail in the workshop for anybody who's interested in learning how you prescribe hormone replacement therapy and then how you follow it.
I just wanted to leave you with knowing that my next book is coming out. I guess I thought it was June, but it's July. In it there is a chapter on hormone replacement therapy where I say draw this hormone and look for these levels, and I try to explain this a little bit more detail than in my previous books. Any questions?
AUDIENCE: Comment.
SCHWARZBEIN: What are the bio-identical estradiols? There are different ones. There's Estrace, there's Gynodiol, there's Climara patches. And the thing is this: it's so easy. You call the pharmacy; they'll know. You just say, �I want an estradiol preparation,� and they'll tell you the ones that they have.
AUDIENCE: �is a drug?
SCHWARZBEIN: �And then for progesterone, there is only one right now on the market that's not compounded called Prometrium. The problem with Prometrium is it only comes in a couple of doses. The thing about hormone replacement therapy is one dose does not fit all. The other way that you get your bio-identical hormones is you work with a compounding pharmacy, and there are many all over the United States. We just write �E-2" � that's estradiol; that's the chemical name for E-2 � and we go E-2, and then we put any amount I want on there, and then I'll add plus a little bit of progesterone, any amount I want, and then I cycle with a much higher level for 11 days or 14 days out of the month. So I'm designing with my patients their hormones and their specific doses. That's how we make it bio-identical and more physiologic for them.
AUDIENCE: Comment.
SCHWARZBEIN: Versus what? Oh, right. Right, yes. If somebody is already taking it continuously, then you want to start cycling ,but just be cautious that usually that is already along with too-little estrogen therapy. So you need to modulate both. Usually you need to stop taking the daily progesterone everyday, switch it to an 11 or 14-days-out-of-the-month cycle. And if it is Prometrium, I do say 14 so that you can take 100 milligrams once a day for 14 days. And then you usually want to look at the estradiol level; it's usually too low. But you'll know; you won't get periods. Or the other thing is when women get cycled on progesterone and they don't have enough estrogen, they feel really awful. So you've got to look for that. On the other hand, there's an exception to that too. You can have the right amount of estradiol and be on progesterone and feel awful because you have low serotonin, so that's another thing that you need to look for if you think the hormones are balanced. Yes?
AUDIENCE: Comment.
SCHWARZBEIN: The question is how do you manage hormone replacement therapy if a woman has had a hysterectomy? I do very well! No! The difference is that you don't have to cycle for those 11 days to 14 days out of the month. But in some women who are very young when they've had their ovaries measured if it's going to be an ovary problem, too, then they like to feel...the brain is what cycles, so a lot of times women feel better if you continue to cycle them until they get older and the brain stops cycling. So we see that a lot. But in general what we do is we give enough estradiol to bring the FSH down to normal, and then we measure progesterone, and we're looking for low follicular-phase levels of progesterone. So every lab will come with their ranges. And that's the other thing as I mention labs, it's really important to remember that all labs are not created equal. There are many labs that are designed to test estradiol levels just for pregnancy and to say yes, it's going up; no, it's not going up. So it's very different when we're talking about when we're looking for qualitative, real numbers versus quantitative, kind of junk numbers.
My favorite was when I would get hormone replacement and I'd start somebody at estradiol .125 � that's a very low amount of estradiol � and their estradiol level would come back like 800 in their local lab. I'd go, �That's very funny!� and so we'd just redraw it in a different lab, and it would come back basically zero because estradiol .125 is a very low number. So you have to be very careful about the labs that you use on your patients or what they have done.
Nichols � you know, Nichols branch of Quest Labs? Not Quest; don't let Quest run the hormones, but their Nichols branch is an endocrine lab, and they will do a very good job for you in drawing hormone levels. So that was one you could do.
AUDIENCE: Comment.
SCHWARZBEIN: What is Estratest? It's actually conjugated estrogens with methyltestosterone. It is a drug. Yes, back there? The question is how is cardiovascular exercise negative? There were just a few of you here yesterday and I guess I didn't want to repeat myself, but the rest of you weren't here last night. In general, when you do cardiovascular exercises, your heart rate goes higher and your blood pressure goes higher. Would you agree with that? The hormones that help with that are the catecholamines, so that's going to adrenaline and norepinephrine, and cortisol. Those are the stress hormones of the body, so you're actually stressing your body out when you do that. What do stress hormones do physiologically? They break down proteins in the body. The catecholamines break down proteins, they break down fats, they break down sugars. Cortisol breaks down proteins, breaks down sugars, and stores fat. Just a little bit of the physiology of these different hormones. So the more you do cardiovascular-stimulating exercises, the higher these levels go. If you then are able to rebuild from all of that � you're eating really well and you're rebuilding back, that's not an issue � but around the age 35 we lose human growth hormone. Human growth hormone starts to go down with age � another hormone that gets lost. Human growth hormone counters the fat-storing of cortisol. So because human growth hormone is protein-building and it's fat-wasting, if you will, we start to lose it so we get more cortisol effect after the age of 35 by doing stimulating exercises. So it's better to do adaptive exercises where when you're doing a set of weights, your heart is going to go up. You're going to get stimulation, but you're going to stop, you're going to let it rest, you're going to rebuild, and then you're going to do it again. That's just as good for your heart as your stimulating exercises are, and it's much better for your physiology � your biochemistry � over time because again, what is aging? Our inability to rebuild from us breaking down. And after a certain time, unfortunately, we are breaking down because we are losing some of our rebuilding hormones. Does that make sense? It's confusing, I know! Oh, depressing? That, too! You do lose serotonin when you do stimulating exercises.
End of session. |