OB-GYN and reproductive health specialist Michael Policar, MD, MPH, offers an evidence-based guide to easing the symptoms of perimenopause and menopause. Providing clear criteria for when a patient has entered either phase, he discusses the range of effective treatments – from nonhormonal options, such as SSRIs, to transdermal estrogen therapy, with potential benefits over oral. Includes useful dosing charts for initiating therapies and finding optimal doses.
uh Thank you to all of us for joining us this afternoon. Uh So as you know, we're going to talk about sort of the evolution of available treatments for managing menopausal symptoms. Um To start with, I don't have any relevant financial disclosures to make uh these are learning objectives, basically. We're going to focus on management of these are motor symptoms uh as well as the symptoms of genital urinary syndrome of menopause. Let me start by just defining some of the terms that I'll be using throughout my talk. And of course, whenever you read guidelines or literature on this topic first is the formal definition of menopause, which is the specific date of a woman's final menstrual period as opposed to last menstrual period. F. M. P. Means the last period she had before she went into formal. Uh Menopause. However, 12 months of a man Maria is required after that final menstrual period. Before you can retrospectively look back. And in that date as a specific date of the final menstrual period, you'll see that more in a slide coming up that shows that graphically next is the menopausal transition. That is mainly a variability in menstrual cycles that can happen months or even years before the final menstrual period and then the perimenopause which will be talking about is to find us the time interval from the onset of menopausal symptoms through that final menstrual period until one year after the final med school period. So here's that graphic way of thinking about it that in the blue line up top there is a reproductive phase when females are ovulating or at risk of becoming pregnant. Then the menopausal transition, which actually formally has two stages. The early and late transition. The early stage typically starting about 47 years old. The late stage typically starting around 49 years old. Then the final menstrual period, which on average is at about 51 years of age when a person goes in full year of Gonorrhea. Before you can then look back and consider the date of the final menstrual period to be the point of menopause. Um, the nomenclature is actually a little bit more complicated than that. We won't go through all these various uh sort of characteristics. But Something that is fundamental in research about menopause is being very specific about these various stages of the females who are involved in in the studies that we'll be talking about. This approach is something called the stages of reproductive aging, workshop or strong plus 10 refers to the fact that the first one came out In the late 90s. And then the second version came out in 2012. But in the lines at the bottom, you can get more of an idea of what's going on with menstrual cycles as well as various and different changes that happened during the menopausal transition. Menopause itself and in the postmenopausal period. Now, the main effects of menopausal estrogen reduction, It's not a complete deficiency. It's not a total loss of estrogen, but it's a significant reduction in estrogen are mainly diesel motor symptoms. We'll talk about what they are and how to manage them, neural behavioral changes, um, particularly sleep problems and a few others uh, and then changes in the lower genital tract, which used to be referred to as vaginal atrophy. That term is now considered to be out of date and is replaced with the term genital urinary syndrome of menopause GSM. The other things that happened as a result of menopausal estrogen reduction is an acceleration of bone loss that can lead to osteopenia and osteoporosis. We won't have time to talk about that today. Uh, and then an acceleration of atherosclerotic cardiovascular disease. So after a period of time, females approached the same rate of heart attacks as males when they lose the protective effect of their own endogenous estrogen. Now, one of the other introductory remarks that I wanted to make has to do with how long it is uh, that people may experience their menopausal hot flashes or their menopausal diesel motor symptoms. The conventional wisdom used to be that a typical person had menopausal hot flashes for about a two year period or so. We also used to say that about a quarter of women may have menopausal hot flashes for as long as five years, but it was felt to be a fairly limited period of time until this study, which is called the Swan study was published in 2015. So they enrolled a little over 3300 females at seven different sites in the United States. This court was followed, believe it or not for a full 17 years with a median of 13 desserts. And what they found was that the median duration of hot flashes in different ethnic groups starting from when the hot flashes started until they went away and menopause being somewhere on that continuum. For African American women was about 10 years. For Hispanic American women was nine non hispanic. White women was about 6.5 years and then chinese american and japanese american. Women typically had a shorter interval of hot flashes somewhere around 5 to 5.5 years. But the main point here is the fact that menopausal visa motor symptoms actually occur for far longer than what we used to think before. This really good quality study was published, I'll just tell you a little bit more detail about it and that is that they found that the median duration of basil motor symptoms without any adjustment at all was about 7.5 years. If you start from the time of the final menstrual period and then track hot flashes on average, that's about 4.5 years. So, remember some people are hot flashing even before the final menstrual period. And then there are some other predictors of hot flashes and hot flash duration as well. So, for example, if a woman doesn't have hot flashes while she's still having menstrual periods, the hot flashes only start after her final menstrual period, then on average, they last about 3.4 years. On the other hand, if a person starts with their hot flashes while they're still having periods, then they're much more likely to have an extended period of hot flashes. So if a woman starts with hot flashes during her pre menopausal years or her early postmenopausal years, Her total Veysel motor symptom duration can be up to 12 years, um and lasting 9.5 years after the final menstrual period. And then finally, there were a number of additional factors related to the duration of basil motor symptoms or their duration or persistence. One was, if you were at a younger age when your hot flashes started, you are much more likely to have them for an extended period of time. The same was true of people with a lower educational level, greater perception of stress uh and sensitivity to symptoms and people who had higher depressive symptoms and anxiety also were more likely to have an extended duration of hot flashes. So, um that gives you a sort of a deeper dive into how long to expect the patients that you see might be experiencing their hot flashes. I mentioned a moment ago that there are a number of neuro behavior changes that happened as well as a result of the reduction in estrogen. One is a a problem of sleep disturbances and uh particularly that includes having a problem of either difficulty getting to sleep or you're able to get to sleep but then have awakening episodes in the middle of the night. And 11 problem that was first described, gosh, 25 years ago, maybe even longer than that, I had to do with some very elegant sleep studies that were done in people who had already entered menopause. Actually tried to correlate hot flashes, sleep characteristics and estrogen levels. And what they found was the fact that that there were a significant number of females who are having um subliminal hot flashes after they went to sleep where the hot flashes weren't enough to wake them up to remember that they were having hot flashes or to remember that they couldn't sleep. But on the other hand, they didn't get into that deep restful sleep, which is necessary to feel like you've got a lot of energy in the following day. So the point is is that if you're having these hot flashes, you're either waking up or not waking up but still experiencing the hot flashes and not getting into a deep sleep, then you might have your ability fatigue, poor concentration on the following day, which in one way, as a consequence of the estrogen reduction, but more directly as a consequence of the fact that you're just not getting a very good night's sleep. And the good news about this is with proper therapy, people are typically able to get a better night's sleep afterwards. Other things that might happen from the neuro behavioural point of view. Uh huh. Our short term memory problems, forgetfulness, reduce computational skills, emotional swings and anxiety. Although depression itself is not directly related to any changes in estrogen level. And they're usually sex sex drive changes that occur in people who are carrying menopausal and postmenopausal. Often there is less interested in sex, which has to do with reduced testosterone levels, maybe with sexual pain. We'll talk in a few minutes about how to treat that. But on the other hand, there actually may be a higher level of sex drive because people realize that once they've gone through menopause and can no longer become pregnant than that is sort of a liberating feeling, basically, which makes one a lot more interested uh insects and more likely to have sexual arousal just because there's not the risk of pregnancy any earlier head. Okay, so enough enough background of the kinds of things that happened. I know the reason you came is to hear about how to diagnose them and how to treat them when they happen. So, I'm a huge fan of really good quality evidence based guidelines. And when it comes to menopause sort of, the benchmark is the North american menopause society. They published guidelines periodically about a variety of issues related to matt lawson the rest of this lecture will primarily be focused on this particular statement to 2000 and 17 hormone therapy position statement of Mam's the North american menopause society. And I'll identify for you on each slide when I'm quoting directly from their guidelines. They have many many other guidelines by by the way that go beyond just torment there. I'm also going to be using the same abbreviations that man's uses in their guidelines. So you will see things like E. T. Which refers to estrogen therapy, E. P. T. Which is estrogen and progestin. He is progestin by itself. VMS is fatal visa motor symptoms. GSM is genital urinary syndrome of menopause. Uh And so I'll define them better for you as well actually get to them and talk. The next thing to mention is the fact that I'm going to I'm going to do three case studies. The case studies are based on an app which was developed by the North american menopause Society which is called Mena Pro uh something which you can download for free onto your ipad or iphone or your android phone. There's one version that's available for women consumers. There's another version which is available for health care providers. Uh And it's really a very helpful way of sort of thinking about the various categories of menopausal symptoms and will be treated. So this is what the entire algorithm looks like. Of course I'm not going to walk you through this now. But I will tell you that it starts with a person with a question about whether or not the patient that you're seeing has moderate to severe hot flashes. Uh If he answers no and not having moderate or severe hot flashes, we're going to focus mainly on the left side of the algorithm. That has to do with treating genital urinary symbol of the menopause. On the other hand, if she does have moderate to severe hot flashes, we're going to rely on the right side of the algorithm uh and talk about either hormonal or non hormonal therapies. So let's take our first case, Who is delores? She's a 48 year old female. Her cycles are still occurring there between 27 and 35 days apart. She complains of mild to moderate hot flashes. That has particularly at night, occasionally feels depressed. But her depression hasn't been fully evaluated or treated. She's a non smoker, doesn't use any medications otherwise generally healthy. She's normal, intensive, tiny bit overweight. Her BMI is 26 she would like treatment for hot flashes, but she's scared of hormones. So, what Delores is asking for is I need some medicine for my hot flashes or something for my hot flashes, but I really don't want to do hormones at this time. I'm worried about side effects and all the things that I've heard about. The so here's the way that many pro looks at this. So first question does she have moderate to severe hot flashes? The answer is yes. Other their moderately severe. So the answer is yes. Next question is is does she want hormone therapy? The answer to that is no. And so the next question is does she want an ss ri drug? If the answer is yes, we're going to try and ss ri or an sn rai. If the answer to that is no, we're going to try something else like that repentance. So let's talk in this branch uh in a little bit more detail. So This section comes from yet another nance guideline called the key points from the 2015 g position statement about non hormonal management of menopause associated with these are motor symptoms. Unfortunately they haven't updated it since 2015 that I've included a few updates. But this is specifically a guideline that has to do with Doris. Who does not want to actually take ones. So the recommended prescription therapies are there is one FDA approved product out there that is non hormonal for hot flashes which is low dose of paroxetine salt. Another evidence based approaches gabapentin and pregabalin. And then they go on to say other Ss Ri or S. N. Rise that yield significant reductions in plant flashes. In large randomized control trials of which there have been 100 there are many, many different studies out there for us to be able to look at. So in a person like flores. What we're going to focus on as we do share decision making is what's her preference for the kind of non hormonal medication she'd like to use. Does she have a co existent mood disorder? Which in Gloria's case she does, she's told us that she's depressed or her hot flashes more bothersome during the day or night. You have some of the therapies uh would actually induce kind of a state of solvents help you sleep and you might go more in that direction if they're more bothersome tonight. Um Does she have side effects to any medications? And a few people have actually had for Mako genetic testing to let them know what the most appropriate treatment might be. I'm going to show you that the various alternatives in the next slide. But basically what names reminds us is that we always want to start with a low dose of whichever medication we use and then titrate up to an effect of making hot flashes less than avoiding side effects that we can. And remembering that the onset of action of these various accessories as Greece gabapentin are usually by two weeks or so. We should see some improvement. The flipside is when we stop, we want to taper that therapy over a week or two. If we started a person on an ss, sorry or sorry. We evaluate them regularly in the nam suggestion that every 6 to 12 months to see if they need a dosage adjustment and hopefully we'll be able to prescribe something, which is on the formulary of the particular health plan that the patient has. So here all that non hormonal medications that are evidence based for treating hot flashes based on the nam recommendation. So the first is paroxetine salt 7.5 mg. Um The thing is is that that particular product bristol is only available by brand name. There is no generic version of it uh and therefore it might not be on a formula. Next is generic paroxetine or generic Paxil. Basically the lowest dose you can get is 10 mg. So what many clinicians do when they want to start paroxetine is to start with a 10 mg dose and then work up from there. And of course that's going to be much less expensive because of the availability of the generic version of proximity. Next is the trial of ram or CeleXA s a trial of bran or Lexapro. And then we have the two snR dustbin the vaccine and then the vaccine, I'm sure that you've heard of the value of Effexor and it's generic equivalents in in treating high flashes as well, starting with the low dose like with them a vaccine of 37 a half milligrams per day and then working up there as needed. And then lastly you'll see gabapentin widely available as a generic um starting with 300 mg at night if that doesn't do the trick for hot flashes, adding a 2nd 300 mg at night. So it's 600 mg at night. And then the next of the next step after that is to add 300 mg in the morning. So now you've worked the person up to 19, I'm sorry, 900 mg and you can actually go all the way into 2400 mg of God. Repented by the way. gabapentin is very popular for treating um females who have who have had breast cancer when they have hot flashes or even for other symptoms of of uh estrogen deficiency. Because of course when a person has been treated for breast cancer, particularly in the last uh they'd been treated within five years. Um we really want to avoid hormonal medications for hot flashes and tendency of particularly medical oncologist and many O. B. G. Y. N. Is to go straight to gather attention in the circumstance where treating hot flashes and people who just can't use estrogen because of their breast cancer history. Now, what kind of reduction in hot flashes can you expect? This is a study that was actually published in the oncology literature years ago, But it starts by looking at five different medications. The middle column is the percentage of patients who were treated who had at least a 50% reduction in their hot flashes. So as you can see with Bella vaccines somewhere between 54 is 70% met that criteria with paroxetine. Again, a majority circling S.A. program. Um gabapentin uh was actually way up there at a max of 84% of people have at least a 50% reduction in their hot flashes. But I also want you to notice what happened in the placebo group, that there was a fairly strong placebo effect. And most of those studies, about a third of women given the placebo actually had a reduction of the hot flashes. But in every one of those studies, the treatment drug did work better than the placebo. So the way to think about this is using an esri or using an S N'dri. Part of it is the therapeutic effect of the drug. The other part of it may be is somewhat of a placebo effect in addition. But clearly they do have a benefit in reducing hot flashes. Now there are a number of other things in the names guideline that might be helpful. Not quite as much as the ones that we just talked about. So things that they recommend with caution or weight loss, stress reduction, certain soy derivatives, a procedure called estella ganglion black, which we don't do in the United States is popular in europe. So there is evidence to support these, although they are not as effective as the SSR is with the Henrys. Um extra things that are really not recommended specifically for hot flashes because there have been studies to look at the value, it really doesn't help for hot flashes. So exercise, yoga breathing exercises, like paced respiration, acupuncture. Um They all certainly have their own health benefits. But at least in randomized control trials, they really don't seem to help much in regard to hot flashes. And then the last category of our things where either they have been studied and there is no benefit or they haven't been studied at all. And there are many over the counter supplements that are out there for treating hot flashes. We'll talk about one of them um in just a moment. Black cohosh, herbal therapies, vitamin relaxation, cooling, trek techniques, avoiding triggers for hot flashes like hot or spicy foods are all things that may or may not help an individual that either they haven't been studied or when they were studied, they just didn't make very much difference. Okay, so how are we going to manage Delores? So in my opinion, the best options for her, given the fact that she not only has moderate hot flashes, but also has my own depression. A good place to start would be with paroxetine 10 mg a day and trying to treat both of her problems and then titrate upward as needed for both. Getting her hot flashes under control. Cantor Depression if that doesn't work. Or she doesn't want to use paroxetine, offer venal vaccine. 37 a half milligrams, then titrate up Uh if that doesn't work or she doesn't want to use those drugs start with gabapentin, 300 mg at night and then titrate up. And if she tries those and they don't help, she said then, and I still want to use something that doesn't require a prescription. Then the most common supplement is our ones containing black cohosh. Most common one in the United States is called estrogen, although there are many, many other ones available in health food stores on the internet. Um There's a slightly better improvement than placebo in most studies. Not much, but at least a little bit better. Uh duration of improvement is usually under six months, but there are very few side effects. And these are not very expensive supplements. So it's another thing people can try but they'll probably have a limited effect for them. Let's go to our next case, who is Nikki. She is a 46 year old female scene with a complaint of hot flashes and irregular menstrual cycles for two years. Premenstrual interval can be anywhere between three weeks between periods, all the way up to three months between periods. Her bleeding is quite heavy for the first three days. She doesn't have any bleeding in between periods and she does have premenstrual millimeter, which are the premenstrual symptoms that most women get Within 12-24 hours before they actually start bleeding in their natural period. You only get those kinds of systemic symptoms of of breast tenderness, breast fullness swelling in your ankles, irritability only in the cycles where you've populated. So it sounds like Nikki is ovulating. She's just doing so irregularly. She sexually active, not using contraception. She doesn't have any cardiovascular risk factors. So Nikki is very clearly a person who is in peri menopause because of the cycle irregularity and her hot flashes, but she's still bleeding. So she's not officially menopausal yet. And one of the best terms I've ever seen for carrie menopause is estrogen storm season. The reason for that is that for our females that are in the perimenopausal phase, there follicle phase, estradiol levels of endogenous estradiol coming from the ovary Is almost always elevated, 20, or more elevation in comparison to earlier in life. There are higher highs and lower lows in estrogen levels coming from from the ovary. In addition, while people like Nikki or a violating and making progesterone after they ovulate, the progesterone peak is lower. So what happens basically in caring menopausal women is there follicle phase, which is the first phase of the cycle before ovulation. Typically it's somewhere around 12, 14 days. But uh it becomes shorter in perimenopausal women. So now cycle interval is typically shorter, 24-26 days and those intervals are less predictable. In addition, the menstrual flow frequently is a lot heavier, just like it is with our patient and the reason for that is because the estrogen has pushed the endometrium to proliferate more. But there's less endometrial maturation because of the fact that the progesterone levels are not as high after ovulation and therefore leading is heavier. She shouldn't be bleeding in between periods, but nonetheless, it often times is more heavy menstrual bleeding as Nikki has. How do you actually make the diagnosis of pairing that deposit? There's a nice study from Canada which looks at eight or nine different possibilities and they say if you have three or more than you are officially appearing menopausal. So a new onset of a heavier, longer flow, shorter cycles, a new onset of cranky painful menstrual periods. I've seen that quite a number of times. And people in their late 40s and early 50s younger in life never had problems with painful periods and it only developed during the the perimenopausal period. New sleep problems, the onset of night sweats, particularly around the Menzies, more breast tenderness and more fibrous cystic change in the breast, A new onset of migraines, A new onset premenstrual tension syndrome or premenstrual mood swings or weight gain without a change in exercise or a change in food intake. So, if you've got any three of those that constitutes the diagnosis of the carrying menopausal period. So what's the best way to treatment. And the answer is is that she's sexually active, she is still at risk of pregnancy, but she is having hot flashes. So the point is is that if we provide her something like oral contraceptives, it will do a variety of things for her number one, it's going to control the unpredictability, the irregularity of her bleeding. You know that people who use oral contraceptives for an extended period of time has lower risk of ovarian cancer. So what this is going to do is mainly treat or hot flashes and prevent pregnancy but have some other side benefits as well. Now. What about using the contraceptive patch where the contraceptive vaginal ring? They probably would work well for Nikki. But there aren't any studies that actually have evaluated for relief of phase or motor symptoms. Now there are lots of women in this age group are interested in actually using their leader in industrial I. U. D. As a way of cutting down on the amount of lead. And it will definitely serve that role of making the menstrual bleeding west and also prevent endometrial hyperplasia. But it won't do anything basically to help out with hot flashes. So the question that comes up all the time is that someone like Nikki starts using low dose oral contraceptives to prevent pregnancy and to treat hot flashes. How long does she need to do that? You know? And the the answer we usually give is we try to predict the agent which she would normally have meant menopause based on either population characteristics or maybe when her mother had menopause Uh and we'd like to continue the oral contraceptives until that point. So she says mom had menopause is 53. We might continue to use low dose oral contraceptives and making until she's 53. But what we're always trying to balance are the side effects and potential complications of Using oral contraceptives in a person in their late 40s and early 50's vs her pregnancy risk, which is low and becomes lower and lower as her fertility wanes. And the point at which we want to transition her about something else like hormone therapy would be at appointment. She's no longer risk the pregnancy sometimes between 51 and 53 years of age. Now is there any particular pill which is best to use? The main thing I would say is any oral contraceptive which has a low dose of estrogen. And there are a whole bunch of them, including generics that have 20 micrograms of ethinyl estradiol in them. Um that's going to reduce the likelihood of beating thrombosis, pulmonary embolism or arterial events. It will improve our hot flashes prevent pregnancy and make her samples regular. Um, she couldn't use a contraceptive vaginal ring with those same benefits best to use it continuously. Use it for a full month at the end of the calendar month. Take the old one out and open up a new package and use that ring continuous take Or a contraceptive patch, although not continuously. Better to cycle 21 days on and then seven days off the patch and then progestin only methods like Deborah Rivera. Next fallen progestin only pills will control her bleeding problems. But it won't do very much quarter hot flashes. Okay, let's go to our third case which is Sarah. Sarah is a 53 year old female who does have moderate to severe hot flashes and difficulty giving it to sleep. Romances were regular until a month ago. Then they became irregular and then they entirely stopped 16 months ago. So of course Sarah is fully menopause it now because she's gone that 12 months of a memory and no bleeding at all. And so she is officially menopausal. She's trying to herbal remedies. Each of them help for a few months. Her medical history, blood pressure, physical exam in normal. But her hot flashes are really tough for Sarah. They affect her work productivity. And she says, look doc, I'm looking for industrial strength treatment here. I have These hot flashes are just really affecting me at work and I really need something which is going to try to get them under control. So this is the kind of patient where we would have a conversation about using hormone therapy. So this is a nice summary from man's that reminds us about the risks related to hormone therapy and why they are with. So number one person's baseline disease status and risk factors, particularly in regard to cardiovascular disease. Did you already have hypertension, diabetes? Is she a smoker and so on. What is your current age? Were much more likely to start hormone therapy and a person who is less than 10 years from menopause. We try to avoid it. And people who are more than 10 years from menopause were older than 60 years of age. Next is how old was she at the time of menopause? The younger she is at her final menstrual period. The worst surveys of motor symptoms are going to be. What was the cause of her menopause? Did she have a hysterectomy with removal of her ovaries? What's called surgical menopause? And in that circumstance, people have much worse hot flashes. How long has it been since our menopause? Again, we don't like to use hormone therapy for longer than 10 years from the final menstrual period. And she tried hormones in the past. And did they help or not? If she did. What type of hormone did she use? How were they administered and so on. And then of course we watch her after we start hormone therapy to see if any new cardiovascular conditions developed. So names would tell us that a person like Sarah, that hormone therapy is the most most effective treatment for her hot flashes. The options that we're going to discuss, including estrogen by itself estrogen and progestin estrogen plus a new uh term, which is called basic oxytocin progesterone by itself without estrogen. Or we've already discussed combined oral contraceptives in people who require or who want contraception. So first let's have a look at the products out there and then we'll talk about how to use them. We have a whole variety of options when it comes to estrogen therapy. So the first column are six different types of oral estrogen pills. The middle column has to do with transdermal delivery system. So there are a variety of catches two different gels, one emotion, one spray of estrogen, And then the 3rd column, our intra vaginal delivery systems for estrogen, a couple of different creams, one inter vaginal tablet, two different kinds of vaginal rings that deliver estrogen. And then the lowest line has to do with products that combine estrogen and progestin together. And we have pills that either give estrogen and progestin continuously or they cycle the progestin. And we have a couple of estrogen and progestin combination patches. So many, many different options to help us. The next issue is how are we going to cycle the estrogen and progestin? So the very first line refers to people who have already had a history active total abdominal hysterectomy, vaginal hysterectomy, super cervical hysterectomy here, I'm assuming was done for benign disease, like public organ prolapse the fibroids, something like that. So they're no longer at risk for developing under mutual hyperplasia that they're having hot flashes. In that case we use estrogen by itself and we use estrogen every day and we'll talk in a minute about how to do that. Next is for females who do have, who have a uterus is that whenever we give estrogen, we have to give a progestin. And the most common version is estrogen every day and progestin every day, which is called continuous combined the next is there some circumstances where we want to give estrogen every day, but we want to cycle the progestin on and off. That's called continuous sequential. And so the person takes progestin for 14 days When they stop the progestin for the next 14 days, they will have a scheduled withdrawal bleeding. That's not abnormal. It's not pathologic is suddenly completely expect in that case, then the very bottom one is a single product out there, which is called continuous and pulsed estrogen progestin therapy. We don't use that one very much anymore. So basically, how do you make the decision? So if she does not have a uterus because of a prior hysterectomy, she gets estrogen only if she does have her uterus in place. The goal is to completely avoid vaginal bleeding. But if we can't avoid vaginal bleeding to at least make it predictable. And her recent endometrial activity is what is going to predict the bleeding pattern going forward. So in other words, if she's had recent spontaneous or induced bleeding, we're going to use that continuous sequential estrogen every day cycle the progestin on and off. On the other hand, if she hasn't had any bleeding at all for two or three cycles, then we're going to use continuous combined with the estrogen and progestin every day, That's what what Sarah needs because remember she's 16 or 18 months post menopausal and she's having no believing at all. So if we're going to use hormones, we're going to use estrogen and progestin every day. Now. Remember that I mentioned that there are both wow oral tablets as well as a variety of transdermal delivery systems, which one should we start with. So Nam says there's really no clear benefit to one route or another. But we do know very quick clearly from a number of well done studies, mainly in europe that for people who use transdermal estrogen therapy and has a significantly lower risk of detainment, thrombosis and pulmonary embolism than people who use oral estrogen. So that risk is relatively low to start with. But as people age, their risk of DVT pulmonary embolism goes up and we know that that risk is not any greater as a result of using transdermal estrogen, on the other hand, when you use oral estrogen, we know that the risk of DVT pulmonary embolism is at least double, maybe even 2.5 times higher than what the baseline risk is. The next thing they point out is that sometimes when people are using systemic estrogen therapy that will take care of their hot flashes, but they still have vaginal symptoms of itching, burning irritability, disprove mia and so on. And so names points out that even in people who are using systemic estrogen therapy that you might also have to add a little bit of vaginal therapy to take care of the vaginal symptoms. And then with either route, whether you're talking about uh a oral delivery or a transdermal delivery system, we always have to use a progestin to prevent endometrial hyperplasia from unopposed estrogen. So always when you prescribe pills or patches or for that matter, uh there's one particular vaginal ring that gets a relatively higher level of estrogen. We always have to prescribe progestin in that circumstance. Now, are there any cases where you want to go straight to transdermal estrogen? And the answer is that if she's had a prior history of DVT or pulmonary embolism, if she has very high triglyceride levels, if it's a person who needs a very steady state for release of the hormone therapy, for example, there are some people who use estrogen and progestin tablets, they take them in the morning, but by the afternoon they're already starting to have hot flashes, irritability and so on. With the transdermal systems, there is a much more steady state release of estrogen from the patch, for example. And so you can avoid those daily mood swings by using more of the steady state drug release that you find in a trance normal system instead of bill. The same is true of people who use hormone therapy who in the afternoon or having migraine headaches and that migraine might be triggered by the drop in estrogen levels as the metabolites their oral estrogen, you can avoid that by using a transferable system. And then finally there's some people who just can't use oil tablets because they can't swallow them on. Can't remember them. Okay, next step in thinking about hormone therapy is what sort of dose are we going to use? So the therapeutic goal is starting with the lowest effective estrogen dose and progestin. Does that We need to get to our goal which is treating the hot flashes, balancing the benefits and risks of using that. And names reminds us rightly, so that lower doses are safer. There better tolerated. They have a more favorable risk benefit ratio than standard doses. So nowadays we always start with the lowest dose of hormone therapy. And we will work up from there. That is because lots of people only need logos therapy. So why start with middle dose therapy and work down when instead you can start with low dose therapy. About half of people will do great with that. The other half of people are going to have to take three doses upwards. And again, we talked about using local estrogen therapy for persistent GSN symptoms. Also remember that lower doses of hormone therapy may take as long as eight weeks before they're fully effective. So whenever I prescribe hormone therapy, I don't bring a person back for six weeks would be the earliest eight weeks would be more more typical for doing that. All right. So when we talk about low dose estrogen, what are we talking about? Well, the generic version of Estradiol is oral micron eyes, 17 beta estradiol And the low dose of that tablet is a 1/2 milligram. Or you can use .3 mg of oral conjugated estrogen. Or you can use one of the low dose patches that have 17 beta estradiol in the as far as projections. These are various projections that are available to prevent endometrial hyperplasia. Here the benchmark is either 1.5 mg or 2.5 mg of p A hydroxy progesterone acetate. You may know that one by its brand name on pro vera. There are many generic versions of it or north indian acetate transparent or the most bio equivalent version which is micro sized progesterone. So those are the starting dose is But then as you work up what are considered to be, the standard doses are now higher doses of micro 9 17 beta tester, bio conjugated estrogen and so on. And then these are the relatively higher standard doses of progestin. So start low and work up towards these doses dosages as needed. So start with the lotus and either a patch or an oral estrogen if a person has a sub optimal response, meaning that they're hot flashes are not under control. Start tight trading the estrogen dose upward if that doesn't work. Change the estrogen preparation. Remember there's six different pills. So if he doesn't respond to one, they'll try a different pill. Next is to change the delivery system. So if you started with appeal and you can't get the hot flashes under control, switch to a patch or if you started with a patch and it's not working very well, then you can switch to a bill. Next is there's some people who don't respond very well to estrogen and progestin, but you can get their hot flashes under control with an androgen. So there's one pill out there, combination of estrogen and androgen, um, has a trade name of Colbert's um, that that may work for some people. It's never a starting medication. But when you've exhausted the other things that I've already mentioned that you might think about adding an androgen, of course, you also have to use a protested in that circumstance. Now, some old timers are still using injectable estrogen and the names guidelines have been very clear for at least 15 years about dissuading us from using injectable estrogen, just because we don't know about dosage equivalency, is and you can't get it back once a person has been given. Now, the next issue is, what about person having hot flashes? Who wants to use hormones, but for some reason can't take oestrogen, recent DVT pulmonary embolism, uh, for example, or other cardiovascular conditions where you just don't want to use estrogen. So in that case, you can try progestin alone to treat hot flashes doesn't work as well as the estrogen containing regiments, but it's better than nothing. And so the formulations that are effective of progestin in treating hot flashes on the rocks. Progesterone acetate 10 mg a day. So 10 mg of oral Provera, generic um Progesterone as a acetate which you may know as my gaze and then micro nice progesterone all um which is from a tree. Um although that's available as a generic as well uh in a dose of 300 mg. Remember that micro sized progesterone has a soporific effect. I think people really sleepy so be sure to get that one. Uh maybe an hour before that time. Oh backspace. Okay, so that becomes yet another option in terms of treating on hot flashes when you can't use estrogen. Yet. Another new option is a combination of conjugated estrogen and a SERM which is called besides oxygen. The name of the product is do A B. And it's uh protected by brand name. There's not a generic equivalent of this yet. But the value is the fact that the basic oxygen is a sermon that prevents endometrial hyperplasia. So here is a way of giving estrogen and a product that will prevent endometrial hyperplasia. And people who can't use a progestin. Who's that? There are some women who either gain lots of weight on projections or the other. Big problem is lots of people will start a progestin like uh M. P. A. And we'll say that my breast tenderness is so bad. I just can't continue to take this medication. So a medication like this one that has basic oxygen in it may be a good choice because it gives you that estrogen therapy uh And the other the basic oxygen component will prevent endometrial hyperplasia without having to use uh a progestin. Now what if Sarah had requested the same compounded hormone therapy that her sister Patty uses? Let's talk a little bit about compounded hormone therapy. I'm sure your patients ask you about that. So the marketing of compounded hormone therapy is that they only use bioidentical hormones. It's a combination of two or three estrogen. So it's at a minimum s throne and extra dial sometimes some estradiol which the third estrogen is thrown in supposedly the dosage is tailored to the individual is supposed to be more pure than commercial products and purportedly safer. However the reality is that the very same estrogen's estradiol are used in either commercial products that you get from the pharmacy and compounded uh Products that have 17 date astrobiology. So this whole idea that somehow this estrogen is safer or better or pure than what you get in a pharmaceutical version just isn't true. Okay all right so some of the safety concerns that names has about using compounded estrogen and progestin therapy. It's just the fact that it's not monitored very well. It's possible to have overdosing or under dozing a variety of other sort of safety issues. Not a whole lot of data about the safety. One of the things that people who are proponents of compounded hormone therapy do is to test hormone levels by taking a salivary sample that nan's insist about the fact that hormone levels, whether it comes from a blood sample or salivary sample, really don't help to guide hormone therapy, give hormone therapy and titrate it based on symptom improvement, not on number improvement. So it doesn't help to check levels of hormones either with the syria example or with the salivary sample. Uh let alone needs the fact that they're going to be bouncing those levels are bouncing all over the place. Uh huh. So, if you use a compounded therapy, you should explain why you've chosen to do that. So, to finish up then about compounded hormone therapy, they'll probably work just as well as commercial hormone therapy products. But the value of adding that has thrown in the industrial really has never been evaluated. Some people are recommending progesterone skin cream. We know that that doesn't work because progesterone is not absorbed through the skin. It is to the vagina, but not through the skin. Compounded hormone doses aren't standardized salivary hormone levels don't help. And an FDA approved hormone therapy product. The ones that we've been discussing will offer bioidentical hormones of both estrogen and progestin. Remember that Micro 9 17 beta estradiol and micro nice progesterone, they are totally bio identical to the hormones that come from the over with a choice of delivery systems and it's going to be covered by your insurance other than the fact that you may have to pay a cocaine. So that's kind of the whole story that mam's gives about avoiding compounded therapy because it costs more without really having a whole lot of benefit. So let's wind up with sarah and then we'll do one more case quickly and hopefully I can take a couple questions. So given the severity of her hot flashes, we are going to offer her continuous combined hormone therapy with micron is Esther dial lowest dose, which is a half milligram Or a 17 beta Estradiol patch in a .025 mg dose. Most pastors are twice a week. There are a couple that are once a week. And in addition to that hydroxy progesterone, acetate, 2.5 mg or micrograms, progesterone, 100 mg at that time. If she prefers something that has a single product that has a single dosage regiment. Okay, what I mean by that is that with the one above micro micro Manchester bile and MBA, we're taking two pills. There are those products out there that combine the two. So you only have to take one. So a combined estrogen and progestin tablet, combined estrogen and progestin patch or the basic oxygen with conjugated estrogen that I mentioned a moment ago. Okay, only a few minutes left. So I'm going to tell you quickly about Marie. She is a 54 year old female two years postmenopausal, no postmenopausal bleeding. Nonsmokers, severe hot flashes has modern hypertension controlled with an ace inhibitor. She's uh she's actually technically obese because her BMI is 31 for recent labs are the fact that her total cholesterol was sort of borderline for LDL is on the high side. Her HDL is 60 which is actually good. It's protective for her. And her fasting. Blood sugar was 95. So she's not a Type two diabetic. Okay, so she has moderate to severe hot flashes. Yes, she wants hormone therapy. Yes. So this is when we get into the issue about cardiovascular risk factors. So the line across the top has to do with how long has it been since your menopause? Less than five years, 6 to 10 years or more than 10 years. And then the three rows are low cardiovascular risk, moderate cardiovascular risk and high cardiovascular risk. So how do you quantitative cardiovascular risk, You just drop it into that cardiovascular risk calculator that you're using already everyday has primary care providers. It's exactly the same one that gives you your five year heart attack risk based on 5%. Are less than 5%. 5 to 10%. 10% or more. Okay, so if you're less than five years from menopause hormone therapy is fine in that low cardiovascular risk group. If you're in the moderate risk group hormone therapy is okay. But the yellow means that transdermal was probably better. And if you're in the high cardiovascular risk group you should avoid using estrogen and progestin therapy. Then if you're 10 years longer or 10 years since your menopause or more than you should avoid estrogen and progestin altogether. Okay. And so if you're in the green zone or the yellow zone, if you had a prior hysterectomy use estrogen estradiol by itself. If you have an intact uterus, you can use estrogen and progestin separately and pills or estrogen's case with a patch or conjugated estrogen with these intoxicated and again that asterisk means that in that moderate cardiovascular risk category Maria is in by the way we can start her on hormone therapy but we'd rather use a transdermal. So the best options from Marie are given her cardiovascular risk factors avoid oral estrogen go in the direction of using a patch twice a week plus micro nice progesterone, 100 mg at bedtime. Or you can use Micro Nice progesterone 300 mg by itself at that time. Or they have a pension starting at 300 mg and working up as we talked about a moment ago or an SS ri or are okay Now there's also a last case I'm not going to have time to go all the way through Betty. But I will tell you about her. She's a 53 year old woman who has total vaginal dryness and irritation, her menopause was a couple of years ago, no postmenopausal bleeding. She's sexually active once or twice a week. But she reports that sex is quite uncomfortable for her and she inter immediately intermittently uses a water based lubricant. No hot flashes or sleep problems. So she has classic genital urinary syndrome of menopause, which can cause vaginal spotting or bleeding vaginal dryness and definitely painful intercourse because of poor lubrication, less vaginal elasticity, which can have a major impact on a person's relationship and their quality of life. So what Nam says about Betty is, does she have moderate to severe hot flashes? No, does she have GSM symptoms? Um If she said no, she didn't mean treatment at all. But if she says yes as Betty did, then the questions are basically, if she is free of contraindications, she can use either vaginal estrogen ill or pasta machine. On the other hand, if she does have a contraindications to estrogen, then what we should be doing is just, is using lubricants and moisturizers. Okay, basically I'm just going to skip over this remind you that there are a variety of over the counter lubricants available. I've listed them for you for people who have vaginal dryness and disprove Nia in the menopausal period. These are always the first thing we do is either water based silicon based or oil based lubricants uh Oftentimes referred to as intimate lubricants that you can buy over the counter in the drugstore or a grocery store. The other group are called vaginal moisturizers And the value of moisturizers is that they prevent dryness and irritation during the day. But they're not helpful for intercourse. They clump up during intercourse and actually make it worse. So use one of those sexual lubricants for intercourse and then use a moisturizer during the day. Or you can use local institution therapy given by a cream, a tablet or a vaginal rape or systemic hormone therapy. If you're also trying to treat hot flashes or a new drug which is called spin off in which is FDA approved for the purpose of of treating a young senator urinary symptoms of menopause. Okay, this is a full listing of the various vaginal estrogen delivery systems. As I said, it starts with two different creams In the middle or two different vaginal rings and the rings by the way worked for a whole 90 days. Next to the bottom is a type of vaginal estrogen tablet called magic. Um And then a new one down to the bottom which is an estradiol vaginal insert which is called a taxi. Uh And in each case you can see the dosage. And how often those medications are used. Uh hm. A thin as I said is a relatively new oral medication which is FDA approved to treat espana. Um does a good job of that. The trouble is is that it too is not available in a generic version. It's only available as a moral version. So typically what we do is to start with Loop with sexual lubricants. one we go to topical estrogen in the form of a cream or ranked second. And if those things don't work or if a person can't directly take estrogen then we would go to us to spend a thing in that circumstance. Then the last right I'm gonna mention is the newest vaginal D. H. E. A. D. Hydro in Vienna Austria. Uh The industrial, its trade name is intra rosa. That also has another name of progesterone and it's a vaginal insert that doesn't contain estrogen. It's used at bedtime. Um And it's thought to work by converting to estrogen and androgen from D. A. G. A. Uh It has some value of improving both general urinary, several menopause and sexual function. But again it's considered to be second line therapy for the most part. So last night is what are the best options for Betty to start with a water based or silicon based intimate lubricant sexual lubricant for all of her sexual encounters. That is not enough. And offer a formulary topical vaginal estrogen cream or estrogen tablet or estrogen releasing vaginal ring if those aren't available or don't work. The next step would be used on spend within orally. If that doesn't work for the patient prefers it. She can try the progesterone uh vaginal insert