Hormone Therapy for Menopause

Podcast Transcript

Erica Newlin, MD:

Welcome to Ob/Gyn Time, a Cleveland Clinic podcast covering all things obstetrics and gynecology. These podcast episodes are intended to help you better understand your health, leaving you feeling empowered to live your best. We hope you enjoy today's episode.

Hi, everyone. I'm your host, Erica Newlin, MD. Welcome to Ob/Gyn Time. During this season, we are focusing on topics related to menopause. On this episode, I'd like to welcome Dr. Pelin Batur who will be talking to us about hormone therapy. Dr. Batur, thanks so much for joining me on the podcast.

Pelin Batur, MD:

Oh, it's my pleasure.

Erica Newlin, MD:

Can you tell us a little about your role in the Cleveland Clinic and about your background?

Pelin Batur, MD:

Yeah. So, I've been here at the Cleveland Clinic since 1998. Pretty much half my life. And I am an internist originally. I did an internal medicine training here straight out of medical school. And then I did a subspecialty women's health fellowship that gave me a lot of focused education on endocrine issues, osteoporosis, hormonal health. And for the first 15 years, I had both a small primary care practice as well as a consultative practice. But like most things, access became difficult for my new women's health consults, so I've since been doing only GYN care within the department of OB/GYN. I lead the sexual health program.

My day-to-day work is a lot of menopauses. I work closely with our International Menopause Society. And I also co-lead the complex contraception clinic. So, a lot of hormonal questions come to me especially if there's some sort of medical complexity to the patient's care.

Erica Newlin, MD:

Perfect. First of all, let's get some terminology out of the way. Can you explain what we're usually referring to when we talk about hormone therapy as treatment for menopause and perimenopause?

Pelin Batur, MD:

Yeah. And let's talk about just menopause definition.

Erica Newlin, MD:

For sure.

Pelin Batur, MD:

Because this is the key question that a lot of people are coming in with: where am I on the spectrum? Unless it's obvious. And what are my treatment options? So, menopause is really one year without periods in the absence of any medical condition that may impact that, right? So, like a medication that you're on that can impact it or thyroid problem or chemotherapy. So, we're assuming you naturally stopped having cycles for one year. Why is this important? Because when you're thinking about hormone therapy treatment options, after menopause, you can get away with a lot lower doses. But before menopause, if you're still ovulating, oftentimes we may need higher doses to control. Ovulating meaning, you know, your ovaries are still producing their high levels of hormones. Post-menopausal hormones may be too low to help in those situations. So, it's important to define where you're apt to figure out you know what your treatment options are.

Erica Newlin, MD:

For sure. And then when would you recommend someone talk to their doctor about what is appropriate therapy for them and whether hormone therapy might be an option for them?

Pelin Batur, MD:

Well, really anytime they have questions about how they feel they should, you know, feel empowered to discuss it. One thing I always do like to say is that, you know, bringing this up during your annual preventive visit is fine, but don't be upset if your doctor or nurse practitioner says, "Hey, let's, you know, have you come back." Because these discussions can take a while. So, I don't want patients to feel blown off like, "Oh my doctor didn't say much about it." And it might be because they're also trying to make sure that all your preventative care is up to date.

Oftentimes this deserves a dedicated, second visit. But the main time that women really are considering hormone therapy is right before you're going into menopause. The years leading perimenopause leading up to menopause itself or the few years after is when we see the bulk of patients trying to make decisions about whether hormones are right for them.

Erica Newlin, MD:

Mm-hmm. And what types of hormones are there?

Pelin Batur, MD:

Obviously, we have close to 100 different hormones in our body. Right? And so, endocrinology does a lot of adrenal ones. Your energy hormones, your appetite hormones. So, in gynecology typically we're talking about estrogen, progestin, or progesterone, testosterone, and DHEA are the main ones that we're dealing with when we treat.

Erica Newlin, MD:

Great. And just briefly, I have a lot of patients who come wanting their hormones checked. Can you discuss whether there's value in that at all?

Pelin Batur, MD:

Yeah. And the answer is it really depends. So, like I said, I've been here for a long time. I've been here for 25 years so I've seen a lot of medical trends come and go. And right now, one of the trends is getting your hormones balanced and checking out full hormone panels. And I like the fact that it's bringing awareness to an issue that really people weren't talking about before. But the downside is also, it's become a little trendy where there's thousands of dollars of, you know, testing that's done that oftentimes is not going to help us. So, if you are, you know, six years into menopause, you're 60, checking hormone levels for at least for the estrogen, progesterone isn't going to be helpful because it's going to show us reliable, the same answers. Where I think a lot of hormone testing is helpful is when women come in and they're very young and they're looking like they're in menopause. They're in their 30s. They're in their 40s. In those situations, I do go pretty gung-ho with, you know, doing a lot of lab testing. And also, oftentimes it's not so much the estrogen and progesterone levels that help us because those during perimenopause are fluctuating up and down. So, you're only getting that snapshot in time.

Erica Newlin, MD:

Right.

Pelin Batur, MD:

So, I don't care if, you know, it looks like you're going into menopause because if you have started to cycle back up. Because we went through two months of not skipping cycles and then you go back to your regular cycles, but we only captured that snapshot in time. You're still perimenopausal. So sometimes hormone testing can lead people in the wrong direction. But, you know, when women come in and they're more the typical perimenopausal ages, I do like to make sure thyroid and blood counts if they're really tired. Has somebody checked the vitamin B12 level? So, it's not that I don't necessarily do testing, but it really depends on the person sitting in front of me and what their concerns are.

Erica Newlin, MD:

Right. And then when we talk about primarily estrogen and progesterone, what different formulations are available?

Pelin Batur, MD:

Yeah. So first we need to define whether it's going to be a systemic hormone or a local hormonal treatment. Systemic meaning you're putting it on your skin or you're putting it in your mouth or as a patch. And the goal is to deliver higher doses to every single cell of your body. And that's what's going to go to the breast, into the heart and the bones versus local treatments are oftentimes vaginal or an IUD also can be local treatment. And in many of those local treatment situations, how much you're getting systemically into your bloodstream really depends on the dose of the product that's used.

But you can use ultra-low doses where if you just have vaginal dryness, you're just treating the vagina and it's not seeping into the bloodstream to any significant amount. So, the first question is whether it's systemic or whether it's a local treatment. And of the systemic options like I said there's pills or you can go through the skin. And then hopefully we'll talk about this a little later, but in general, we try to avoid injections or pellets because that can be very unpredictable. And if a woman doesn't, obviously, you can do contraceptive injections. But for postmenopausal hormone therapy, if you get unpredictable levels with those, it's hard to undo it. So, we're not there yet for using pellets.

Erica Newlin, MD:

Great. And can you explain the role of estrogen versus the role of progesterone in hormone therapy?

Pelin Batur, MD:

Yeah. So, we have estrogen receptors throughout our whole body. In our joints, in our brain. So, there's a lot of benefits to estrogen throughout our system. For progestin, the main role in hormone therapy is to really protect the uterus. Because as we're going to probably talk about later, it turns out that estrogen alone oftentimes has lesser risks in terms of breast, or it has a better risk benefit profile for the heart. And it turns out progestin is what contributes to the breast risks and steals from some of the heart benefits of estrogen.

But you always need some sort of progestin if you have a uterus because the uterus does not like just estrogen being blast added. It needs balance otherwise you can increase your risk of uterine cancer. So typically, if women have had a hysterectomy, they can just use estrogen alone but if they have still their uterus, they're going to need some sort of estrogen plus progestin replacement.

Erica Newlin, MD:

Mm-hmm. Perfect. Thank you. When might birth control pills be used instead of conventional hormone therapy? You alluded to this a little bit before.

Pelin Batur, MD:

Yeah, whenever, especially in the complex contraception clinic, we see a lot of women that are perimenopausal or having symptoms. So, they might have PMS, PMDD where they have a lot of mood symptoms. They might have headaches around the time of their menses. If the symptoms are not typical menopausal, but they seem to be around the menstrual cycle, you oftentimes are going to be offering some sort of contraceptive dose hormone whether it's just progestin only or it's estrogen plus progestin. Because you need something to control the ovulation. Versus after menopause and once you've stopped cycling, then you can go away with ultra-low doses of the hormones that can still help. Because the problem is, I mean, there's no hard lines in the sand.

I mean, there's always flexibility in my practice. So, do I sometimes use postmenopausal hormones in women going through perimenopause? Yes, but the problem is if you're not controlling ovulation, sometimes you screw up bleeding patterns too.

Erica Newlin, MD: And if women are coming in saying, "I already feel hormonal all over the place," you're just adding one more hormone.

Erica Newlin, MD:

Right.

Pelin Batur, MD:

So, it doesn't always work as well as, you know, something that really helps control their hormones and stabilize them. But the biggest thing is I don't want to open up Pandora's box of testing with bleeding for women who still are having, you know, breakthrough ovulation despite the treatment.

Erica Newlin, MD:

Mm-hmm. And then what symptoms of menopause are hormone therapy designed to treat?

Pelin Batur, MD:

So technically, they're FDA-approved to prevent osteoporosis, to help with vaginal dryness and pain, as well as to help with hot flashes. But in, throughout medicine we don't use medications just for what they're FDA approved for, we use medications whenever the science tells us that the benefits outweigh the risks of the of the prescription, right? And so there are a lot of women come in with concerns about their sleep, about their mood, about their libido, vaginal dryness. They might be getting more urinary tract infections because of the lack of estrogen in that urogenital system. So, all of those, especially the hot flashes and night sweats. Those are some of the biggest reasons women are coming in asking for hormone therapy and can be quite effective. Some lesser-known things are sometimes, for example, hair. Anytime, you know, estrogen tends to be good for hair and driving down testosterone and the male hormone levels, that tends to do well for hair loss. And then also joint aches, tooth decay, preventing cataracts. There are some lesser-known benefits as well.

Erica Newlin, MD:

Great. And then what side effects might someone expect when starting hormone therapy?

Pelin Batur, MD:

Oh, and then before we go to the side effects the one thing, I do want to say is that we also should, because I don't want to promote this as this is going to help you with everything.

Erica Newlin, MD:

Okay.

Pelin Batur, MD:

Because I think there's too much of that right now in social media take this and it's going to fix every single, you know problems you have. So, it doesn't mean that it's going to positively impact all those symptoms for every woman.

But it's one of those situations where when you try it, sometimes you're pleasantly surprised that you have fewer joint aches.

Erica Newlin, MD:

Right.

Pelin Batur, MD:

And, you know, that your eyes and your mucosal membranes feel a lot healthier. But I don't want to pretend that it's going to be, it's a fix for everything.

Erica Newlin, MD:

For sure. Mm-hmm. And then what kind of side effects might someone expect?

Pelin Batur, MD:

Yeah. So, in the first three to four months when you start a hormone regimen, you can expect some bleeding. In fact, a lot of my colleagues will say you can ignore bleeding for up to six months. I guess maybe a little bit more conservative. I usually tell people if you're doing some light spotting, just watch it over the first three to four months. If you're having any kind of excessive heavy bleeding, let me know. So that can happen. And anytime you make a hormonal change, I always tell people give it really three to four months to judge because that's where the full benefits are kicking in. Especially for a vaginal dryness and such, it really does oftentimes take 12 weeks to really work. And initially women might notice like, do I feel a little breast tenderness? Do I feel a little bloated? Do I feel a little water retention? Most of the time though, especially if you're using reasonable doses and not mega high doses and pellets and other things, most of the time those symptoms go away. So, what I usually am tell my patients is if you hate how you feel, please reach out. But if you're saying, "I don't know about this," then just wait it out because those nuisance side effects tend to get better and better.

And the, you know, benefits get better and better as well.

Erica Newlin, MD:

Great.

Erica Newlin, MD:

And then in what patient populations are hormone therapies not recommended?

Pelin Batur, MD:

Yeah. And I might be the wrong person to ask because you know, I am a person that believes in making decisions together with the patient. I don't have a lot of hard nos in my practice. I get referred patients so that I can really spend the time talking about making a list of the pros and the cons for that person. But there are some risks that really give us pause because, you know, when I think about the big risks of hormone therapy in the short term if you're going to try it, let's say, for three to six months to see how you feel, blood clots is something that we have to think about.

So, if somebody has had a personal history of blood clots, especially if it was a pretty major blood clot, then, you know, I might think twice before reaching hormones. And then also if, a woman has a history of estrogen sensitive cancer, so breast cancer, uterine cancer especially if the uterine cancer is more late stage, those are the situations where we take pause. Now, I say take pause because are there certain breast cancers that don't have, I mean, for example situations where a woman is diagnosed with breast cancer at a very young age. It was caught early. It's estrogen progestin receptor negative and she's had a mastectomy on both sides, and she's feeling miserable.

You know, her bone health already looks like it's starting to deteriorate. You know, we'll have a conversation between the patient, me, and oncology team and we cautiously do start some women on hormone therapy. But that's a very small percentage. Typically, estrogen sensitive cancer and blood clot are the blood clot of the arteries or the veins. So, if they've had a massive stroke in their past, those are some of the things that would make me take a pause before reaching for the hormones.

Erica Newlin, MD:

Great. What about patients that you would more strongly recommend consideration of hormone therapy?

Pelin Batur, MD:

If a woman has active gallbladder issues, there's a little higher risk of to need a cholecystectomy like a gallbladder removal.

Erica Newlin, MD:

Right.

Pelin Batur, MD:

And women on hormone therapy. So that's one thing to also keep in mind. It's not an absolute reason not to be on it.

But something to keep in mind. I just want to call this out because there's a lot of confusion. Oftentimes we can use progestin only treatments if women have had a history of a blood clot, because the estrogen is the main contributor to that clotting risk. So, it doesn't mean that the history of blood clots all hormones are off the table, but it just might be that we're either going to stick to ultra-low doses of estrogen.

Erica Newlin, MD:

Right. No, that's okay.

Pelin Batur, MD:

I wanted to digress there. So, the younger a woman is the more likely we are to encourage it especially if she went through premature menopause. So premature menopause is before age 40.

And in those situations, all experts agree, all guidelines agree, unless you have a really main reason like that woman is actively being treated for breast cancer at the moment something very obvious, typically, we do not withhold hormones. So, if you had a hysterectomy for a benign reason, and you had your ovaries removed, it's like saying, "We're going to take your thyroid out, but we're not going to give you thyroid medication back."

So, there are very few situations that are where it isn't recommended. And in fact, the studies show that if you don't replace the estrogen in those situations, you increase the risk of heart disease, death, and dementia, and a lot of neurological syndromes in addition to patients not feeling well. I also more strongly recommend it for women who are having a lot of symptoms, who are within the decade of menopause. There's something called the window of opportunity or the timing hypothesis. So, if you're newly menopausal within a decade, this is where your arteries are healthier.

And there's probably more pluses than minuses to hormone therapy versus if you are in your 60s and 70s and you went all those years without hormone therapy, there's going to be a little bit more risk to consider.

Erica Newlin, MD:

And can you speak a little, I know I'm opening a can of worms here, to the history of hormone therapy and why there seems to be such a controversy even among medical professionals.

Pelin Batur, MD:

Yeah. Where do I begin? So, I think the part of the problem, and I'm not trying to disparage my medical community, right? But sometimes there's “yes or no” or “good or bad” type of philosophies and like most things in life, the truth is somewhere in the middle. So, there was a study called Women's Health Initiative done 20 plus years ago. And prior to that everybody was being offered hormone therapy because, you know, even men were being studied for giving estrogen to see if it'll decrease their risk of heart disease because we thought, "Oh, it's going to help this and help that." And, you know, there's nothing that's a one-size-fits-all all for anybody - just goes back to that. And we knew about some of the risks, but yet people strongly felt that these benefits were much greater than the risks and everybody was being placed on hormone therapy. Then the Women's Health Initiative study which really did a very good job, it's the gold standard of how we study women, Right, giving half the women, you know, just a dummy pill versus half, and they signed up for this, half the women hormones and following them see what happens over time.

Well, then we start to identify the risks versus benefits more clearly. And so there was concern about the breast cancer risks and such. And so, then we saw 90 percent of women in this country come off their hormones. And, you know, for those of you in my generation, you know, NY Times, Newsweek, you know, we all watch the same news, it was flashed everywhere. And it scared women and people were thinking, "How could we have gone so wrong?" And it's not that, we went wrong, it's just every time you have more data it's like you have another piece of the puzzle to make the picture clearer. But this is why we don't want to think, "Oh, this was all wrong and this was all good." So, what happened is that there was 20 years where people kind of washed their hands of hormones. So, there was 20 years where younger generations of doctors, if they weren't at a menopause center, they really wouldn't get that training. And then the data became so complicated to sort through, it's like, "I don't have time to discuss this at my annual visit," which is why I say you really want to make a dedicated visit.

And then if, again, fell out of favor. So, I think now the tide is turning because what's happened over these 20 years is that every few years we look, look at the women and we understand, "Oh, because these women that have the greater risk." So, the puzzle pieces fit.

The picture becomes clearer, right? Now, women are knocking down our doors because they're saying, "We're not going to take no for an answer. I want to discuss what this means for me, my personal risks versus benefits." But now we don't have enough menopause clinicians which is why we're really working hard to do these podcasts, to train folks. And if you are from the generation where you got to work in a menopause center, you're lucky please, you know. You spread that wealth because this is where I don't believe in the trends in medicine. Truth is always somewhere in the middle. That was too philosophical of an answer, but I can't help myself.

Erica Newlin, MD:

No.

Pelin Batur, MD:

I mean this is really where we need some humility and medicine too, so that we can't just swing with the trends, you know.

Erica Newlin, MD:

For sure. And I think it's worth noting OB/GYN residencies now still devote very little time to it, and you alluded to that we're in a learning surgery, we're learning obstetrics. And so, I encourage all the residents here. I always like going to Dr. Batur's clinic. It's great.

Pelin Batur, MD:

Happy to have you work with me anytime, yeah.

Erica Newlin, MD:

Yeah. I just, I think many patients are still wary and they remember all the WHI news and then even when I looked on the National Institute of Health website it says very clearly, the WHI demonstrated that the use of estrogen plus progesterone after menopause increases the risk for heart disease, stroke, blood clots, breast cancer and dementia, which is a pretty scary sentence to read on the NIH website. Can you explain why that may or may not be overstating the risk?

Pelin Batur, MD:

Yeah, and this is really what makes my practice difficult because I can talk to somebody about their individualized risks versus benefits for an hour, but they go home, and they open up the package insert that sounds exactly like that NIH website that you just described. Or they go to their friendly podiatrist, and they say, "Oh, no, haven't you heard hormones are bad?"

And it says we did not spend an hour in clinic, you know, talking about that woman's risks. So, let's break down some of these. For example, breast cancer is on everybody's mind, right?

Erica Newlin, MD:

Right.

Pelin Batur, MD:

So, it turns out that it really is the progestin that's the main contributor to that risk. So, what we learned as we followed these women in WHI over 20 years is that women on estrogen alone had a statistically significant decrease in their risk of breast cancer. And in fact, it wasn't just the lowering of breast cancer, they had lower breast cancer deaths for the estrogen-only users.

Now, what we don't know is if it's specific to the type of formulation that was used in the study or if this is for estrogen in general, but this is pretty compelling. And this good news never makes a splash, right?

It's always bad news. And we live in a very risk-adverse society. People want to always make sure that they've talked about the risks with the patient, which is fine. That's important. I mean, people need to be informed. But we need to spend the same amount of time talking about the benefits so they can make an informed decision. So, when it comes to the breast cancer risk, when you have estrogen plus progestin, after five years there can be a bump in the breast cancer risk.

So that's why I'm oftentimes comforted that if somebody's just needing hormone therapy just to get through a rough few year, they're probably going to go under the radar of what, before their breast cancer risk increases. So, after five years there can be a bump in the risk, but this is what's considered a smaller bump. So, if I write a thousand prescriptions and keep refilling them for five years, I might impact the risk for two to three women if they are using a progestin.

That risk, level of risk is comparable to, if you decide to have a few glasses of wine per week. So, I mean, there are other things that you could do by, you know, keeping up with your mammograms, keeping weight as ideal as possible and then minimizing alcohol use to offset any of those risks.

And if women are on estrogen-only replacement, they don't have to worry quite as much about the risks of breast cancer. And the one other thing that we're learning is that some of the different progestins might have different breast risks and in fact, we'll probably talk about bioidentical hormones in a second, but the FDA-approved bioidentical progestin, it's called micronized progesterone. That one is really associated so far with a much lower risk of breast cancer. So, there's ways to offset that risk.

Erica Newlin, MD:

Great. What about the risk for coronary heart disease and stroke?

Pelin Batur, MD:

Yeah. And so, for the arterial blood clots, luckily this is rarer in women who are in their 40s and 50s. So, the package insert is really talking about if I give a systemic, let's say, by mouth, estrogen plus progestin to a woman in her 60s and 70s who really didn't need it. They went through all those years feeling just fine, then I can increase her risk of heart disease. So that's what that package inserts and that NIH warning is referring to. Those increases in heart disease risks do not seem to be significant in women who are in their 40s and 50s. And I'm hedging a little bit because depending on whose study you read, some show that there's a benefit, some show that there might be a little risk, but it's just not quite statistically significant.

Just a few patients out of a thousand. So, I think this goes back to what I mentioned that window of opportunity, and what we're learning is that the healthier your arteries are, when you initiate the hormone therapy, the more the protective effect is gonna be a little stronger because there's a lot of protective effects of the estrogen on the arteries. It helps with keeping the arteries open and if you are kind of in your phase of life where your arteries are a little bit more clogged, diseased, that's where the blood clotting risks of the hormone therapy especially in the first year might put you at a little increased risk. And that's what most of the study shows that there might be an increase in heart disease risk in the first year if somebody is in their 60s and 70s and you're initiating them, which is why we try to avoid in those years.

Even the American Heart Association and the European Society of Cardiology have come out with guidelines. If anybody wants to look at them, I believe they're in 2020. And they call out in their guidelines saying for women who have early menopause who are within, you know, a decade of their menopause essentially 40s 50s or younger, that there's overall more cardiovascular benefits than risks including decreased diabetes, decreased insulin resistance and, you know, if they have symptoms they should not be afraid of that package insert, and they can safely use.

I mean, I feel like that package insert sounds like I'm trying to murder somebody. And it's understandable people want to proclaim the risks, but those risks don't apply to every patient. And the stroke risks are even less. So, it's roughly about one out of a thousand patients. If I write a thousand prescriptions for five years you might bump up the risk.

Erica Newlin, MD:

Mm-hmm. What about that dementia risk?

Pelin Batur, MD:

Dementia gets a little bit even more convoluted. So, it's interesting that they call out dementia risk in the package insert, but it's because, again, it was in the women in their 60s and 70s that they saw an increase in dementia risk. If you look at the latest 20-year published data from the WHI, estrogen-only users actually had a reduction in their chance of dying from Alzheimer's dementia.

So, depending on what study you read, you might see some that suggest protective, some suggest no change. Some suggest a little marginal bump in the risk. And what that tells to me, again, I hate to put on philosophical hat here, again, but if after 50, 60 years of studying hormones, if we're still so confused about is there a signal of risk, is there a signal of benefit, it means that the risk must be so darn small that we're really having a hard time consistently measuring it. And in my humble opinion, I think it goes back to how healthy your arteries are because Alzheimer's is related to a lot more genetics. But the one of the leading causes of dementia, at least in the United States is vascular dementia. So how healthy your arteries are going to your brain makes a big difference. So if you're somebody who has a lot of cardiovascular risk factors, those are the risk factors which dementia too, age, you know, advancing age 60s, 70s, 80s, smoker, lots of high cholesterol, or you've been diagnosed with clogged arteries, those are situations where I take pause whether I'm thinking about cardiovascular stroke or dementia risks when prescribing hormone therapy. And if we must use hormone therapy in a higher risk situation, we typically try to stick to going through the skin, the transdermal as we call formulations because those have been shown to be associated with a lesser chance of both artery and vein blood clots, which formulations and how they might impact dementia risk is really unknown because that really is an area that needs future study, more rigorous study.

Erica Newlin, MD:

Great. And then in the context of all these potential slightly increased risks, what have they found in all-cause mortality, meaning?

Pelin Batur, MD:

I'm so glad you asked me that because I got sidetracked by the risks of this conversation that I promised I wouldn't do. But the one big picture in all of this is that none of us want to get breast cancer. None of us want to have a heart attack that's treatable, right? None of us want any of this. But the big picture is that we all want to live long healthy lives with a good quality of life. And the one thing that shines through all of these studies is that hormone therapy users die less often. Plain and simple. I mean, it's multiple studies that show this. And it's like, by about a third if you average out all these studies. And the younger you are when you start and again in that safer window, the more obvious this is, okay? So, we don't know if future studies will confirm this, but multiple studies suggest women die a third less when they are hormone therapy users.

Erica Newlin, MD:

Right. And on that note, what kind of risk reductions do you see? We've talked a lot about increased risk. But what decreased risk is.

Pelin Batur, MD:

Yeah, and we never talk about this, right? So, estrogen and progestin users talked about how they have an increase in breast cancer risk. But they actually have a reduction in colon cancer risk. And colon cancer is one of our major, you know, health threats as women.

Pelin Batur, MD:

And also, it decreases all types of fractures. And the one thing that I think is important because putting on my osteoporosis hat right now is a lot of the newer osteoporosis medications that we use now after they've been used, you know, a decade, we're really recognizing they have these unusual side effects, right? These unhealing wounds of the jaw, these unusual fractures of the hip. And the longer you use it the more that risk is there. Well, estrogen therapy does not have any of those risks. So oftentimes if you're feeling miserable and you're in your 50s and you want to start hormone therapy and you've got a bone density and it shows that, you know, there's room for improvement or you have osteoporosis, well, fine. You can go on hormone therapy for the five years that you need it. You're doing something for your bones.

And then you can still use them, switch over when you don't need the hormone therapy anymore, use something for your bones later when you're at a higher risk of fracture. But it does protect you from fractures during those years that you're on it. And then we also talked about the decrease in diabetes risk and insulin resistance, which is important. I mentioned that estrogen-only users had a decreased risk in breast cancer even at 20 years, decreased chance of dying from breast cancer with the estrogen only. And the one thing I like to highlight is all these benefits are silent, right? So, I can show a graph of the WHI results.

I pull that up and it has everything that's bad in red and in blue, everything that's positive. And when you look at that one graph, most of the stuff on that graph is blue. But all those are silent. So, when we're clicking away at our computer in the patient room, there's no pop-up that says, "Congratulations. You were supposed to be diagnosed with diabetes this year."

Pelin Batur, MD:

But you weren't because you're on hormones, right? But if somebody has a blood clot, everybody is going to be quick to blame the hormone therapy on that, whether it's caused by the hormone therapy or not. And those things we want to do no harm and we feel bad as clinicians.

You prescribe something and, you know, one out of eight of us are going to get breast cancer. Very few of those are related to hormone therapy. So, if somebody gets breast cancer in your mind, you're thinking, "Oh, did I contribute?" So that kind of "do no harm" fear and then we don't see these benefits, it really impacts our decisions to pull out the prescription pattern. We have to keep in mind that these benefits are silent but they're there. And they're very real.

Erica Newlin, MD:

Great. And then can you speak about bioidentical hormone therapy? What does that refer to?

Erica Newlin, MD:

And then their safety and whether they may be beneficial to a patient.

Pelin Batur, MD:

Right. And so, this is the question I get, you know, probably 20 times a day. But in the true sense of the term bioidentical just means the same as your body chemistry. So, what your ovaries produce, something similar to that. So that would be estradiol and that would be micronized progesterone, versus there's a lot of synthetic estrogen and progestin options that are also available similar to what's used in the birth control pills. So, do we have proof that, you know, there's a huge safety difference? No, there's no huge safety differences between synthetics and natural ones.

But, you know, most of us want to use something natural. And there are actually subtle signals that it might be a little safer. Now, there are multiple FDA approved ways to choose bioidentical hormones. What some people also talk about custom compounded bioidenticals, that's a little bit different story... And I don't want to say I don't compound, I probably do more compounding than a lot of my colleagues do, but I refer to compounding only when the FDA approved options are not there, available, not appropriate for the patient.

Because when you get into custom compounding, you introduce one more element of error, human error. You know, FDA approved products have a lot of vigor that they have to go through to make sure the accuracy of the percentages and you don't have that oversight when your custom compound. So, we do see a lot of weird things where people are promised that this is what they have in it, and you check a level and it's not they have sky high testosterone like male hormone levels of testosterone for this alleged tiny dose. So, there's that human error. Nobody is trying to do anything wrong but there are pretty strict ways that hormones have to be produced. And the one other thing if you are getting custom-compounded hormones, I do want to call out it was over a decade ago we published from our center, series of women who came in with uterine cancer. It was very unusual because these were very low risk women for uterine cancer.

And the one thing that they all had in common was the custom compounded hormones. So, we started looking at what kind of hormones they were using. And when you have a cream that's put together, has estrogen progestin, testosterone, everything in it, it sounds convenient. But if you have a uterus, you have to be careful because that estrogen is readily absorbed, but the progesterone in that compound may not always be absorbed, and it may not be absorbed in enough quantities to get to the uterus and protect your uterus.

So that's the situation. That's, you know, compounding 101, if you are going to deliver estrogen and high enough amounts that it's going to get into your system, you have to have adequate progestin. But, you know, I do, I think a lot of us really like the regimen of transdermal estradiol because there you're minimizing the clotting risks and micronized progesterone which comes in the brand name promethium in the US. And I don't get paid by anybody.

Erica Newlin, MD:

Right.

Pelin Batur, MD:

I don't, you know, I don't get money from any pharmaceutical company. And these are available in cheap generics. Not as cheap as we want it.

Erica Newlin, MD:

Right.

Pelin Batur, MD:

But relatively cheaper generics. And that's becoming a popular option if women tolerate it because the micronized progesterone seems to have lesser breast risks. Those are, those were the two main things that women are worried about, the clotting and the cancer risk and that regimen does help to make that risk benefit more favorable, but we try to stick to the FDA approved formulations to ensure purity.

Erica Newlin, MD:

Great. And then we briefly alluded to testosterone recently. What's the role of testosterone?

Pelin Batur, MD:

Yeah. So, testosterone and DHA are what we call androgens. So, they're more of the male hormones. But we all have them. 

Just men have more of them. So, testosterone has been studied. It's been shot down to get approved in the US. But multiple medical societies have reviewed the data and found that testosterone is safe and appropriate to use as long as you're using low doses that stay within typical physiologic ranges for women. And so, these have been published internationally, these guidelines.

The problem is that since we don't have an FDA-approved way to use it, it becomes difficult to prescribe it. So, you either have to use one-tenth of male hormone doses or you have to compound which again you have to be careful with compounding. As I mentioned, it can have human error. So, adding testosterone adds a level of complexity to the care. The main reason we would add testosterone, really the only thing that's been well studied for is increasing libido.

But it's touted for a whole heck of a lot that it really hasn't been shown to help. So, you just have to be careful. Buyer beware. If somebody's promising that this pellet is going to help you with everything under the sun, you just have to be careful because there's no magic bullet anywhere. And in our clinics, we do see a lot of women coming in with male hormone testosterone levels because of the pellet that they used. Who knows? Maybe in a decade we will have figured out how to dose the pellets.

Pelin Batur, MD:

But we're not there yet. And so, it takes a while to detox them off because it is a steroid. And people say, "Well, you know, my libido was great, but all my hair was falling out. My skin was terrible. I gained weight around my middle." And so those are some of the testosterone related side effects. And, you know, we can't aim for superhuman libido, right? And so, injecting male hormone levels to stop, I'm not talking about the transgender populations. There, you know, a doctor that's you know, prescribing, monitoring. But just for wellness for long term is not something that's recommended. Now, DHEA works great inside the vagina. So, what we have found is that oral DHEA, I mean, you can go and get DHEA supplements over the counter, but in studies hasn't been shown to help much with menopausal symptoms or libido, but for vaginally, when you deliver the hormone straight where it's needed for dryness, for improving orgasm, can be helpful. And there's an FDA approved way to do that vaginal DHEA hormone 6.5 nightly inside the vagina.

Erica Newlin, MD:

Great.

Pelin Batur, MD:

Great stuff. But it's expensive, unfortunately.

Erica Newlin, MD:

Are there other hormone formulations or hormone-adjacent therapies that I left out?

Pelin Batur, MD:

Yeah. The one thing that we didn't talk about is what we call SERMs, Selective Estrogen Receptor Modulators. A lot of words. And what this means is that they sit on the estrogen receptor, but depending on the medication that we're talking about, they work as a pro estrogen and some body parts and as an anti-estrogen some body parts. So, some of these are used in the infertility realm, but there are really three main SERMs that are used in the menopause realm.

One is raloxifene and that's FDA proved to treat of osteopenia, osteoporosis and prevent, and it's also used to prevent breast cancer. There's something called ospemifene. That's used for vaginal dryness and then also we have something called, it's a brand name called Duavee. It has bazedoxifene associated together with estrogen. So instead of using estrogen plus progestin, you're using that combo. And so, what we call informally designer estrogens. So, depending on the person sitting in front of you might be a nice option.

They all have a little bit of a different side effect profile so some might increase hot flashes but not by too much. And they all, we presume that all of them can potentially increase blood clotting risk too because they're activating. They're sitting on estrogen receptors.

Erica Newlin, MD:

Thanks so much for being on the podcast.

Pelin Batur, MD:

My pleasure. It was a great morning. Thank you.

Erica Newlin, MD:

Thank you for listening to this episode of Ob/Gyn Time. We hope you enjoyed the podcast. To make sure you never miss an episode, subscribe wherever you get your podcast or visit clevelandclinic.org/obgyntime.