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- [00:04]
Dr. Kelly Casperson
Welcome to the youe Are Not Broken podcast. I'm your host, Dr. Kelly Casperson, a
- [00:09]
Dr. Kellen Kelly
board certified urologist, thought leader and conversation
- [00:13]
Dr. Kelly Casperson
starter on midlife living, hormones and sexuality. Enjoy the show.
- [00:18]
Dr. Kellen Kelly
Hey friends, welcome back to the youe Are Not Broken podcast today. I am very excited to have Dr. Lobo with me today. He is a renowned professor of obstetrics and gynecology at Columbia University and he is widely recognized expert in women's health, particularly in the areas related to menopause, PCOS and in reproductive technologies. You have an extensive background in clinical research, have published widely, and I want to amplify your voice. So thank you for coming on the podcast.
- [00:47]
Dr. Lobo
Thank you, Kellen Kelly. Happy to be here.
- [00:50]
Dr. Kellen Kelly
So how did you get started in research and publishing in addition to being a clinician?
- [00:55]
Dr. Lobo
Yeah, so in our field of OB gyn there are subspecialty areas. And I knew because of my interest in reproduction in general that I wanted to do a fellowship. So that's how it all started. I did a formal fellowship in California at University of Southern California in reproductive endocrinology and infertility. And so I am what we call an rei and have been that for years and years. And after my fellowship I started delving into research. I was in many types of research. We actually established at that point a clinical trials menopause center back at USC. And this goes back to the 80s basically. And I've continued to be involved both in clinical research and practice of the whole scope of what we do in REI is reproductive hormones. You mentioned pcos, everything art, you know, leading up to that, but also very major focus on menopause, running clinical trials and so forth. And then, and then I came to New York. I mean, I was recruited to Columbia to be the chairman of the department in the mid-90s. And I was chair for a while. And those years when I was chair for about seven, eight years, something like that, because of administrative burdens, I stopped my clinical trials. I had, you know, passed it on to someone else. But I still continue to see patients and remained active that way. And so, you know, I've been involved in the field. I've been a member of all the major sort of menopause and reproductive to societies and written several textbooks and published and in this whole general area, amazing.
- [02:31]
Dr. Kellen Kelly
Just diving in on hormones in general, picking pcos or infertility or menopause. What's like the biggest myth that you think clinicians or women have about female hormones?
- [02:41]
Dr. Lobo
I think each of those is relatively important. I think there's you know, the whole PCOS stuff, which I don't think is your focus here, but it's a whole other area of misdiagnosis and misunderstanding and knowing really what PCOS is. And so many patients are misdiagnosed and their symptoms are ignored and, you know, on and on and on. So it's lack of knowledge in that regard. In menopause, it's understanding what menopause really is. And then when it comes to hormones, interpreting what hormones really are, because menopause in very few women just stops very abruptly, right? There's this whole what we call perimenopause, it's this whole climacteric which starts from the end of reproductive function onwards. And there's a lot of fluctuation, right? The hormones, hormones are up and down and it's in a way a moving target. So you get established in menopause and then for a long time and we were just off cuffed. Speaking earlier that because of some clinical trials like the NIH which were carried out now many years ago, where the message which was incorrect got out that hormones are bad in general, it wiped out a whole generation of women to be treated appropriately. And I'm not saying hormones for everybody, but I'm saying just the lack of understanding and the fear and because of that people haven't been adequately trained. And so you have a generation of physicians and providers of different specialties that just assume, not deal with it because they just lack the knowledge base to be able to do that. So I think that's, you know, those are kind of like the major areas involved in and understanding.
- [04:24]
Dr. Kellen Kelly
Yeah, I agree. Can you share with us, because you were practicing when the WHI dropped in 2002. Do you have a very clear. This is the world before that hit and this was the world in the five years after.
- [04:37]
Dr. Lobo
Yeah. So let me just give you a very brief summary of that whole episode. So hormones have been used for a long time, Right. So estrogen was established, it was developed in the 20s really and was starting to be used in the first 40s and 50s. And so there were a lot of women who were on hormones or not on hormones and it was a little bit abused. Right. I mean in the 60s there was this famous quote, unquote feminine forever hormones for all women for, you know, sort of too far the other way, but rational, making sense, taking care of women. Use of hormones was used for a long time to the extent that there was a fair amount of a database. There are databases of the Nurses Health Study Branch of Bernardo In California Leisure World, there are a bunch of what we call cohort studies, epidemiologic studies of users of estrogen in the past. And when you compared their use to women who never used it, and these were largely women who took it for hormonal hot flushes and so forth, it was very, very obvious that the risks and benefits, the benefits way outweighed the risks. Cardiovascular benefit primarily. Right. Reduction in cardiovascular mortality and so forth. And so back. So I'm moving forward. Back in 92, Deborah Grady was commissioned by the American College of Physicians to do a meta analysis of all the studies and come up with recommendations. And at that time it was very, very clear that based upon long longevity and quality of life, that use of hormones would actually, if used at the time of menopause appropriately, would actually increase the lifespan of women by one to one and a half years, which in epidemiologic terms is huge. Right. So that was the current thinking and that's back into the early 90s. And then around that time it was discovered that, oh, it hasn't gone through the rigors of the, you know, randomized clinical trial for approval, even though there are some motions towards getting it approved for, for example, preventing cardiovascular disease. So the first iteration of the trials were secondary prevention prevention trials. So Steve Holly and others looked at women. If estrogen was going to be good for heart disease, it should help women who have heart disease. And so the initial trials, which are really poorly designed, unfortunately, in retrospect, Steve Holly and others did secondary prevention trials, women who have had established heart disease. So the average age were women in the 70s, already 67 actually, but we went into 70, 75 women who had heart attacks and they went on full dose hormone therapy for the first time and lo and behold, they had more heart attacks. So that was the first blow. But before those results were actually published and acknowledged, WHI started. And WHI included a whole span of women from 50 to 75. But the 2/3 of women were 8 not symptomatic women at menopause. They were older women. It was skewed towards women in their late 50s or 60s on to age 75. And it would take us hours to discuss WHI. But I don't want to insult your intelligence. I know you know it very well. The bottom line that came out was that in totality there was no benefit. And there was an excess in breast cancer with the estrogen plus progestin combination, not just estrogen alone, actually estrogen alone and the estrogen alone trials decreased breast cancer but the E&P regimen caused an increased breast cancer. Because of that and no overall coronary benefit, hormones should be used. And it pertained, even though they used one regimen, they said it pertained to all hormones, all types, all roots of administration, which again is not true. And to all age groups, which is definitely not true. Because when they looked at their own data, both estrogen alone and estrogen plus progestin, there was a benefit in younger women. And combining those two trials in women up to age 60, the fewer women in that database, which is actually odd, 2 to 3,000 women, there was actually about a 40 to 50% protection, which is what they showed in the epidemiologic studies. And it was also determined that while the estrogen alone arm reduced breast cancer, the E P regimen that actually increased breast cancer was pretty much relegated to those women who were prior users. So it was longer term therapy for many years with this regimen. So we've learned that long term exposure to synthetic estrogens does promote breast cancer. It doesn't cause breast cancer. But if some women, because it takes so long to develop breast cancer, if you have a microscopic lesion, it's promotional, right? It's ERPR positive, so it will add fuel to the fire, particularly if you add a synthetic progestin. So we've definitely.
- [09:40]
Dr. Kellen Kelly
Yeah, I was going to say the role of the medroxyprogesterone acetate made a
- [09:44]
Dr. Lobo
huge difference because concurrently there are trials in Europe, largely out of France, using micronized progesterone, that did not show an increase. When you added that as part of the regimen, particularly on a non continuous basis, and then on the coronary benefit side of things, we know that women 60 and above, particularly women who have had previous heart disease, you do do more harm than good. That's not somebody who should be prescribing full dose hormone therapy for the first time.
- [10:13]
Dr. Kellen Kelly
Oral. Are we going to separate that between oral and transdermal?
- [10:16]
Dr. Lobo
Yeah, I think, I mean we can drill down a little bit more, but I think in general the data at hand, which was all oral, which suggests that that population should not be initiated with hormones for the first time. So no secondary prevention, prevention, benefit. And in fact, not only does it do harm, but the arteries have lost their ability to respond. Because when you get plaqued through a lot of epigenetic and other mechanisms, estrogen doesn't work anymore through any of its mechanisms to reduce atherosclerosis called vasodilation and all the things that lead to a conoring benefit. So it really has most of its benefit in younger women clinically close to menopause and who don't necessarily have bad risk factors that would preclude this being used. So I think you're alluding, Kelly, to the fact that, you know, safer ways to go in terms of estrogen exposure are non oral oral estrogen hits the liver through something we call the first pass mechanism, incites clotting factors and unknown factors in patients who are thrombophilic, you know, have a risk factor of thrombosis and most of the initial events of coronary thrombosis, heart attacks are thrombotic. So thrombosis is a major risk factor, hence also some increased risk and stroke. So in higher risk individuals, particularly even in younger women, non oral preparations, transdermal tight preparations, and you can monitor the type of level you want to get, as long as they're not excessive, are safe. The other argument is would you ever use estrogen for the first time in somebody at age 70?
- [12:01]
Dr. Kellen Kelly
Yeah, we need to talk about that. The boomers are pissed that they missed 20 years after the WHI and they want to protect their bones now.
- [12:08]
Dr. Lobo
Yeah, exactly. In fact, there's an editorial I kind of divulge, but I reviewed it for a leading journal that is making the comment that if you really look at the data carefully, older women shouldn't necessarily be excluded if they fit into the right category. And so, you know, nowadays. True ha. And other things, there are risk assessments that you can do and if a woman falls into a reasonable risk assessment using and she needs it for various reasons, using a low dose with appropriate monitoring and measuring levels and so forth of a non oral preparation, like a low dose patch is perfectly appropriate. And in fact, as you, as you probably know, there's something called Mennostar, right. Which is a very low dose patch. It's only 0.014 milligrams and it's only used as primary indication is prevention of. Prevention of osteoporosis in older women. So there is the precedent for that and it is effective and there are ways to do it. But you really need to know what you're doing because it is a little bit more of a high risk situation.
- [13:10]
Dr. Kellen Kelly
Yeah, I see a lot of those women. I'm healthy, I've never had, you know, I take no meds. I would have been on hormones had they been offered. I was never offered. My biggest risk is a hip fracture. You know, like I see tons of those women and you know, within my group of People who chew on this. My understanding of this, going back to the secondary prevention trials is they had a slightly higher risk. Women with known heart disease, you now throw them on estrogen within the first year, but then it evened out with the placebo and it didn't help them, but it didn't make them any worse than the placebo group.
- [13:44]
Dr. Lobo
Yeah, it was, it's what we call early harm. It was within the first year, year and a half. And interestingly enough, in that cohort, if women were already on a statin, they were somewhat protected.
- [13:58]
Dr. Kellen Kelly
Interesting.
- [14:00]
Dr. Lobo
The big issue though is the benefit side of it. So even if you get away from not having any harm, you know, you get past that early harm and you're in your third or fourth year and you're doing okay. And. But you, you don't have the benefit
- [14:15]
Dr. Kellen Kelly
anymore as far as cardio protection because you, you aged out of the benefit window.
- [14:20]
Dr. Lobo
You will get the mood, you'll get the hot flushing, you'll get the vaginal, you will get the bones do all of that, but you won't get the coronary benefit because the vessels just don't respond anymore. They're receptor neutral at that point. They just don't respond.
- [14:34]
Dr. Kellen Kelly
So let's say that woman's in our clinic. She's 73, she's never had a cardiac event, she's not on any blood pressure meds, she's healthy, she's like, I want a low dose transdermal for bone protection. Let's say that's the story people will discuss. What's the right screening test besides just a heart risk calculator? And some people are starting to get coronary calcium scores. My argument is I don't have any data to show that calcified plaques are a contraindication given the secondary prevention data that we have. Do you have a strong opinion on what we should we be checking lipids, like besides just doing a cardiology of
- [15:11]
Dr. Lobo
that age, should, should be having all that anyway. I mean, you should have lipids, you should blood pressure check, maybe crp, things like that. The business of getting coronary calcium has been sort of a go to thing for making a decision on statin therapy or not statin therapy. But as you know now, the general recommendation of statins for everybody, which is also a little bit, a little bit overblown, but I think that the risk assessment is just to make sure that they're not at greater risk than you otherwise perceive and then have that informed consent decision that I can't do it very much more to prevent your heart disease. But if you do want protection for bone and you want to use some form of transdermal, and it would only be a transdermal type product and we'll monitor it carefully, it's okay to do.
- [16:02]
Dr. Kelly Casperson
Yeah.
- [16:02]
Dr. Kellen Kelly
To me, it gets frustrating when people are using absolute cutoffs in a woman that hasn't had an event, right. A cardiac event, and they're saying, you can't have hormones because we found this asymptomatic something, instead of doing an informed consent saying, listen, we found some risks, let's try to optimize them. But they're using a black and white like can't have hormones after a certain scan or lab value that I don't think data supports being that black and white.
- [16:29]
Dr. Lobo
Right. And the fact that data doesn't support not giving it to anybody, which is some people's perspective as well.
- [16:37]
Dr. Kellen Kelly
Yeah. It's an interesting conversation. Right. Because the experts never want to say hormones for everybody. But then we can also say most people are going to be pretty safe given the informed consent discussion.
- [16:50]
Dr. Lobo
Right. But you have, as you well know from your practice, like all things in life, there are extremes in both directions. And you do have some women who really do need hormones, but because of the fear instilled in them, they don't use hormones and won't use hormones and rather get a heart attack than use hormones. And particularly breast cancer, which is a major fear women have, which I understand, but you have that population that you have to do other things to help support their. From lifestyle variables to diet to exercise to things to support their bones and other health. And then you have the other candidates who are on the extreme that you suggested, some who would be good candidates, but some who are really, really women who have lots of comorbidities who you just shouldn't go there. And so you have that spectrum. I mean, I've had women much, much older who refuse to get off birth control pills way back when. I mean, it's just. That's the spectrum.
- [17:53]
Dr. Kellen Kelly
I think, especially in my world of trying to educate. This is a complicated topic. Right. We're talking oral transdermal, Are we talking synthetic estrogen, are we talking estradiol? There's so much to it. And then on, you know what I see on social media, people are like, just give me the absolute best dose, best level, black and white. And it's like, no, that's not what the practice of medicine is ultimately.
- [18:13]
Dr. Lobo
And it is very individual. There was an old review article many, many, many years ago sold that was entitled flexible prescribing. And that's exactly, that's the name of the game. I mean, you just need them. And this is something that a lot of physicians don't know because they haven't been educated sufficiently in this regard, is that unlike oral, which oral for a young healthy woman is perfectly fine. I don't want to belittle that in any way. I mean, there's a lot of evidence, in fact, all the epidemiologic evidence will, is with oral in younger, appropriately treated women. But when you use a transdermal product, and again, transdermal of some, whether you use Estrogel or Divagel or Primera Patch or Vivald Daughter, you know, any of those products, the absorption varies considerably. And whereas with oral we don't advocate measurements because again, it hits the liver and you get a whole slew of metabolites, estrone, estrone, glucuronide, so forth. And most commercial acids cannot determine accurately what your level is. And most of it is estrone and its conjugates. It's not estradiol. But with estradiol you're giving estradiol with a patch and you can determine what the level is. And a big unknown is that for a given woman with a given patch, you assume it's going to be at a certain level. 0.025 is a low dose patch,05 is like a medium dose patch and so forth. Some of those women with that patch, some will be too low and some will be way too high. And particularly when you're trying to manage their endometrial development and how much progesterone they need and so forth, you need to know at what level your estrogen is and you don't want to be too high and you want to be. And particularly in older women, you'd be much more conservative with keeping the levels at or below say 20 or 30 picograms as opposed to somebody who really needs it for hot flushes where the values are more like 50 or 60 picograms per mil. So that is something that, you know, some people, I do a lot of blood measurements, but I think the common provider of non oral estrogen does not check a blood level and it does make a big difference.
- [20:34]
Dr. Kellen Kelly
I agree. And I think to me the blanket statement of oh, if your patch is.05, you better be on 200 milligrams of oral micronized is like, but we don't know what the blood level is. How can we say that it's a dose that requires a Higher progesterone versus a level that requires a higher progesterone. Do you have thoughts on that?
- [20:54]
Dr. Lobo
Absolutely. In a given woman, 50 could be 25 or it could be 75. And it's been documented. I mean, there's literature on this. There are women on a 50 microgram patch that have 200 picograms per mil of estradiol circulating. And I've had women also where their levels are. They don't feel better. You know, it hasn't helped their hot flushes. And you do a blood level, and the estradiol level is almost undetectable, just not absorbing it. And it's because sometimes they switch from a generic to a brand to a. You know, so there are different ways to play with it, but you need to know what you're dealing with before you can determine whether it's the right way to go.
- [21:31]
Dr. Kellen Kelly
Yeah. I have a young woman who's on a 0.75, and her estradiol is like 13. And she's still like, I feel like a. I have no energy. She just feels still crappy. She's young, she needs more. And thank you for getting into the weeds with this. There's so many people who are at our level. They are going to love this. Is there a blood level where you're like, you need 200 milligrams of micronized progesterone to protect the uterine lining? Or how do you. How should people navigate when you need enough micronized progesterone?
- [21:59]
Dr. Lobo
Yeah. So from a safety standpoint, the first thing I want to know is the level. Because you want to eliminate the 200 picogram ladies and get them on the right dose. The appropriate dose for women who have hot flashes is kind of like a 50, 60, something like that. Younger women, they need more. But that. That's a good level. The second thing, and this is what I do when I as I practice, is I want to know what their lining is doing. I want to know what their endometrium is doing. And there are some women, even with an adequate amount of estrogen, like 50 picography, that don't proliferate very much. And you may only need to give them progesterone every two months, for example, you know, if you're prepared to monitor them closely. But there are some women with even lower doses, like 20 or 30 picograms, that within a month, their lining is like 8, 10 millimeters double thickness, where it becomes a big concern. And there are some women, you know, progesterone as you well know, it's not well absorbed orally. Right. So circulating levels of progesterone are not great. So the length of time is important. So it's at least 12 days or so. But there's some women who actually need a little bit more, or in some women where it's very difficult to control the endometrium, you have to go to some sort of synthetic periodically to. Otherwise they end up with endometrial hyperplasia. And that's. That's been well documented. So, again, very individualized. And you just have to, you know, monitor and work with a woman to be able to do this.
- [23:28]
Dr. Kellen Kelly
Yeah, I love it. I'm just going to stay in the weeds because I love that you can handle these questions. So the endometrial hyperplasia and uterine cancer data, it's old. That was synthetic oral estrogen where we discovered, oh, we need to counteract the effects of the synthetic oral on the endometrium. Let's add a progestin. So that's a standard of care. Now, some experts who know the literature will argue we don't have endometrial cancer data on transdermal estradiol dosing. Do we really need to be harping so hard on a progestin progesterone on those people? Nobody's gonna do this study. It would be considered unethical. We're extrapolating oral synthetics to transdermal bioidenticals and still having this big fear of needing the uterus project protected.
- [24:18]
Dr. Lobo
For me, that's a fairly easy answer. I think it's biological. I mean, estrogen is an estrogen. What it does to the uterus is going to be a little bit of variability, but it's going to have that effect. So if you're giving a transderal product at a certain level, as we said, 50, 60 picograms, if you give it unopposed without progesterone, you're going to get endometrial pleasure. Depending on the individual, it's going to be less or more at a given point. You mentioned bioidentical. It's not as easy to find the literature where there's three or four papers in literature on endometrial cancers because it used to be said, use bioidenticals, it's safer, and so forth. It's not particularly with the doses. And there are many cases. Now there are at least three or four papers in the literature showing endometrial cancers in women using bioidenticals. And because it's been ignored, it's been not monitored. And typically what happens is you're giving a decent slug of estrogen because that's what you want in terms of symptom control. But the bioidentical absorption of progesterone is poor because if you're giving natural progesterone, whether it's transdermal or even oral, you're not getting adequate amounts of progesterone for that amount of compounded estrogen. So I think in this regard, the biology is the biology. And I certainly have seen women with endometrial cancer on transdermals who have not taken adequate progesterone.
- [25:50]
Dr. Kellen Kelly
Good. Nice to get a solid thought on that. So one of my favorite publications that you were part of was a 2017 editorial in the Menopause Journal titled Menopausal Hormone Therapy for Primary why the USPSTF is Wrong. Amazing paper. Do you want to explain or I can explain what the USPSTF is. Besides, very hard to say. And then let's talk about why they said we shouldn't use hormones for primary prevention and then our opinion about that.
- [26:20]
Dr. Lobo
Well, you lead it off and I'll chime in. U.S. prevention Task Force is a very sort of epidemiologic group, right?
- [26:30]
Dr. Kellen Kelly
Yeah, It's a group of people self selected, who advise, but then Medicare will make payment coverage recommendations on their advice. I know this because I'm a urologist and I know what they said about prostate cancer screening and I also know how that turned out. So the urologists already don't love this group based upon prostate cancer screening, make
- [26:52]
Dr. Lobo
recommendations on not doing PSAs, on frequency of mammograms and frequency of Pap smears and things like that. And some of the recommendations are reasonable. But, you know, so the dogma, back to your original question, is that there's no evidence based on WHI for cardio protection. So therefore, based upon summary data from whi, it shouldn't be used for preventing heart disease. So our argument, and we have another paper, back to the future, it's called, it's an atherosclerosis. If you really look at the WHI data and it's separate publications, it's not the whole WHI where you look at women 50 to 59 or less than 60. And again, this is all with oral estrogen, there was a significant protective effect. And there are data from with to your point, on transdermals, there are data from Tomi Mikola from Finland using transdermal. Same thing about a 50% protection protective effect. And if you look at a Cochrane analysis of randomized trials, which includes whi of the younger population, there's also a 50% protection. And so being conservative, when I tease the whole thing like a poor man's meta analysis, I come up with a 30%. I think it's reasonable. Even the old epidemiologic studies, very few were up as high as 50% protection. I mean, I think a very conservative number is a point estimate of 0.7, which means about a 30% protective effect. And I think that's reasonable. And even though Cochrane showed 50, if you look at a lot of the other studies and you put them together, somewhere in the range of 30 to 40% protection is reasonable. And so in young healthy women, and for sake of argument, it's easier if she has hot flushes, she will definitely get that coronary benefit effect. Right? I mean she's 50 to 59, say she's 55, she's within, she's otherwise healthy, you will be able, even five or six years of use, you will get that cardiovascular protective effect which is primary prevention. So the argument is even women who don't necessarily need hormones for hot flushes, but they're otherwise healthy and they're open to using hormones if it's suggested. I feel very comfortable telling them that our data suggests that you will get a coronary benefit and it's not forever, but if you take it for five, six, seven years, as the younger women at WHI did, you'll get up to a 50% but more like a 30 to 40% reduction, which is huge for coronary disease. Right, because it has this huge case fatality rate. And then you also get benefit on bone as well, so you don't have to commit forever. But that is the mode of prevention, preventative medicine, because if you look at other measures like lifestyle management and so forth, the overall coronary benefit for that isn't the 13, 15% range reduction, it's half of what estrogen would afford.
- [30:05]
Dr. Kellen Kelly
Yeah, the blanket that everybody should is a very, that's a high bar. We don't say that for baby aspirin, we hardly say it for statins. I'd say statins are the closest to like a primary prevention medication that we'd use. And in my analysis, the number I did, I researched the number needed to treat, I forget what article I pulled it from for estradiol, but number needed to treat for primary prevention for estrogen was about 250 people. Number needed to treat for primary prevention for statins And I'm not sure if this is sexual specific. It was 400. And if you look at the amount of people on statins compared to the people on hormones. We have it backwards.
- [30:45]
Dr. Lobo
Right, exactly. And there are data that my good friend Howard Hotas, he comes from the atherosclerosis world. Right. And he's not a gynecologist, he's not a reproductive endocrinologist, but he says there is really no good evidence for statin use. For primary prevention. Yes. In women. In women. For men. Yes. And for secondary prevention. Yes. But what we're talking about, primary prevention, particularly in younger women, talking about mortality as an endpoint. There is no evidence for its benefit for primary prevention in women. And most cardiologists will push back on that. But if you really. But if you look at the data. And I've been halfway. Right. I mean, Howard is passionate in that regard. He also says that statins increase the risk for diabetes, which it does, but it's not massive.
- [31:40]
Dr. Kellen Kelly
It's small. Also breast cancer, but it's small.
- [31:42]
Dr. Lobo
Yeah, exactly. So that's that whole part of the disease. It's not as good as people would make out to you. So even if you listen to Howard and you look at some of that literature, which is supportive, I think the conclusion is that there's no strong evidence that there's this primary prevention benefit. And yet for standards for primary prevention in women. Right. And yet there's so much data on
- [32:06]
Dr. Kellen Kelly
the estrogen side, it's crazy. I feel like. I mean, you and Howard must feel crazy that because you know the data so much and it's basically screaming at you, yet here we have a world where we're sicker than ever, we're living long, but not healthy. Chronic disease is the number one thing that's bankrupting our healthcare system. And we have something that prevents, not 100%, but it's pretty good at preventing chronic diseases.
- [32:33]
Dr. Lobo
Yeah, absolutely. And then you can go beyond to talk about bone health and arthritis risk and, you know, on and on and on, lots of other things as well.
- [32:42]
Dr. Kellen Kelly
Yeah. I think the other argument's the wrong word, but for primary prevention is the role of hormones on metabolic health and decreasing the risk of diabetes.
- [32:53]
Dr. Lobo
Yeah, absolutely. Yeah. So that's that analogy with statins. Right. So statins don't have that primary prevention role. Estrogen does. Statins may increase diabetes. Estrogen lowers diabetes risk, new onset diabetes. So it tips the scales in that regard.
- [33:08]
Dr. Kellen Kelly
And 83 million people in America are on statins.
- [33:11]
Dr. Lobo
Yeah. Oh, huge. Yeah.
- [33:13]
Dr. Kellen Kelly
It's huge. Of the top 10 medications prescribed in America, two or four of them are statins. You were talking about. What was this? It might have been a metabolic paper. And I don't mean to put you on the spot, but just something I had never. We think of FSH or follicle stimulating hormone. We kind of think of it as this benign signal that goes up after perimenopause. It fluctuates and then it goes up after menopause because it's trying to get the ovaries to give some hormones. But I think we think of it kind of as this, like, benign flag you were talking about. Maybe there's some role with that and weight gain or people with lower FSH levels have a higher rate of metabolic syndrome. I'm in the dark on any of this. What do you know?
- [33:54]
Dr. Lobo
There are a few papers, a couple of papers. There's some. There's a basic science paper, I think, out of China, and there's a clinical paper. So women who have higher fshs are at greater risk for metabolic syndrome. And metabolic. There's an interaction with adipocytes and not breaking down fat adequately.
- [34:11]
Dr. Kellen Kelly
If you ever know that fsh, what's FSH doing? And second question is, what's a higher number mean fsh lab wise?
- [34:19]
Dr. Lobo
So I think in clinical terms, it's not that interesting, quite honestly. It's like an epiphenomenon more than anything else. And the basic science behind it is that there are receptors on fat cells, like, there are receptors everywhere. And so the FSH interacts in that way, preventing adipocytes from breaking down and so forth. Forth. I mean, that's the theory behind it. But in practical terms, FSH is one of those funny fluctuating hormones. It starts going up in perimenopause and stays up until a woman is much, much older. So if you're menopausal, by definition, you can have an elevated fsh. And targeting FSH is not the way to go because the amount of estrogen you need to drive FSH down is. Is much, much higher than you would need for hormonal replacement. So it's an interesting kind of, like, epiphenomenon. It might explain why women, even beginning in the perimenopause, when they start having an elevated fsh, are starting to have changes in body composition and so forth and more fat deposition of the abdominal area, visceral fat, all that kind of stuff. It might explain that phenomenon a little bit more as well. But it is not enough to change prescribing habits.
- [35:37]
Dr. Kellen Kelly
But you think it's more than. My question is like, is it correlation doesn't equal causation? Is it just an associated finding or do you think there might be something too fsh?
- [35:46]
Dr. Lobo
To me, it's just an associated finding. That may add a tidbit to it, but it's not the major player.
- [35:52]
Dr. Kellen Kelly
So many people ask me, and these aren't doctors, these are like laypeople. They're like, what level should my estrogen b for bone protection, for heart protection, for dementia prevention. My response is we do not have the data to be solid on giving that advice, except for the fact we've got data that says you need a pretty low number to start helping the bones. Do you think we're going to get that data? Do you think people are going to look at the heart needs a level of 40 post menopause? Where do you think we're going to get as far as getting a little more specialized on how much estrogen is protective for each organ?
- [36:30]
Dr. Lobo
So I think you're right. We don't know. We don't know. And I don't think we're ever going to get the data. You're right in saying that the amount to prevent bone loss is less. Right. And we know that from women who have been on Lupron and then replaced with estrogen to prevent bone loss when they're on using Lupron for endometriosis and other diseases, fibroids, what have you. So the amount is a little bit, you know, 20, 20 to 30, 20 to 25 is probably enough to at least maintain bone mass. It's not going to help that much, but that's the threshold for hot flushes. Huge spectrum. And that's why we will never get data. I mean, there's some women who just take a little bit of estrogen and get relief. Right. And there's some women need much, much higher doses. My guru in cardiovascular medicine is Tom Clarkson, who passed away. Tom was a. He was a person. He was a vet by training, but ran that department in North Carolina for many, many years. He's passed away, but he did all those trials in the cynomologous monkey. He was the main person that coined the term timing hypothesis that you need to treat early or you lose the benefit if you treat late. Those are elegant studies done in the monkey model. Originally back to Tom. Why, why I'm digressing to that is Tom was a person who said that for cardio protection, you need 50 to 60 picograms. That was an Extrapolation from his monkey data. So I can't tell you it pertains to women, but it follows the scenario that you probably need less estrogen for bone, you need a little bit more for heart, and you may or may not need more for heart flushes, depending on the age of the patient and what her individual brain is going to be responding to. And cognition is all over the place. Right. I mean, that's even difficult discussion in terms of whether there is a cognitive benefit and so forth as well. That's very, very, very mixed data.
- [38:33]
Dr. Kellen Kelly
Yeah. I'm reading papers on autopsy studies looking at brain levels of estrogen and testosterone, which doesn't correlate with the serum levels of the lab draws.
- [38:44]
Dr. Lobo
Right.
- [38:44]
Dr. Kellen Kelly
And so you've got that whole thing of if we're measuring serum, does that even matter? Because it's the levels in the tissue that matters, which you can't measure when you're alive, at least for the brain, is kind of where I got on that. Your opinion on testosterone.
- [38:59]
Dr. Lobo
So it's gone back and forth a number of times. So the. I think there are some women who would benefit from testosterone, but it's not everybody. Okay, so the original formulations that were available, the old estra test, I don't know if you're familiar with that, it was primarily, it was methyl testosterone. It was primarily prescribed for difficult to control hot flushes, not for sexual dysfunction. And yet we did a trial that actually I was the primary orthodon, where we randomized patients to estro test and the estrogen component without the testosterone component. And there was definitely a benefit of the methyl testosterone. Okay, so there is a benefit in terms of hirachtosexual desire disorder in a very generic sense, but it's not necessarily for everybody. There are some women who do perfectly well with estrogen alone. And the difficulty we have, as we well know, is that in the absence of something like estro test, and I don't even know if you can get it anymore.
- [40:03]
Dr. Kellen Kelly
I think you can because I know some people who are using it.
- [40:06]
Dr. Lobo
Yeah. So it's not a bad product at all. But again, again, if you want to stay away from oral and particularly methyl testosterone hits the liver, you know, all those kinds of issues. Although it's relatively safe, there are no good products available. And women, they started out trying to get Intrinsa approved, which is the testosterone patch. I never saw the day FDA just wouldn't have it because they didn't. They wanted to have long term data.
- [40:32]
Dr. Kellen Kelly
Even though we've been using testosterone in women since the 40s.
- [40:35]
Dr. Lobo
Right. So it was prescribed in Europe, but I understand there was very little pickup, so they've stopped even making it available.
- [40:44]
Dr. Kellen Kelly
So it was only approved for surgical menopause, not regular menopause. So they're like, oh, it didn't sell much. And it's like, well, you only let the surgical menopause people have it.
- [40:54]
Dr. Lobo
Well, it's been largely. The testosterone story has been largely a regulatory one. So I think there are women who benefit from it. I do have some patients on it, but it's, again, you have to monitor because since you don't have specific products, if you're cutting up patches or using parts of gels and things, you have a tremendous chance of having an overshoot and having too much testosterone. The data from Susan Davis and others is that to get a therapeutic benefit, your testosterone level needs to be at the upper range, if not a little bit above the normal range range. But you don't want to get into the male range. And part of the problem also in this area is that the testosterone assay has been geared to measurements in men, so it's far less accurate in women. But, you know, in the normal range, 20 to 50 or 60 nanograms per deciliter, that should be the normal range. So I think a value of 70 or 80, somewhere like that would be acceptable. And according to Susan's data, that's probably what you need for a therapeutic benefit. But you don't want to get up to the male range. I mean, not only. I mean, that's going to cause side effects and whatnot, but there are some women with even in, you know, status bso, right, who have had oophorectomies where their levels are even much lower because they no longer even make precursors. They do perfectly fine with just estrogen alone, Right? They do perfectly well. And so that's how complicated the whole brain is. It's, you know, they don't necessarily need it. And yet you have some women who may have even normal, quote, unquote, adequate levels of testosterone that feel there's something missing. In which case I consider a what, what I call a therapeutic trial with all the difficulties of prescribing and so forth. I give it a shot, see if they feel better as long as we monitor them and then kind of take it from there.
- [42:45]
Dr. Kellen Kelly
I love it. That's exactly what I do. I mean, I started out giving the testosterone to the men because I'm a urologist, right? So I'm like, these small micro doses for women don't scare me. But I agree with all of your points. We don't have a great lab test. We don't have a great reference range on the lab test. And it's like, you know, we're still operating with. We're bloodletting with leeches on this. Basically. We don't have a product. We don't know how many androgen receptors you have. We don't know how sensitive your androgen receptors are. Like, there's so many pieces to this.
- [43:18]
Dr. Lobo
Right. And there's a lot of individual variation as well. Some women do better than others to wrap up.
- [43:24]
Dr. Kellen Kelly
I mean, thank you so much for spending the hour with us. Do you have any, like, advancements that are coming down the pipeline? Like anything that's really exciting you in this field right now or things you're working on?
- [43:35]
Dr. Lobo
More of the same. I mean, we started the conversation saying education as a big piece. And I think in terms of doing a service to women's health in general, if there was some way that we could just educate the masses of providers out there to be able to take care of women because no one person, Kelly or myself or anybody can do it. Right? I mean, so that's the main, main thing in research. There will always be some other products. I mean, over the last several years we've been delving with E4 estetral, which is a fetal estrogen, but it has some fantastic interesting things in. I don't want to get into the weeds on that. But I mean, that's something that may or may not hit today because it's just a very interesting natural molecule that's evolving and now it's in the. It's an oral contraceptive as well. But the menopause therapy is developing and of course you. We now know we have Feutosa and others and in case three receptor blockers to, to target the areas in the brain that specifically are related to the thermoregulatory. So it doesn't do all the other things we talked about. I mean it does it. I think it does have a role, particularly in women who cannot or should not take hormones for. Who are bothered by hot flushes. Having said that, we just don't know long term what's going to happen in terms of overall safety and so forth. It has a role. So that's part of our armamentarium now. But it doesn't do anything for bone, doesn't do anything for heart, doesn't do anything for necessarily mood or anything like that. So I think those are the kind of the things right now we have. There used to be so much active research in this area, and it kind of just stopped after whi. There was no interest in it. All the companies that would otherwise be funding it shy away because they're concerned about liability and other concerns post whi. And this is kind of where we stand. We would have had much more products and much more innovation had there been some financial backing for the this process. So I go back and say, well, where we really need to start is prevention. I mean, is education. So people can then rise up from there and understand that, yeah, we could do this even a little bit better if we could.
- [45:51]
Dr. Kellen Kelly
I think the prevention discussion is just starting, and I think it's a grassroots. I mean, what you're publishing to educate the people who are reading it, but then really grassroots from the women themselves. They're turning 50, they're seeing their parents age poorly, they're wondering what they can do. They're hungry for this information. So I think there is a grassroots prevention because Western medicine, we treat disease, we rarely try to prevent disease. It's really a paradigm shift in the traditional Western medicine clinic to talk about prevention. So I think it's very exciting and I think it's driven by the women,
- [46:30]
Dr. Lobo
as it should be.
- [46:32]
Dr. Kellen Kelly
Doctors are too busy. Like, you really need time to be curious and to learn something new that you didn't learn in medical school. And so the women coming in, hearing these discussions, they're the ones who are Dr. I've had Doc. They're like, a lot of women are really coming in asking for this. I better learn now, right? And the role of that grassroots change to improve people's lives is fantastic.
- [46:56]
Dr. Lobo
So hopefully it's starting.
- [46:57]
Dr. Kellen Kelly
It's starting. Well, thank you so much for joining me today. I had a blast.
- [47:02]
Dr. Lobo
Oh, thank you. I enjoyed it.
- [47:04]
Dr. Kelly Casperson
Thank you for listening to this week's episode of youf Are Not Broken. If you want to dig deeper with me, sign up for my Adult Sex Education Masterclass where you learn adult things like communication skills, anatomy lessons and desire types, and how to talk to your doctor about sexual health concerns. If you want the Adult Sex Education Masterclass for free, join my monthly membership for more in depth exclusive content, more time with yours truly. A private podcast, coaching and educational empowerment, and you can watch my interviews live and get them immediately without advertising. Head over to www.kellycaspersonmd.com for the membership and adult Sex ed masterclass members get the master class for free. This podcast is presented solely for educational, entertainment and informational purposes only. I am a doctor but not your doctor in this format and all of my platforms and guests including on this podcast are not giving individual medical advice or practicing medicine. See and consult with your own care team for your individual needs and concerns. This podcast is not intended as a substitute for the care and advice of a physician, therapist or other qualified professional. This podcast does not constitute the practice of medicine, in case you were curious about that and no doctor patient relationship is formed. But I still love you. Using the information on this podcast or any of my platforms is at your own risk. Until next time, remember you are not broken.