The All In Podcast

Episode 39 - How HA affects your heart health with Dr Chrisandra Shufelt, MD

• Florence Gillet • Season 3 • Episode 39

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In this episode, Dr Chrisandra Shufelt returns (she was already our guest on Episode 28!) with more groundbreaking facts on HA and heart health but also an invitation to join her current research!

Dr Shufelt, MD, is the chair of the division of general internal medicine and associate director of Women's Health Research Center. She is a women's health internist with Fellowship Training in Vascular Biology and Women's Health and a Certified Menopause Practitioner. Her NIH funded research focuses on young women with hypothalamic amenorrhea, evaluating the impact on immune and vascular health.

Link to Dr Shufelt's research on Functional Hypothalamic Amenorrhea and Preclinical Cardiovascular Disease here

(USA only) Join Dr Shufelt's new research here

(All countries) Join the REVEAL (HA patients) registry here

To reach out to Dr Shufelt,
Contact her on X (Twitter) @CshufeltMD
Or via Mayo Clinic https://www.mayo.edu/research/faculty/shufelt-chrisandra-l-m-d/bio-20542101

To find support in your HA recovery:
Get the "No Period. Now What?" book at noperiod.info/book.
Get the French version "Je n'ai plus mes regles" book at noperiod.info/livre.
Get the German version "Keine periode - was jetzt?" at noperiod.info/buch.

To join our support groups, please visit noperiod.info/support
for English, noperiod.info/communaute for French, and noperiod.info/community for German.

To make an appointment with Dr Sykes and get individual support to get your period back or improve your fertility, please go to noperiod.info/appointments
To make an appointment with Florence Gillet and get help with the body and mind changes happening in recovery please visit www.beyondbodyimage.com

You can find us on social media:
Instagram:
@noperiodnowwhat in English
@jenaiplusmesregles_livre in French
@keineperiodewasjetzt in German

...

Welcome to All In, a straight shooting, science based podcast about periods, fertility, and nurturing health outside of unrealistic beauty expectations. We will mostly, but not exclusively, focus on hypothalamic amenorrhea, HA, a component of relative energy deficiency in sport, formerly known as the female athlete triad. I'm Dr. Nicola Sykes, scientist and author of the book No Period, Now What? I specialize in helping people understand how their eating, exercise, and lifestyle habits are keeping them from hormonal health and their best life. My work focuses on regaining periods, improving fertility, and breaking free of the rules underlying diet culture. My name is Florence Gillet. I'm a certified eating psychology coach, a former HA patient, and an advocate of health at every size and body neutrality. I help people let go of their obsession with size and appearance to regain self confidence, finally appreciate their bodies, and live an overall fuller, more joyful life. Every two weeks, the All In podcast brings you real recovery stories, expert insights, and new scientific research on HA, hormonal health and fertility, with an unmissable touch of body respect and women's empowerment. Just a reminder that this podcast represents the opinions of the hosts and their guests. This content should not be taken as medical advice, it's for informational purposes only. And because each person is unique, please consult your primary care practitioner for any medical questions. Music by the Andy Shulman Band, available on Spotify.

Nicola:

Hello, everybody. We're very excited today to speak again with Dr. Chrisandra Shufelt, MD, who we first spoke to in episode 28. Dr. Shufelt recently moved to the Mayo Clinic in Jacksonville, Florida, where she's the chair of the division of general internal medicine and associate director of Women's Health Research Center. Dr. Shufelt is a women's health internist. with Fellowship Training in Vascular Biology and Women's Health and a Certified Menopause Practitioner. Her NIH funded research focuses on young women with hypothalamic amenorrhea, evaluating the impact on immune and vascular health, which is a really relevant topic for all of us. It's so nice to speak with you again, Chrisandra. we'd love to start with learning a little bit more about you. How are you finding your recent move to Florida and, tell us something about what you enjoy doing in your spare time, if you have any.

Dr Shufelt:

Oh, thank you. And thanks for that introduction. And also for having me back. This is a passionate topic for me, for my research and moving the field forward and really helping young women with this condition who, you know, otherwise have not been getting the correct answer. And also, really, really strongly, pointing out that the NIH is funding this research. So these are our tax dollars at work. So that's the exciting part is that the NIH is now focusing on young women's health, which is obviously very important. So, yeah. So I moved to Mayo Clinic, Florida, which is in Jacksonville. So that's north. It's on the coast. It's on the ocean. And I moved here about a year and a half ago. We have a fantastic and a very strong women's health program here, which is within the department and the division of internal medicine. So that was one of the reasons I really moved here because, well, along with my family, my husband and two children, we really enjoy it. And it also helps that Florida is great for equestrian riding. We have a horse, so if you don't find me in the hospital, you'll probably find me down at the barn with a bunch of carrots. um, so yeah, so it's a great place. Fantastic move. It was a great fit for our family. And I jokingly say there's parking at Costco because in Los Angeles, you can't park at Costco. There's no parking anywhere, and at Trader Joe's. So that it's been a great move overall. So thank you for asking.

Florence:

So when you spoke to Nicola in 2022, that's one of the few episodes that I wasn't part of sadly. But it's very nice to meet you finally. On that episode 28, I really send our listeners to re listen again to that episode, but could you give us again a bit of a synopsis of what we had talked about the first time we met with you in 2022?

Dr Shufelt:

In 2022, we were finishing a study in Los Angeles where we were actually recruiting women who had HA, and we were comparing them to healthy, what we call normal controls, which is just means that they have their menstrual cycle every month, because we wanted to compare women that had very low estrogen, no menstrual cycles to women that were having regular menstrual cycles and look at their bone, their heart and their immune health. And the immune health really means their inflammation, how much inflammation is in your body, because inflammation plays a role for our immune system. To answer the question, is it just about estrogen, right? Because estrogen in one group of women, same age compared to another group of women, same age. You're comparing age comparisons. We brought in a third group of women. We brought in women that had naturally lost estrogen. And those are recently menopausal women. So average age of 52. So we brought a group of 30 women with HA, 30 women with regular menstrual cycles, and 30 women who were recently in menopause. No one could be on hormone therapy. So we wanted to make everything on the same playing field. We got three groups of women. And what we did was we measured vascular health, bone health and immune health in all three groups. And so what we found very early on is that there was a stronger signal for vascular health in the women with HA. And we'll go a little bit into exactly what that means. Bone health was also impacted. We know bones are thin in women with HA, but interestingly enough, the bone health in women, which we're about to present at the upcoming endocrine society meeting was exactly the same in the lumbar spine as compared to a 52 year old woman

Florence:

Wow

Dr Shufelt:

that the bone health is just as important vascular health is. And then we also saw more inflammation. And my hypothesis was that women with HA, because they don't have estrogen, and we know estrogen promotes nitric oxide. It opens blood vessels and because they don't have estrogen by design, because of the way that HA Shuts down that ovary. My hypothesis is that they would have more challenges with their blood vessels compared to age match controls. What I didn't show was I thought that they would be very similar to menopausal women who don't have estrogen naturally and in actuality they were worse. So, walking around with no estrogen in your twenties or in your thirties is not good. As opposed to walking around with no estrogen in your fifties, which is a natural normal transition into menopause doesn't set you up for vascular problems in the future. So that's really an overview of what we found, and it was an exciting study. It got us to our next funding by the NIH to look at how this could be a marker and who's getting these vascular health problems.

Nicola:

That's really interesting to know. So, you were the lead author of a study that was recently published in 2023. We'll put the link in the show notes. Looking more at these sort of preclinical cardiovascular disease signals in women with HA. So you measured something called Relative Hyperemic Index, which is also known as RHI, as a measure of endothelial function. can you explain what that means in layman's terms, please?

Dr Shufelt:

So it's RHI is actually reactive hyperemic index and reactive. Yeah. And it's an index of how well your blood vessels dilate and constrict. So how bouncy are your blood vessels? Now what controls the blood vessel itself? And we're talking about blood vessels throughout your whole body in your brain and your heart. And we are able to do non invasive. So we don't have to stick to tubes and needles in you, we're able to measure this using a blood pressure cuff and two devices that sit on your fingertips. They actually feel like little pillow cushions. We actually inflate them so they're actually constricting the little areas of your tips of your fingers. So what controls how well we open and close our blood vessels? Like let's say your heart rates goes up, you need more blood flow, you vasodilate. What controls that is the one cell lining of all of your blood vessels, the inner cell is called the endothelium. It's only one cell thick. And that is what controls your body that tells you, okay, now we need to open and can open up this blood vessel, get more blood, or we need to constrict it down. This happens during exercise. We know that estrogen can act on that one cellular lining, signal it to vasodilate or open up. And so that really became the working hypothesis or understanding of what happens to women that have low estrogen levels. So, that's one of the testings that we did.

Florence:

So, in the study, you found that 35 percent of the women with HA had endothelial function that was at a level that is associated with future cardiovascular disease. How long might you suggest it would take before further impacts would be noticed and what might happen?

Dr Shufelt:

Yeah. So to our surprise, we found a signal for endothelial dysfunction and endothelial function would be a healthy, normal artery that opens and closes and opens and closes. I liken this to a rubber band. Like you find a really nice rubber band in the drawer. You open it. And you know, you can wrap this rubber band around a bunch of mail. Endothelial dysfunction is your, your blood vessels are opening and closing, but they're not doing that good of a job at it. So it's almost like finding a little bit of an older rubber band. You start to stretch it out and you're like, well, I could use it, but it might not be good. And then if you wait another year, you find that same rubber band in that drawer. It might be a little crusty. So your question really comes down to when would we see? We know endothelial dysfunction is the first in the cascade that can lead to heart disease. And it's not good to have endothelial dysfunction in your 20s because we know 10 to 15, even 20 years later, you can develop heart disease. So that's putting young women and midlife women at risk. But the good news is here is that we can identify it, and this is a stage, endothelial dysfunction, while it is the first domino in the cascade, it's reversible. So that's the good news. So I, I think my take home here is that yes, we found a signal that that rubber band isn't as stretchy, but it's time to think about how we can reverse it because it doesn't mean that you're destined to get heart disease. It doesn't mean that you're just like, it doesn't mean you're destined to get a fracture. If your bones are thin, it's just awareness. And understanding that this condition is probably not just impacting one system, right? We know it's not just impacting low ovaries. It's not impacting just the bone. Now we're looking at the heart. And we know it can impact mood. It can impact fertility. So it's probably more of a complex condition. That is impacting a lot beyond the bone. So I think while we identified one third of women with this condition had it endothelial dysfunction, the goal now is to really understand who with HA has that endothelial dysfunction. Is it your stressors? Is it your overexercisers? Is it your under eaters or restricted eaters or disordered eaters? Is it your weight loss? Or is it a combination of a little bit of each, sprinkling of each? And I think that's what makes this condition so complicated, understudied, underrecognized, is because doctors just don't ask questions about all those conditions. But our research now is diving deep into who's getting this condition. Because if we can say, okay, it's probably the overexercisers, then we can like start making guidelines to say, if you have a person that exercise excessively, you know, we want to look at their heart. Is it the people who have thinner bones? Okay, woman goes in for a bone scan at 20 because they had a fracture. Their bones are thin. Okay, well, now we need to also look at their heart. So, It's a signal, but it also, I think it's an important signal to tell us who's, who could possibly be getting this and setting themselves up for future risk.

Nicola:

So one thing I was wondering is whether there's a correlation between the length that somebody's been missing their period and, their endothelial dysfunction. So is that something that you looked at in this, in this study at all? Or do you think if you didn't look at it, does your experience suggest that there might be a correlation between length of amenorrhea and dysfunction?

Dr Shufelt:

We recruited, so we looked at it and we could not find a correlation. And I'm not sure that that's the answer because we only had 30 subjects with HA. And also self recollection of when you had your last period We asked how many periods have you had in the last 12 months? How many periods have you had in the last five years and when was your last period and so? We asked it, we looked at it, and we could not find a correlation, but I don't think we were, quote, powered to look at that. I don't think we had enough women in the study to really understand if there's a correlation. My suspicion is there likely is, because the longer you sit with HA, the longer you're going to have low estrogen, as well as other endocrine disruptions, and then we know that that's associated with thinner bones. So that probably is associated with more likely endothelial dysfunction So it's a great question and we hope to answer it in our upcoming study and that we'll be talking about Coming up here. But at the end of the day, I do think that there is probably a correlation. As you've noted in your book, I mean women can recover and not get their period back. So, you know, even though they don't get their period, are there some women that might have subtle recovery and then they still don't get their period? We need to look at this further.

Nicola:

I think it would also be interesting to know if having been on birth control pills for some amount of time is protective for endothelial function. So I think it'd be really interesting to know if it does improve vascular function, if it makes a difference or not. So,

Dr Shufelt:

Really good. We asked about history of birth control pill use too, but recollection of how many years and how many months you took it was, is challenging. Always that recall bias, right? People that, You know, wrote it down in their books. They can write, they can tell you, right? Exactly. Some people say, Oh yeah, I took it maybe for a month or three and I couldn't tolerate it, but you don't have the exact science. So it's a great question.

Florence:

Yeah, I remember you mentioned that on episode 28 as well, this recall bias, and actually, I mean, as a coach accompanying these women, you have that a lot. There's very few women that know exactly when they went on birth control, when they had their periods. Even the first one, I find that it's kind of blurry. So it's quite interesting. What you found also with that study was the association with high cortisol and the lack of stretchiness of the blood vessels. And you said, The problem was worse in women with H. A. than those that have gone through menopause naturally. But also, can you tell us more about the impact of high cortisol, so the high stress hormones, on the endothelial function that you talked about?

Dr Shufelt:

Yes. And I think this is of utmost importance because it's not just about estrogen, right? So HA is a condition that is complex. It can feed back to the brain. And then one pathway it shuts down is our hypothalamic pituitary ovarian access. The other pathway it upregulates is the adrenal access. And the adrenal gland is who makes our cortisol. And cortisol is our stress hormone. And cortisol is actually in small doses. In small bouts. Important, right? It fights off inflammation. It's what can fight off infection. Doctors might prescribe cortisol pills during bouts of really bad or severe infections because it can suppress inflammation. But when you have long bouts of cortisol and when cortisol has been elevated for a prolonged period of time, it works reciprocally. So it actually does more damage than good. And so this is where, while estrogen promotes that lining, that one cell lining of the rubber band that can open and stretch and promotes nitric oxide, cortisol is working in the opposite direction. So it's almost like a two hit theory now is that it's not just about estrogen. And we prove that with, if you look at just the women with no menstrual cycles from HA compared to them to no menstrual cycles from menopause, still menopause didn't have endothelial dysfunction. We saw it in HA. So it's probably beyond just one hormone. estrogen It's more about a two or even three hit theory. Maybe it's insulin, maybe it's cortisol, maybe it's this clustering together. But we do know the underlying pathophysiology or the pathway that women get this in the brain activates both pathways. And it doesn't matter if you get it just from stress, if you get it from exercise, if you get it from disordered eating or losing weight. It's a common theme that everyone has elevated cortisol. So high cortisol in the setting of low estrogen, probably a really bad combination, low estrogen in the setting of menopause, not a bad combination cause that's natural normal. But again, I think that there's more to be dived into here and understand how these pathways interact and, and again, it's complicated and it's not just about estrogen.

Nicola:

So, when we first, when we first chatted before we started recording, you were telling us a little bit about the results of the study that you recently published, where you were replacing estrogen in women with HA, and you found some very surprising results from that. So, could you tell us a little bit about that and how this plays into the context of the cortisol?

Dr Shufelt:

Absolutely. And this was totally not what I hypothesized. I thought women don't have estrogen. Give them back estrogen in the form of bioidentical, which is estradiol, and which is what we use in hormone replacement therapy. It's not what we use in birth control pills because it's not strong enough to suppress an egg from being made, but it's the form of hormones that we use in hormone replacement therapy is called bioidentical estrogen. It's similar to what your ovary makes every month. And what we did was we took all those 30 women that had HA and at this point in the study, we randomized them to get a patch of estrogen. Or a placebo patch, and they wore it for 12 weeks continuously without progesterone. These are not advised by medical providers. We don't want to give continuous estrogen alone. But in these women, the lining of the uterus was so thin, we could just give pure estrogen. And we, scientifically, we wanted to answer, what does just giving back estrogen do? So we gave it continuously for 12 weeks. Everybody wrote down how many patches they changed. It was a scientific randomized trial we measured vascular health at the beginning. And remember, these are women that had endothelial dysfunction. A third of them did. And we measured it at week six, and then we measured it at week 12. And here's the drum roll. The results demonstrated that estrogen replacement, and we gave it to physiological levels, meaning we pulled these women's levels that got the real estrogen up to 100, was about the average of what a regular menstrual cycle. The peak was 165, the lowest we got was 85. So we were pulling these women's estrogen level up to what would be an average monthly cycle level if you took every day and we demonstrated that the estrogen replacement in bioidentical form did not improve vascular function after 12 weeks. So really, again, this is actually echoing the fact that this is a complex disruption of the hypothalamic pituitary axis, right? Cardiovascular consequences, maybe beyond just the loss of estrogen. So wit as a surprise. This is why we do research. This is why we do science. Some of the questions we got, cause I presented that as an oral presentation in front of doctors at the American Society of Reproductive Medicine last year. And some of the questions we got was, did you think we used enough estrogen? Right. Maybe 100, getting it to a level of 100, which by the way, the placebo level, the women that were on placebo, their levels were 13 and some down to 16. So we, we really bumped these women up. But do we think we give enough estrogen? We don't know. But we did give a form of estrogen that is similar to what the ovary is making. So it's not like a birth control pill, which is what you brought up before, is that that's a synthetic estrogen. So if a bioidentical estrogen didn't change their vascular health, I would then hypothesize that probably a birth control pill wouldn't change vascular health, but birth control pills, higher doses, much higher doses of estrogen. Now, the other thing we looked at was cortisol. And we said, well, maybe if we give that estrogen, it might change cortisol levels because these women with this condition. They have high cortisol levels and after 12 weeks of estrogen versus placebo, there was no difference in cortisol. So cortisol levels didn't change either. So the hopes was that estrogen would be anti inflammatory to the cortisol, and that would possibly come down as well. But it didn't. So the underlying condition is really the driver of this condition.

Nicola:

Okay. So just as a take home from that: hormone replacement therapy is not as good as getting your natural menstrual cycles back.

Dr Shufelt:

Absolutely. That is a great take home. The endocrine society's guidelines, 2015 guidelines state that though, that if you haven't had your period for six or nine months, that a trial of transdermal estrogen is for bone health. Now, again, we weren't looking at bone health, so we need to take into consideration that there's more than one system down. We were looking at heart health. So there probably is an impact for bone health, which is good if women don't have their periods but for heart health. We want them to regain their menstrual cycle.

Nicola:

The thing I find myself wondering is if you were to do estrogen plus progesterone, would that then have a different impact

Dr Shufelt:

so, so drum roll. Remember, I presented the results from the 3 months continuous use for safety reasons. The last 2 weeks of the study. So, between week 12 and week 14, we gave estrogen and progesterone. Because if you just give estrogen, that lining of the uterus can get very thick. And even though these women have walked around and some of them hadn't had their period in over, you know, two, three years, we had to have that as a safety built in. So if you got placebo patch, you got placebo progesterone. If you got the real patch, we gave you real progesterone. So we were able to look at that and we didn't see an uptick in the vascular health

Nicola:

Okay.

Dr Shufelt:

Which to me, That's not surprising because progesterone, it doesn't really activate that rubber band. It's the estrogen that promotes nitric oxide. Now, progesterone is anti inflammatory, very highly anti inflammatory. So that might play a role, but it didn't, but it was only two weeks. It wasn't the 12 weeks, but we did look at that.

Nicola:

Great. Great. So Another thing that we find, and we discussed this in the last podcast, again, episode 28, folks should go back and listen to it. A number of people that we've been in contact with either clients or support groups, are found to have mildly high total cholesterol. In the study that you published back in 2023, those with HA had slightly higher levels by an average of 12 milligrams per deciliter. But it wasn't statistically significant. Um, Does cholesterol have an impact on the endothelial function? So might there be a correlation between that higher cholesterol and less elasticity?

Dr Shufelt:

Absolutely. So there is, and that's been shown in older women in larger studies, and we know estrogen plays a role on LDL. I said it before, l is for lousy, H is for healthy, and so we do certainly know that estrogen can promote lowering LDL and raising HDL, good cholesterol. So without estrogen withdrawal, you would see, and we've seen this in menopausal women. After menopause, we see a shift of LDL go up and HDL go down, and that's a natural. transition of losing estrogen, right? So the abrupt loss of estrogen and HA, it would only make sense that you, we would see a shift for LDL and HDL because of the low estrogen. Cortisol also can play a role with cholesterol as well. It can make things shift in the wrong direction. So again, that two hit theory, but we didn't see it in our study. And I'm going to go back to what I said before. And this is a term in science that we use over and over. We weren't powered to see it. It wasn't one of our primary outcomes. And I imagine with a larger cohort or with a larger set of women, we would just certainly see, we saw a trend. As you mentioned, we saw a trend in the wrong direction. Now, what we're looking at, and it does play a role in endothelial dysfunction. Cholesterol can cause endothelial dysfunction. Cholesterol can, is a known risk factor for heart disease when you have high cholesterol or high LDL cholesterol. We call a traditional risk factor. It means it's a risk factor for both men and women, high cholesterol is

Nicola:

hmm. Mm hmm.

Dr Shufelt:

Now I've been speaking with some very well known cardiologists that are lipid specialists. And our next idea is to look at the fractions of the HDL and the LDL because there are different sizes of these molecules that might play a bigger role in here. And while you see a tip up, we didn't see a significant, but you see an elevation in LDL. So it might be that the type of LDL that we're seeing changes. And the function of the molecule might change as well. So stay tuned. That's something that we're really diving into now is not just looking at LDL and HDL, those are just components, but actually the function and the size of each one.

Florence:

Wow.

Nicola:

interesting.

Florence:

If I recall correctly, last time we spoke, you also mentioned that within three months of losing your period, you would actually have an effect on vascular health. Am I correct there?

Dr Shufelt:

Well, we don't have the science to say exactly it's if it's 3 months. That was the criteria to get into the studies. They had to have at least 3 months of no period. It's not that three months of no period, and now your vascular health is low. Because if you look at the average age of our study, and the average age was 26 of the women that had HA, and the average number of months of menstrual cycles was 12. But there were women that had as low as five months of menstrual cycles all the way up to 34. There were a few that had beyond that. So it's a range and that goes back to the question. The longer you have it, does that impact it? And that's probably true.

Florence:

So I guess my question is do you know a bit about the timeline of the hormonal changes that happen in terms of when you lose your period, but also when you recover? I think a lot of the struggle with recovery is the unknown and really dealing with the feeling of having no control. So do you have even just a hint as to how long it would take to normalize your vascular health coming out of HA?

Dr Shufelt:

So since this is such an early signal that we're finding, and the goal is now to try to determine who of the HA women that are getting this condition, the next is going to be to determine what happens after we recover and bring these women back a year after they've recovered. And measure their vascular health again, and so that's the build into the next grant and the next opportunity for research, because, of course, we want women to have their menstrual cycles back. Every time I get a phone call from a woman who said their menstrual cycle back. I'm like, yes, this is fantastic. And the new study that we're doing is actually a three month study. We'll talk a little bit more about that, but there's been a few women that have recovered during that three months. So they're still enrolled. So we're actually still measuring their vascular health. It's too early to say if that early recovery is a signal, but we'll have that, we'll have that data to look at. But my thought is. What's going to happen a year after recovery or two years after recovery or five years after recovery when you want to get pregnant, you know, are your blood vessels back to that really nice, stretchy rubber band? And my theory is likely they are. Having your own estrogens is good for you. It's protective,

Florence:

You had mentioned on the other episode as well that, you know, the beauty of this is that it is absolutely reversible. So I'll just mention it again for the people listening to us. It's sometimes really stressful to hear that it has a direct impact, but it is also reversible.

Dr Shufelt:

So, reversible.

Nicola:

You mentioned pregnancy. When one is pregnant, that is a time when estrogen estrogen is quite high. Um, so I would suspect that, if somebody gets pregnant not too long after recovery. I would hope the added blood volume from being pregnant and the added estrogen would be helpful in that scenario.

Dr Shufelt:

Absolutely. We would hope. And what we want to make sure is that women have recovered before they get pregnant, as opposed to women that still actively have HA, and then go into a fertility doctor and get shots that can make them pregnant, because while having active HA, you are infertile right? It's a form of infertility. It is a reversible form. I think the theme here is reversible, right? Like, let's reverse the condition and then we'll reverse all of these, these things that we're finding. But I think there's two different types of things to consider here. Active HA getting pregnant through fertility means versus a woman who's recovered and gotten pregnant. I think those are probably naturally healthier pregnancies. After the recovery, but going through active HA and getting pregnant, you know, our cortisol levels are still high, you know, we can give these these medications, but we need to know what happens to those pregnancies and that's where we're actually looking at a database called the nurse's health study 2 not nurse's health study 1, not to be confused. This is a group of nurses that have been followed now for over 30 years. That was the first cohort. Now they're looking at women that they're following them now. They followed them for about 20 years and nurses health too. And they're going back and they're asking questions, questions about menstrual cycle regularity between the ages of 18 to 22. Did you have your period? And we're looking at this in terms of their pregnancy outcomes. So if they had irregular periods, is that associated? Now, everyone throws their hands up and says, well, that's just PCOS. Well, to really try to differentiate the question, is this PCOS, we also have the BMIs or the body mass index or the weights of these women during that time. So we can cut down and do more of the thinner BMIs, 22 and under, 21 and under, because then that really takes out, is this possibly PCOS and we'll see if there's a signal for pregnancy.

Nicola:

Interesting. Interesting. Yeah. Yeah. Um, um, Yeah. I'm gonna have to think some more about that. There's lot to about to think about in that question

Dr Shufelt:

It's a lot to unfold. It's just another area of interest and research to go into. Yeah.

Nicola:

So speaking of research, can you tell us a little bit more about some of your latest results that you've spoken about at conferences, but that haven't necessarily come out in written form yet?

Dr Shufelt:

Well, the other big finding that we were able to present at again, in last year at that reproductive science medicine meeting ASRM is the inflammation markers. And we compared the inflammation or what we call cytokines. These are, your body has the ability to promote inflammation when we have infection, when we need to get rid of a virus. And we know inflammation plays a key role in endothelial dysfunction. So if these women a third of them have endothelial dysfunction, we wanted to look at their inflammation. So we know that when you have your own estrogen, that's anti inflammatory, so it can push down bad inflammation. And so what we found in women with HA compared to women who were having their menstrual cycles, same age, same BMI. We found that women with HA had higher pro inflammatory cytokines. What does that mean? That means that these are Inflammation markers that have been found to lead to endothelial dysfunction. So now we're trying to determine, is it the chicken or the egg? And what I mean by that is, do these women with HA have high cortisol, they get high inflammation, and then that leads to endothelial dysfunction? Or is the endothelial dysfunction promoting Inflammation or is there crosstalk back and forth? So that's something that we presented at that meeting. And remember, we gave back estrogen patches or placebo patches didn't make a difference in the vascular stretchiness of the vessel, but we'll actually have the ability now to go back and look at the inflammation markers. It might be that the estrogen started to push down the inflammation markers early. Before we see a signal for vascular health. So it might not be that we didn't give enough estrogen. It might not be that we didn't look at it long enough long term because 12 weeks might not be long enough. So, so stay tuned. That was another big finding of our research and then our current research study that is underway right now that we have a travel stipend. So any woman across the country can come. It's a two visit travel, site visit onto our Mayo Clinic, Florida campus, which is beautiful. Very picturesque park, Jacksonville, Florida, and you come here for one day. It's only about a three to four hour visit, and we do exactly what we did before, which is we measure the vascular health. You get a bone DEXA scan, and then we fit you with a Fitbit watch. Because we want to track exercise, sleep and heart rate because heart rate's a big predictor of stress. So we're measuring inflammation at the very beginning and at the very end, you wear the Fitbit for three months. You answer a couple of questionnaires from your home on your computer in the interim at month one and two, month two and three, right in the middle. And then you come back at the very end and we measure vascular health again. See, because the idea is to say, okay, we need to phenotype or physically determine which are the women that are getting the endothelial dysfunction. So that's where I'm saying, is it the athletes? Is it the under eaters? Is it the stressors? Is it a combination of all? And so we're going to be able to really answer that question in a group of 100 women. And we're about a third of the way there. We've recruited about 35 women so far, but if you're interested, that's where you can put up the QR code in the show notes to the study, so you come to the Mayo Clinic campus for 2 visits with a travel stipend, stay the night before at our onsite hotel, right on our Mayo Clinic campus, have the testing done and fly home and wear the Fitbit. So, again, I can't underscore the need for more research in this field. If you go back to 2015, right? That was when the endocrine society put out guidelines on FHA. Commendable guidelines, but their call for research was huge in those. Their conclusion was we need more research. So, since 2015. So to now, so almost a decade, if you look at original research, that's been done, these are scientific research, like the clinical trial that I mentioned with the estrogen patch, not review articles, there have been less than 200.

Nicola:

Mm hmm.

Dr Shufelt:

less than 200! So it's not a surprise that doctors don't know what to do with this condition, because it's not being studied. And if you look at that same time period, and I don't want to compare because it's all women's health, and I promote women's health. I'm a women's health provider, but if you look at that same time period for PCOS, there's over 8,000

Nicola:

Wow. Wow. Mm-Hmm

Dr Shufelt:

So there's a deficit of research in this area, and that's why I call out the NIH for really promoting and supporting this research. And that's why we need women to enroll, because we're not going to be able to get more research studies done if we don't have the women to enroll. So, that's obviously my passion, because I want to get the right answers out there.

Florence:

That's actually a good segue into the question you mentioned about the continuing medical education credits, right?

Nicola:

Sure, yeah. You recently published an article about HA in the Mayo Clinic Proceedings, that physicians can read and take a quiz for continuing Medical Education Credits. So do you have a sense of the number of people who are taking advantage of that and we'd love to hear about work on educating medical professionals about HA.

Dr Shufelt:

Oh, boy. I wish I had the answer to that. And I'm going to go back now to the journal and ask that question because I want to make sure that the individuals and doctors and providers are getting the education on H. A. And scientific journals are one avenue that we can educate, but I think we need to really build this into more of the curriculum in medical education, whether it's in nursing education, in advanced practice medication or medical schools, we really need to be calling out the importance of this condition because I can tell you, I don't remember learning about it. And I did medical school, you know, 15 years ago, but I don't remember learning actually two decades ago now. I don't remember learning about it. And we had six weeks to learn endocrinology. And this falls under endocrinology, and so, you know, think about how vast endocrinology is. And then they probably mentioned it in 2 or 3 line sentences in my notes. So it doesn't stand out to me.

Nicola:

menstrual cycle.

Dr Shufelt:

Of course. Yeah. Yeah. And so that actually, you know, that actually really does speak to the fact that we need more education. Because doctors won't ask questions if they aren't aware of the condition.

Florence:

This is really the feedback that we hear a lot, obviously. And you also mentioned that you're starting a new registry for those with HA. So can you tell us about this and how listeners can participate? Are there particular criteria that need to be met for someone to register?

Dr Shufelt:

Absolutely. This is where we're going to take HA research to the next level, because we're going to be able to answer a lot of the questions that we're bringing up right now. So the overall purpose is to create an international registry.

Florence:

Amazing.

Dr Shufelt:

We're calling it the'REVEAL' registry. Which is the REgistry of Very Early estrogen loss and AnovuLation. So it's an acronym, because we want to reveal what's happening to women with HA. So we're building a registry to have women enrolled that have a diagnosis or may not or don't have a period with HA and we need to understand how common this condition is, how common it is. We need to know racial and ethnic diversities. We need to know country diversity. We need to know underlying causes, risk factors. We need to know what's happening. How long, we need to know what's happening for recovery. What are women doing that's working? And we really want to know the overall experience of HA, including symptoms, care they've received, how they're gathering their information. We really want to know how this is impacting their work, how this is impacting their school, and their social structure. And then we're also going to determine what we call social determinants of health. So, childhood adversity, you know, what's happening with pregnancies. So, I think this is going to be an opportunity to really answer all of these questions. Now, how does a woman get in the registry? She would self identify as having HA or being told. We would then ask them to sign the consent all electronically, everything will be done from the comfort of their own home, as long as they have a computer. Right now, we are starting out in English for the questionnaires. We will be translating it pretty soon into Spanish and then into other languages, because in order to make a worldwide impact, we have to have it, as you well know, because of all your translation from your book, we need to make it available to many, many, many women. And at the same time, these women, if they don't know, if they haven't seen a doctor, but haven't had a period in five months. And they fit that questionnaire that we would suspect that they have HA. We're actually working with a company that has a blood spot technology to measure hormones. So we will mail them a kit. They just do blood spot. And then they would mail it back to the company and through a special prioritized serum separator. It's a very fancy paper. We can get their hormone levels and determine if that's the diagnosis. And then they would be enrolled. So, the questionnaires are going to be, they would get 1 questionnaire, about 10, 15 minutes to fill out, also includes a 3 day food diary, collecting all your food and nutritional information for the very beginning and then at three months, and then after that, it would just be annually. You get one questionnaire once a year. And so that would be a way that we can now prospectively longitudinally scientific words. I know) but collect going forward information about women's experiences because again, Florence, you mentioned it: recall bias. I brought that up before. What women remember in the past is challenging, but now we have an opportunity to collect it going forward. So I think this is an opportunity that will really change the footprint of research and will really change the understanding of this condition and how we then can train doctors to know about it more.

Nicola:

This is phenomenal. I am so excited. So I'll make a URL for listeners to go to so it will be noperiod.info/reveal. And I also have one that's noperiod.info/heart2. That's the number two for anybody that wants to sign up for the study that's ongoing in Florida, with the travel stipend and the three month study. But, please, anybody that's listening and has HA, go to noperiod.info/reveal and sign up for this registry. I think this is amazing. I'm so excited. Thank you so for sharing this with us.

Dr Shufelt:

absolutely. Thank you to both of you for promoting and the understanding and the awareness because it's through these types of forums that more women get their education about this condition and what to do and how to gather. So, I'm the scientist, I'm the clinical doctor that's just making the research, but what you're doing is so impactful because women are getting the correct information. You know, I always joke that Dr. Google doesn't have a medical degree, and it's true.

Florence:

Definitely,

Dr Shufelt:

Don't start Googling about this condition unless you're going to real valid websites and forums like this. So I thank you for doing that as well.

Florence:

It's an honor to have you on and to bring the latest results to our listeners. I mean, we're definitely very grateful for that. You remember Dr. Shufelt, we asked you, how are you all in right now in your life?

Dr Shufelt:

Oh, gosh, as you can tell, I'm all in for my research and I'm all in for women's health in my career, which is pretty passionate, but I'm also all in for my family and I think it's that work life balance that makes your life so happy and I could go home and be with my family and travel with my family. We got to go to South Africa last year on safari, which was fantastic and an opportunity to get back into kind of the post COVID real world modes, you know. Parking at Costco, going to the barn to see the horses and also enjoying just an early Sunday morning football game with my kids. So all in to me is really being happy and fulfilled on both ends.

Nicola:

Absolutely. Absolutely. Thank you so much for joining us today. This has been a wonderful conversation. I'm so excited about your research. Bouncing up and down on my chair here.

Dr Shufelt:

Yes.

Florence:

We may have to have you back on again.

Dr Shufelt:

Once we start getting preliminary information from that registry, we'll definitely have a lot more to talk about.

Nicola:

That's fantastic

Dr Shufelt:

Yes.

Florence:

Great. Where would be a good place to send people if they want to get in touch?

Dr Shufelt:

So I'm on social media, I'm on Twitter, and I know that a lot doctors are on Twitter because we like to go to conferences and post slides and make comments. But I do post a lot of our research on Twitter. So that's@cshufeltMD so M is in medical doctor. So M. D. That's where I post the most information about the research that's ongoing or conferences that I'm attending or speaking at. Otherwise, it would be through our study flyer. We have a study flyer with a QR code that can take you directly to the landing page where you'd fill out a quick form if you're interested in the research. And of course, I'm on the Mayo Clinic website. You can just look up Mayo Clinic and my name. So those are my social media platforms.

Nicola:

Fabulous. Instead of a QR, if you want to just type it in, it's noperiod.info/heart2.

Florence:

Wonderful. We'll put all of those in the show notes and we're so grateful to have had you on again, to hear about all these discoveries and unveil more about what's going on with our heart when we actually suffer from HA. So thank you again so, so much for being on our podcast once again.

Dr Shufelt:

Thank you for having me. It's a

Florence:

All right. Bye. Dr. Schufelt.

One thing that always strikes me is how different each person's all in journey is. As I often say, there are many paths to HA and many paths out of it. Your journey is unique. That is so true. If you need more support on your journey, you should definitely start with NoPeriodNowWhat, which you can get at noperiod. info. com. And Florence and I both work with people on different aspects of period recovery and so much more. If you'd like more personalized advice and attention, you can go to noperiod. info slash appointments to schedule a time to speak with me on fixing issues underlying missing periods, blood work, diagnosis, and lots more. or beyondbodyimage. com to work with me on the fear of weight gain and making peace with food exercise in your body. I also take care of the new French version of No Period Now What through the Instagram account je underscore livre. We also have joined clients and online support groups so you can access both our domains of expertise and get the physical and mental help you deserve to put an end to disordered eating once and for all. If you enjoyed this podcast and found it helpful, please subscribe and drop us a review to help more people find it. Also, join our online recovery community at noperiod. info slash support in English and noperiod. info slash communique in French and let us know how All In is going for you. All In is not just about period recovery, it's about getting your life back. See you in two weeks!