Progesterone 101 With Shelby Sheppard. What Every Woman Needs to Know: With Shelby Sheppard

This week we welcome back Shelby Sheppard for a deep dive into progesterone.  A hormone that impacts everything from our mood to our sleep, and is unfortunately not well understood. Thankfully, Shelby simplifies things in this crash course on progesterone. 

In this episode you will learn:

• Progesterone 101: What it does and why it matters.
• The difference between progestins and micronized progesterone (AKA bioidentical progesterone).
• The difference between compounded and pharmaceutical micronized progesterone. 
• How progesterone can help with perimenopause symptoms like anxiety, mood swings, and sleep issues.
• About the effectiveness of oral, vaginal, and transdermal progesterone.
• The risks associated with progesterone and progestins.
• Some practical advice for advocating for your hormone health.

Connect with Shelby:
Instagram: Hormone Optimization by Xone Precision Medicine
Instagram: Preventous
Facebook
Website
LinkedIn

Resources
How to find a menopause certified practitioner.

• The Menopause Society
• British Menopause Society

Studies mentioned in the episode:

• PEPI Trial
• ESTHER Study
• E3N Study

Thank you so much for listening to the show. Here is how you can connect with us at This Is Perimenopause.

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Transcript

Shelby: 0:00

It's not just estrogen that provides a lot of the benefits in terms of treating some of those symptoms that we experience throughout our years either menstruating or in perimenopause or menopause, and how a simple treatment with just natural micronized progesterone can really impact your quality of life. And so if you're out there and you're listening and you're suffering with any of the perimenopausal symptoms and a lot of these more atypical ones like brain fog, anxiety, mood, joint pain, those are things that can be addressed by progesterone alone.

Mikelle: 0:37

Welcome to. This is Perimenopause, the podcast where we delve into the transformative journey of perimenopause and beyond. I'm one of your hosts.

Michelle: 0:44

Michele, and I'm your other host, Michelle and we know firsthand how confusing, overwhelming and downright lonely this phase of life can be.

Mikelle: 0:53

Join us as we share real-life stories and expert advice to help you navigate this journey and advocate for your best health.

Michelle: 1:00

We used to think menopause signaled an end, but really it's just the beginning.

Mikelle: 1:05

We're delighted to have nurse practitioner Shelby Shepard back on the show today. She's here to talk about progesterone, what it is, why it can be confusing and how it can help with perimenopausal symptoms like mood, sleep, acne and so much more. Shelby's going to explain why she often refers to progesterone as the forgotten hormone. For more about Shelby's impressive credentials, check out the show notes and welcome back Shelby. Hi, shelby, welcome back. Thanks for having me back. Oh, anytime, you're a favorite for sure. So today we wanted to talk to you about progesterone and how it's perhaps misunderstood.

Shelby: 1:46

Yeah, it is one of my favorite topics to talk about. I think this is probably the most forgotten of the hormones and really understated in terms of its importance in for women, and perimenopause is no exception to that.

Michelle: 2:02

Mikkel's done a few deep dives on this, but I'm new to a lot of this, so I'm very excited for the conversation as well. Educate me please, absolutely.

Shelby: 2:15

Maybe we'll start with why our bodies need progesterone and what it does so yeah, basically we go back to sort of biology class with this, where we have the two main hormones in our menstrual cycle estrogen and progesterone and basically progesterone, progesterone, progestation it is sort of really important in pregnancy and it spikes in the later half of our period after ovulation.

Shelby: 2:47

It spikes in the later half of our period after ovulation and in doing so it helps try to create a really healthy environment for that potential egg to implant and then hopefully sustain that pregnancy. And we see a lot of benefits of progesterone that happen in that latter half and when we have lower levels of progesterone. That's what we often see issues with PMS symptoms. So mood anxiety, acne, bloating, breast tenderness, headaches, and then it's really that decline in that progesterone level that kickstarts the period, that really exacerbates a lot of those PMS type symptoms. So the main reason we have progesterone is to help sustain that pregnancy. So the main reason we have progesterone is to help sustain that pregnancy. But really I always say it's kind of the yin to estrogen's yang.

Mikelle: 3:35

And they work synergistically together, but they also sort of oppose each other's flaws, for lack of a better word. Interesting and man, all those symptoms you listed loud and clear and I couldn't believe the difference progesterone made when I started taking it and I can't imagine life without it. So, yeah, thank you for spreading the word. Yeah, it's also very confusing because of the different types of progesterone, so maybe we could get into that. Let's start there.

Shelby: 4:06

Yeah, first of all I want to preface this by saying that the terminology is quite problematic when we're discussing progesterone, and even us as medical providers, we struggle to really grasp the nuances between them all.

Shelby: 4:22

So it will be really challenging for us to expect the average person, when they're sifting through the internet or any research or trying to understand what their options are, to really understand the difference between progesterone and progestins, because often those terms are used interchangeably and not correctly.

Shelby: 4:42

So basically the correct term to encompass all progestins and progesterones is progestogens. Progesterone refers to what your body naturally produces, as well as the bioidentical formulation that we can get pharmaceutically or compound, and then progestin refers to sort of any synthetic type of progestogen. So things in birth control pills, the IUD, nexplanon and some of the older hormone replacement therapies like Provera that was really famous in that WHI study. The problem is is when we lump them all together, it implies that they all have the same effect, but I always tell my patients not all progesterones are created equal, and that's the problem is that all of the negative effects of progestins that got the bad rep through all of those long-term studies and older studies we're now sort of painting natural progesterone with the same brush, when we have a ton of data that shows it's actually the complete opposite.

Mikelle: 5:48

Yeah, so maybe we could talk a little bit about what some of those differences are. Yeah.

Shelby: 5:54

So natural progesterone, or micronized progesterone as it's sort of known pharmaceutically is made exactly or bioidentically. So the molecule is the same as what your body is producing, Whereas progestins there can be a number of different types of progestins and how they react with your body can be quite different. So, for example, there's medroxyprogesterone acetate, which was in the WHI trial, there's levanododestrol, which is in your IUD. So there's a lot of different types of progestins as well and they all act differently. So what we know is that natural progesterone has a lot of health benefits. So it helps decrease your risk for breast cancer and breast cancer reoccurrence. It helps reduce your risk for heart disease. It sort of works in tandem with estrogen and improves those cholesterol parameters, Whereas with synthetic progestins we actually see a worsening of cholesterol levels.

Shelby: 6:55

Blood clot risk is elevated with synthetic progestins, whereas there is no risk of blood clot with micronized progesterone. There was a really great study that actually showed women who were put on. So they started on medoxyprogesterone acetate so Provera, which was in that WHI trial, and they were switched to natural micronized progesterone and they showed improvements in mood, depression, anxiety and sleep just from that simple transition. So it just goes to show that it's not a class effect between all of them. Another great way I think about it, too, is that natural progesterone does not have a benefit in terms of contraception. So that just goes to show that they don't have the same benefits, because synthetic progestin, like what we see in birth control, is going to work very differently than that of natural progesterone, and that's what provides you that birth control effect that you will not see if you take natural progesterone.

Mikelle: 7:58

So, in addition to being better for preventing pregnancy, is there any other reason or use for a synthetic progestin versus progesterone?

Shelby: 8:10

Yeah, I actually am a big fan of the IUD. I think well for one, it does help very well in terms of preventing pregnancy. It's sort of a leave it and forget it method, but it's a synthetic progestin that works a lot more localized to that uterus so you don't get as much of that systemic effect or the side effects that you get with some of the oral progestins and it can really help women transition through that perimenopause, especially if one of their primary concerns is very heavy periods or regular periods that are really dysfunctional and affecting their quality of life. So that's one area where I really like a synthetic progestin is in the IUD.

Mikelle: 8:52

Yeah, and heavy bleeding too, as I understand, can be better managed with a synthetic. Yeah, yes, amazing. Maybe just a couple more things about the different types. So you mentioned compounded versus pharmaceutical. Maybe you could just give us a quick explanation, okay.

Shelby: 9:10

Yes. So I think this is where the bioidentical like school of thought gets a bit of a bad rep. We have pharmaceutical grade bioidentical formulations, the same way you have, you know, advil, tylenol, the brand names. There's Prometrium, which is bioidentical, natural micronized progesterone, and it's created in a big pharmaceutical warehouse where there's large quality control procedures and safety. And that's one consideration that people need to have is when you are looking at compounding. We can compound any medication. I think we think about compounding, we think about hormones, but during the pandemic we compounded children's Tylenol because we didn't have enough of it. But the safety standards are subject to that pharmacy that you're working with. So essentially, you want to make sure, if you are getting a compounded formulation, that the provider you're working with understands what compounding pharmacy they're working with, what their safety and regulations are, so that you can ensure you're actually getting the product that you're working with understands what compounding pharmacy they're working with, what their safety and regulations are, so that you can ensure you're actually getting the product that you're intending to get essentially.

Shelby: 10:22

But you can use compounding for a lot of different reasons. For one, many people don't know this, but the commercially available progesterone has peanut oil. So anyone who is allergic to peanuts, they can't actually take the commercially available oral capsules, and that's where compounding might be a better option. Alternatively, if you know, dosing is an issue, especially with trying to titrate to an appropriate dose. Some people really need to start a lot lower than what's commercially available to try to get up to a level that's deemed therapeutic or safe. And then other reasons is just if you want a different formulation, because again, we have oral capsules, but maybe you want to treat someone with a sublingual tablet, because one of the reasons I utilize that is because it doesn't make people sleepy the same way that the oral does, which can be helpful in things like postpartum depression, for example.

Michelle: 11:20

Shelby, can I ask you a quick question? Absolutely. When I started my journey about six years ago, I started on a transdermal progesterone from a compound pharmacy. I now am on HRT, so I've got the estrogel, and I'm on prometrium, so an oral. What's the difference and why was there a change in my prescription?

Shelby: 11:40

Yeah, this is a great question and unfortunately, again, I think this is another area where that idea of bioidentical and compound is sort of get a bad rep, and that's in the transdermal creams. So there are no studies to date that show that transdermal progesterone provides endometrial protection. So meaning protecting that uterine lining from endometrial cancer. And if you have a uterus you need to ensure and you're taking estrogen, you need to ensure that you have adequate progesterone to ensure that you reduce that risk of developing endometrial cancer, progesterone to ensure that you reduce that risk of developing endometrial cancer. The skin really hard to get through for progesterone and it really just doesn't provide good levels in the uterus to help sustain that level of protection that you need. And so there's no study that supports the use of a transdermal or cream progesterone formulation.

Michelle: 12:36

For that reason, Since I've switched over to the HRT, I've heard that, oh, maybe transdermal doesn't actually do that much. Was I just getting some placebo effect? It felt better, I was sleeping better, my moods were better.

Shelby: 12:49

No, I don't think that it's necessary placebo, because you will get some absorption from it through the skin. You just won't get enough to provide that level of protection that's needed in order to ensure you reduce that risk of endometrial cancer, because endometrial cancer is completely preventable in the sense of when you're treating someone with estrogen, if you are giving them enough progesterone, you won't see that growth in that endometrial lining. So, yes, you will feel better because you're going to get some absorption through your body. You're just not going to reach the levels for safety in that uterus. Gotcha, thank you.

Michelle: 13:25

We've talked a little bit about how progesterone can help with PMS symptoms. Does it also help with perimenopause symptoms?

Shelby: 13:31

Absolutely, absolutely and this is sort of my go-to start for most women that are presenting with sort of a straightforward case of perimenopause.

Shelby: 13:42

First of all, women in perimenopause are often in this generation really dealing with a lot of life transitions, whether it's career, kids, marriages, and so there's a lot of stress. Stress and then losing those hormones doesn't really help the situation. Women are not sleeping as well, more anxiety, mood changes, and progesterone actually has the ability to cross over our blood-brain barrier and affect some of the receptors in the brain, causing a calming effect. We know that there's a ton of studies that support its use for improving sleep for women in perimenopause. As well as mood changes or depression, we often see some changes or irregularities to bleeding and although I would say micronized progesterone is probably not the top heavy hitter in terms of improving heavy menstrual bleeding, it does help a bit more with those periods. And then, in terms of things like some women get more of those PMS type symptoms even in perimenopause, so headaches, breast tenderness and bloating weight gain, all of which progesterone helps to sort of mitigate.

Michelle: 14:57

Sorry, selfishly. I have a girlfriend who suffers from severe, severe cyclical migraines, and so should she be asking for progesterone.

Shelby: 15:05

Yeah, so migraines are so tricky because especially in perimenopause we have women. Some women do well sort of on hormone replacement therapy and some women actually it worsens them. But in terms of cyclical migraines, ones that are influenced more around that period, micronized progesterone absolutely can be a consideration in terms of trialing it and seeing if it does cyclical. Often it's that PMS sort of decline in progesterone where we see the worsening and the headaches sort of occur, and then supplementing that progesterone will help improve those symptoms.

Michelle: 15:44

Transdermal or oral. I know you can't really diagnose, but just curious.

Shelby: 15:50

No, Obviously talk to your doctor, but I would say, anytime I'm using progesterone I never use transdermal creams, it's always oral vaginal suppositories if oral can't be tolerated, although that is off label. And then sometimes I compound sublingual capsules, especially if it's someone that needs to take progesterone throughout the day and oral would make them too tired to really keep up that sort of regimen.

Mikelle: 16:17

So thank you, yeah, so that's. That's a lot of benefits, but progesterone really isn't widely used or known. Why is that?

Shelby: 16:31

Well, I think part of this goes back to the WHI trial, where they used a synthetic progestin medroxyprogesterone acetate is the one they used and we saw that increased risk for breast cancer occurred in individuals who were taking the estrogen plus the progestin. So I think that's one of the big reasons. So again, second being terminology, where we lump them all together and instead of really understanding the nuances of it all and seeing the literature that compares and contrasts those progestins and progesterone, where we see, for example, yes, certain synthetic progestins do increase the risk for breast cancer. However, we see an actual reduction in rates of breast cancer in individuals taking natural micronized progesterone. So, basically, I think part of this goes back to lack of knowledge, lack of understanding of the literature and studies that were very powerful in terms of delivering the impacts of progestins and then, as a result, fear.

Shelby: 17:37

I know a lot of our medical education still doesn't delineate or differentiate between those two compounds and then, because of that, we're still sort of taught that progesterone's only use is for endometrial protection and if you're giving someone progesterone, that's the reason you're giving it to them, and if they don't have a uterus, then why would you give them progesterone? Because you're going to subject them to all of these sort of harmful effects of the progestin. But we've missed the point that progesterone is not progestin.

Mikelle: 18:13

Good clarification, thank you.

Shelby: 18:16

Yeah, I hear it all the time. I still. I have a patient that I had put on progesterone. I was talking to an OB and they had said you know, she doesn't have a uterus, you don't have to put her on progesterone. And I'm like it's not the reason I put her on progesterone. She's sleeping better, her moods are better, her anxiety is better. Those were her primary concerns when she came to see me and she'd had a hysterectomy and was already on estrogen therapy for menopausal symptoms, but she wasn't on progesterone and she just said like I don't feel like myself. You know, I feel personally like I'm going crazy. My husband thinks that there's like something wrong, like I just don't feel good, and we started her on progesterone and a lot of those symptoms improved.

Shelby: 19:10

But it's interesting just having conversations with these very these individuals who I truly I think are amazing physicians and I really respect. But you can see that that adage sort of runs true for them is like they said well, shelby, you know that she doesn't need progesterone, she doesn't have a uterus and it's like okay, so you know, if you're so, how would I expect the average person to understand that concept if I have this very well respected physician I'm talking to, who is so brilliant, so smart, but that's just the training that they've endured and it just isn't an area that they've chosen to sort of expand their knowledge or understanding on. And so then you know, you're told conflicting things. Especially for patients, it's hard. Who would you trust the gynecologist? Or you know, your primary care provider, or a nurse practitioner or someone else who obviously they are the experts? But oftentimes it's just a lack of knowledge or a lack of understanding.

Mikelle: 20:11

Really, yeah, Do you have any advice for someone a listener who might be experiencing some of these symptoms and how they might broach this with their provider?

Shelby: 20:23

That's a great question because it can be. It's interesting. In my practice I find that hormones like of all the practices I've done throughout my career, this seems to be the most of all the practices I've done throughout my career this seems to be the most controversial area, which is kind of interesting. But I think, just trying to go in with your own understanding and I know some providers may not be as open to this as others but if you can find any resources that are evidence-based, any literature or there's a lot of great accounts you can follow online that are like OBGYNs and urologists who really promote women's health and perimenopause, and finding that like true evidence-based literature that you can sort of bring with you and open that discussion with them.

Shelby: 21:09

I know it's not easy either, but if you aren't getting anywhere with your current provider, finding someone who specializes in that area because I usually tell people it is truly a subspecialty we don't learn a lot about that in our basic training and individuals really have to have taken an interest in this area and done extra training in order to really understand the nuances and make sure that you're being treated like holistically with all of the hormones involved. So if you have that luxury that you can find someone in your area that specializes in it. That's probably your best approach, especially if your provider is not really super keen or open to it, because at the end of the day, you know you really have to advocate for yourself and quality of life is so important, and I think that's a part that gets missed through this sort of menopausal and perimenopausal journey and are you so you're referencing like a NAM certified practitioner?

Shelby: 22:05

So anyone who's NAM certified, anyone who has like looking through their credentials, understanding, like, what training that they went to I myself went to a world link medical under a very world renowned physician, dr Neil Rousier, who is amazing and that's where I did a lot of my training. So it's just recognizing, basically doing a meet and greet with this person too, to understand, like, are we aligning? Because we, we can't. You can't get a lot of this sort of alternative medicine piece and there's nothing wrong with that. But it depends on what your goals are and what you're looking for.

Shelby: 22:42

And if you're looking for more traditional medicine, it's meeting with an individual and understanding sort of what's their approach, what do they really know? Are they able to talk about literature or the research or back up, exactly why they're doing what they're doing and really educating you and working with you in the journey. And I think that that's really an important piece is understanding that person's credentialing, because unfortunately, I think that's part of why hormones maybe gets a little bit lost too is there can be a wide range of people who are like adequately trained in the area medically and people are taking a little bit more of that alternative medicine approach. And, again, nothing. I'm not saying anything negative about that. It's just that that might not be the route that you're looking for.

Mikelle: 23:30

Shelby, we've talked about the risks, some of the risks with taking progestins. Are there risks when taking progesterone, micronized oral progesterone?

Shelby: 23:41

So actually micronized progesterone is really well tolerated, I would say the biggest side effects you see is sleepiness, which is often warranted for a lot of people, and breast tenderness. Otherwise, really there's been no significant adverse effects associated with micronized progesterone. We know that there's no increased risk of blood clots in any study that we've seen to date. Again, protective against breast cancer. It also works with estrogen to help improve bone density, so there's really no significant risks. I have seen some people who don't tolerate the oral formulation as well, in terms of having maybe some significant heartburn and at really high doses progesterone can cause constipation, which is one of the reasons that pregnant women tend to be quite constipated. But in terms of overall side effects they tend to be quite minor.

Michelle: 24:40

Good to know, can we circle back to something you said earlier? You mentioned? I've just never heard of vaginal progesterone before. I've heard of testosterone, I've heard of estrogen. Why would someone prescribe vaginal progesterone?

Shelby: 24:54

Yeah, so we have vaginal suppositories for progesterone. So one indication that they're often used for is in pregnancy and trying to prevent, like first trimester, miscarriages, because in that first trimester you're really trying until that placenta takes over. In that second trimester your body's producing all the progesterone, so that's one of its like indications. I'll use it in individuals who don't tolerate the oral formulation, because we have the studies that show it does protect your uterus and also provides good systemic effect in terms of improving the anxiety, mood, sleep, etc. And again, if in someone who maybe is a little bit more hesitant on getting a compounded formulation and they want something that is commercially available but they don't tolerate a oral formulation, a vaginal suppository is a great option. Very cool, thank you. It's just very unfortunate because you do really see, like you said, mikkel, like how life changing it can be to just start someone on progesterone.

Mikelle: 26:08

Even, even, like when I got PMS acne it was like a tumor on my face, like unbelievable and nothing worked, nothing helped. It was painful, it was uncomfortable. They just don't happen anymore. Full stop Like that alone. That's amazing. Why wouldn't it Like if? Yeah, my God, nevermind all the other benefits, yeah, it's impressive?

Shelby: 26:27

Yeah, exactly, it's amazing what a difference it can make for people. I will say people will always come to me and they'll be asking about estrogen and perimenopause and you have to kind of provide a little bit more background education about like hey, this is why I want to start you on progesterone first, because estrogen actually can be more problematic in perimenopause because you usually, if you're cycling decently regularly, you're probably producing a significant amount of estrogen and it really is targeting that progesterone first and leveling that out before we get into trying to give you any more estrogen something else I wanted to ask you um hot flashes.

Mikelle: 27:07

Can progesterone help with hot?

Shelby: 27:09

flashes. Oh yeah, I'm glad you brought that up. Actually, they absolutely do so. There is really great studies and it's actually in the North American Menopause Society guidelines that said 300 milligrams of micronized progesterone at night can treat vasomotor symptoms, so hot flashes and night sweats associated with perimenopause and menopause. So hot flashes and night sweats associated with perimenopause and menopause. So it's a great option, especially in individuals who maybe are a little bit more hesitant about estrogen whether they have breast cancer, had a previous breast cancer, had a previous blood clot or had a family member and they have a little bit more of that hesitation or fear around estrogen specifically, but are really struggling with those hot flashes and night sweats. You can use progesterone completely on its own and the studies do support that it is extremely effective in improving those symptoms.

Mikelle: 28:05

Amazing. Are there any other studies that maybe we should include in the show notes, you know, for people looking to become better informed?

Shelby: 28:18

Yeah, I would say the big studies. The one that put micronized progesterone probably on the map is called the PEPI trial.

Michelle: 28:20

I don't know if you guys have heard of that one.

Shelby: 28:22

It's postmenopausal estrogen progestin therapy. Its parameters. We're looking at the safety in terms of endometrial protection for progestins versus micronized progesterone, as well as certain heart outcomes, and that's where we saw that micronized progesterone works extremely well to protect the uterus, but it also has that beneficial effect on cholesterol levels with estrogen, whereas the progestins don't. So that's one really great study. There is a study from France called the EPIC-3N trial. That was a large, long cohort study, essentially looking at differences between micronized progesterone and progestin, amongst a number of other things in terms of perimenopause and risk for breast cancer, heart disease, diabetes, things of that sort, and that's where we also saw the differences between progestins and progesterone. So those are two of the more like landmark type studies. And then the Ester trial, which is the one that focused more on the risk of blood clot, which is where, again, we saw no increased risk for blood clot with the estrogen plus a progesterone, but did see an increased risk with the estrogen plus progestin.

Mikelle: 29:40

Amazing. Maybe we could we trouble you to email us those.

Shelby: 29:43

Yeah, I'll send you. I'll send you that stuff. Yeah, thank you.

Michelle: 29:47

Thank you, that is a great idea, mikkel. We should be including more of those in the show notes. Yeah absolutely Shelby. What is the one thing you would love every woman to know about progesterone?

Shelby: 30:04

That's a great question, everything I would want women to know. I think that I would just want women to really understand how important it truly is and that it's not just estrogen that provides a lot of the benefits in terms of treating some of those symptoms that we experience throughout our years, either menstruating or in perimenopause or menopause, and how a simple treatment with just natural micronized progesterone can really impact your quality of life. And so if you're out there and you're listening and you're suffering with you know any of the perimenopausal symptoms and a lot of these more atypical ones like brain fog, anxiety, mood, joint pain those are things that can be addressed by progesterone alone, and estrogen and progesterone they work better together, so it's always nice to use both of them to your advantage rather than focusing just on one.

Michelle: 30:57

That's great information, thank you.

Shelby: 30:59

No problem.

Mikelle: 31:00

Thank you, shelby, that was fantastic Thank you.

Shelby: 31:05

No, this was great. I'm glad you asked me to talk. It's a topic that I really wish more people understood.

Michelle: 31:12

Thanks so much for listening to the show. If you like what you hear, please take a moment to rate and subscribe to our podcast. When you do this, it helps to raise our podcast profile so more women can find us and get a little better understanding of what to expect in perimenopause.

Mikelle: 31:28

We also read all the reviews the good, the bad and the ugly to help us continuously improve our show. We would love to hear from you. You can connect with us through the podcast, on social media or through our website. Our information, as well as links and details from our conversation today, can be found in the show notes. This podcast is for general information only. It's designed to educate, inspire and support you on your personal journey through perimenopause. The information and opinions on this podcast are not intended to be a substitution for primary care diagnosis or treatment. The information on this podcast does not replace professional healthcare advice. The use of the information discussed is at the sole discretion of the listener. If you are suffering from symptoms or have questions, please consult a qualified healthcare practitioner.