Ep. 486 The Ultimate Progesterone Masterclass for Women, Part 2

We have a follow-up from our last mashup episode on progesterone today, featuring Dr. Amy Killen, Dr. Anna Cabeca, and me, as we share our insights on the significance of progesterone for women’s health and the importance of personalized hormone therapy.

In this mashup episode, I explore the importance of individualized hormone therapy and the benefits of progesterone, even post-hysterectomy. Dr. Amy Killen explains how progesterone sensitivity affects some women, discusses the importance of laboratory tests when evaluating hair loss, and cautions against popular but ineffective treatments. Dr. Anna Cabeca emphasizes the need to build foundational health before starting bioidentical hormones and outlines her approach to hormone replacement.

Join us for an informative discussion on how progesterone, when tailored to individual needs, can support hormone balance and overall well-being.

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Statistically, from age 35 to 55, we lose 75% of our progesterone. So why wouldn't we be replacing it?

– Dr. Anna Cabeca

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Connect with Dr. Anna Cabeca

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Transcript:

Cynthia Thurlow: [00:00:02] Welcome to Everyday Wellness Podcast. I'm your host, Nurse Practitioner Cynthia Thurlow. This podcast is designed to educate, empower and inspire you to achieve your health and wellness goals. My goal and intent is to provide you with the best content and conversations from leaders in the health and wellness industry each week and impact over a million lives.

[00:00:30] How are you recommending dosing for micronized progesterone? This is from Jennifer. Nightly, or dosing differently in follicular phase versus luteal phase. So, the answer is it depends. Number one, micronized progesterone is the generic formulation that is immediate release. It is manufactured in peanut oil. So, if you have a peanut allergy, you can't take that, but it works like you take it and it starts working right away. I think that if you're in perimenopause, it depends. Some women just need it the week before their menstrual cycle. Some people need it two weeks before their menstrual cycle, so that's the luteal phase. The hallmark of the beginning of perimenopause is less circulating progesterone because your ovaries are getting ready to go into retirement. 

[00:01:13] Remember I just talked about the eggs? Our egg reserve just starts to precipitate and drop off. So, when we talk about progesterone therapy for some women, they really need progesterone therapy two weeks of their cycle. Some women need it one week of their cycle. The farther you get into perimenopause, you may need it throughout your cycle. Obviously, women in menopause benefit from taking it typically six days a week or having three to four days off a month, however, you want to make that work, and that's to keep the receptors kind of sharp. But I would say that starting with the cheap stuff, the micronized progesterone made with peanut oil, that is very inexpensive. It is immediate release. For a lot of people, that works just fine. 

[00:01:56] For a lot of others, they need compounded progesterone that has sustained release so that it's a longer acting medication and that is compounded in a pharmacy. Usually, the dosing patterns are anywhere from 50 mg to 200 mg . There's someone in my Facebook group that was saying they were on 600 mg of progesterone. I'm not sure I've ever seen that.

[00:02:17] Having said that, everyone's an individual. Dr. Lindsey Berkson talks a lot about progesterone. She's actually a fan of progesterone both intravaginally, so placed inside the vagina, as well as oral progesterone, really depends on the individual.

[00:02:32] Jody asked, as a healthy, fit woman at 72, can I take HRT if I've never taken them in earlier years, risks and benefits? Jody, this is a great question, and what I would say to you is it depends. Can you start vaginal estrogen anytime? Yes, because it is localized to the vagina. So, if you're having a lot of genitourinary symptoms, chronic UTIs, friable skin, pelvic floor issue problems, incontinence, vaginal estrogen, you can start at any point.

[00:03:01] The other issue is how many years have you been into menopause? And I actually had a discovery call today and we talked about this. There's this opportune time to initiate hormone replacement therapy, and that has a lot to do with what starts to change internally in the blood vessels, the endothelium, which is this lining of our blood vessels. We know with less and less estrogen circulating that there's more and more inflammation, oxidative stress. And so, it has to be very much a conversation about risk, benefits. I think that even if you're healthy at 72, you probably have had 20 years of no exposure to estrogen and so you really have to do a very thorough cardiovascular workup. You really have to look closely at labs. You have to have a conversation with a provider that's willing to have that conversation. 

[00:03:48] I think the longer you are in menopause, like when you get over 10 plus years, I think a lot of providers get a little hesitant. I can tell you that a lot of my colleagues and I believe this fervently vaginal estrogen, you can start that at 90. I mean, if you're having those symptoms of genitourinary symptoms of menopause, I think that we have an obligation to offer that to women because it stays localized, it's not a systemically absorbed drug, or if it is, it's very, very minimal. 

[00:04:16] But my statement to you, Jody, would be we would have to find a provider that would be comfortable having that conversation and also doing a very thorough cardiovascular workup to make sure there's no plaquing. We know that timing hypothesis is one that a lot of people embrace, that there's an optimal time. A lot of us will say it's the first five years into menopause or starting prior to menopause, maybe up to the 10 years. I've had women in programs that have been told you're over the age of 60, I'm not willing to give you hormones, which I think is ridiculous. There's a lot of very healthy people, but they have to be able to provide some degree of risk assessment and that's where a very talented, competent, conscientious provider could help you with that. The question is finding that person in your area. 

[00:05:03] Jess said, I love your mission so much. I'm 40, I have estrogen-dominant symptoms, which means I had extremely dense sore breasts before my period. My Dutch Test, which is generally a urine and saliva test from a few years ago, showed that my estrogen was going down an unfavorable pathway. She mentions my liver doesn't clear toxins or estrogen well. She has a family history of breast cancer. Could she still benefit from HRT? Okay, just because your family member, your aunt, died of breast cancer does not-- That is not a contraindication to taking hormone replacement therapy. I'm going to say this again, just because your first-degree relative or second-degree relative died of breast cancer, that's not a contraindication. This is where having a really good discussion and having a really good history with your provider is going to help illuminate what you need to be focused on. 

[00:05:58] I just interviewed Dr. Corinne Menn. She is a breast cancer survivor. She was diagnosed at 28. She is counseling women almost daily basis about the cost benefits. She is a breast cancer survivor and she is now on hormone replacement therapy. So, you really have to work with someone that understands the risks, like not just the relative risk, the absolute risks, and can properly counsel you. 

[00:06:22] Jess also mentions my progesterone is almost nonexistent on my recent labs, which is common in perimenopause. When I added over-the-counter progesterone cream, I felt more moody, hot flashes and worse insomnia. Okay, I'm not a fan of progesterone creams. I think that if you are taking progesterone for the purposes of replacing hormones, orally, is going to be superior to something transdermal. If you are in menopause, the only option is oral. If you are in perimenopause, you might be able to get away, at least initially, maybe with some cream, but if it's over the counter, we don't know. I mean, there's so many variables that can impact how it's absorbed, what formulation it is. 

[00:07:03] Yeah. And especially, I think that this is where working with someone that is experienced and can walk you through the benefits of oral, even if it's just for a week or two out of the month. I think given the degree of high estrogen dominance symptoms you're experiencing, based on what you said here, you may really benefit from oral progesterone therapy, but discuss that with your provider to see what they think. 

[00:07:27] Liz says, if menopausal on HRT, what are the optimal estrogen and progesterone blood levels to help protect brain, bone and heart health? This is a great question, and I'm going to go back to saying there are some providers that treat based on symptoms. There are some providers who like to look at labs. I can tell you that it is a very-- It's like the wild-wild west right now. There are certain camps that people as clinicians kind of fall into. I think it is much more important that we are monitoring your symptoms. So, if your symptoms are quiet, does that mean that we should bump up your estrogen? Possibly, but I think there's a lot that remains to be seen. You'll see some numbers for bone and heart health greater than 50 mg/dL. Some people don't tolerate that much estrogen, number one. 

[00:08:15] I see other clinicians that are using oral estrogen, which I know, depending on the researcher that you follow, some researchers feel like that's the best form of estrogen to protect your heart. We can't right now measure brain estrogen levels. Dr. Lisa Mosconi and I kind of talked around this. She's doing research in this area. I'm actually part of her research study, so I do plan on asking her more about this. But I think that the question is, I think it's more important to be on some hormone replacement therapy than get obsessive about what those certain values should be. 

[00:08:48] I can tell you with testosterone that a lot of providers get funny when women have-- Depending on whether it's a LabCorp or Quest, you can have free testosterone levels anywhere from 6 to 8 to 10 mg/dL. And that's where they like those numbers to be. I think people get a little more antsy around testosterone, although they think that's silly. If you're on pellet therapy, you know that you're not going to have a therapeutic number. You're going to have supratherapeutic numbers just by virtue of the pellet, as opposed to transdermal applications, oral applications of drugs. 

[00:09:23] So, Liz, not to not answer your question, what I can tell you is there's a lot of consensus and I think providers are really, for the most part focused on symptom reduction and symptom amelioration, meaning getting rid of the symptoms than they are on driving it towards a number, an empiric number. I can tell you personally that there's a ratio that we want to see ideally with progesterone and estrogen, and that can get a little bit of a sticky wicket in terms of depending on who you're talking to. So, I will just leave it at that and tell you that I've had many providers on the podcast and their opinions on this are very variable. 

[00:10:04] Kavs says, I am 45 years old and I have trouble with sleep only during the luteal phase of my cycle. Anything to help with this other than HRT? Well, I would say lifestyle. So, if you know that your progesterone levels are low in perimenopause, to me it makes sense to give progesterone. Call me crazy. I don't think-- there's no other supplement that's going to mimic what progesterone does in the body. And one of the things that progesterone does is it upregulates a particular calming neurotransmitter called GABA. 

[00:10:39] So, I would say during luteal phase of your cycle, take some oral progesterone, call it a day. The lifestyle stuff is important. Some people do better increasing either high quality carbohydrates. Some people do better with restorative yoga and less intense exercise. I think that a lot of it has to do with you as an individual. But oral progesterone, call it a day, make it easy. 

[00:11:01] Alicia said, I'm 49 with regular cycles, but I'm experiencing increasing perimenopause symptoms, heavy periods, increased PMS, irritability and sensitivity. I got a prescription for 100 mg of oral progesterone to take the second half of my cycle. When I've tried it seems to give me a lot of bloating and just not quite feeling right. I'm not sure if I should continue to take it and see if I adjust it or maybe I'm just not in need of this hormone yet. At 49, you are in perimenopause. It may be that you need a lower dose. It could very well be. I have some people that are on 50 mg. It could be that-- You just find it sedating. Some people need to take it earlier in the evening. I would say talk to your provider that wrote the prescription if taking 50 mg might be something worth considering. 

[00:11:52] The fact that you're getting increasing symptoms tells me that you definitely have lowered levels of progesterone. That's what's driving the heavy cycles. The more PMS, the irritability. For a lot of people, they've gotten so accustomed to having low progesterone levels for such a long period of time that when they start kind of adding in a little bit of progesterone therapy, sometimes it can be too much too quickly. And so maybe backing down on the dose might give you some improvement. But again, talk to your prescribing provider. 

[00:12:20] This is just a first initial C. “Good morning. I have the Mirena IUD and was put on 100 mg of progesterone daily.” So, the Mirena IUD is synthetic progestin IUD. So, it's secreting some synthetic progesterone. And she said, I'm put on oral progesterone as well. “Was wondering why they told me not to cycle it just the last two weeks of my cycle.” I'm not sure I know what the question is, “Wondering why they told me not to cycle it just the last two weeks of my cycle?” So, probably because in the luteal phase of your menstrual cycle, that's when progesterone used to predominate and now there's less circulating progesterone. So, some people do fine with both. I have some older patients that they have a progestin IUD put in because they don't want to deal with taking progesterone and they're using it to protect the uterus. So, I think that there's a degree of experimentation. And yes, typically when you start taking oral progesterone, it's usually the week before, two weeks before your menstrual cycle starts, if you even get a cycle, and if you've got an IUD and you may not be getting a cycle at all. 

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[00:13:23] So let's talk about progesterone. And I say this with great love and respect that I think many individuals that are sensitive to progesterone feel like their symptoms are not really addressed. They're just told, “Okay, you don't tolerate progesterone, so you're going to just have to grin and bear it,” and you do a really beautiful job. If you are not subscribed to Amy's Substack, you need to be. I feel like I learn a lot. And if I'm learning a lot, then I know there's a lot of incredible value that's there. Let's talk about the spectrum of progesterone sensitivity because this was fascinating, absolutely fascinating.

unintelligible [00:14:01] Dr. Amy Killen: Yes. Well, so first of all, about 10% to 15% or so of women are sensitive in some way to progesterone. Like, it doesn't work for them as well as everybody else. So, I think they get frustrated because all the rest of us are like, “It's so wonderful. [Cynthia laughs] It's let me sleep.” We're all raving about it. And then there's this subset of people who it just is not great. 

[00:14:23] So, of those people, there's kind of three different types of progesterone is bad, or whatever, it doesn't work for me. One type is called intolerance. And that is like, kind of basically just means that you are more sensitive to it than other people. So, you have the same kinds of things. Like instead of, it could help you sleep, but then you sleep too long, and it can calm you down, but then your mood is too calm, you're too flat, you're depressed. So, it's like the same symptoms as regular progesterone, but people are very sensitive to it. 

[00:14:52] And then the second type is called paradoxical progesterone response. And that is essentially when one of the metabolites of progesterone, called allopregnanolone, it goes to your brain and binds to your GABA receptor. And in most people, that causes this relaxation, this inhibition of the brain. In some people, though, that GABA receptor is configured differently. And so that binding actually causes excitation. So, it makes them wound up and they can't sleep and they're anxious and irritable and so that's the second type. And that is also pretty common. Those first two are both pretty common. 

[00:15:28] The third type is a hypersensitivity, which is actually an allergic reaction. It's an IGE-mediated allergic reaction. So, it's an actual allergy, rash, hives, bronchospasm, swelling of the face. Very rare. Less than one percent of people, but more serious also. 

Cynthia Thurlow: [00:15:45] Yeah, it's really interesting because I feel like for every 20 of us that are brave about progesterone and you're never going to have-- you're never going to stop taking progesterone because you feel the benefits, there are a few people that will say, I get-- And what I typically hear from people is not so much that they feel like they can't wake up or they feel depressed. It's that they feel stimulated, so they get this glutamate receptor stimulation as opposed to GABA. And so all of a sudden, they're like the opposite. They're not falling asleep. They're totally irritable. And so, for those that suspect they may be on this spectrum, what are some of the things that they can do? Now, you talk about this in particular in your Substack article, which, again, excellent. Must go subscribe to it. What are the options for people that feel like they get this magnification of symptoms? What are some of the options that they can do that still protect the uterus? Because there are concerns around there. What are some of the other options they have for treatment? 

Dr. Amy Killen: [00:16:47] So the probably the easiest option is just to change forms. So instead of doing oral, like, instead of doing a pill which is going to get metabolized heavily into that allopregnanolone, change it out for like a vaginal progesterone or even a rectal progesterone or even a troche, like underneath the tongue. So, anything that's not a pill going into your stomach and then into your liver is going to create much less of that allopregnanolone and so that is going to be much less excitatory, essentially, to your brain. 

[00:17:15] And the other option, second option, is to actually either increase or decrease your progesterone dose if taking it orally. Because it turns out when it comes to the paradoxical response, there's this sweet spot in the middle of serum allopregnanolone level that causes disturbance. And if you're higher than that or lower than that, then it actually doesn't cause the same disturbance, which is kind of weird. 

Cynthia Thurlow: [00:17:40] It is. It's bizarre. So, for listeners benefit like typical progesterone route of administration is oral, dosing somewhere between 50 mg to 200 mg, depending on the individual. When you're talking about those that have this paradoxical response, are we talking about doses of like 400 mg or are we talking about teeny-tiny-- Like the range of doses, teeny-tiny, like 25 mg. Is that typically what you're thinking? 

Dr. Amy Killen: [00:18:06] Usually the worst doses for those people are between 100 mg and 200 mg orally. And then again, everyone's different, but if you can go lower than that, like if you're-- 50, unfortunately doesn't offer uterine protection at 50 mg a day. But if you're taking some other kind of progesterone also, then 50 mg is usually okay. And if you go up near like 400 mg, then that's also usually okay. But everyone's a little different. But that's kind of the range that most people-- Most people the worst range for them is the one that we give them, [Cynthia laughs] which is 200 mg. 

Cynthia Thurlow: [00:18:38] [Laughs] And if you're changing the route. So, if someone's taking intravaginally intrarectally, does the-- Sorry, I don't know the answer to this question. Does the dosage also correspondingly change? Because I would imagine like rectal absorption is very different than intravaginal absorption, I would imagine. 

Dr. Amy Killen: [00:18:55] Well, so most of the studies that we have are in vaginal. We don't have a lot of studies at least in the hormone space. We have some in the fertility field. But most of our kind of HRT studies are looking at vaginal progesterone. And the uterus gets to-- The progesterone goes into the uterus first, which is great because it's a uterus first pass effect. And so, the uterus gets up to 10 times the concentration that it would if you were taking it orally. 

[00:19:21] In theory, you could go with a lower dose. You could take 200 mg orally, you could probably take 100 mg or even less vaginally. But the British Medical Society Guidelines on this from 2022 are just take the same dose both ways. So, it's super simple. And what's kind of a cool trick is you can actually take your oral micronized progesterone gel caps, the one like the Prometrium, you could take that vaginally. And then you could also take it instead, if it was easier, you could do it rectally. That's just not as well studied, but from what we can tell it's similar. 

Cynthia Thurlow: [00:19:53] Yeah, it makes sense. And from years and years ago when I went through infertility treatments, I actually took intravaginal progesterone for the duration of my first trimester. And I remember what the irony is, I recall it made-- Well, it could have been a multiplicity of things. You could be pregnant and bloated. But I remember thinking, like when I started taking oral progesterone as a perimenopausal female, I was like, “Oh my God, I hope the bloating that I experienced years ago, it has not been problematic.”

Dr. Amy Killen: [00:20:20] Yeah. 

Cynthia Thurlow: [00:20:21] So, I'm happy to report that was not an issue. But that's actually what my reproductive endocrinologist recommended, was to take it intravaginally, obviously for a different purpose, but good absorption there as well. What are your thoughts on progesterone's role in hair pause? 

Dr. Amy Killen: [00:20:35] So progesterone is a weak 5-alpha reductase inhibitor. So, it weakly blocks the conversion of testosterone to dihydrotestosterone. And certainly, medications that are used in men like Propecia or finasteride, which is a very strong blocker. Those medications work really well for men's hair loss. I mean, they have problems, but they do work well for hair loss. So, progesterone has some of that weak activity where it's a little unclear clear what else progesterone is doing for the hair follicle. 

[00:21:05] Estrogen is pretty strong. We know estrogen is very important for the hair follicle. Progesterone we're not quite sure about. And we're also not quite sure about DHT and androgens. If anything, they're probably not great, but even that evidence is a little bit confusing. 

Cynthia Thurlow: [00:21:19] Yeah, no, certainly helpful to have that. And when you're talking about lab work that you think is beneficial to evaluate hair loss, I think a lot of people just automatically jump to sex hormones. But you do a really nice job in that Substack talking about like, “These are accessible labs for everyone. These are not unusual labs. These are not functional integrative medicine labs.” What are some of the labs that you think are important to do to evaluate hair loss issues? 

Dr. Amy Killen: [00:21:47] I mean, some of the key labs are thyroid and including, obviously all the like TSH, free T3, free T4 at the minimum, like at least get those three and making sure that you're in that kind of sweet spots, hopefully kind of towards the upper end on the T3 and T4 of the reference range versus the lower end and that can make a big difference. And then ferritin is also another really important lab to get. A lot of women when you're menstruating, you're losing blood every month and that of course you're losing iron. And ferritin is just the stored iron form. 

[00:22:18] And hair-- there's a number of good studies that show that you want to have a ferritin of at least 50 to 80’ish for good quality hair in women and that in men as well. But a lot of women, their ferritin is like 20, but no one's checking it because it's not on-- you're not anemic. Your hemoglobin, hematocrit are normal on like the basic test your doctor does. And unless you just add on a ferritin test, you don't know about it, so that's another big one and pretty easily treated with just high iron foods and supplements if needed. So, those are two certainly the hormones, all the hormones we talked about, estrogen, testosterone, those kinds of things.

[00:22:57] And then sometimes-- I don't tend to check all the micronutrients, but you can check like B vitamins, you can check selenium and cadmium if you have specialized tests for those. I do like omega-3 fatty acids also from that in that. And then also just like general inflammation markers, getting a CRP or some sort of test. And I think it's important to do anyway. CRP, blood sugar test. We know that any metabolic diseases of all-- Any kind of inflammation that's bad for your body is also bad for your hair, so you got to think about those things too. 

Cynthia Thurlow: [00:23:29] Well, I think a lot of people don't realize like if you're chronically stressed, if you go through a stressful period. When I spent 13 days in the hospital in 2019, I had so much hair loss after losing 15 pounds that I didn't need or want to lose that I remember my hair person was like, “You may need to think about extensions.” And I was like, “Absolutely not,” because that will then become another long-term thing. But cortisol elevation can actually impact the hair follicle quite significantly. 

Dr. Amy Killen: [00:24:00] Yeah, absolutely. Whether it's physical stress, like you're sick or emotional stress. Emotional mental stress, anything that's causing that cortisol to be up over time. And the thing is the hair loss usually starts like three to six months after the stress. So, it's not like you're stressed out and your hair starts falling out. It starts six months later and you're just like, “What is going on,” like it kind of comes out of nowhere. And so, it's difficult to pin down sometimes what's causing the hair loss because who knows what was happening six months ago. 

[00:24:28] And also similarly, when you get to treating it, it usually takes three to six months before you start to see benefits also. So, it's very difficult because who wants to be on a medication or whatever for six months and not know if it's even working or not? 

Cynthia Thurlow: [00:24:41] Yeah, that can be super frustrating. I'd love to end the conversation today talking about things that you feel like are overrated or even ineffective in the longevity space. And by this, I mean things that you -- Because you understand the science at such a deep level, you look at it and say, okay, well, there's a-- it could be one of those like pop up IV places that's administering things that are ineffective, you can't actually absorb them or these detox teas or professionals that are still prescribing oral contraceptives as HRT, which is not HRT.

Dr. Amy Killen: [00:25:17] Yes, well, all of those things that you just said. I don't think that detox teas, pills-- There is a way to detox your body, but I do think you have to be very strategic with the provider, who knows what they're doing to really do that properly. I am not a fan of alkaline water, I think it's a total scam, like the water that you're drinking to try to alkalize. That's ridiculous. Your body is not so easily tricked, if you will.

[00:25:42] I don't think NAD IV is really all that-- I think it's expensive. Who wants to pay $1,000 for something that really doesn't have good evidence behind it? And if you want to increase NAD, you can just take a supplement like NR or NMN or other similar supplements and those work just fine to do that and they're much less expensive. So, yeah, don't like that. I don't love progesterone cream and I especially don't love like the Yam creams that you can get like over-the-counter. It turns out that rubbing Yam cream on your skin gets absolutely zero progesterone made into your body. So that is a total waste of time. It is all placebo effect if that works for you. 

Cynthia Thurlow: [00:26:24] Yeah, I think it's important to have these conversations. And what's interesting is I did a podcast on NAD with a physician researcher and learned so much getting prepped for that podcast. I thought to myself, I've never gotten IV NAD or NAD, but I'm so glad that I never did because now I understand it's too large of a molecule to get intracellularly you need the precursors that you mentioned, the NR, NMN. And I love that you brought up the progesterone cream, because without naming names, I will just suffice it to say you can eat all the yams and sweet potatoes in the world and it is not going to raise your progesterone. 

Dr. Amy Killen: [00:26:56] It is not. Progesterone can be made from a specific type of Mexican yam in a laboratory. There's a molecule called Diosgenin in there that can be made into progesterone, but the thing is, your body cannot do that conversion. It has to be done in a laboratory. So, eating yams, put them on your body, none of that. Yams are fine, they're delicious, but it's not going to help your progesterone. 

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Cynthia Thurlow: [00:27:24] Next question is from Anonymous. “I've heard you talk about oral forms of bioidentical hormones like progesterone and estradiol, but what about other routes? As I'm in perimenopause, should I use oral or another form?” Well, Anonymous, I think so much of it's dependent on where are you in your perimenopause journey, what are your symptoms, how is your sleep, how are you managing your stress? I think in many situations, I think oral progesterone, even if it's used just during your luteal phase of your menstrual cycle, can be a really very effective way of helping support sleep, anxiety, depression, etc. 

[00:28:02] Now, obviously there are women that benefit from starting even estradiol therapy or an estrogen patch during the perimenopause. And I've heard Dr. Peter Attia mention more than once that he actually likes to start women on HRT in perimenopause and not wait till they're in menopause, which I think is completely reasonable. So, I think it's dependent on your hormones, your symptoms. I do not like oral estrogen. I do not recommend anyone take oral estrogen. It gets a very large first pass effect. It magnifies all the side effects. I think that starting with oral compounded or generic progesterone, obviously the generic progesterone is the least expensive option, super inexpensive, like $6 to $9. I recall when I was filling mine, very inexpensive. If that doesn't work effectively, you can move on to a compounded option which usually has sustained and immediate release and some people need that. 

[00:28:58] And then thinking about estrogen, I think about estrogen patches, very inexpensive. It's usually E2 or estradiol, which is the predominant form of estrogen. And then sometimes providers like to use a combination of estradiol and estriol, which is E3 that can be breast protective. Sometimes you'll hear that described as biased, but I do think that there are very inexpensive options that are available that you can fill at your local pharmacy without a compounding pharmacy. And if they work well for you, awesome, like awesome. 

[00:29:31] Now, testosterone, it's important to talk about testosterone. There is no FDA approved form of testosterone for women, which is criminal. So, some providers will give women a tenth of the dose of a male dose. So, a men have these Androgel packets and they're not very big. I think trying to give someone a tenth of a dose is really hard. You probably get too much one day and not enough another. So more often than not, what you see is compounded testosterone for women either in perimenopause or menopause.

[00:30:01] Now, not every woman navigating that transitional period needs testosterone. About 25% of women still make enough testosterone on their own. And I actually listened to a lecture by Dr. Pam Smith and she was saying, I'm one of those people. I actually have very healthy, robust testosterone levels. I'm not one of those people. So, I actually really benefit from compounded testosterone because for me it's a big differentiator for-- I know everyone always focuses on libido, but I think about motivation, a desire to go to the gym, muscle building, which for me is the predominant reason why I take it, because I think it makes a big difference for me. I will never be super ripped. I'm never going to be one of these women, like those mesomorph bodies where they're super ripped, that's just not my body phenotype. I'm just thin and lean. So, for me it's about allowing me to have the opportunity to build that. 

[00:30:57] So, getting back to Anonymous’ question, a lot of it depends on symptoms and testing. I think this is a really good indication for working with someone that is savvy with being able to support women at the stage of life you're in. Sometimes people will also make recommendations about DHEA, sometimes pregnenolone. Pregnenolone is known as this memory hormone. Those things are over the counter, but I don't generally recommend them unless you are low or deficient. And then obviously, looking at other hormones I think can be helpful. Full thyroid panel, looking at cortisol, looking at all those things can be helpful for providing a total clinical picture.

[00:31:33] Okay, next question is from Erica. “A friend of mine just started taking pellets and recommended them to our friend group that others should start them too. We are all in our late 30s, early 40s. I don't agree with this because I've heard more mostly negative things about pellets, but wanted to hear your thoughts.” Erica, it has been my experience clinically, I have never received pellet therapy, so I want to be totally upfront about that. I think there are some very well-meaning people that are using pellets and have had good results. I think they're pretty conservative. But what I've also seen is a lot of antiaging clinics and pill mills is usually what some of us will call them where everyone's getting pellets and people feel really good initially and then it's just not consistent. 

[00:32:19] And there are probably listeners to this podcast that have had great experiences and if you are one of them, that is great. I typically see the people who've had a negative pellet experience and in talking to colleagues of mine, many of whom have been guests on the podcast, we almost always have conversations around this topic. I think judiciously in the hands of a very competent, capable, conscientious provider, I'm sure there is some efficacy for pellets, but again, I usually see the people who felt great when they first got pellets and then they feel terrible. 

[00:32:52] I've had women come to me in programs that have said, “I know my testosterone is low, I have no energy,” and then we look at testing and their testosterone is actually in a very healthy range. And that's not the issue for why they're tired. So, I think on a lot of different levels we have to think about like why in a younger woman? So, if you're not menopausal, if your testosterone is low, is it because you're insulin resistant? Is it because of estrogen-mimicking chemicals? Is it because of chronic stress? I think those things are important to look at before consideration of hormonal replacement therapy in an otherwise healthy individual. 

[00:33:26] And then I think if it's something you're not comfortable with, Erica, I think it's not the right decision for you. And there's so many other options. I do think that there is a place for HRT used judiciously and appropriately, but I think we have a whole generation of individuals that are just not sleeping, they're not managing their stress, they don't eat a healthy diet, they overexercise or don't exercise at all. They're over fasting or eating constantly. And so, I think the lifestyle piece has to be kind of dialed in before we start doling out medications if it's something that would otherwise be fixed with lifestyle, so hopefully that helps. But I would say trust how you feel intrinsically. If you feel that pellets are not the right answer for you, that is totally okay. 

[00:34:11] And for everyone listening, we do have a free guide that we will make sure we link up that if people want to get access to a list of vetted professionals. When I say vetted, these are people that I know socially. I have not per se gone and seen every one of them as a clinician or as a patient, but individuals, both physicians, nurse practitioners, midwives, PAs that are in the United States that offer hormone replacement therapy. Probably different modalities, but we'll give you some other options. 

[00:34:43] Okay, next question is from Heather. “I have had a complete hysterectomy when I was 54 years old and I'm now 62.” So Heather is eight years into menopause. “I was placed on estradiol 18 months ago, which has greatly reduced my hot flashes. Is there any benefit at all to also taking progesterone?” So, Heather has had a total hysterectomy. They took her ovaries and her uterus and her cervix. And she's asking if there's benefit from taking progesterone. And my answer is always yes. I think that there is so much benefit from progesterone.

[00:35:19] And I recently stumbled upon a researcher for anyone that wants to go down and read more about this. Her name is Dr. Jerilynn Prior. She oversees the Center for Menstrual Cycle and Ovulation Research or called CeMCOR. And she talks about how-- And she's on the forefront of progesterone research and talks about that progesterone decreases hot flashes and night sweats and improves sleep. And there's good evidence that progesterone also increases bone formation. So, it's not just estrogen that can be helpful. For the sleep, I always say progesterone is great for inducing sleep. Estrogen is oftentimes great for keeping us asleep.

[00:35:53] Same thing with bones. It's not just about estrogen. We also know we have progesterone receptors and testosterone receptors diffusely across the body. We know that progesterone can be taken by itself. And kind of the conventional wisdom for a long time has been if you are without a uterus, you don't need progesterone. And I always say the same thing. We have progesterone receptors diffusely across our body. And so, for that reason, and especially for the sleep support, for a lot of people who still feel like a little anxious, maybe they're feeling like their sleep isn't as good, they struggle to fall asleep. There are a lot of women that express these things. I think that can be very beneficial. So, we know, based on some of the research that I was looking at, that she has conducted that oral progesterone at a dose of 300 mg, this is a little bit higher than what I typically see. I typically see her range of 100 to 200 mg at night increases deep sleep by 15%. 

[00:36:47] Now, that's quite significant because deep sleep is something that starts to become more challenging as we're getting older. Deep sleep is when we consolidate memories. It's when the glymphatic system, which is this brain detoxification system, that's when that is activated. And so, as we get older, it is very common to see deep sleep erode. So, very, very significant.

[00:37:11] I think the research that she was doing was looking at 300 mg, which, again, is a little bit more than what I typically see. But at that dose, a 15% increase in deep sleep, I think that's quite significant. And we also know that it helps stimulate and form new bones. So definitely things to be considering. I would encourage Heather to go back to your GYN or your internist, whoever's prescribing your HRT and have that conversation. 

[00:37:37] I always say, when you're wanting to have a conversation with your healthcare provider, just coming from a place of curiosity and just saying, like, “I would like to learn more about this. Would you consider prescribing me progesterone because I know there are benefits that extend beyond just the uterus.” I think coming at it is a sense of curiosity. Even for myself, my own primary care provider, I'm super respectful. We don't always agree 100%. We generally agree most of the time. But sometimes I will ask, “Help me understand why we are doing things this way.” And I think if you come about things in a differential way, you will definitely get a whole lot farther. And really, ultimately, we want to be in partnership with our healthcare team. 

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Cynthia Thurlow: [00:38:22] And I'm an example of thin phenotype PCOS, which is why I was never properly diagnosed. But the irony is, when I started going for infertility treatments because I wasn't ovulating and they put me on Clomid and then I did IUI to get pregnant. I remember having a conversation with multiple aunts and each one of them said, “Oh, that's what I had to do.” And I thought to myself, why aren't we having these conversations with our family members to at least make them aware, like there are multiple family members that very likely have some genetic susceptibility, these luteal phase defects, which is the lack of progesterone, which exacerbates all of these symptoms that you're referring to. 

[00:38:22] Now one of the questions that came in multiple times was, “How do I know when I'm ready to start bioidentical hormones? My doctors are not open, so I don't know who to go to. Thank you.” That question is asked so frequently, I could add ten names to that question. But many women feel like they are struggling to find providers that will actually address with bioidentical hormones and not waiting until they go into menopause. Because we know the research suggests starting bioidenticals when you're younger can actually be very helpful for alleviating a lot of the symptoms that women experience in perimenopause. 

Dr. Anna Cabeca: [00:39:45] Yeah, it's a really good question. And the answer is so individual. So, teach my approach to that answer. And so, if a patient comes in, whatever the situation, I do my foundations first. I want them to do, Keto-Green 16 recipes in my book Keto-Green 16 because it's the shortest, quickest, easiest, and they're excellent medicinal recipes. I want them to work with intermittent fasting. Follow that. And I support them with adaptogens. For me, it's my formula, Mighty Maca Plus adaptogenic. Through the years, we've shown an increase in day 21 progesterone within two months. And so, it helps support your body's natural hormonal production as well as detoxification elimination. It's very alkalinizing. 

[00:40:31] And I have clients check their urine pH. I want them to do this first because it takes more than hormones to fix our hormones. And take it from me, it was able to extend my menopause till age 56 because of these practices and principles versus my early diagnosis of menopause initially at age 39 and then-- and full-blown perimenopause at 48. I had to learn to shift things in order to preserve ovarian function and adrenal function.

[00:41:03] So, then it's like-- I like to clean up-- you've got to clean up the terrain, so to speak. So, detoxification becomes key. What could be causing the hormonal insufficiency and the imbalance to begin with? Is it cortisol? Is it insulin resistance? Is it hormone disruptors? There's something genetic with methylation defect or it could be anything. And so, a sulfation defect, especially anything that can affect our P450 enzymes in our liver. So, we want to clean that up. Just like you send a car in to get an oil change, we want to do a good filtering. And because it's going to have to process our hormones and we want to-- If we're replacing hormone, replenishing, I like to say I replenish hormones, not replace them. 

[00:41:49] If we're replenishing hormones, then we want to do it safely. So, your body's metabolizing them well, and that also comes in why the medicinal menus are so important and fixing the gut, healing the gut is critical to hormone balance because of our estrobolome and it's also critical for longevity. So, with that said, like, I want the foundations taken care of and yet still I’m very symptomatic. I can say, “Look, I'm going to start you on these hormones—Look, I’d like to start you on these hormones now. We may be able to wean off them, especially that perimenopause time period.” So, but I rather like seriously, within 16 days, we see an 80% to 90% improvement in symptoms and we can retest and see where do we need to supplement. So then, the adaptogens come in. I start with my progesterone and pregnenolone combination first. That's my balance cream because those are the mother hormones. And from there we'll support our steroid hormones, our sex hormones, DHEA, testosterone and estrogen, so we'll support those top down that way. 

[00:42:57] And that's the first hormone statistically, within our-- From age 35 to 55, we lose 75% of our progesterone, so why wouldn't we be replacing it? In contrast, we lose 50% of our estrogen during that time. So then when do we add in estrogen again? Gosh, we can talk about this a lot, Cynthia, I'm going off on a tangent, but I usually start with adaptogens, cleaning up and detoxing. And then progesterone and pregnenolone, usually cyclically in the perimenopause and then continuously with exception of one day off a week or three to five days off per month in the post menopause and then DHEA and then testosterone and estrogen. 

Cynthia Thurlow: [00:43:41] Questions also about HRT. How do you know when to increase estrogen versus progesterone dosing? Are there specific symptoms that you are looking for? I know that's nuanced. 

Dr. Anna Cabeca: [00:43:53] Yeah, it's very nuanced-- And again, first thing that comes to mind. I'd like to take a look at your genetics. Because some people can't tolerate progesterone very well and especially oral progesterone also if you're in a high stress state, is shunting directly to cortisol and you're going to start gaining weight and you will know right away that this is not working for you and so, there's ways we manipulate. Transdermally, certainly, the pregnenolone with progesterone has a nice even distribution and half-life. So, we have to look at that and as far as your symptoms--

[00:44:28] one thing is I do lab testing. I like to test client’s labs. But depending on how you're getting the hormones, whether it's oral, transdermal, troche, vaginal, injection, pellet, etc., it's going to depend on how we look at that, is it going to be blood work, is it going to be urine, is it going to be salivary, what are we going to look at? So, with that said, I would typically look at-- Initially when I evaluate my clients, I look at initial blood works, I look at total estrogens and estradiol level, I look at free and total testosterone, DHEA sulfate and you've got to look at the thyroid, you've got to look at other markers. I look at other markers for longevity in my routine labs and then I typically will follow up with a Dutch Test because I've been doing this 30 years. I'm a good clinician, solid. And I always teach my physicians that I'm training treat the patient, not the labs. 

[00:45:25] Ultimately, you have to treat the patient and not the labs. There is such bio individuality to how we need it. So, if deciding to use a low-dose estrogen patch on you to start, I'm also going to counsel you, look, you may need more, you may need less, we're going to see how you do with this and then also we're going to watch your estrogen detoxification pathway. And the same with progesterone, for myself and for many of my clients, we do oral progesterone a night, taking a few breaks. Oral progesterone at night and use the balance cream, the progesterone with pregnenolone during the day. My mind is just better that way. And I notice, it has those benefits so we've got that covered. 

[00:46:09] And for other clients-- I have another physician client and she's on 400 mg of oral progesterone, always only bioidentical at night. And so that's a heavy dose for me. I need 100 mg and I use the cream. So, I get a 24-hour distribution versus a 16 hour with just the oral progesterone. So, I want to look at those things, what works into your lifestyle because that matters too. Do you have small children then I don't necessarily want topical hormone creams and I rarely want you rubbing it on your arms where you're going to embrace a kid, let alone testosterone. So, we're going to look at how do we want to use that too like injection, etc.

[00:46:53] So, when do we need to increase versus decrease really is individual and it depends on your symptoms. There are people and this is where testosterone gotten into so much trouble. They just like, “Oh, a little's good, a lot's going to better,” and then you're super physiologic until you maybe crash or have some other physiologic side effects. So, you have to pay attention to that. The ebb and flow is really important. I mean it really is bio-individuality with that, but knowing if you're still getting hot flashes on estrogen, I say--

[00:47:25] Well first I really work to make you as insulin sensitive as possible because insulin resistance is a key contributor to unrelenting hot flashes. So, if you're still having hot flashes on estrogen and you’re insulin sensitive and we need to increase the estrogen, but if you're insulin resistant, we got to keep working on that insulin sensitivity. And usually within two weeks, your program with intermittent fasting with mine with Keto-Green 16, you become insulin sensitive relatively quickly to make a difference.

Cynthia Thurlow: [00:47:59] If you love this podcast episode, please leave a rating and review. Subscribe and tell a friend.

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