PMOS Explained: How to Read the Patterns (and What You Have Missed)

Polyendocrine metabolic ovarian syndrome. Could this be something that you've been dealing with all your life? And if so, how would you know? And then what would you do about it? So the episode I created on June 24th, that dropped June 24th, about polyendocrine metabolic ovarian syndrome has hit a nerve for so many women. And today what I'm going to do is I'm going to talk through my own personal history and see if this lands for you, because the challenge is is if you exhibit some of the hallmarks of PMOS, especially earlier in life, you probably got missed if you weren't just the classic ovarian cyst, no periods, infertility person, right? We believe 1 in 8 women are— is actually suffering with this. The vast majority don't even know. So let me go through my personal history because maybe this rings true for you. So if anybody's met me, I'm 5'3". I'm barely 5'3". I'm, I'm short. I'm what I like to call vertically challenged. However, I'm a curvy girl. I'm curvy girl. But when I was younger, until I hit puberty, I was underweight and smaller than my counterparts, not just because I was vertically challenged, but I was actually very, very petite. But literally overnight, when I started my period, it was kind of like everything exploded in multiple directions. So I started my period, which kind of freaked me out. And, you know, basically I, I had what I called the Brenna butt. So my dad's family— I am actually not of their genetics, but my dad's family, all the women in the family had a very large rear end, right? And my brother would call it the Brenna butt, and my last name was Brenneman. And but I, you know, I was always like, well, I don't know how I'm going to turn out, but I have a badonkadonk butt. Thank God for J.Lo and the Kardashians, because they made having butt, you know, a positive thing. So what really happened when I hit puberty, it was kind of like I exploded in all these different directions. I, I had body changes that were very dramatic, and all of those were significant waking. So I went from being undersized, petite, you know, pretty much metabolically able to sort of do what I want. But as you know, and I ate a lot, I was a kid that ate a lot. I had a really, really, really serious appetite. And I remember, you know, the family joking on Friday taco night about the amount of food I could consume. But I also burned a lot of it off, as you know, just kids do, right? But when I hit puberty, it was like everything shifted. All of a sudden I went from being undersized to basically having struggles with weight. Right. So my, my body weight went up dramatically. Now, my periods were abnormal, especially early on, but we know that that's also a very common hallmark of starting puberty. Right. So if you're a grandmother or a mother and you're watching a young girl go through her cycle starting, it doesn't pop up normally and come every 28 days perfectly without a bunch of pain and discomfort and all that stuff because the body is in a chaos zone. And we know that. Right. So that's what my, my, my puberty looked like. Now, when I went off to college, I started taking the pill. You know, it was in the middle of the AIDS days and it was also very much something that I wanted to control my fertility. And so I was on the pill. And so what does the pill do? The pill artificially suppresses your natural ovulation. And so basically you have synthetic hormones that bind irrevocably to the receptors on the ovaries and, and basically block ovulation. So what you see is you don't see the hallmarks of what's really happening metabolically behind the scenes. Through the shifts of ovarian hormones. However, the metabolic activity is still there, right? So if we were to look at somebody who has polyendocrine metabolic syndrome, I mean ovarian syndrome, what you would see in somebody who's, let's say, in their 20s and 30s, not on suppressive hormone therapy like birth control, is you would see luteinizing hormone elevated. You would often see androgens also elevated. You would see estrogen relative to progesterone low, you may or may not ovulate, right? But you may have periods, right? So one of the things that gets missed is you may have normal periods, but still have the hallmarks of what's going on because you're not necessarily developing ovarian cysts. And you may or may not be ovulating on a regular basis. We've known that about postmenopause or perimenopause for a long time. Women still have periods, but often aren't truly ovulating. Right? So if you're on birth control, that's all being hidden behind the scenes. But the metabolic derangement is still there because my 20s and 30s were time periods where I had to— it felt like I had to do heroic things to just maintain body weight, not, not try and lose significant weight. But I was always somebody that had to watch my caloric intake, watch my carbohydrate intake. I was very, very hypoglycemic in my 20s and 30s. And actually, at one point in my mid 30s, probably about 33, 34, had a glucose insulin tolerance test. Um, not because I was pregnant or trying to get pregnant, but, but because I wanted to see what insulin did. And my actual glucose levels didn't really rise radically. Uh, what happened was my insulin was way overshooting. So what it would do is number one, it would store fat first because insulin's job is to kind of say, okay, use this fuel or, or, or take this fuel to get put to fat, right? But I would get this hypoglycemic event where I would feel lightheaded and goofy. So if I had anything that was very high in carbohydrates, like if— let's say if I got up and had a bagel, or I had a cup of oatmeal— dear Lord, if I ever had oatmeal, even with protein powder in it, I would feel shaky, sweaty. And it was just— I wore— I was just like, okay, no carbs for me, right? So in my 30s especially, I was into bodybuilding, and so I had this very restrictive bodybuilding diet, and I could get weight off, but I had to— I'm not joking— I lifted heavy 6 days a week, either high intensity and frequency or heavyweight, low repetitions, but 6 days a week. And I ate on average about 1,300 calories a day, and I could get weight off, but it took like 2 years to do it. And I was starving the whole time, obsessed with food, just starving. And it was sheer willpower, right? Now, when I get into my late 30s, I come off— or mid-30s, about 36— I come off the pill and I get a tubal, right? So I get a tubal, and what that does is it reduces my ability to have a baby, so I don't have to be on the birth control. And I really I kind of came off birth control and went straight to tubal. So I didn't go for a long period of time to find out whether I would have cycled normally at all. But after that tubal, the shit hit the fan. And I am not kidding. I started losing my hair. I had acne show up across my chin and under my chin. And I kept thinking, oh, it's because you work out heavy, you're sweating. It's the sweat running down your face into your makeup and your hairspray and all that stuff. No, this was cystic acne, cystic, cystic acne. And I started packing on pounds despite doing what I would already— was already doing. I was working more. The stress was higher. You know, and, and it was definitely a time period in my life that was extraordinarily stressful, but I started packing on weight like nobody's business. It was like a font, right? I gained like 35 pounds and I'm 5'3", so imagine 35 pounds as a nutrition professional, mind you, as a nutrition professional who worked with people that were struggling with autoimmune conditions, but I had been in the bodybuilding community. I knew how to manipulate the diet, but my, it was like my body went Oh my God, right? And so here's the thing. So, so that's my experience. So I fought with my body, then my periods in this time also start coming together closer together. So my cycles are every 21 days on average. So what does that mean? So for those of you that might be my girly where you had shorter periods, they started getting closer together as you entered into your 40s and you're like, damn, I thought they were supposed to get further apart. What that is, is, is basically a luteal phase defect. Progesterone's not climbing high enough. You're not getting a normal follicular. So ovulation's really not occurring the way it's supposed to. Luteinizing hormone may or may not be normal. Your estradiol on a blood draw on day 21 might be normal, or day 19 might be normal. Your progesterone might be normal, right? All of those things that we would look at in a premenopausal workup that might say, hey, what's really going on? And I was still cycling. I, you know, I was still cycling and there were crime scene cycles, but But those are all hallmarks that there could have been this metabolic derangement behind the scenes. Now, even if you had regular cycles, you may not be exactly like me, but what I was told by the functional medicine community is that you're estrogen dominant, right? You're estrogen dominant and you are, you know, you're gonna gain weight because of estrogen dominance. So I was terrified of estrogen, honestly, cuz I was like, I'm already 5'3". I just packed on 35 pounds. I had to buy all new clothes and I And I dealt with that for a decade. That's why I went back for my PhD. Now, here's the other thing that happened. This is when pellets and testosterone therapy starts ramping up in the functional medicine community. And we do some labs and, you know, my testosterone's low. Do we check all the other androgens? Not really, because it was testosterone and free testosterone that was important. And I can tell you, my libido sucked. I was, you know, unmotivated. There was a lot going on. And so I get put on testosterone therapy and I get a pellet because at the time that was when they were popular. I was like, cool, I don't have to do anything for 3 months. Let's check it out. Well, I felt great for the first time. I had libido in a long time, but I pack on another 8 pounds over the course of 3 months. All right. So now I'm at all, like all-time high. And of course the practitioners, you know, say, oh no, no, no, it's water weight gain. It's, you know, testosterone causes weight loss. That's not true in women. That's true in men in some cases, but it's also an anabolic hormone. So if you, if you have other androgens that are high and it raises IGF-1, you have basically an insulin resistance coming and a fat storage coming from IGF-1. GF-1 and mTOR, right, which are two pathways stimulated by protein and insulin-like growth factor that testosterone drives independent of insulin, right? So, so I'm like, oh crap, I can't do testosterone anymore. I'm terrified of estrogen. I'm on progesterone, but I'm not getting the benefits that you would expect. I can't sleep very well. So I get an ablation because I have crime scene periods. So now I can't track really what's going on. So if this is tracking with you, you can probably understand it. So I'm using blood work to track it the whole time I'm struggling with my metabolism. And I go back for my PhD and I start pulling apart what's really happening. And what I did was several fold, right? I definitely changed my diet. I understood the metabolic effects of estrogen. I started taking estrogen therapy along with the progesterone. And now, you know, years later, I am on testosterone also. But what I'm telling you is what I know now just, just from my history and my experience is I was one of those PMOS women who was missed because we called it PCOS and you had to have ovarian cysts and you had to have, you know, a lack of periods to get diagnosed. Cuz I asked multiple times if this is maybe what's going on. And even the functional medicine community's, you know, agreement. I had lots of my clinicians that I was either friends with and or the ones that worked with me in the clinic say, yeah, that's probably what's going on. But how to address it was completely missed, completely missed. And so I moved through my forties in this sort of zone when I could have possibly caught it through lab work, maybe in my late thirties or early thirties. But now in the forties, it's very hard to pick up the lab work for PMOS. So what I'm gonna talk about today is how do we un— how do we unravel this and how do we pull these pieces together and how do we understand what's, what's really happening in particularly PMOS labs so you can understand if this happens to be you. So before we get into specific numbers, I want you to think about the framework here. So PMS lab testing is where most providers get it wrong, and we're also looking at lab ranges that are in a normal window and maybe not optimized. And we have to look at metabolic targets that are clear that insulin resistance occurs well below the lab ranges that you see. And, and the reality is, is PMOS has an underpinning of insulin resistance and hyperinsulinemia response to carbohydrate content. However, that does not mean that you eat protein alone and see the same effect, right? We're gonna go into that. So, so no single lab value is gonna tell you what's happening. You have to read the patterns. And testosterone often looks normal, but is SHBG normal or low? Free androgens are often elevated, but if you're not looking at all of those androgens like androstenedione, androstenol, and your other compatriots like DHT, you might be missing it because it's not just about testosterone or just about DHEA. Yes, your functional people often miss this. And we have to also understand that insulin resistance starts way below the 24.99 on labs. Anything over 10 is a good sign that we've got major things going on. And I would call an optimal range between 2 and 7. So, those are some things that we have to look at. Problem number 3 is we're often looking at the wrong stuff for perimenopausal women. A woman like you that might be dealing with this, they might look at FSH, estradiol, maybe testosterone, or not even testosterone, but your thyroid panel. And even if they're doing a functional thyroid panel, they might run T3 and all the other ones and a basic metabolic panel. But what often gets missed is that fasting insulin. The HOMA-IR, if you can find that on labs, not all labs do it, but that's an insulin resistance score that can sort of pull those pieces together. Hemoglobin A1C, free testosterone, DHT, SHBG, DHEA sulfate, and androstenedione, androsterone, and some of the other androgens that could be missed are red blood cell magnesium and some inflammatory markers like hs-CRP. Because if you're struggling with this, you will often have elevated hs-CRP despite working really hard at taking fish oils and doing anti-inflammatory diet because because you have metabolic syndrome behind it, acting especially in the absence of estrogen and a progesterone inherited deficiency. So, so let's talk about it. So testing, right? Fasting insulin. This is probably one of the most important tests that every woman needs to get, but especially if you think you're in this PMOS framework and you've aged out, I'm gonna, I'm gonna air quote that aged out of the easy diagnosis, right? Because you're no longer cycling or your cycling is so abnormal now we can't see it if you happen to be pre, uh, perimenopausal. So we have to look at fasted insulin and if it's elevated, anything over, you know, really like a 10, I wanna know why. Is it you're not sleeping very well? Because the early insulin resistance is where your pancreas compensates by creating more and more insulin to move glucose into cells. And then when you can't, you can move it into the fat cells. And at this point, glucose often looks normal. So it's not elevated in the morning, but it's really, really important. So if your fasting insulin is like 15, 20, God, 24, this is happening, right? Elevated insulin is doing two things that directly worsen, worsen this. It's driving androgen production in the ovarian cells, right? So this is the theca cells in the, in the ovaries and the adrenal glands. And so the more insulin we have, the more androgens we drive, right? And in, and you can see SHBG being suppressed potentially in the liver. But if somebody's not running those, we gotta see. So optimal labs are going to be, you know, under 7 in a fasted state, and definitely like a 2 to a 7. When we start getting into PMOS concerns is where we start to see this kind of 8, 9, 10, especially a fasted around 10 and above. That definitely means on a fasted insulin there's probably something going on. A 2013 study in Human Reproduction confirmed that insulin resistance is present in 65 to 70% of women women that would be PCOS, PMOS, regardless of BMI. So even if you are one of the women that maybe were diagnosed with PCOS when you were younger and it affected your fertility, but maybe you didn't have the version with weight gain. So there's a PCOS, PMOS in this case, that doesn't have weight gain, right? They're the atypical thin PMOS, but most women experience the other side where they had weight gain. But we saw that, you know, so, so the, the, the, the issue is there regardless. Now, homo- HOMA-IR stands for homeostatic model of assessment of insulin resistance, and it's a fasted glucose in milligrams per deciliter times fasting insulin in milliliters per, or milliliters per liter divided by 405. So basically you want your HOMA-IR to be under 1.5. Insulin resistance is present above 2, and significant insulin resistance is present at 2.5 or above. And if you can find this, but you can also calculate your own by using that math and, and look at it. One of the other tests that's really important here is your A1C, your hemoglobin A1C. In the normal labs, right, it's going to— going to be between about a 4.7 to, you know, basically a 5.7 on the ranges. And this reflects your average blood glucose. So kind of where does it go down to and where does it rise to and what's the average between those two over 90 days, but it has limits. Right? So a standard normal would be under 5.7. A functional optimal would be about a 4.7, 4.8, to about a 5.3. POM— PMOS hemoglobin A1C can be falsely low in women with rapid blood cell turnover. So if you actually have red blood cells that doesn't— don't really survive 90 days, you can get a false, you know, assurance here. And it doesn't catch early insulin resistance in the way fasted insulin does. So your A1C will often be normal for a really, really long time. It's a downstream marker and using it alongside a fasted insulin, don't use it instead of. All right, what's the other one? A fasted lipid panel, particularly triglycerides, right? So LDL, we always focus on, right? Cholesterol markers, your doctors are always really hyper-focused on cholesterol, but the most important number, particularly in PMOS, can be the triglyceride. Right, and the triglyceride to HDL ratio. Triglycerides are almost directly related to insulin resistance, and some women will produce more triglycerides than others. They'll see that rise first before glucose. Other women might see glucose rise first. But when insulin resistance is high, the liver overproduces triglycerides, and elevated triglycerides also enables the production of small, dense LDL particles, the atherogenic kind, the kind that causes arterial plaquing. So if your LDL doesn't remarkable, this could still be going on. You could have a— so what, what does that mean? My LDL could be completely normal, but I am doing this behind the scenes because the triglycerides are better, are, are, are driving this. So what's the good triglyceride? What's the better? The lower the triglycerides, the better, right? So your, your ranges will go all the way up to un— 150. It's gotta be under 100. And I actually like it under 79, you know? And what's even more important is that triglyceride to HDL ratio. So we want it under 2. Um, basically above a 3 is a significant sign of insulin resistance. And if your triglycerides are over 140 and your HDL is 45, your ratio is 3.1, right? That's a good way. So if you're in those ballpark ranges, you got an issue right now. Fasting glucose, uh, we would call a standard normal 100, right? A fasting optimal in a functional range is 70 to 85. What I watch for is somebody that's hovering in that 90 to 99 and constantly there. But in the context of high fasting insulin, it tells me that insulin, insulin resistance is fully compensated, but won't stay outta the way. So what does that mean? If you're somebody that's got a 95 all the time, your doctor's like, you're cool. You finally do a fasting insulin and maybe your insulin is a 10 and they're like, oh, you're cool. And it's consistently there. This tells me that insulin resistance isn't fully compensated, but won't stay outta the way. So this is where we know there's things going on. Women with PMOS carry a 3 to 5-fold lifetime increased risk of developing type 2 diabetes compared to women without the condition, right? This is an accelerated activity and it accelerates during the perimenopausal transition. This was a 2023 art, uh, research article that shows that this is a future problem and it starts in perimenopause, right? So many, many women keep getting told that they're okay and then they get on the menopausal side and all of a sudden they're like, hey, by the way, did you know that you are, uh, diabetic or pre-diabetic? And it's because it's been brewing behind the scenes. And if your doctors aren't looking at the right stuff, you might get missed. All right. Test total testosterone, right? Normal female ranges, if you look on the reference ranges, are going to vary wildly by, by labs. Typically, we're going to see a 15 to a 70 in, in a perimenopause to menopausal woman. What total testosterone misses as a free fraction amount of the biologically active portion, right? So free testosterone tells you how much is free. And if you do SHBG, that'll tell you how much is free freed up, um, which is often low in somebody who's insulin resistant. And a normal total testosterone can also mask a significantly high free total androgen excess. So what if you're making androstenedione, androsterone, DHT? What if the total androgens are actually elevated, but your total testosterone doesn't show it? We've seen in our clinic and also with women in our telemedicine company that have a total testosterone of maybe 42, 35, who have significant hirsutism. So chin hairs, you know, mustache, hair loss on the scalp and thinning, and androgen-driven acne because their SHBG was like 18 and their total free testosterone may or may not have been high, but their other androgens could be high, right? What was happening to me when I came off the pill and had my tubal? I got massive cystic acne. I started getting massive hair loss. I had significant weight night grain, significant activities of having kinda hypoglycemic events. And when I looked at my hormones, my total testosterone actually on labs wasn't that dramatic. And actually my free testosterone looked fine. But at the time, we didn't check all these other ones. We did check DHT and my DHT was not wildly elevated, but we never checked androste— androsterone. We never looked at those in depth. Now, SHBG is probably the most under-ordered test, particularly in PMOS. It's produced by the liver and it binds to testosterone and estrogen, keeping it inactive. Insulin suppresses SHBG, and especially in a woman, estr— estrogen, estradiol stimulates SHBG. So depending on where you are on in the perimenopausal journey, you may not see this while you're looking at labs. If we're trying to assume what's really happening, the optimal ranges are about 70 to 130. If we have PMOS, we want a SHBG under 40 because that'll significantly drive androgen estrogen activity, even with low or normal T, right? Low or normal testosterone. What drives it down is insulin resistance, obesity, hypothyroidism. That almost always is a problem. And then oral estradiol, if you're doing any kind of oral estradiol, this will make it worse. And then what drives it up or improves it's transdermal estradiol, right? So topical forms of estradiol for perimenopause and menopause, thyroid optimization, insulin sensitivity improvement. It. So this is really important, and a lot of your practitioners don't understand the nuance right now. Free testosterone can be measured, right? And this is, this is calculated, and most of the time it's a calculated free. It's not an actual measure. And so if we have what they call the free testosterone and free androgen index, it's also known as FAI. You can calculate this by taking your total testosterone and divide it by SHBG, Right? Get your SHBG and then multiply that by 100. It's a quick calculated, and we want this optimal FAI under 4. In PMOS, we'll often see above 5 to 6, which, which will also often have hair thinning, acne, maybe chin hair and mustache growth, all of those things. So if you're, if you're 4 and above, this could be a really, really interesting thing to, to understand because this may be driving things. And a lot of times in menopause, menopause, doctors, including functional doctors, will look at it and go, well, we expect hirsutism because we, we get fuzzy, right? I, I was like, where did the peach fuzz come from? Why do I have chin hairs that grow 6 inches within a day? How come I can see him in my rearview mirror, but I can't see him in my own bathroom? Whole nother problem right now. This is important. So a 2020 study following women with PMOS through the menopause transition found that while total testosterone declined with age, the free androgen index remained significant elevated as estrogen declined compared to age-matched controls, particularly with women in insulin resistance. So what this means is, is women with PMOS in menopause will have a total decline of testosterone, right? So you'll look like everybody else, but you may have insulin resistance driving an androgen index that is elevated. And if you aren't looking at these other androgens, it may be missing. Especially if you don't have estrogen replacement and progesterone replacement to help mimic what was really supposed to be happening in your body. Now, DHEA sulfate, DHEA sulfate, dihydroepiandrosterone, is the primary androgen in your adrenals. In PMOS, the adrenal androgen excess is commonly overlooked, and DHEA can definitely tell you whether the androgen burden is primarily ovary, ovarian, or androgen or both. Both. So what does that mean? You can have androgen dominance being driven by your ovaries while they're still cycling, while they're still doing something, and you can also have androgen excess being driven by the adrenals. And this often gets missed because we assume that DHEA is really being driven by adrenal function, but that's not necessarily true. Your functional optimal range is around 150 to 250 for women in their 40s. If you have a dil— elevated DHEA sulfate, that suggests androgen excess from the adrenals, right? Often linked to this sort of HPA, so hypothalamic pituitary adrenal axis dysregulation and chronic stress. So if you've been stressed out, this probably played a role somewhere along in your life. However, low DHEA sulfate can occur later in perimenopause and is associated with fatigue low libido, and mood instability. And this is its own clinical problem, right? So you may have been elevated early, but when you're in the throes of perimenopause and menopause, often we see low levels. And so then your doctors go, you couldn't be PCOS, renamed to PMOS, because you don't have high DHEA sulfate. So you could still exhibit this without an elevated DHEA sulfate, but if it is elevated, then that's what's really going on. Now, DHT, this is underrecognized. It is converted from testosterone by the enzyme 5-alpha reductase. So genetically you either do this really strongly or not. It is significantly more potent than testosterone, about 7 times at, at the androgen receptor. So think of hair follicle, think of fat cells, think of, think of acne, right? So DHT is more active at the receptor than testosterone. Most conventional labs do not include this. So you have to ask for it specifically. Elevated DHT with normal T is common in PMOS. Now DHT can also be acting on your scalp. I've had a lot of conversations about this on the podcast in the past. So if you're experiencing androgen-like hair loss where you're losing across the scalp in this area and your DHT looks normal in the blood. It could still be accessing the receptor in the hair follicle causing hair loss despite having normal blood levels, right? So this is a target for intervention, particularly like zinc, saw palmetto, 5-alpha reductase inhibition with things like, uh, spironolactone also. Now, to the other test, luteinizing hormone and follicular stimulating hormone. In reproductive age women with PMOS, the classic finding is LH is elevated. Compared to FSH, usually a 2:1, because high LH drives androgen production in the ovaries, not the adrenals. In perimenopause, this can get really complicated cuz FSH rises as ovarian, uh, reserve declines, and that can normalize the ratio. So if you're like me, and I never looked until I was in my forties, right? Well, I, my FSH was higher than it was normally when I'm 20 and 30 probably, right? And so all of a sudden it doesn't look abnormal. So if you're looking for a high LH, you may not see it because FSH is already elevated because your egg reserve is low and the brain now is telling the ovaries to get to it with FSH. So what I'm actually looking for is context. So FSH is climbing above 10 to 15. We're in perimenopausal territory. If LH remains disproportionately elevated relative to FSH, even in perimenopause, that's telling me the ovarian androgen drive is still active. And even as they climb, you'll see them elevated as they climb in post-menopause, right? Estradiol. So perimenopausal ranges obviously go all over the place. I've had lots and lots of conversations of those and they can swing, you know, 30 to 300, 400, 500, depending on, you know, where you can go. And in perimenopause, it could go from 30 to 500 to 300, back down to 30. What we watch for is the trend, right? So if you're still cycling, we're gonna watch for a trend where a woman might be bottoming out at a 20 to 30, losing estradiol's protective effect on insulin and SHBG, which then makes everything work. And if you're still cycling, this is where drawing your hormones actually on day 3 so first day of your cycle, you go out 3 days and look at the follicular phase baseline. If that is off, that is a sign that something is going on here and you have a follicular phase defect, probably because a luteal phase defect on the other side, even if you're cycling and even if you're still cycling normally. Now progesterone, right? So this is one of the hallmarks in women with PMOS and especially in perimenopause and anovulatory cycles. You're not ovulating. You may have cycles, therefore not producing progesterone in the luteal phase, you're gonna be significantly low, right? This is, um, if you draw the luteal phase and look at day 7 after ovulation or day 21 of a 28-day cycle, anything above 5 nanograms per milliliter indicate ovarian ovulation probably occurred. And anything above a 10 really suggests adequate luteal function. So if you get yours done kind of in the cycle or on day 21, you're still producing progesterone. Low progesterone that occurs because you don't have the LH sort of fluctuation and you have a luteal phase defect. Often this is happening and you could still be cycling. Now in the low progesterone context of PMOS, this contributes to things like sleep disruption, anxiety, estrogen dominance picture that I talked about, right? I had all the hallmark symptoms of estrogen dominance. And, you know, because progesterone counterbalanced that and supports GABA, I had a horrible experience with sleep, the estrogen dominance symptoms and everything else. And it's because that progesterone really wasn't coming up on its own. And I was on progesterone. I was on progesterone and didn't really see the improvements that should be seen. So if you're given progesterone and you're a perimenopausal woman and your sleep isn't getting better, your anxiety isn't getting better, your cycles aren't getting any better. This could be a sign that you have issues going on underneath and it's really not being addressed because the progesterone itself is not enough to make up for that luteal phase defect and the metabolic activities below. Now, the other test is obviously a full thyroid panel. We need TSH, free T3, free T4, reverse T3, thyroid peroxidase antibodies, thyroglobulin antibodies, we need to know that the TSH is widely varied, but I like to see, you know, if we're looking at labs and we're looking at those optimal ranges in research and our clinicians that we work with both in the clinic and in telemedicine, we like to see it between like a 2 to 2.5. Ideal range is a 1 to a 2. We don't wanna suppress TSH. TSH is really important to bone support. Also, thyroglobulin independently supports bone. So if we suppress it too much, we may see bone loss even though the thyroid, everything else looks normal. What we often see is that important thyroid hormone, free T3, can be low with a normal TSH, and the conversion of T4 to T3 can be impaired by insulin resistance and inflammation. So if you're a woman that maybe has never had your TSH out of balance but your free T3 is low, or maybe your doctor never looked at it but it's always low, it can be made low by insulin resistance and inflammation being driven by the metabolic sort of derangement that goes along with PMOS. And you may be fighting to get it up and still not be able to get it up. If you have antibodies that are elevated, that's Hashimoto's, and then we have even more issues, and that's often co-occurring with women, and it becomes worse during the perimenopause to menopausal trans— transition. The problem is, is endocrinology would say, if your TSH is not off, you do not have hypothyroidism, but what you have is T3 conversion problems. It's still a problem. It's just not classic diagnosis of hypothyroid, needs to be addressed. Addressed, right? Needs to be addressed for sure. But if you go fight with endocrinology, they're going to tell you your TSH is normal, your thyroid is working as expected, but the conversion is underperforming. And that's where having a really well-informed clinician that understands not just the, just the perimenopause and menopause, but actually understands the interrelationship with thyroid is important. Now, there's a couple other domains here. So inflammation and nutritional markers, specifically hs-CRP, or highly sensitive C-reactive protein, is an acute phase inflammatory protein produced by the liver. In women with PMOS, it's chronically elevated. Anything over 1 is, is significant, but we want it under 0.5. In PMOS, we'll see it between 1 and 3. Above a 3 is where we start to see cardiovascular risk. And a lot of women are walking around with this all the time. Sometimes it can be acutely elevated with illness, injury, infection. So don't get it done when you have an infection, get it done when you're kind of baseline so you can see it. There was a 2020 2022 meta-analysis that confirmed women with PMOS had significantly in— elevated inflammatory markers, including hs-CRP, interleukin-6, and TNF-alpha, independent of their BMI. This is not a weight problem, it's a biological phenotype, right? Phenotype is your genetics and your environment and your body physiology working together. And so we have to look at all of those things. That's why we have the phenotype quiz at Minerva, because we can actually help you understand, are you metabolically this by looking at your history and your experience. So what this means is, is women with this condition will have more chronic inflammation, which increases our risk for diabetes, increases our risk for cardiovascular disease, stroke, heart attack, and all other chronic inflammatory diseases. So we wanna test it and we wanna test it every time we get blood work cuz we wanna know where it's moving. Vitamin D, right? Deficiency is almost near universal unless you're getting it and taking it. We wanna be 60 to 80 in most cases. Vitamin D. Receptors are expressed on your ovaries and your pancreatic beta cells. Deficiency worsens insulin resistance, impairs ovarian function, and amplifies inflammatory signals. I had a family that we worked with years ago in our clinic, and their son was diagnosed with early onset, um, type 1 diabetes. They caught it so early, they were put into a study where all they did was give them high-dose vitamin and omega-3s. And in that study, it was, it was significant. So they had a portion of the people that responded, had clinical significance that it actually reduced the beta cell damage and preserves some of the insulin production in the beta cells just by inducing and putting in vitamin D and omega-3s, right? So multiple studies have shown this, that when we— when women start vitamin D in PMOS, they get improved insulin sensitivity and reduced androgen levels and improved menstrual irregularity Alright, that's in your classic people. So even if your menstrual cycle is normal, you need vitamin D. RBC, red blood cell magnesium is also really important. We want a 5.5 to a 6.5. This is a cofactor in 300 different chemical reactions, including every step of insulin signaling, glucose metabolism, cortisol regulation, PMOS, PMOS-associated insulin resistance itself can drive urinary magnesium levels down. Loss. So you're peeing it out and creates a self-reinforcement depletion cycle. So almost all women with this almost always have relatively low amounts, and you wanna be on the optimal side, and you need to probably supplement regularly because you're gonna be losing some of it through the urine. Now, in the stool, beta-glucuronidase, right? So bacteria in your gut produce beta-glucuronidase. It's an enzyme produced by many of your bacteria, and it's there to help recycle compounds in the gut back into the bloodstream. Stream. This is a, this is kind of a symbiotic relationship we have with our microbes. And when we have gut dysbiosis, leaky gut, inflammatory activity, what we see is an increase in beta-glucuronidase production. It also goes up and the bacteria that produce it go up as we go through menopause. And here's the thing, it is elevated when we have gut dysbiosis, especially if we're eating a high animal protein diet. Diet. And what it does is it basically takes the wrapper off of estrogen-like compounds that are slated to go out in the stool and pushes them out into the bloodstream. This drives estrogen recirculation, which can worsen the estrogen to progesterone imbalance and then the overall hormonal burden. Elevated levels means we have a gut that is recycling estrogen activity and we need to address it. Things like calcium deglucarate and improving lactobacillus species and working on fiber and gut permeability is really important. And I just did a, a podcast on how to increase your fiber in your diet and why it's so important. And so here's the things, right? So we have these patterns, right? And so when you have these labs, we can get to pattern recognition. And this is where we have the classic insulin-driven picture. This is gonna be a fasting insulin of like 12 or above. Above. Insulin resistance score, the HOMA-IR, usually a 2.5 to 3.5. Fasting glucose is going to be the 90s and above. Triglycerides are going to be elevated above 130, and your triglyceride to HDL ratio above 3. Androgens are going to be elevated, usually with a sex hormone binding globulin that's low, and your free androgen index and hSCRP are all going to see this. So clinically, insulin resistance is the primary driver here. So we wanna look at all of these. And so the insulin resistance is directly suppressing HBG and driving and adrenal and ovarian androgen production, creating this inflammatory activity. So this is where we start insulin resistance first. Everything else improves downstream of that. This is where a high fiber diet improving the sensitivity to insulin with ingredients like inositol, berberine, alpha lipoic acid, and insulin, and doing things like time-restricted eating and closing the window a little bit, not drastically, a little bit. So 3 hours before bed and ideally fasting about 12 hours to 14 hours overnight and also improving insulin resistance by adding resistance training and more daily activity of movement. So moving more each day because women need that more than men. And I would include at least 1 to 2 zone 2 trainings each week. Now I'm not gonna go into those here because I could go on for hours what those look like and make sure your vitamin D is adequate. Inadequate. And this is where dietary change produces the fastest and most— and fastest and most important results. So this is where you have to double down on the diet, right? Double down on the diet and get that fiber level up before you see the weight change, right? We got to get that because until that insulin control comes down, we're going to have issues. So pattern number 2, adrenal driven. This is a fasting insulin that might be borderline, like a 7 to 10. DHEA sulfate is either elevated or high normal. Normal. Total and free testosterone are probably on the higher side, if not high normal, if not above. And if you get your other androgens like DHT, androstenedione checked, you're probably high on those as well. Cortisol is elevated. If you do like a 4-point, you look at it, it's high, right? You've got high cortisol and especially a morning spike and possibly a poor evening drop, meaning it stays elevated all the time. Your HSCRP is probably elevated and your thyroid looks normal, especially on TSH, but your free T3 is low, right? So this is the adrenal problem driving it. What this means is the HPA, so hypothalamic pituitary axis, the stress response system is the primary driver here. Adrenal androgen production is elevated. The cortisol pattern is dysregulated. The low T3 with a normal TSH means that cortisol is impairing thyroid conversion and utilization. If this is you, you often present with anxiety, insomnia, hair thinning, primarily at the temples and over here, and you describe feeling wired and tired. I spent my entire latter half of my thirties and my entire forties feeling that way. I was so exhausted. I couldn't sleep and I wanted to slap the shit outta everybody. I was so worn out. I controlled myself, but I was so worn out. So where do we start here? This is where the adrenals are causing it. We need stability of the HPA axis, sleep architecture, cortisol rhythm improved. Vitamin D, sun exposure in the morning, and circadian rhythm support is really important here. Adaptogens, ashwagandha, phosphatidylserine, rhodiola are all helpful here, and especially magnesium glycinate at night with B6 helps address some of that magnesium loss and also supports the kind of calming of the central nervous system. And we may need to address thyroid concerns and make sure that you're getting T3, whether it's through conversion support with the right nutrients like zinc, iodine at the right levels, not too much, or maybe actual T3 supplementation with a medical provider that can actually do that. Insulin works— work runs parallel, but this isn't the primary lever here. So if you're this adrenal person, you gotta get this stuff dialed in. Then you layer in the insulin-resistant one, the pattern number one, but you have to get this dialed in. For me. I could not sleep. I could not— I could not get my wired and tired under control until I sort of dialed in this side. Then I worked on the insulin resistance. Now, pattern 3 is where it's inflammatory-driven and dominant. This shows with a high hs-CRP, high fasting insulin. Triglycerides are often elevated, but not always. Low vitamin D, often under 25. 5, red blood cell magnesium is often low. And especially if you have estrogen recycling or estrogen dominance-like symptoms and your beta-glucuronidase is elevated, this can all be a sign that something's going on. And often this is where the autoimmunity stuff shows up. Hashimoto's autoimmune, celiac, colitis, all those, right? If you're an autoimmune person, you got inflammatory dominant profile anyway, right? You, you're fighting that on a regular basis. So estradiol is very variable if you're in perimenopause during this time period, but it's trending lower than what it was before. The problem is, is you don't know what it was before, so you may look like you're in the normal ranges depending on where you get it taken, right? Because again, if you're cycling still, you don't know what you don't know. You could be mimicking a normal cycle but still have low estrogen, right? Let that sink in. Now what the labs will show, they'll show all of that, but how do we fix it, right? So what this really means clinically is the inflammation is starting and, and residing in the immune system and the gut, and that's the primary driver. The autoimmune is the common co-occurrence, especially Hashimoto's, and gut dysbiosis is making this worse. So we have to get that under control. You often have things like joint pain, bloating, skin issues, not just acne. I'm talking rosacea, eczema, mood instability. You get Heidi rashy, you know, could it co-occur with histamine? For sure. Right. But what does this all tell us? We gotta start with the gut. We gotta remove inflammatory dietary triggers. We gotta aggressively support vitamin D, omega-3s, support magnesium, help reduce beta-glucuronidase by feeding the good guys, the lactobacillus, getting fiber in the diet. This is not the time to do carnivore or hardcore keto, because the reality is it's going to make it worse. Calcium D-glucarate as a supplement at 1,500 milligrams a day has been shown to help keep beta-glucuronidase activity reduced and keep the estrogen bound in the stool to help remove it. That can help, and it's one of the components that I use in my Estro Balance Mastery to help the detoxification and the support of estrogen, particularly in perimenopause and menopause. Pause when you're already in the chaos zone, right? So the PMOS pattern really tells you where to intervene. So from a supplement standpoint, like I said, the Estro Balance Mastery really helps with the inflammatory dominant feature. The Energy Boost Mastery and the Stress Less Mastery help with the adrenal-driven picture. So if you go to Metabolic Blueprint, you can find these products because again, often these are all co-occurring. These are all supplements I took as I moved through sort of my resetting of my metabolism. Metabolism. I don't have that extra 35 pounds that I had. I lost all of it as I went through menopause and started working through this sort of metabolic history. And now it's gone. And then the insulin side, having things like berberine, gemena sylvestris, alpha lipoic acid, and inositol and myoinositol, all those things can help. And so my, my product Blood Sugar Mastery helps this. And then we also have inositol product as well. So the reality is, is we can, we can often see these of things co-occurring and supplements and the lifestyle matter, but you can't supplement and not do the lifestyle. Believe me, I tried, doesn't work. So here's, here's your take, right? Here's what you need to think about is if you're working with clinicians that don't understand this, this is the wake-up call to start working with somebody who does, because when you go into perimenopause and menopause, this is still active. This is still true. And if you don't have the right labs, you can't tell. Well. And even with the right labs, we may not be able to see it if you're in menopause because a lot of the hormonal ovarian production behind it is messed up. But we can start to unravel that with your history, with your experience, with your other information that we can get and start to fix it. So here's the way to think about it. PMOS is not a single disease. It's not anything about cysts on the ovaries, and it's a syndrome, which means that it has multiple phenotypes. Types, right? That classic, the adrenal, or the inflammatory. So the insulin, the adrenal, or the inflammatory, and often they start to commingle, but the primary driver is the important one and it requires a lab-guided approach and requires an understanding of the phenotype approach. This is why I really, if you get a chance, I would love for you to go out and take my phenotype quiz. And how you get to that is go to quiz. Drbettymurray.com, and you can take that phenotype quiz and understand exactly which, which area you are in, because we can see it. And this is why the exercise more, eat better, calories in, calories out is wildly insufficient and is wildly insufficient for women as a whole, but especially a woman who might have been dealing with this their entire adult life. So here's what you need to do. Go home, look at your labs, right? Check out your labs, because your chances are you're in the car, you're walking, you're doing something while listening to the podcast. Go get labs out if you can and see what labs you do have and see if some of those trends are true. Go back and listen to part 1, the, the initial podcast on June 24th, so you can understand the actual activity and see what's really going on and why PMOS is so prevalent and being missed. And then come back to this episode and start to dig through and understand where this may be playing a role for you and then get a PMOS HS literate clinician. And this really is more than just one. You need somebody that can absolutely do the hormones and do them correctly, address the adrenals, the estrogen, the testosterone, the progesterone, the DHEA, the insulin, and the thyroid together, and help walk through the dietary lifestyle and supplement changes you really need. And if you're still struggling, right, this is your opportunity to really look at where you're at today and get help with your team, right? And your team is probably gonna include a nutritionist, health coach, and your clinician that can help you with the medical side. That's why at Minerva and even our clinic in Dallas, we always have that triad of support because the reality is usually what helps us get better and stay well is a combination of diet, lifestyle, exercise, stress management, sleep, hormone balancing, improving our outlook on life. And getting all of these things taken care of. So hopefully this helps you. We had so many questions about PMOS online on Instagram, and then even after this initial podcast release that I had to come out and actually answer some of these questions. So thank you for listening to Menopause Mastery. I know this was a loaded, loaded podcast. You'll wanna go back and listen to it again. Definitely get online and even watch it on, on YouTube so you can get your answers, and I'll see you next week.