WOMEN'S HORMONES Explained: Energy, Mood, PMS, and "Normal" Labs
In a recent episode of A Whole New Level, Levels editorial director Mike Haney sits down with Dr. Anjali D'Souza, an integrative medicine physician who runs a functional health clinic in Washington, DC, with a focus on women's health. The conversation dives deep into women's hormone testing and how to interpret common markers that often get dismissed as "normal" even when someone feels far from well.
Dr. D'Souza walks through the major hormones that affect women's health---estradiol, progesterone, testosterone, and others---explaining what they do, when to test them, and what optimal ranges really mean. She shares her approach to conditions like PMS, PCOS, and perimenopause, emphasizing that hormone panels are only useful when you understand the timing, the ratios, and the metabolic context behind the numbers.
The discussion also covers how stress affects progesterone, why testosterone matters for women's health and longevity, how birth control impacts testing, and when hormone replacement therapy makes sense. Throughout, Dr. D'Souza makes the case that hormones are central to quality of life---affecting everything from energy and mood to bone health and cardiovascular risk.
If I had to pick one area where you could really move from feeling eh to amazing, it would really be your hormones.
— Anjali D'Souza, MD
The functional medicine approach to women's health
Mike Haney: Anjali D'Souza, welcome back to the podcast.
Dr. Anjali D'Souza: Thank you so much for having me.
Mike Haney: So the context for this conversation that we're having is that Levels is expanding into blood testing, or rather expanding into expanded blood testing. We've had a pretty small panel we've offered for a couple of years, but now we're offering a much more expanded set of blood markers that people can get. So we're doing a series of conversations on the podcast with experts in various functional areas to dive deep into sets of markers. And today we're going to talk about women's health and hormone markers in particular. So maybe as a place to start, a little background on you. I'll just set up that you run a functional health clinic in DC that focuses a lot on women's health, but maybe talk a little bit about your journey, how you got there, and what the clinic focuses on.
Dr. Anjali D'Souza: My journey started very early on as a young kid being exposed to nutrition and meditation as just bread and butter of being well. And this is what prompted me to want to go into medicine and was a little bit surprised when I learned that these aren't the things that are part of your medical care. But nevertheless kept moving on and pursued more and more training around how to think about people holistically, how to integrate nutrition, exercise, how to even think about utilizing the principles of functional medicine. I got that training and then after having my own experience of being a patient and really feeling shocked at how subpar that experience was, especially as a clinician, I just had to do something about it. And so I founded the District Center for Integrative Medicine and we do see all humans. I happen to specialize in women's care, partially because of that personal story that really makes me extra passionate about helping women feel their best because they are very vulnerable to having symptoms that don't really have answers but from a functional medicine lens often do.
Mike Haney: So what's your day-to-day look like? Tell me a little bit about the kinds of concerns that folks are coming to you with.
Dr. Anjali D'Souza: Yeah, most commonly I see a range of brain fog, fatigue, autoimmune conditions. So that's quite common and that can either be someone who is pretty advanced in their autoimmune condition and still just not feeling well, or someone who maybe is early on, recently diagnosed, has been given a laundry list of medications that they should take and is a little bit hesitant about jumping right into that and wants to see what else can I do potentially to improve my health and immune system. Definitely a lot of hormone related issues. So that ranges from PMS to PCOS to perimenopause to menopause, weight gain, body composition changes are huge. And the last big category would be, well maybe last big two categories would be something in the digestive health world. So IBS or even people with inflammatory bowel disease like Crohn's or ulcerative colitis that are looking for a more holistic way to care for themselves. And then finally, some mental health concerns as well.
Mike Haney: What does a functional approach mean in this context? What's different about somebody's experience when they come to you with one of these particular problems that you're talking about versus what they might get at a traditional doctor?
Dr. Anjali D'Souza: Most classically and maybe most simply, and we can unpack what this means, is we're really curious about the root drivers for the condition. So the way that I was taught and the way medicine works is we understand the pathophysiology of a disease and it has a name. Each disease may have a name and each one of those diseases typically has a set of medications most classically that are used to manage that disease. It may decrease the symptoms or it may halt progression of a disease but isn't necessarily trying to ask the question of well why did this happen in the first place? And I don't want to communicate that everything under the sun has that answer, right? But it's certainly an approach where I'm curious about that. I want to understand why that might be happening. And for the most part, there are drivers for conditions that include like what's happening with stress physiology. What's your gut microbiome look like? What's your nutrient status and nutrition? Do you have toxicity of some sort? There are many things that we can look at that actually turn things on in the body that then turn into this disease state that we kind of more classically know.
Mike Haney: And practically what's different then for the patient that you're working with when you go through this approach? Are they more likely to have lifestyle interventions to address it then go straight to a medicine of some kind? Do they see a different kind of resolution to the problem?
Dr. Anjali D'Souza: Yeah, that's a great question. So I think fundamentally most functional medicine practitioners are either versed in nutrition and lifestyle themselves. That's me, particularly my background is in nutrition and so there is a heavy focus on food is medicine as a very first important intervention early on. And I wouldn't say that physicians don't think that this is important that work in a conventional setting, but either they don't have the training or they don't have the time to really talk about this. And they may say something a little bit more cursory or very simple like, well, you should think about your diet. Well, what does that mean? Like what exactly should I think about? And the specifics of that might actually be quite different for the person and what they're coming in with. How do I integrate that with their beliefs and nutritional template? Like it's actually pretty complicated when you think about it. So yes, a deep dive on food is medicine and really focusing on these most important foundational health metrics like your sleep and your stress, community, spirituality if that's important to you and that could be nature, right? How do we incorporate these things that we know are healing to the body into a treatment plan? And outside of that and maybe more globally, it's time. I have a lot of time with patients. My initial intake is always 90 minutes long. It's rare that I see somebody for less than 30 minutes. Probably never. So I have a lot of time and that gives me such an advantage to be able to do very long histories to really start to make connections between things. And then yes, there is an intention to see what I can do without pharmaceutical intervention. Although I'm a physician, I went to a regular medical school. I have a prescription pad and I definitely use it. But it's more of a either a temporary stop gap or something that's an adjunct as opposed to the only thing I'm offering you.
Mike Haney: So I'll ask you the question we get all the time in the context of this conversation. How do I find a functional medicine provider or at least a provider that is sympathetic to a functional approach?
Dr. Anjali D'Souza: Yeah. So, the place that I was trained is called the Institute for Functional Medicine, and they have a find a practitioner link that you can look at that will give you a whole list of providers that you can look at. There's also the American Academy of Anti-aging Medicine, so A4M, and they also have a directory, and they are also functionally inclined where you can look for clinicians that have been trained in this approach. And not all of them are running private clinics. Some of them have just sought out this information and want to at least be knowledgeable about it and may be practicing in a more conventional setting. You have to have reasonable expectations about what they can offer because they don't have the 90-minute initial appointment, but at least they might be sympathetic to it. If you don't find something in that Venn diagram, then I would say if you look at someone's background education-wise, if you see maybe that they were an undergraduate in nutrition or they've taken nutrition courses, this is probably someone who you can reasonably guess might be more sympathetic to this more holistic approach.
The role of blood testing in functional medicine
Mike Haney: You and I had an earlier conversation probably a couple years ago now that is out in the podcast in which we dove deep into your background more and functional medicine in general. So, you talked about the intake. Where does blood testing or other sort of diagnostic assessment fit into that intake? What are you doing when somebody initially comes to you?
Dr. Anjali D'Souza: Yeah, blood testing is absolutely integral part of my assessment. The first part of my assessment is actually doing this in utero to current history taking, which is a very unique approach to taking a history. Typically, when you go to the doctor, it's like, oh, well, you know, I have reflux. Okay, like when did it start? What makes it better? What makes it worse? Do you have anyone in your family that has it? That might be the extent of the history taking that happens. If you come to see me, I might be asking you like, well, what was your mom's pregnancy with you like? And what kind of factors influenced your time in utero? Did you have allergies when you were a little kid? So, I'm collecting all this information that gives me a sense about systems in your body that may seem totally irrelevant to the thing that you came in for. But that is what allows me to then think about all the things that I'm going to order from a lab perspective. And there are some things that I just consider my standard which is probably more considered comprehensive in the context of this situation, in the context of medicine generally speaking. But the reason I do that is because it helps me cast this wider net that lets me look at things like, you know, okay if you're fatigued I might be a conventional doctor and I might run your thyroid panel and I'll see like nah it looks fine, but if I am looking at this I've run your thyroid panel and I've also looked at what is your zinc, what's your iodine, what's your selenium look like, how's your vitamin D, and your thyroid panel might be normal but if your nutrients are abnormal, it may give me information about how well is that thyroid having an end action at a tissue. The number looks okay, but the internal efficacy is not so great.
Progesterone is one of my favorite hormones actually. It is like natural Xanax that exists in your body as a woman. It's responsible for calming the brain. It's responsible for good sleep.
— Anjali D'Souza, MD
When and how to test hormones
Mike Haney: Where does hormone testing fit in? What hormones do you test sort of standard when anybody comes in and are there ones that you look at specifically depending on the condition or the state that somebody's coming to you in?
Dr. Anjali D'Souza: So for women that are coming to me with hormone related stuff, let's just start maybe with PMS. So with PMS, the most common thing besides certain nutritional things and lifestyle things, I'm wondering about this estrogen progesterone ratio that's happening. And I really am curious because typically, although there's some nuance to this, people that are struggling with PMS are really feeling poorly right before the bleed part of their cycle, right? They have insomnia, they have irritability, they may have major mood shifts and changes. And what I find is this is often related to a low progesterone response. So, they may have actually ovulated, but the strength of that progesterone release is a little sluggish, and this is part of what's causing their symptoms. And so, for a woman like that, I definitely want to catch more of a luteal phase assessment of hormones. So, I would look at an estrogen, a progesterone. I would throw on a total testosterone, free testosterone, and sex hormone binding globulin there. And in the early phases, I might look at a prolactin just to rule out that there are any major issues with the system overall. But I really want to know what's actually happening with the end result hormones in that luteal phase. And if someone is symptomatic and their progesterone is less than 10, I might be curious about, can we support your progesterone and help you feel better? And some of that is food, right? There are certain seeds and nuts that can help with that. There's also certain supplements that can support a more robust progesterone release. Something called Vitex is something that can be quite useful here. After a certain age there may be less efficacy with a medicine like that. And then I have also used a bioidentical progesterone for women that are really suffering. And you know to be fair there are some interactions between hormones and neurotransmitters when we're talking about PMS. So sometimes there is a role for very low doses either pulsed or continuously for SSRIs or anti-depressants or if you're looking for the natural approach then something like a 5-HTP which is a precursor to serotonin can be really helpful here.
Mike Haney: We're going to dive into each of those hormones that you just mentioned there. But maybe let's set the context just generically. What are hormones and what are they doing in the body?
Dr. Anjali D'Souza: Yeah. So, hormones are compounds that I would say if I had to pick one area where you could really move from feeling eh to amazing, it would really be your hormones. They're involved in your energy, in your brain function, in overall sense of vitality. So, really important in this kind of base quality of life. How are you walking around feeling in any given moment? But they also play a role in your cardiovascular health, your actual brain health, in your bone health, especially for women. It's so super integral to wellness.
Understanding estradiol
Mike Haney: So let's just walk through some of the hormones that somebody might get tested in a standard panel. And maybe we'll start with estradiol.
Dr. Anjali D'Souza: So estradiol is the most active form or the most common form of estrogen that we have in the body. We've got three different ones, but estradiol is the one that's probably most tested, I would say, and the most active as far as its action in the body. And estradiol is going to be released in part from your ovaries as you move towards the dominant follicle being picked as you go through your menstrual cycle. And it will release estrogen. And estrogen will have a role in your energy, in your body composition, in your mood, and it also is part of this very beautiful symphony of hormones that cycle to create your menstrual cycle. So, really important.
Mike Haney: Do we ever test the other forms of estrogen?
Dr. Anjali D'Souza: Sometimes. Estriol is a form of estrogen that you're going to more see in pregnancy and estrone might be seen more in the perimenopausal or menopausal woman. And I have sometimes looked at those especially more as women age to just get a sense of how is the whole cascade of these hormones looking when we're thinking about menopause. Definitely not before that as far as age goes.
Mike Haney: For somebody who's in their reproductive years, not post-menopausal or premenopausal. What's the best time of the month that they should think about getting their hormones tested?
Dr. Anjali D'Souza: Yeah. So, there are two big tranches that I think about. I like to look at hormones in the luteal phase. So, that's the second part of the cycle. There's the follicular phase where the follicle gets ready and chosen to be the one that is released and potentially ready for fertilization. The second part is that ovulatory phase. And then the third is called the luteal phase. And the luteal phase essentially is happening when that follicle that was released turns into a different character that is able to send out progesterone to the body. And if that egg becomes fertilized and you're pregnant then there's a new way for progesterone to be released. If there's no fertilization, progesterone will drop and you will actually start bleeding. So that luteal phase I think is quite important when we're thinking about whether it's PMS or PCOS, is really what I want to look at. Generically we would say maybe that's day 19 to 21 of a menstrual cycle, but I have also had women get more nuanced about it and actually purchase an over-the-counter ovulation predictor kit that they will use every day after they stop bleeding until it becomes positive, which allows us to know, okay, the luteinizing hormone, the LH has surged a little bit. And typically about 5 to 7 days after that is going to squarely be your luteal phase. Now, keep in mind like we can do all of that and game this out perfectly and then someone can just have a rogue period that shows up the day after I ask them to take the test. So we can plan in the best ways possible and we also have to be kind of flexible.
Mike Haney: So timing depends in some part on what is the issue that you're trying to learn about.
Dr. Anjali D'Souza: The other place, so I mentioned the luteal phase. The other place where I may look at hormones is more the day 3 to 5 period of your menstrual cycle. And here I might be more looking closely at FSH and LH. So these are hormone signals that come from the brain and talk to the ovaries. And here I might be more inclined to look at this in more of a menopausal situation where I'm looking at how is the FSH trending where higher levels may be telling me this brain is working really hard to talk to the ovaries to ask those ovaries to work and it tells me okay we might be getting closer to menopause. I may also look at these when I'm looking at ratios of FSH to LH that gives me a little bit of information around PCOS, although not routinely true. In more of a PCOS situation, which stands for polycystic ovarian syndrome, which is a hormonal condition affecting women, almost shy of 10% of women struggle with this condition, where they've got menstrual irregularities, you'll see an elevation of LH sometimes by two to three times to FSH where typically we expect them to see that they're more like one to one to each other.
Mike Haney: How do we think about the estradiol levels depending on somebody's life stage?
Dr. Anjali D'Souza: So, generally speaking, when we're in our adolescence and we're starting menarche, there's a lot of an erratic nature of estrogen, estradiol, because the system's getting revved up. It's starting to learn how to work. And it sometimes spurts out and sometimes doesn't. And so, there may be a lot of variability in what you see during this stage. As you move more into your solid reproductive years, if we're talking about the standard person who has a regular menstrual cycle, no real issues hormonally, there's a range that we look at. It may vary a little bit each cycle because not every cycle is the same, but there's a standard range that we see. And then in time we look at the graph over time---even though there's the standard range we're generally speaking starting to decline overall in estrogen as we move towards perimenopause and menopause. Those numbers are going to keep going down and down and down. And essentially that's just saying the ovaries that are responsible for helping us create that estrogen have been used. They've done their job and they're no longer with us anymore.
Mike Haney: And how movable is estrogen by behavior, by activity?
Dr. Anjali D'Souza: Yeah. So, I mean, I'll give you an example of someone that maybe has a very high level of estrogen that you might see more with obesity and or people that are very much struggling with xenoestrogen. So, they've got lots of endocrine disrupting chemicals that they've either utilized or they have in their life. And I will see, and it may not be overnight but I will see over time if we're doing steady changes on metabolic improvements and thinking about environmental exposures of estrogens, that estrogens will go down. And as a reminder like every cycle is different so there's also like if I test you last month and your estrogen was 200 and this month it was 70, I'm not necessarily worried about that because it's just a different cycle and I have to ground that in like what are the symptoms and what are the needs you have for me to actually decide I need to take action against something.
Progesterone: The calming hormone
Mike Haney: So you mentioned progesterone a couple of times. What is progesterone and what is it doing in our body?
Dr. Anjali D'Souza: Progesterone is one of my favorite hormones actually. It is the natural Xanax that exists in your body as a woman. It's responsible for calming the brain. It's responsible for good sleep. And it is, if we're talking about physiology, what is released by that early follicle that was taken out to potentially be fertilized. It's released by that corpus luteum of that follicle to potentially get ready for could you become pregnant. It also will overall decline in time because as you have both less number of follicles but also less quality of eggs, the amount of progesterone that we release is going to go down. This is the single thing that I find most effective as an intervention for women that are struggling with hormone dysfunction. Not just because it helps with sleep and with anxiety. So that can help with PMS. Women with PCOS, polycystic ovarian syndrome are having trouble with ovulation. So they often can be really supported by improving their progesterone profile. And women with perimenopause and menopause have declining progesterone. And sometimes and or in perimenopause have fluctuating estrogen. And that progesterone really helps balance. And I mean, when we're talking about something that single-handedly improves quality of life for women all the time, I would definitely say it's progesterone.
Mike Haney: And is that because outside of those natural declines over time, is it a hormone that's likely to just get disregulated for some reason?
Dr. Anjali D'Souza: Well, progesterone is very sensitive to stress. Stress physiology which obviously we're all dealing with and I as I probably have said before, women are uniquely sensitive to stress because of this connection. As we increase stress and cortisol we actually downregulate how well we ovulate and how much progesterone is being secreted. So yes, those things are very highly connected.
Mike Haney: So how movable then is progesterone when you talk about addressing it to improve somebody's energy, to improve their symptoms? What does that look like?
Dr. Anjali D'Souza: Depends on the age range. So in someone, and this is broad so the nuance might be different depending on the person, but let's just say someone in their 20s or 30s probably still has good ovarian capacity and if I'm trying to do things to move progesterone I probably will have pretty good luck with that with like cleaning up their diet, improving their glucose control and maybe giving them some things that improve ovulation overall, like that encourage good ovulation. As you move into your 30s or 40s, some of those things may help, but it may be that you're actually getting to a place where the ovaries maybe are not as able, they're not as capable to do it. And so, here's a place where I might actually give you real progesterone, right, as a hormone that I will prescribe to you to take. Typically when we're talking about someone who's still menstruating regularly, I would pulse that in the part of their cycle where they would naturally have a rise in progesterone to kind of keep mimicking the natural rhythms of hormones. And in a menopausal woman, they would just get it throughout. And when we ask about how movable it is, I do see progesterone levels improve as we do some of this.
Mike Haney: You mentioned that stress connection. Can you talk more about physiologically why progesterone and stress are related to each other?
Dr. Anjali D'Souza: So, a couple reasons. As you increase your stress and increase cortisol, like you're essentially going to be, if we start from the beginning, like all steroid hormones---cortisol is one, progesterone is one---come from the same place. And as we push down a pathway that's more stress related, making more and more cortisol, the pathway where we would have bifurcated to make our sex hormones is just going to be less traveled. We're going to push down the cortisol pathway and we're going to make less progesterone. So that's one mechanism. The other mechanism I would say is just stress generally speaking is going to have an inhibitory effect on the entire hormone cascade such that we're less likely to ovulate. We may have an anovulatory cycle and literally not even release an egg that's going to give us progesterone.
Testosterone definitely is going to support our mood, our cognition. It's important for our bone health and for body composition and libido---so in some ways all the things that we care about for men, but for some reason it's not so important for women.
— Anjali D'Souza, MD
Testosterone in women's health
Mike Haney: So, let's move on to testosterone, which of course is typically thought of as the male hormone, but actually plays a pretty critical role in the female body as well.
Dr. Anjali D'Souza: Yeah. So, I think testosterone is a definitely forgotten hero when we think about women's health. Testosterone definitely is going to support our mood, our cognition. It's important for our bone health and for body composition and libido. So in some ways all the things that we care about for men but for some reason like it's not so important for women, right? But it plays a huge role in our health in that way. And I would be more cautious about giving someone a hormone replacement form of testosterone in the early ages, but it's something I feel quite strongly about using in the right candidate in perimenopause and menopause and it can be pretty dramatic the changes, especially because as women move towards perimenopause and menopause because they're naturally going to have a loss of hormones that are going to make them more inclined towards metabolic disorders. And that's not just an aesthetic issue. That's a health and longevity issue. So, potentially bringing in some testosterone if you're going to think about hormone replacement can be really helpful for somebody to protect them against disease.
Mike Haney: What is testosterone's role in PCOS?
Dr. Anjali D'Souza: So, in PCOS, testosterone is elevated, too elevated. And when testosterone is high, there are a couple of things that can be problematic. It's going to drive up insulin resistance. So insulin resistance is essentially a condition where our bodies are no longer having a proper relationship between glucose and insulin. And insulin has to work really hard to get glucose into the cell or where it needs to be. And as insulin rises, you're going to be more inclined to struggle with weight gain, with lipid abnormalities, with metabolic syndrome, with blood pressure elevations. And this essentially is part of the problem with PCOS. As testosterone rises, you have more insulin resistance. As you have more insulin resistance, you have ovulatory dysfunction. And part of this happens because we talked about FSH and LH, LH, luteinizing hormone, which really should just come in at one part of the cycle and then go away. With the connection with testosterone and because of some changes with the pulsatile nature of how we tell LH to be released, which happens in PCOS, LH is always going. And when you're thinking about a relay race, right? If I give you something and you take something and go to the next place, if you've got someone always running in with a baton that's not part of the relay race, suddenly the whole thing is messed up, right? And that's what's happening with PCOS. We've got this insulin resistance problem. We've got an elevation of LH. And essentially, every time we send out a follicle to potentially be ovulated, there's a disruption in that system. And we're sending out more and more of these eggs that essentially never go to their end position. Right? So women are not ovulating. They'll have trouble with potentially infertility or abnormal menstrual cycles. They also because of the insulin resistance will struggle with weight gain and a lot of metabolic type of symptoms. So changes in lipids. They can be at increased risk for hypertension and overall long-term like diabetes and heart disease.
Mike Haney: What's the relationship between estrogen and testosterone and how do they move in relation to each other and how does that change over time? We talked about estrogen levels naturally fall over time. Does that mean testosterone levels increase over time or do they also fall?
Dr. Anjali D'Souza: So kind of interestingly like I was mentioning early when you start menstruating you have this little bit of erratic estrogen and then maybe some steady-ish state and a lowering of estrogen. You'll see early on girls will actually have elevated levels of androgens or testosterone. They have high levels. It'll come into more of a steady state and then as you move into perimenopause, there's actually like a big push for the androgens again before they come down again. So there is this variation that happens between them and testosterone can actually be what's called aromatized into estrogen. So, they have the ability to go back and forth. And you'll see this with PCOS. Going back to that question, because there's all this excess testosterone around, women tend to in the peripheral tissue aromatize to estrogen. So, profile-wise, when you're looking at a lab for women with PCOS, you might see elevated androgens or testosterone. You might also see elevated estrogens and you'll see low progesterone.
Mike Haney: And what am I looking at outside of a PCOS context? What am I looking at when I look at the lab result for testosterone which typically is free testosterone and also total testosterone. So maybe what's the difference between those and how should I read those results?
Dr. Anjali D'Souza: Yeah, great question. So you'll get a reading for total testosterone which essentially tells you like how much is in your body, how much was produced by your body total. This isn't the total amount that your body is able to utilize because it is bound by something called sex hormone binding globulin which essentially I think of as the Uber that will transport hormones to where they need to be but also potentially when they're bound they're not actually able to do their action. So that's what the free testosterone level tells us. It's what is actually bioavailable or what can be used by the body to actually make a change.
Mike Haney: And is that free testosterone number movable by behavior, by lifestyle?
Dr. Anjali D'Souza: I mean, it's movable per cycle on some level. It's never going to be exactly the same. And I certainly see if we're going back to the more extreme example of PCOS where you might be struggling with higher levels of testosterone, there are interventions including improving your metabolic health. Spearmint tea, for example, if I did nothing else and I had a woman with very high testosterone levels and she started consuming spearmint tea a couple of times a day, I would probably see a pretty dramatic drop in just the testosterone levels as a result of doing that.
Mike Haney: Okay, now I have to ask, why spearmint tea?
Dr. Anjali D'Souza: It just happens to improve the removal of testosterones in the body.
Sex hormone binding globulin (SHBG)
Mike Haney: Some sort of compound within the spearmint tea. Interesting. You mentioned sex hormone binding globulin. Let's dive into that one a little bit more. What else is it doing besides binding to testosterone in your body?
Dr. Anjali D'Souza: So I mean it can be a separate biomarker indicator for certain health things. So yes it's binding testosterone and it's helping with that transport as I said, but I also independently look at it to understand a few things. Most specifically because I'm very focused on metabolic health. If I see a sex hormone binding globulin that's 40 or below, I'm thinking even in the absence of other markers that might look normal from a metabolic panel that there's probably some insulin resistance around. So that's one way I look at it. On the other hand, if I see it quite elevated, it might be a clue that someone's getting some exogenous estrogen. You'll typically see a very high sex hormone binding globulin, women that are on birth control or taking estrogen of some sort. That protein will get elevated and I will also see it either with liver issues or some kind of sluggish liver issue or hyperthyroidism.
The impact of birth control on hormone testing
Mike Haney: You mentioned birth control there and it's a reminder. Let's step out for a minute to the whole idea of testing hormones. What are we going to see differently if we're on birth control?
Dr. Anjali D'Souza: I mean, first of all, I pretty much don't test hormones if someone is on birth control because we are artificially creating a unique state of your hormones when you're on birth control to prevent pregnancy and or to manage your symptoms of hormone dysfunction. And so any levels that you get there are really very artificial. Most likely you're going to see numbers that are overall a little bit low.
Mike Haney: In the context of it being artificial, it's still whatever your hormone numbers are, right? Influenced by the birth control, but does that tell you something? Is there still, would you still see some level of dysfunction or is it that when you're on birth control, it's regulating so narrowly what is going to be there that you're not going to see fluctuations that are going to tell you something?
Dr. Anjali D'Souza: I mean to be honest I don't test people regularly on birth control so I probably couldn't give you an answer based on my observation over time on that. But in the end it comes back to the practical reality of if somebody comes to me with a hormone related complaint and they're on birth control, my hands are pretty tied on what I can do if you're on birth control. I can help you with your metabolic health. I can improve your nutrients. I can help your gut microbiome. But I'm not going to have a lot that I'm going to be able to do with your actual hormones because of what you said, like that's just being tightly controlled. And looking at it over time is even kind of irrelevant because somebody chose that either to prevent pregnancy but most commonly at least for the patients that come to see me it was their method to manage whatever symptom was bothering them.
Mike Haney: Right. So if you suspect you might have some sort of hormone issue or you want to dive into that more, do you recommend people go off birth control for some amount of time?
Dr. Anjali D'Souza: Yeah. So I mean actually everyone that potentially comes to our practice speaks to one of our onboarding coordinators and one of the things that I have really instilled in that consultant is to say no requirement but please know that if you are on birth control there may be limited things that Dr. D'Souza or whichever doctor you're seeing at DCIM is going to be able to do because that is going to be a very static part of the treatment plan.
Mike Haney: And does that then impact other things that you might test because those hormones are controlled? Does it have a cascading effect?
Dr. Anjali D'Souza: Well, I mean, not necessarily test, but I often will see, this goes back to some of the lab marker questions. I will often see an HsCRP, the highly sensitive C-reactive protein, be quite elevated when someone is on birth control and of course the sex hormone binding globulin as I mentioned. And that's a little, it can be a little bit of a red herring because I don't know for sure if is it the birth control and so I have to do my due diligence to figure out is there something else causing inflammation in this person. But often times it's the birth control and women will ask me like oh my gosh, does that mean something bad? Like, what does this mean that it's causing inflammation in my body? And in the end, I don't really know the answer. I mean, we have lots of history with people being on birth control and doing just fine, but the bottom line is it does seem to be causing some kind of an inflammatory response in the body.
Understanding FSH and LH
Mike Haney: Let's get back to our list of hormones. You've talked about luteinizing hormone a little bit, but maybe start from the beginning on what luteinizing hormone is and what it does and again, what am I looking at if I'm testing that?
Dr. Anjali D'Souza: Sure. So if we step back like just a reminder that the menstrual cycle overall is this just incredibly coordinated baton handoff of hormones that are talking to each other. In the early part of your cycle essentially everything is pretty low and the first hormone that's going to come out to request some action is the follicle stimulating hormone. So that's the FSH. And it's going to ask the ovary to start deciding who's the ovary that's going to be picked to go do the job this cycle. And once that happens, you'll see that a follicle will start secreting estrogen. So it starts this cascade early on in the cycle. And as estrogen rises, this is a signal for FSH to come down. And LH then is handed the baton. So LH stands for luteinizing hormone. And it's involved in the secretion of testosterone. It helps to prompt testosterone secretion, but is also most commonly thought of or known as the hormone that stimulates ovulation. So LH is released in this very intense released high, comes down after a small period of time where you might have that opportunity to ovulate. As you do that, you sometimes get like a little baby bump of estrogen and then progesterone is going to be made by that follicle that was ovulated that was able to go out to the party and now is in a different state releasing progesterone. And as you get to the end of that cycle, if you don't have a fertilized egg, you're going to have a bleed and then you start all over again. So luteinizing hormone I may look at most commonly when I'm thinking about PCOS because in PCOS you're going to have that aberrant pulsatile nature of luteinizing hormone. It's not doing what I just said where it's like I'm quiet and then I go up and then I go down and then I'm out. It's always there and always elevated. And this confuses the picture of are we ovulating? Are we not ovulating? What are we doing? And so it can be helpful when you're thinking about PCOS. I will say not every female who has PCOS has an elevated LH to FSH ratio, but oftentimes they do and it can be a helpful diagnostic tool.
Mike Haney: You mentioned, unpack FSH a little more. You mentioned the ratio that is important and you talked about its role in the cycle, but maybe just in the context of blood testing, what is FSH telling us?
Dr. Anjali D'Souza: So the way I use FSH is mostly when I'm thinking about either assessing how close someone is to menopause. So reminder that FSH is the request to make estrogen and estrogen is something that declines as we move towards menopause. So when I'm looking at FSH, I'm trying to figure out how much is FSH screaming at the ovaries to get them to do their job. And if I see that number is creeping up into the 20s and the 25s and higher, I know that brain is really working hard to ask the ovaries to work. And that's likely almost exclusively because the ovaries have no more to offer. They're about to retire, right? And that can both guide our thinking when we're thinking about how to counsel women about what to think about as far as what's coming up next in their lives. Although it's not accurate enough to say like well this number is 27 and that means in 2.5 months you're going to go into menopause, it still is a way for us to assess. And then on the other hand, when thinking about potentially hormone replacement, it can be a number that you look at to see, are you reaching a reasonable target? If I'm replacing hormones, and remember, there's that feedback loop, right? Estrogen is telling the brain, I'm here, so you don't need to scream at me FSH. If I replace estrogen, but the FSH is still really high, then I know maybe this person needs a little bit more estrogen to get that FSH to back off, and I'm in a better place as far as giving this person what they need.
Anti-Müllerian hormone and prolactin
Mike Haney: Okay. What about anti-Müllerian hormone?
Dr. Anjali D'Souza: Anti-Müllerian hormone is a hormone that most classically or historically was used in the context of fertility medicine and essentially gives us a window into how much ovarian reserve. So that's a fancy way of saying like how many eggs are available for you to potentially have a baby, get pregnant with. And there's different ranges that exist depending on your age. So, it's important if you get this number to not just look at it without context. But generally speaking, if you're on the lower end for your age range and you're trying to get pregnant, this might be something that you want to at least talk to someone about to make sure that there isn't something more proactive you need to do. On the other hand, like about 0.2 is the number that I typically see classically tells me that a woman is very close to menopause, right? So, as that number decreases, this is telling me like there are essentially no eggs or no follicles left here and they're very close to menopause.
Mike Haney: And that's not a hormone I'm guessing you would do replacement with then. It's just something that naturally comes down over time.
Dr. Anjali D'Souza: That's correct. Yeah, that's correct. And women ask me all the time like when do you think I'm going to be in menopause? And unfortunately, I can't know. But every once in a while, if someone is really like, can you give me a closer estimate? I might actually run an AMH, probably more unusual, not something I do routinely for a perimenopausal menopausal woman. And I'll just see like, okay, is that number at one? And then, okay, probably not super soon. Is it 0.2 or lower? Then yes, we're in the ballpark of pretty soon.
Mike Haney: So, also not something you're going to try to move then. It's really just diagnostic.
Dr. Anjali D'Souza: Correct. Yeah. And even then, it's not perfectly accurate. I think it's more accurate in the setting of IVF specifically. I've certainly seen it where women want to come see me and ask me to run it and they don't know that they have a fertility problem. They just want to know and that number may not be where they expect it to be and it creates all kinds of anxiety and stress about what this potentially means, oftentimes when it doesn't have to. So, it's just important to know that like yes, like many things, it's a metric, but not, unless you're in IVF and you have someone counseling you on it and potentially offering a specific intervention, it may not be something you do just for fun.
Mike Haney: Right. And finally, how about prolactin?
Dr. Anjali D'Souza: Prolactin is the hormone that is responsible for lactation in women and important and desirable in someone who is pregnant or in fact breastfeeding. But it can be elevated in certain medical conditions. So there can be pituitary tumors, small pituitary tumors that can essentially secrete prolactin. And when prolactin is present and elevated it can inhibit your ovulation and this can obviously be problematic if you're trying to conceive but can also cause menstrual irregularities. The other reason that it might be off is potentially stress but more commonly certain medications. So medications that inhibit or lower dopamine can cause this change in your prolactin.
Mike Haney: So is prolactin something if you're not in the lactating stage you shouldn't see at all or is it always there in some amount and you're just looking for an elevation?
Dr. Anjali D'Souza: That's right. Like it will always be there on some level. In someone who's presenting with amenorrhea with no cycles, you might want to run a prolactin as part of your standard workup to make sure that's not the reason.
Common hormone patterns and what to do about them
Mike Haney: So maybe as a place to wrap up, we've talked about all of these individual ones. Are there common scenarios that you see or what kinds of things might you maybe most commonly encounter when you run these hormone panels for women in terms of just this is often elevated, this is often low, and here's what we do about it?
Dr. Anjali D'Souza: Given the kind of practice I run, I will often see that people may be struggling with excess levels of estrogen. So, this is referred to as estrogen dominance. It's something that not all clinicians agree on, but I certainly see this reality where people have excess estrogen and they're dealing with weight gain and irritability. They may be more inclined to be struggling with fibroids or endometriosis or painful fibrous breasts. And there's something that we can do about it. We can think about, we can look at what is their estrogen metabolism like. Like are they actually removing estrogens well? Do they have xenoestrogens or estrogens from endocrine disrupting chemicals in their body that's increasing their estrogen load and attempt to bring it down to a balanced level? I'd say in general when we're seeing things like well above 300 regularly, I'm thinking about this. The other pattern I see is the opposite. So normal or low or no progesterone generally speaking. And this as we talked about before is going to be connected to most of the things that I see for women. So PMS, PCOS, even in perimenopause you'll see that low pattern. And then as we move closer into menopause, perimenopause and menopause, it's testosterone that I see as low and can be really helpful to replace or support for women.
Mike Haney: You mentioned there's some controversy around estrogen dominance. What is it that people don't believe? It sounds like it's just a high estrogen level and that seems like a clinical finding.
Dr. Anjali D'Souza: Well, because it doesn't actually fit into this diagnostic realm, right? It goes back to like the root causes. Someone might say, "Well, you've got fibroids and that's like this mass that's in your uterus and we can remove them or we can treat them with certain medicines." And yes, it's correlated with high levels of estrogen, but no one is dominant in estrogen. That's not a thing. But when you think more from a functional medicine lens, you're thinking about patterns between hormones and how they relate to each other a little bit more. And also when you see observation and clinical wise when you remove and balance those hormones that they actually improve, it's very hard to deny that reality. I'm a little confused about why people feel so strongly that estrogen dominance doesn't exist. I mean, it's essentially what you said. It's like a pattern where your estrogen is higher than your progesterone.
Hormone replacement therapy: An evolving approach
Mike Haney: Maybe the last thing to touch on here because it's come up a couple times in passing is hormone replacement therapy, which is getting much more common. Talk a little bit about what it is, what the kind of journey of hormone replacement therapy is, and maybe to tie this back to the blood panel, maybe reiterating some things you said before, what you might look at in a blood panel that might tell you this is a potential intervention for somebody.
Dr. Anjali D'Souza: So just to go back historically, hormone replacement therapy, when I think about even my mom, I watched her go through the phase of she was offered hormone replacement therapy and then she was quickly told she had to throw it away. And that was because probably almost now 24 years ago the Women's Health Initiative which is a study that was done, a huge study, because we actually saw really positive benefits to women's health with respect to cardiovascular disease and we wanted to study it, was done. And essentially the findings at the time which have now been more finely analyzed and reassessed were okay there's a signal here for breast cancer, there's a signal here for worsening heart disease and so like stop the study. And primary care physicians everywhere just started calling their patients saying you've got to stop HRT right now and there's a whole generation of women that basically didn't have access to this.
Mike Haney: To unpack that, so as part of the study people were taking hormone replacement therapy. There started to pop up signals that that intervention in particular was leading to breast cancer or that was the thought, was leading to cardiovascular issues and that just shut it down.
Dr. Anjali D'Souza: Correct. And essentially not to get too into the weeds on this, but what was later analyzed is both the overall numbers, right? Like that they were actually, the overall risk was actually significantly lower than we thought. We're talking about like 10 in 10,000 people when we're talking about breast cancer. But on top of that, the population that they studied instead of being like a true perimenopausal age range, which would be closer to the 50s, was much older, like on average in their 60s and higher. And so there's an incidence of disease that's happening at a regular level in those older women that was getting confounded with, well, this was the HRT that they were taking. And there's a few other issues with the study, but the bottom line is after this long analysis and rebranding of HRT, it's now becoming something that people consider again. And there are some changes to how we think about it. So, we're mostly using bioidentical forms of hormones, which doesn't mean it came from my body. It just means the actual structure. It's still man-made, but the actual structure is more similar to what your body makes. And this tends to generally speaking be more favorable. And so we're seeing this rise in women talking about their journeys through perimenopause and as these hormones have been re-evaluated like really asking for like can I think about this. And we've got lots of thought leaders out there that are very vocal about helping people understand that this actually is something that can be helpful both for symptoms in the moment which classically we think of as hot flashes, but I mean, the list is just innumerable. I mean, hot flashes, brain fog, weight gain, muscle aches, frozen shoulder, increased risk of UTI. There's like a hundred things. And so you're seeing more and more of people being able to have access to these medicines. I also see people that come in now to my office that just ask me, well, can I be on HRT? And I do think that there's a benefit to your brain and your overall well-being. But I still am curious about what are we doing with the HRT? What's the reason that we're giving you HRT? I like to be strategic about it, but that's more because my philosophy is everything has some risk associated with it, right? And we're not going to just throw things on people for no reason. But yeah, it's definitely used more.
Mike Haney: There was a second part of your question that I think I might have just---how it relates back to blood testing. When you've got somebody who comes in who's asking for it in addition to looking at maybe symptoms and is it something that can be addressed, would you run blood tests and look at levels to decide whether or not HRT was appropriate?
Dr. Anjali D'Souza: Yeah. So interestingly this is also something that's a little bit debated. Generally speaking, the idea is that we can essentially use symptoms alone to decide that you need HRT. And that could be a combination of hot flashes or severe brain fog. That could be sometimes weight gain, lipid changes as part of that. But I do like to look at the numbers and part of that is because it helps me understand where you are and how that relates to certain metrics. So bone health is one, right? And right now the standard is not for women to get a DEXA scan as they are in perimenopause. That's not the standard. We often wait until they're 65 to get their first DEXA scan, which is a way to assess the strength of your bones, right? Do you have osteopenia? Do you have osteoporosis? But if I know your estrogen levels are below 60 and I see this, I might say like, okay, let's get this DEXA scan. Let's talk about where this is for you and I might be more inclined to both give you estrogen but then also look for how are those levels of estrogen improving because I know that above 60 you're going to get some benefit to your bones as an example. But I like to use the numbers. I think more data here is only helpful but there are plenty of clinicians that have good outcomes without any numbers at all.
Mike Haney: And then would you continue blood testing once somebody's on HRT to see how it's working?
Dr. Anjali D'Souza: So I do not on a super regular basis, but I do like to look at labs at least once a year for people on HRT to just keep an eyeball on how the numbers are looking. And I also tend to add at least once a year what's called estrogen metabolism. So, it's looking at how we remove estrogens from the body because there are certain pathways that can actually be more likely to lead towards cancer and some pathways that are more favorable. This is also something that's not necessarily done as standard, but when I'm thinking about introducing an intervention like I want to mitigate risk from all angles and so this is something I do ask people to do at least once or twice a year.
Estrogen and cardiovascular health
Mike Haney: One more thing I want to tack on because you mentioned, I realized we didn't talk about in the context of estrogen, is that there is a relationship between estrogen and cardiovascular risk. Is that right?
Dr. Anjali D'Souza: Yeah. So estrogen has an enormously protective impact on the health of our blood vessels and our heart generally speaking. So you will, there's a protection against like how elastic your blood vessels are which is favorable overall to contractility and specifically to cholesterol and cholesterol markers. So, I will routinely see a woman that maybe I've known for 10 years that always had perfect cholesterol and then they move into perimenopause and suddenly their LDL is like 170 and they're horrified like what did I do? Am I eating something wrong? And no, it's probably, if everything else checks out, the influence of the loss of estrogen.
Mike Haney: And is that another reason then why you might consider HRT?
Dr. Anjali D'Souza: It's not considered like an FDA reason to consider HRT, but it's certainly part of an analysis. Yes.
Mike Haney: Well, I think that's a great place to wrap up. So, thanks so much for joining us.
Dr. Anjali D'Souza: Yeah, thanks for having me. It's been great.