In this episode, we discuss:

Allie and Tracey’s backgrounds
Important health considerations unique to women
Choosing the best form of birth control for you
Why women’s hormone issues cannot be addressed in a one-size-fits-all approach
Using hormone replacement therapy for anti-aging benefits
The Functional Medicine approach to hormone regulation
The nuances of hormone testing
The pros and cons of hormone replacement therapy

Show notes:

Hey, everybody, Chris Kresser here. Welcome to another episode of Revolution Health Radio. This week, I’m really excited to welcome Tracey O’Shea and Allie Nowak as my guests, and we’re going to do a deep dive on the topic of women’s health. This has been a frequently requested topic over the past several months. And it’s been a while since I’ve discussed it on the show, so I thought it would be a good time to do it.

I’m glad that Tracey and Allie will be joining me. I have quite a bit of experience treating women’s health issues in my decade plus of seeing patients, and Allie and Tracey together have even more experience with particular aspects of that, like hormone replacement therapy [(HRT)]. So I thought it’d be really valuable to have their input. So, in the show, we’re going to talk about things like the most important considerations that are unique to women’s health. What’s wrong with the conventional approach to treating women’s hormone issues? What’s wrong with the standard integrative medicine HRT approach to treating those issues? Because those are two different problems. How we think about hormone issues in general, from a Functional Medicine perspective, what some of the best tests are to consider, and then a discussion of the pros and cons of hormone replacement therapy.

I think this is going to be really helpful to a lot of you listeners. I really enjoyed the episode, and I hope you do, as well. Let’s dive in.

Chris Kresser: Tracey and Allie, [it’s] such a pleasure to have you on the show. I’m really looking forward to this episode. We’ve had a lot of requests over the last few months to address women’s health, and here we are finally doing it.

Tracey O’Shea: Happy to be here. Thanks for having us.

Allie Nowak: Yes, thank you.

Allie and Tracey’s Backgrounds

Chris Kresser: So why don’t you both tell everyone a little bit about who you are, your background, [and] how you came to be here as a starting point, and then we can jump right in.

Tracey O’Shea: Allie, go ahead.

Allie Nowak: Sounds good. My name is Allie Nowak and I’m a physician assistant. I currently reside in [the] Twin Cities area [of] Minneapolis. I worked in family practice for about two years, and prior to that did an internship with Dr. Terry Walls, and realized that Functional Medicine truly was my passion. And later, [I] did training under Chris with the ADAPT programs and Kresser Institute, and have since dove into Functional Medicine. I worked in women’s health for about five years, and now [I] currently work at CCFM. And it’s definitely been a great tool to have in my arsenal, as far as treating women and seeing those patients.

Chris Kresser: CCFM being California Center for Functional Medicine for those of you that aren’t familiar with the clinic I co-founded with Dr. Sunjya Schweig several years ago. Tracey, go ahead.

Tracey O’Shea: All right, thanks for having me. So, if you haven’t come across my name yet in some sort of relationship with Chris, I’m Tracey O’Shea. I’m a nurse practitioner, and I originally started working in chronic pain, and was trying to merge the Functional Medicine world and the conventional approach to chronic pain management. And eventually, I figured I would really like to work with someone that could show me a little bit more and I could mentor with, and along comes Chris and this amazing opportunity to work with him and Dr. Schweig at the California Center for Functional Medicine. So I have been working with Chris in some capacity, I think for at least five or six years now. [I] shadowed him for a couple of years, co-managed patients, and now I am managing my own patients at the California Center for Functional Medicine and have been doing that for some time.

And I’m also the director of the [ADAPT] Practitioner Training Program that Chris started a handful of also five or six years ago, I think now. So, yeah. I’m at the California Center for Functional Medicine treating all kinds of conditions, including women’s health. So that is what has brought us here today.

Important Health Considerations Unique to Women

Chris Kresser: Great. Well, let’s dive in. Thank you both. From both of your perspectives, what are the most important considerations that are unique to women’s health?

Allie Nowak: I’ll start off, Chris. And I would say women have dynamic and fluctuating hormone levels and they change throughout their lifespan. This first major shift becomes apparent around menarche, which occurs around age 12 in most girls. Hormone fluctuations are seen during a woman’s fertile years, throughout pregnancy and during the postpartum months, especially in women who are breastfeeding. Later, we see a second shift that occurs in perimenopause, which can start as early as age 35 and precedes menopause, which occurs around age 51 for most women.

We should view our hormones as a vital sign and a representation of downstream consequences. Hormone levels are impacted by diet, gut health, inflammation, stress, sleep, nutrient imbalances, blood sugar and insulin dysregulation, thyroid function, toxin exposures, as well as our emotional and social health.

Tracey O’Shea: Yeah, Allie, like you were saying, I think there are occasions where hormone imbalances can be this more direct result of a really serious endocrine disorder that really does need to be addressed and figured out. But I would say, more often than not, at least in my experience, these imbalances are often connected to issues like you mentioned, gut imbalance, thyroid dysfunction, [and] toxin exposures. And they often start to present early in life or adolescence.

So we start to see this imbalance presenting as a woman starts to go through her hormone journey, if you will. And I think it’s important to mention that the assessment of those burdens and imbalances [is] really what I’ve seen impact hormone levels and ratios and metabolism most often. I think, there’s an example, or I mean, we have a ton of these, but one patient that comes to mind that really embodies this example is, we had a 28-year-old female patient who came to the office with the typical complaints that you get of weight gain, fatigue, hair loss, [and] irregular menstrual cycles with pretty significant premenstrual syndrome symptoms. She had been on birth control, [which is] also not totally surprising at this age, for about 10 years prior and had stopped a couple [of] years before coming to see us. And the cycles became more irregular. We checked her hormones, of course. We’re not just, like, not checking hormones and just assuming it’s diet. But we checked hormones, thyroid, [and] other blood markers, to assess her metabolic health and nutrient status and [came] to find out, not too surprising[ly], I think, to me, but she was dealing with hypothyroidism, vitamin D [deficiency], and [vitamin] B12 deficiency. She did have some hormone imbalances [in] her labs. But we started with the low-lying fruit, supporting the nutrient levels, balancing the thyroid, and we started to see these hormone imbalances improve.

And for this patient, her cycle started to normalize, her fatigue improved, [and] hair loss got better. She was still experiencing PMS symptoms and difficulty with weight loss, which I often see. It’s, unfortunately, the last thing to improve in this system. But we just kept working on those imbalances and things further improved. But it’s just an example of how all of these things are interconnected.

Chris Kresser: Yeah, and it’s an important one, because, and we’ll talk about this a little more later, but I think one of the key things to understand with hormone imbalance is they don’t just come out of nowhere. And when you take a Functional Medicine approach to looking at these issues, you have to look at all of the things you mentioned—diet, nutrient status, gut issues, toxins. It’s not or shouldn’t be, in my opinion, I think you both agree, just a question of hormones are low, let’s bring them back up by prescribing hormone replacement therapy. This will be a theme that we come back to again and again throughout the show, but I just wanted to highlight that because it is important to understand.

Allie Nowak: Yeah, Tracey, I’ve had similar cases to this in my experience, as well. And I think another key consideration is the balance between estrogen and progesterone. We view [estrogen] more so like your gas pedal. It’s a growth signal; it makes tissues grow and divide. And progesterone, on the other hand, is like the break. It’s the anti-growth signal. And additionally, estrogen tends to be more inflammatory, and progesterone is more anti-inflammatory in nature. So we tend to need to have those two things balanced in order for women to feel their best.

Even though estrogen and progesterone get the most attention, it’s also important to include cortisol, testosterone, [dehydroepiandrosterone] (DHEA), and pregnenolone in the discussion, because our balance is key; it really is a hormonal symphony.

Chris Kresser: Yeah, the endocrine system is so complex. I mean, so is the immune system and a lot of other systems in the body. But it is, a symphony, I think, is a great analogy, because you have all these individual elements that have to be functioning well on their own, but then they have to be coordinated with one another and getting the proper direction from the conductor, which is the HPA axis, right?

Our hormone levels are impacted by everything from diet, sleep, and social health, to insulin dysregulation, thyroid function, and toxin exposures. In this episode of RHR, I talk with women’s health experts Tracey O’Shea and Allie Nowak about how Functional Medicine can help women address and suppress hormone imbalances throughout the body. #chriskresser #womenshealth

Choosing the Best Form of Birth Control for You

Chris Kresser: So one of the most common questions that comes up in this discussion is the role of oral contraceptive or any kind of contraception. We’ve all seen, Tracey just mentioned a case study where [her] patient had been on birth control for 10 years and had what some refer to as post-birth control syndrome with hormone imbalances that accompany that. So there’s a lot of questions about contraception, and what the best method might be from a functional and integrative medicine perspective. How do you two view that?

Allie Nowak: This is a hot topic and often debated among specialists. In my opinion, various forms of birth control, as well as [the] use of hormones, have their place in both conventional and Functional Medicine. For example, the prevention of unintended or undesired pregnancy is super important. So we do want women to have access to these options. And, for example, condoms range in effectiveness from 85 to 98 percent, which means [between] two in 15 women out of 100 may experience an unintended pregnancy while using condoms. For this reason, the addition of more reliable and effective forms of contraception [has its] place.

In my experience, however, receiving comprehensive informed consent regarding the use of hormones often is lacking. For example, it’s important for women to be educated regarding the potential impact the birth control pill can have beyond preventing pregnancy, including some of the nutrient depletion we see with the pill, like zinc and [vitamin] B12, the increased risk of stroke and blood clots, which I think is, well, once women are well-educated on that risk, the lowering effect of testosterone and thyroid levels via the mechanism of sex hormone binding globulin, which kind of binds up those free hormones. Microbiome disruption, difficulty conceiving after stopping the birth control pill, and possible post-birth control syndrome.

Post-birth control syndrome, as the name implies, generally entails a variety of possible symptoms that arise within the first six months after going off the hormonal birth control. These symptoms can range in severity from acne and hair loss to gas and bloating, to depression, anxiety, and the more severe cases are loss of menstruation that does not spontaneously return after three to six months. As a provider, my goal is for my patients to understand the long-term benefits and risks as well as pros and cons so they can make a personal decision that best serves them. If they still decide to be on birth control, then I make sure to support their bodies with nutrients, monitor other lab values that may be impacted, and intervene when necessary.

Chris Kresser: Tracey, anything to add? Thanks for that, Allie. It was really helpful. Anything to add, or does that cover it for you, as well?

Tracey O’Shea: Yeah, I think that covers it. I think the biggest part here is the informed consent part. And that really is important. Like, make a decision that’s best for you, but just like with any decision that you’re making, here are the pros and cons. And the reality is, I think a lot of women are in their late teens and early 20s when they’re often making these decisions, some not. But that’s the majority of the population, I think. So it’s sometimes hard to have the awareness and the intention to know what this [is]. Because you’re not thinking about 10 to 15 years from now [or sooner] when you want to start having a child. So I think it really is up to the practitioner to have that discussion and make sure they really have time to think about it.

So I’m really glad you brought it up, because I’m hoping that that will make a big difference in people’s decisions. But yeah, I don’t have anything else to add for that. But I really like the conversation around informed consent. I think it’s important.

Why Women’s Hormone Issues Cannot Be Addressed in a One-Size-Fits-All Approach

Chris Kresser: Yeah. So if someone has hormone issues, and they go see their primary care clinician, what are the possible issues that might come up? What are the challenges that they might face? What’s lacking often in the conventional medicine approach to treating female hormone issues? Starting from even doing the right testing to determine whether there is a hormone issue, and then if one is identified with low levels of a particular hormone, what are some of the issues with the conventional medical treatments that might be deployed in those circumstances?

Tracey O’Shea: I want to be careful, because I’m sure there are conventional providers out there [who] are approaching female hormones with a comprehensive approach and a better understanding of how to really come across and approach this holistically. But [in] my experience, I think there’s quite a few shortcomings with [the] conventional approach. And, I think there’s often a one-size-fits-all to managing hormone issues, regardless of age, sexual history, family history, and menstrual history. None of those things are considered or the right questions aren’t necessarily asked. And there just doesn’t appear to be a whole lot of interest, honestly, in investigating what the underlying cause or burden is that might be driving that person’s symptoms.

Like you said, Chris, “Oh, you have a symptom. Here’s [a] replacement hormone, or we’ll just get [you] on birth control so you don’t have a normal hormonal cycle anymore.” Those things are concerning to me. And, I think there’s a lack of focus also on the diet and lifestyle modifications that we know. We’ve seen hands down, those can sometimes be the biggest parts that impact people’s hormone levels, and this knee-jerk reaction to put patients on synthetic hormones to control the symptoms. I mean, I’ve seen it time and time again, [and] I’m sure Allie, I’m sure Chris, you have, as well, for things like acne or facial hair growth, to treating PMS, which, by the way, doesn’t work very well. Using synthetic hormone birth control to control those symptoms often doesn’t really work as well as they would like it to.

But, I just had this happen to me, actually, a couple [of] weeks ago. I [have] a friend [who is] 36, has had two children, [and] just all of a sudden started having bleeding and significant pain, lots of bloating and cramping, [and] her cycles are starting to become irregular. And she [went] to her doctor and her doctor just [told] her, “That’s normal. That’s what you should expect at this age,” and just [sent] her on her way. And I was just devastated for her because she doesn’t feel well, and something is wrong with her body. And she’s just disregarded that this is normal for your age at 36. Come on. So, it’s disheartening when you see that.

But, I think the other piece of concern, on top of the things I mentioned, is the tendency to just remove the organ that’s causing the problem. I think we’ve all seen that, right? Maybe a little less often in the perimenopausal woman. But definitely in the menopausal woman, there’s some bleeding or spotting or pain that’s happening, [and] the first recommendation is to remove the uterus and the ovaries because, “You don’t really need that anymore.” And I think there’s probably a lot of people that would disagree with that. Allie, I don’t know if you also have experienced that or what your thoughts are about that approach. But those things just drive me crazy.

Allie Nowak: Yeah, Tracey, during my several years of experience in a traditional OB/GYN office and what I’ve gathered from other practices is that they really do try to attempt to exhaust other more conservative options to manage patient symptoms. At least that’s my personal experience, because they do have the best interests [of] the patient. But, for example, like you just mentioned, a perimenopausal female having abnormal uterine bleeding, in this case, offering her an intrauterine device, progesterone, and possibly, in nonresponsive cases, even an ablation if she is nearing the age of menopause, tend to be preferred over a more radical procedure such as a hysterectomy, which involves removal of both the uterus and ovaries, in most cases.

Hysterectomies do have a time and place, such as cancers, cases of chronic unresponsive anemia, or bleeding that continues to impair a female’s quality of life. But I do find that the conventional medical system tends to have a smaller arsenal of options to manage symptoms. And this could result in them needing to offer hysterectomy and less frequently addressing some of the root imbalances or causes. So, on the reverse side of things, some women are told that they no longer need a particular hormone and not to worry about it, like progesterone, for instance, in the context of a hysterectomy. Even though you don’t have a uterus and don’t need progesterone to protect your endometrial lining from growing, because that’s essentially the function of adding progesterone, you still have breasts and a brain, and both of those areas benefit from progesterone.

Along the same lines, a 2013 study in the American Journal of Public Health estimated that over the past decade, between 18,600 women and 91,600 young post-menopausal women ages 50 to 59 who had a hysterectomy may have died prematurely because they did not take estrogen. Estrogen is super important for many things, including cardiovascular health, brain health, and bone health. Deeming a hormone is no longer needed is inaccurate and, unfortunately, results in not only compromised symptom management, but it can also decrease the woman’s lifespan. The conventional approach infrequently checks or monitors hormone status, especially once various therapeutic interventions are initiated, and this is for sure something that I saw in my practice experience. We mainly treated symptom management but rarely checked and monitored hormone status.

Determining ongoing hormone need and assessing metabolism is necessary for the ongoing safety of hormone replacement therapy. Finally, a problem I have with our current healthcare approach is that lower cholesterol is not always better. Hormone production begins with cholesterol. Women who do not have enough body fat or a healthy diet can negatively impact cholesterol production. In my experience, we need a total cholesterol of roughly 140 to ensure the necessary building blocks are present to make hormones.

Chris Kresser: Yeah, thanks, Allie and Tracey; I couldn’t agree more. Of course, the caveat here, as you said, Tracey, this isn’t a dig against conventional practitioners in general. Most of the conventional practitioners I know are doing a great job and practicing what they were taught to practice. It’s really a bigger issue with the system and the paradigm and the approach. And even things like in a 10- to 12-minute visit, what kind of progress are you actually going to be able to make on all these things that we’re talking about anyhow? So a lot of practitioners just feel like their hands are tied. And even though they know all these things are playing a big role, there’s not much that they can do within the limitations that exist in their particular practice or the way that they were trained.

Using Hormone Replacement Therapy for Anti-aging Benefits

Chris Kresser: So there’s another side of this coin, though, which is, in the integrative medicine world, the anti-aging community, there’s been an approach to hormone replacement therapy that goes something like this. A woman who’s in perimenopause, or menopause, who’s experiencing a decline in estrogen and progesterone levels, maybe testosterone, as well, goes and sees one of these practitioners and then is prescribed hormone replacement at a level that is designed to return her hormones to where they were when she was 24 years old, or something like that, a young, pre-menopausal woman. What do you think of this strategy? Is this what you do? Well, that’s kind of a leading question. I know, it’s not what you do. But why not? Why don’t you do that? Why is that not a good idea? And why did we take a different approach, typically?

Tracey O’Shea: I think we probably all can sit and just [use] common sense, look at that scenario, and think, what benefit is that providing? I mean, the whole goal of this is to benefit the patient and the person and to provide optimal health and put them in a situation where they can work through life, age gracefully, have this vital life, and there are risks to some of these approaches. And I think that this is a method that really gives me a lot of pause, this kind of extreme on either end. This concept, like you’re alluding to, is that every woman, regardless of age, history, or symptoms, should just return to pre-menopausal levels. Like everyone’s given the same dose, no matter what, and just kind of sent on their way. I think it’s dangerous, to be quite frank. I think there isn’t really any evidence to support that that approach is safe or effective or even necessary, for that matter.

And I don’t think every single woman needs hormone replacement therapy, and a comprehensive evaluation. Labs should be run, consider the symptoms, and [see if it] is an appropriate therapy. There’s just so much that goes into making those decisions. I’ve talked to lots of women in their 50s and 60s, and they don’t want to be a 20-something-year-old again. They’ve been there; they’ve done that. So the goal here is to provide symptom relief, and then, of course, protection to the body’s symptoms that are most impacted by this drastic decline in hormone levels. And those, I think, are women that are candidates for hormone replacement therapy. So I’ll leave it at that for that particular topic, because I have had women [who] have come in on pellet therapy. And listen, I don’t do pellet therapy; I don’t have a lot of experience with it. But I have concerns. Women are coming in with these super physiological doses of testosterone and estrogen. And it just seems a little odd to me to really be going against what nature should be alluding to.

And on the other extreme of that is the people who don’t think anyone should be on hormone replacement therapy and just let the body move through the process on its own. I don’t know about you, but I’ve been told by some of my patients, whose quality of life has been severely impacted from symptoms related to menopause. Like if I told them that I was taking away their hormones and that we were coming off them, they would be extremely upset and frustrated people, because the quality of life that that has provided for them is pretty significant. And then I also feel pretty good about the level of protection, like the stuff we’re not seeing, right?

Chris Kresser: Yeah, I think it’s important to point out here, there are lots of reasons that people take hormones. And what we’re mostly focusing on here is hormonal treatment and therapy from a health and wellness perspective, rather than for gender transition, for example. And that latter topic is not one that I really have any experience or expertise in at all. I couldn’t even pretend to speak to that with any level of understanding or credibility. So I’m not even going to try to do it. But it just occurs to me that as we have this discussion, we should clarify that we’re really speaking more to the issue of someone who’s experiencing a fluctuation in their hormones that’s affecting their health and wants to address it from that perspective. Because, of course, that’s one discussion that’s very different from the other discussion.

Tracey O’Shea: Yeah, good point. I think that’s really important to talk about.

Chris Kresser: Yeah, and we’re using terms like “male” and “female” here. And that’s just for ease and keeping it more within the realm of health and looking at hormones from that perspective. But we understand that the terminology is problematic and difficult and want to recognize that, as well.

The Functional Medicine Approach to Hormone Regulation

Chris Kresser: Let’s talk a little bit more about hormone issues from a Functional Medicine perspective. We’re focusing on women’s health in this program, of course, [but] that doesn’t mean men don’t have hormone issues. We’ll talk about that maybe on a future show. But for now, we’re focusing on female hormone issues from a Functional Medicine perspective. We touched on this earlier already, Tracey. Not surprisingly, we look at this holistically and we look at it from a root cause perspective. So why don’t you lay out some of the considerations, like when someone comes to see us in the clinic, what are the things that we’re going to typically be looking for as a starting place?

Tracey O’Shea: Yeah, [it’s] also probably not totally surprising to your audience that we are trying to approach hormonal imbalances and symptoms from the systems-based approach, which is really different from symptom or disease management. We talked about, you have a symptom, [and] we’re going to put you on a synthetic hormone. You have a symptom, [and] we’re going to take out that organ that’s causing the symptom. And really, we’re looking for imbalances or body burdens that can be driving the hormone imbalances, or also, significant endocrine disorders that could be driving some of what you’re experiencing. And it can really include a variety of considerations and possible imbalances. But I think most commonly, I’m seeing thyroid imbalances, metabolic disorders, like insulin resistance, obesity, blood sugar metabolism issues, of course, the nutrient and vitamin deficiencies that we’ve talked about that can exist either post-birth control syndrome, while you’re on birth control, or even just, unfortunately, without any other hormone support. Methylation impairments and then also environmental and biotoxin exposures that also include heavy metal issues.

Chris Kresser: Yeah, that’s a lot.

Tracey O’Shea: Yeah, the list [is] huge, so it can be overwhelming.

Chris Kresser: Yeah, this is one of the reasons, Tracey, even in our Practitioner Training Program, we don’t include hormones in level one because we know from our experience that all those things you mentioned, like if someone has a blood sugar issue, or if they have a thyroid imbalance, which, of course, is a hormone, but we’re talking about sex hormones here, or if they have a gut issue, or HPA axis dysfunction, all those things are going to cause an imbalance in hormones. So it makes sense to address those things first, rather than diving right into the hormones, and again, that’s really the focus on root causes.

Tracey O’Shea: Yeah, I think it’s important to establish that communication with our patients. And Chris, I know you and I have [have] had this conversation lots and lots of times. People come in for hormone issues and they see that their hormones are imbalanced, and they’re like, “Okay, give me something for that. Give me a hormone; help me figure that out.” And it’s really just the education piece of this that it doesn’t make sense to come in guns a-blazing replacing hormones and trying to just fix the hormone. That’s downstream. The goal really is for us to start figuring out what’s impacting the hormones. Why are these symptoms happening? Because if we can address lower lying fruit and get those things normalized and optimized, we’re going to have a much better likelihood of impacting the hormones once we get the foundational health stuff taken care of.

And I think a lot of that also includes supporting and optimizing your diet, and addressing lifestyle factors that can contribute to hormone imbalances. And I think the reality of the situation is women who are starting or females who will play that role in their family dynamic are either working, having a bunch of kids, or having [a] very stressful environment, where, I mean, we’re all in a pretty stressful environment right now, I think we could say. So those lifestyle factors and how stress and sleep and responsibilities and workload, it all really impacts our health. And so those are big parts of the conversation, as well, in Functional Medicine. So [the] goal is to find macronutrient ratios in your diet, ways to support your sleep and stress, [and] helping patients deal with trauma. Sometimes there are unresolved traumas that have happened for people, and really just helping guide our patients through that is, I think, what sets the approaches apart when it comes to Functional Medicine.

Allie Nowak: I agree. I just wanted to highlight that despite addressing all of these root causes, and really aiming to uncover those imbalances, symptom management is still super high on all of our lists. And we do want to support our patients and help them have a better quality of life. So we typically do this in conjunction with trying to find the underlying imbalances. And often, we do this with supported vitamin nutrients. Again, back to the diet, exercise piece, stress management, and various herbal supports that are really instrumental and frequently improve hormonal balance, as well, while we’re addressing those underlying causes.

The Functional Medicine approach utilizes appropriate testing to assess hormone levels. There’s a lot of symptoms that overlap with various hormone imbalances, both lows and highs, so it’s important to test and not guess when it comes to hormone replacement therapy. For example, I’ve had several patients, but this one is a recent onset of anxiety in a perimenopausal female. And this can be from low progesterone, or, in some cases, low testosterone. And without testing, we really wouldn’t know how to best support her. So using a patient’s subjective experience is often very helpful, but [it] can also be tricky to guide choice and dosing of hormone replacement therapy.

Chris Kresser: Yeah, I couldn’t agree more about symptom management. It’s long-term with Functional Medicine where the way that we get at symptoms is by addressing the root cause. But that doesn’t mean we don’t need to take care of symptoms, [and] give people relief right away. We often hear “root cause”; that’s obviously using a tree as a metaphor. And when you learn Functional Medicine, you learn the root and branch approach, which is looking at the root causes but also tending to the branches, which would be the symptoms. And a classic example of this is pain, which Tracey has a lot of experience with. She used to work in a pain clinic. And the pain is so intense that it can actually further root causes, and you can get stuck in a pain feedback loop. And it’s really good to interrupt that.

Even though some of the hormonal symptoms may not be that extreme, I think some of the same things can happen there, and it’s necessary to provide a little relief. A classic example would be if the [patient’s] hormones are so out of balance that the patient can’t sleep, then that insomnia is going to further the hormone imbalance, which makes the root cause worse. So doing something to help with sleep, even if it’s just managing the symptom initially, is a good option. And I appreciate that distinction. It’s important to communicate that.

The Nuances of Hormone Testing

Chris Kresser: All right, so this is a big topic. We’ll see how far we can get with it. We’re already 40 minutes in, so we may not have time to give it full justice, but testing for hormones. [It’s] controversial, complicated, murky, [and] inherently problematic because of how hormones fluctuate throughout the cycle and the month. And even with, of course, we know with hormones like cortisol, they even fluctuate throughout the day. So they’re really, really hard to pin down. We’ve done a lot of different things over the years, Tracey and Allie, in terms of hormone testing. So why don’t you break this down a little bit, Tracey, for us, and Allie, you can chime in, and like I said, we’ll see how far we can get. Because we could do an entire episode or two just on this topic.

Tracey O’Shea: I’ll do my best to keep it as simple and quick as possible. But yeah, I think there are basically three main mediums for testing, which is serum, urine, and saliva. [There are] lots of different options and opinions on what’s the best way to test. But ultimately, there [are] pros and cons to each of these things, and it really depends on the practitioner’s preferences and what you’re looking for. And [a really] quick review for everyone, remember that steroid hormones are made from cholesterol backbone. So like cholesterol, steroid hormones aren’t soluble in water, which makes it a little tricky to test within the serum, because they’re fat loving and water heating. I’m not going to go into too much detail. But when hormones are in the serum, they have to be bound to protein carriers because they are hydrophobic. So it can be difficult to really get an idea of what the free or bioavailable form of that hormone is in serum because of those binding proteins.

There are some limitations when doing serum hormone testing, so I think it’s complicated and tricky. And I like serum testing mainly because it’s covered by insurance. The reality of the situation is not everyone can afford some of [this] other testing. And the advantages are they’re widely available, they’re generally easy to access, [and] they’re easily accepted as a mainstream marker. But I think the disadvantages are, it really is a snapshot of the hormone at that point in time. It’s just a single point testing, which I think can potentially be a disadvantage, because hormones are secreted in a pulsatile nature throughout the day, so you’re just getting a glimpse of what’s going on. It’s really not giving you a big picture idea. And it’s also not the best way to monitor certain methods of hormone replacement therapy, like transdermal or transmucosal therapies. I do use serum testing for a good chunk of my patients, especially when I’m trying to keep costs low. And it’s a little difficult to do outside options, but I almost always combine them with urine hormone testing. I don’t know, Allie, if that’s your approach, as well.

Allie Nowak: It definitely is, Tracey. Serum testing does seem to complement urine hormone testing, in my experience. Both tests provide slightly different pieces of information. Serum testing reflects our circulating hormones, like Tracey mentioned, including those bound as well as those that are free and active. Urinary testing, however, is the best way to evaluate hormone metabolites. And I think that’s really what is the advantage of urine testing. However, it’s an indirect measurement and does not take a look at the hormone itself. The dried urine testing for comprehensive hormone test, also known as the DUTCH test, which is what is the gold standard of urinary testing, involves urine spot testing that collects dried urine to assess hormone levels. Studies have shown a strong correlation between liquid and dried urine testing and serum hormones, and we see clinically that those results also correlate well with the patient’s clinical presentation. Since estrogen is metabolized by the liver, we’re able to see the various estrogen metabolites in the urine via detox pathways. This can clue us into imbalances and estrogen metabolism that may confer greater risk, including breast and prostate cancer risk when we’re talking about males, that is.

Estrogen can be metabolized through different detox pathways. Some are considered more protective with anti-cancer properties, like the two hydroxy pathway. Conversely, the four hydroxy pathway is considered the most genotoxic, and its metabolites can create reactive products that damage DNA. The third pathway, the 16 hydroxy pathway, is the most estrogenic of all the metabolites, although still considerably less estrogenic than estradiol. It turns on the estrogen receptor. So if overall estrogen levels are high, production of 16 hydroxyestrone may exacerbate high estrogen symptoms. And on the flip side, women with very low levels of estrogen may have less low estrogen symptoms if the 16 hydroxy metabolism is preferred.

Having information about urinary metabolites of hormones allows us to support estrogen metabolism in a variety of ways with diet, diindolylmethane (DIM), indole-3-carbinol (I3C), sulforaphane, and more. And it also essentially allows us to assess patient risk when either they’re on hormone replacement therapy or not on any hormones at all.

Chris Kresser: Yeah, this has been a game changer, right? In the hormone testing field where it was really hard to get this information before, if not impossible, in an outpatient, non-research setting. You’d have to cobble together a bunch of different tests, and even then, I don’t even know that most of them were available. So with this, we get a lot more information than just like, what are your circulating hormone levels, which are important, but as you pointed out, Allie, this can tell us things about cancer risk and other things even, which we haven’t gone into yet. Some of the hormone things metabolites can tell us about [are] inflammation, [and] they can tell us about thyroid levels and stuff that can be really useful even just outside of quantifying somebody’s sex hormone levels.

The Pros and Cons of Hormone Replacement Therapy

Chris Kresser: Sorry to interrupt, [but] I want to make sure we at least touch on this other really big topic, which is the pros and cons of HRT before we wrap up the show. [It’s] another very controversial and murky topic, [and I] would love for you both to share your take on this. Is there a place for it? And how do we think about it?

Allie Nowak: This definitely is a hot topic, and opinions and science [have] really shifted dramatically over the last 15 to 20 years. At this point, we’ve all heard about the shortcomings of the Women’s Health Initiative (WHI) study, but just in case you aren’t familiar with it or haven’t heard about it, I’ll just give you a quick rundown. The WHI was one of the largest randomized trials that looked at the use of hormone replacement therapy in women with a mean age of 63. The overall age was 50 to 79. There were two study groups. One group of women had a hysterectomy, and they were given conjugated equine estrogen only, which is a synthetic form of estrogen. The second group comprised women with a uterus, and they were given the conjugated equine estrogen together with medroxyprogesterone acetate, again, both synthetic hormones.

There was also a placebo group. It was stopped three years early based on the findings that hormone replacement therapy increased the risk of heart disease, stroke, and blood clots. And this actually sent a wave of fear among women who were on hormone replacement therapy at the time and has since shaped how a lot of how most doctors actually still approach hormone replacement therapy. However, there are some important considerations and shortcomings that have been discussed in length. And one of them is that the [WHI] did not stratify these women by age and did not talk about how many years the women were actually from menopause. And after looking more at the data, only about 10 percent of the women were actually aged 50 to 54. So we really cannot generalize [these] data to a younger patient population in the range of 45 to 55, which tends to be the patients that we actually start hormone replacement therapy with. It’s that perimenopause to menopause transition when they’re experiencing hot flashes and night sweats and those huge fluctuations.

The second consideration is that the HRT used in the study was synthetic hormones and that additionally, fewer than 10 percent of the women were symptomatic. I actually find this quite surprising that they were giving women that were asymptomatic hormone replacement therapy in the first place. Additionally, 70 percent of the women in the [WHI] were overweight or obese, 50 percent were current or past smokers, and more than 35 percent had high blood pressure that needed treatment. All of these factors confer greater cardiovascular and metabolic risk. So I feel like the patient population that was represented in these studies provided some false conclusions and weren’t super transferable to the patients that we typically start hormonal replacement therapy on. Therefore, I feel like you can’t extrapolate [these] data that show the increased risk of cardiovascular disease, stroke, and blood clots to all forms of menopausal therapy and to younger women.

Tracey O’Shea: While we’re on the topic of cardiovascular disease, I’ll try to keep it quick, because I think the main thing here is that there’s a lot of old studies that were published way back when that weren’t done correctly and that are coming out scaring people into using some of these therapies that are helpful. And I think the main takeaway is that, like you said, they’re using synthetic hormones; they’re not really telling you how long women have been in menopause between the time they were in menopause and the time they’re starting hormone replacement therapy. So it’s not surprising that there’s a lot of mixed information. And I think that the shift that has really happened is away from synthetic estrogens, no longer using oral estrogens, and using transdermal estrogen therapy to help protect the heart. Progesterone preferably is also given orally in women who have a uterus. It has been the most well studied and safe in terms of cardiovascular disease.

I just want to [quickly] go through the benefits, like some of the benefits that we know of hormone replacement therapy and why we’re using them. I know we’re short on time, so I just want to try to. Is that okay?

Chris Kresser: Yeah, you can just cover them briefly, because I think a lot of people have been scared away from it. And, if it’s not done properly, there are potential concerns for sure. But again, as you’ve both said, that doesn’t mean we, I hate this saying, I need to find a better one, but throw the baby out with the bathwater. There’s a right way to do it and a way that can provide a lot of benefits. And these are all evidence-based and in the peer-reviewed literature. So why don’t you summarize those briefly, Tracey, and then we’ll finish up?

Tracey O’Shea: The benefits of HRT include cognitive health, preventing shrinkage of the brain volume needed for healthy neurotransmitter levels, supporting bone mass density and reducing risk of osteoporosis and fracture risk, [and] cardiovascular health; back to that same concept, estrogen helps keep and maintain blood vessels flexible and fluid. Relief of vasomotor symptoms is a big part of this, hot flashes, nighttime sweating, sleep disturbances, palpitations, growth and repair of skin, and also helping to reduce breast tissue changes that occur during menopause.

And there’s a long list of other things that testosterone and DHEA also help and provide, save time, if we can find that somewhere else. But I think if we can give just a quick summary of things to consider, unopposed estrogen, meaning without progesterone, can be problematic for women with a uterus. So both hormones should be together to prevent hyperplasia of the uterus. The sooner women start HRT in relation to menopause, the more beneficial and helpful it appears to be. There’s less known about the benefit of starting HRT more than 10 years after menopause and what risks that confers. It’s also generally considered less risky or bioidentical hormone replacement therapy, as opposed to synthetic hormones, is generally considered less risky and more effective. And the goal of bioidentical hormone replacement therapy is, of course, reduction of symptoms. And like you mentioned, Chris, optimization of health and aging. And then monitoring hormones, as we’ve talked about, is so important here. Using a combination of serum and urine DUTCH hormone testing to assess production and metabolism.

Chris Kresser: Let’s pause and reiterate that because I would say 80 percent of my patients who’ve been prescribed hormone replacement therapy, maybe 70 percent, are not monitored after that. They’re started on hormones and then there’s never, not once another test done after that. And I think we can do better. We have the testing, and it’s important. We don’t want to overdo it; we want to shoot for the Goldilocks range. And there are problems with too much of these hormones, as you pointed out throughout the show. So I think that’s really important. Tracey and Allie, thanks so much for doing this and joining me.

For folks who might want some support with hormone balancing, you can find both Tracey and Allie at California Center for Functional Medicine, the clinic that I co-founded with Dr. Sunjya Schweig many years ago, and they offer virtual appointments in some cases, and for local patients who are able to travel to the clinic. We’re not doing that right now, right? Because of COVID[-19].

Tracey O’Shea: Yeah, it’s 100 percent virtual right now.

Chris Kresser: Yeah, so this is the world of COVID[-19].

Tracey O’Shea: Yeah, here we are.

Chris Kresser: This is how it goes. Yeah, so awesome that we can do that. That was a big deal for all of us and all of our patients so that we’re able to keep providing that kind of care, which is great. Thanks, everybody, for listening. Thanks, Allie and Tracey. Keep sending your questions to ChrisKresser.com/podcastquestion. And the URL for CCFM is CCFMed.com. You can also, of course, just Google California Center for Functional Medicine. We’ll see you or talk to you next time.

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