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RHR: The Right and Wrong Way to Treat Hormone Imbalance


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Revolution Health Radio podcast, Chris Kresser

This RHR episode is about how to address male and female hormone issues.  This is a question I get a lot, but I realize I haven’t really specifically addressed it either on the blog or in the podcast, so that’s what we’re going to do in this new, shorter podcast format.  Let us know what you think about these new shorter segments in the comments.

In this episode, we cover:

2:55 The right and wrong way to treat hormonal problems
8:48 What you need to know about taking hormones
12:13 5 critical systems every hormone treatment program must address

Full Text Transcript:

Steve Wright:  Hey, everyone.  Welcome to another episode of the Revolution Health Radio Show.  This show is brought to you by ChrisKresser.com.  I’m your host, Steve Wright from SCDlifestyle.com, and with me is integrative medical practitioner and New York Times bestseller, Chris Kresser.  How are you doing, man?

Chris Kresser:  Steve, I’m pretty good.  How are you?

Steve Wright:  I’m bouncing back from a well-deserved cold that I got.

Chris Kresser:  Oh, right.  Yeah.  I recently had one of those that Sylvie brought home from her preschool.  It’s one of the joys of having a young child in preschool.

Steve Wright:  Gotcha.  Yeah, I don’t have that problem yet, but I have the joy of still not understanding the respect I need to give my body with sleep levels and travel and trying to run a business.

Chris Kresser:  Yeah, that’ll do it, too.

Steve Wright:  Well, we’re going to change up the format today and do kind of a shorter segment that’s very focused in.  What’s our topic?

Chris Kresser:  Our topic is how to address male and female hormone issues.  This is a question I get a lot, but I realize I haven’t really specifically addressed it either on the blog or in the podcast, so that’s what we’re going to do today.

Steve Wright:  All right, awesome.  Well, before we get into that, I want to let the listeners know that if they haven’t signed up for ChrisKresser.com membership, well, there are already 99,442 people that have joined, so I think you’re missing out and you should totally hop over there and join in.  And when you do, what Chris has done is he’s gone and aggregated all the content that he’s put together over the last few years including a 30-part email series and all of his best tips and tricks including audio seminars and eBooks on various topics and symptoms and diseases that you might be dealing with.  So if you haven’t signed up yet for ChrisKresser.com membership, definitely head over there and check that out.  There’s going to be some sort of symptom guide or disease guide.  Whatever you’re dealing with, he has something in there for you.  Get that, and that will help you with your health.

Talking about hormones, Chris, before we get into hormones, what kind of breakfast did you eat today?

Chris Kresser:  I had some plantains fried in a little bit of expeller-pressed coconut oil, and I had some bacon and some eggs and some raw sauerkraut, so pretty straight forward this time.

Steve Wright:  Nice.  Very nice.

Chris Kresser:  Good, though.

Steve Wright:  Yeah.  OK, well, let’s kind of set the table.  Most people, I guess, we’re going to assume are eating paleo at this point, and they’re having some hormone issues.  How do we go and begin to correct these or even understand what’s going on with them?

The Right and Wrong Way to Treat Hormonal Problems

Chris Kresser:  This is going to be applicable to anybody regardless of whether they’re eating paleo, but let’s say that a nutrient-dense, real food diet, including paleo, is a great starting place but not necessarily the solution in all cases.  The most important thing that I want to get across as context for this discussion is that there are two different models of endocrinology, which is the branch of medicine that deals with hormone issues.  There’s the replacement model of endocrinology and the functional model of endocrinology.  The replacement model is basically measuring what’s low and replacing it.  So you go to the doctor and they measure your hormones.  Let’s say you have low estrogen and progesterone, and they give you estrogen and progesterone to replace those and bring those levels back up.  That’s the replacement model.  The functional model is different.  It is concerned with determining the underlying cause or source of the problem and addressing it at that level, and then once you do that, the hormones basically take care of themselves because there are basic systems in the body that are required for proper hormone function, and if you make sure those systems are functioning well, then the hormones will usually be in balance and at optimal levels.

An example of this might be low testosterone in men.  The typical approach, again, is if you go to the doctor, they test your testosterone levels, they’re low, and they give your testosterone to bring the levels back up.  But one of the problems with that is what if the cause of the low testosterone symptoms or the symptoms that are being attributed to low testosterone is actually aromatization of testosterone into estrogen?  This is something that’s quite common in men dealing with andropause, which is also known as “manopause,” a much catchier term.  Male menopause, so to speak.  What happens is with insulin resistance, an enzyme called aromatase gets up-regulated and that increases the conversion of testosterone to estrogen, which in men is not a good thing.  So if you take more testosterone in that situation, that could actually just lead to higher levels of estrogen because the testosterone is getting converted into estrogen.  That’s just one example of how this can play out and why it’s so important to focus on the underlying causes rather than just using this replacement model that has become kind of the de facto approach in treating hormone issues in conventional and even in alternative medicine.

Steve Wright:  Are there some groups of people where the replacement model is the right call?  I’m sure you and I are always going to lean towards trying to get to the root cause, but is there merit there for a certain group of people?

Chris Kresser:  Well, let’s put it this way:  Sometimes it’s necessary to replace hormones, but there’s never a case where you would only use the replacement model.  Let’s just say that the functional model is always the best choice, but within the functional model, sometimes replacement is part of the treatment program.  Does that make sense?

Steve Wright:  Totally.

Chris Kresser:  So we’re still addressing the underlying causes to the extent to that’s possible, but in some cases addressing those underlying causes may not be enough to fully address the problem.  A great example of that is in people with Hashimoto’s thyroiditis, an autoimmune thyroid disease that can cause hypothyroidism.  What happens there is the body attacks the thyroid gland and destroys thyroid tissue, and thyroid tissue is where thyroid hormone is produced.  And at least as far as we know, once the thyroid tissue is destroyed, it doesn’t come back, so if you’ve had Hashimoto’s for many years before it was diagnosed and before you took any steps to reverse it, it’s possible that you’ve lost so much thyroid tissue that you don’t any longer have the capacity to produce adequate amounts of thyroid hormone internally.  So in those cases, taking supplemental or replacement thyroid hormone such as Synthroid or Armour or Nature-Throid or any of the “bioidentical” replacements is necessary and beneficial because the benefits of thyroid hormone are so great and thyroid hormone is so universally needed in the body that the benefits of replacing it with medication far outweigh any potential side effects of that medication.  So that’s one example where replacement would be part of any kind of functional plan that involves addressing the underlying causes.

Steve Wright:  Gotcha.  Now, when you’re using some sort of – like, you mentioned testosterone – supplementation, is this true with all hormones, but there are some hormones I know for sure, like testosterone, where when we give them exogenously, say there’s not a tissue damage concern, actually the body will then down-regulate its own internal production, which kind of offsets the purpose, right?

What You Need to Know about Taking Hormones

Chris Kresser:  Yeah, and that’s a great point.  That’s exactly one of the risks with taking hormones over a long period of time, as you pointed out, Steve.  The way that the body regulates hormone production is through a process called negative feedback.  We have glands in our brain, particularly the pituitary gland, that monitor levels of hormones in the body, and this is true whether you’re talking about thyroid hormone or estrogen or progesterone or testosterone or whatever.  Let’s say that your thyroid hormone levels are low.  Well, the pituitary as the control tower that monitors these hormones will pick up on that, and it will send out larger amounts of thyroid-stimulating hormone, which then acts on the thyroid to produce more thyroid hormone.  The converse is also true.  If you have high levels of thyroid hormone in your blood, the pituitary will see that and it will send out less thyroid-stimulating hormone in order to make less thyroid hormone because it sees that there’s already too much in the blood.

So what happens when you take exogenous – which just means supplemental from outside of your body – hormones?  Well, the levels of those hormones go up in the bloodstream and then your pituitary gland sees that and it reduces your own internal production of that hormone.  Now, that may not be much of a problem when you’re taking that hormone because the hormone is coming into your body from outside, and even though you’re not making as much, you’re still getting what you need by taking it.  But there’s another problem that happens when you have chronically higher levels of hormone in your blood, which is that the receptors for those hormones get down-regulated.  That means that a given amount of hormone in your blood will actually have a lesser effect because the receptors aren’t sensitive to that hormone anymore.  So you can develop this hormone resistance problem, and I’m sure a lot of women or men who’ve taken supplemental hormones have experienced this.  What happens is the dose that they started on that was effective at first becomes no longer effective as that hormone resistance develops, and they have to continue to take higher and higher doses to get the same effect.  That’s a problem that develops over time.

Let’s just say that there are some cases where hormone replacement is necessary, and at the same time, we want to do everything we can to address the hormone imbalances without using additional hormones if possible.

Steve Wright:  Yeah, I’ve even seen some studies on, like, hydrocortisone where that feedback mechanism happens in days, where it starts to shut down internal cortisol production.

Chris Kresser:  Yeah, and we talked about cortisol resistance on a previous podcast.  It’s really fascinating.  Some of the research suggests that what we’re calling adrenal fatigue syndrome is often not related to high cortisol or low cortisol or even cortisol rhythm problems, but instead it’s more caused by cellular resistance to the hormone cortisol.

Steve Wright:  Yeah, so we have all these feedback loops.  How do you begin to make sense of this for, say, a woman who’s having some PMS issues and some stuff going on?

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5 Critical Systems Every Hormone Treatment Program Must Address

Chris Kresser:  I’m going to break it down.  There are five critical systems that you need to focus on in order to ensure optimal hormone production and balance, and this is true whether you’re male or female and regardless of what the hormone is that we’re talking about.  I’ll name these five systems now, and then we’ll talk about them in a little bit more detail.  The idea is that before you even start to fiddle around with taking hormones, you need to make sure you have these things dialed in.  In some cases, it’s fine to take some additional hormone while you dial in these things, but you should never take hormone without focusing on these things as well.  The systems are blood sugar, adrenals or hypothalamic-pituitary-adrenal axis or HPA axis is two, number three is the gut, number four is detoxification/liver and gallbladder function, and number five is essential fatty acid balance.  Let’s talk about them in a little more detail.

The first is blood sugar regulation.  Now, insulin resistance, which is often a problem with blood sugar issues, affects hormones in several different ways.  Insulin surges can up-regulate aromatase, which I mentioned earlier, and aromatase is an enzyme that converts testosterone into estrogen.  In men, what you often see is a normal or low normal testosterone level but a high estrogen level, and this is commonly seen in andropause or “manopause,” and in order to fix it, you really have to address the insulin and blood sugar issue because the problem isn’t low testosterone, per se, although the symptoms are caused, in a sense, or are reminiscent of low testosterone symptoms.  The problem in this case is insulin resistance.

Now, in women, the way that insulin resistance or high insulin tweaks hormones is that it up-regulates an enzyme called 17,20-lyase, and this increases the production of testosterone and leads to PCOS, which is the number one cause of infertility, and it also causes thinning of the hair or hair loss in the scalp, facial hair growth, weight gain, depression, and a whole bunch of other nasty symptoms.  And as a side note, PCOS, I think, is a more common cause of hair loss in women than hypothyroidism.  Even though when a woman is losing hair the first thing a lot of us will think about is hypothyroidism, often PCOS, increased production of testosterone and/or inflammation are to blame there.  What’s interesting is that not only do testosterone levels go up with insulin resistance in women, but estrogen levels can also go up because 17,20-lyase converts DHEA, which is an adrenal hormone, into the estrogen-testosterone pathway, so all of the hormones in that pathway go up, including estrogen, but testosterone goes up more proportionately, which is why you see the PCOS symptoms.  But estrogen going up suppresses FSH, which is a pituitary hormone that acts on the ovaries, and that suppression of FSH is actually what causes infertility in that particular pattern.

That’s the story with blood sugar, and so taking steps to address blood sugar dysregulation, like eating real food, avoiding flour and sugar and industrial seed oils, adjusting your carbohydrate intake based on your blood sugar response, doing high intensity strength training and not sitting as much, getting enough exercise, making sure you’re getting enough sleep and managing stress – all the things that we normally talk about in terms of addressing blood sugar – are important here, of course.

Steve Wright:  Is there any sort of supplement that could be universally talked about for these people as well?

Chris Kresser:  There are definitely supplements.  Some of the compounds in cruciferous vegetables can help reverse some of the issues that we’ve just discussed here, so upping your cruciferous vegetable intake from a food-based perspective is helpful.  DIM can help in some studies, although in others it doesn’t.  There’s mixed research on it.  It can help reduce the conversion of testosterone into estrogen, and most of the bigger supplement companies, Designs for Health, Pure Encapsulations – the better brands that we’ve talked about – have a formula for dealing with aromatization in men, which is where testosterone gets converted into estrogen, and also dealing with this 17,20-lyase problem in women where testosterone and estrogen production goes up.

The second problem is HPA axis dysregulation, which is also referred to as adrenal fatigue syndrome.  I think this and the next problem we’re going to talk about, the gut, are probably the two biggest issues with hormone imbalance.  Pregnenolone is the mother of all hormones.  It’s the precursor to all of the different adrenal and sex hormones that are produced in the body, and the enzyme that converts cholesterol into pregnenolone – so cholesterol is the precursor to pregnenolone, and that’s why cholesterol is so important in the body.  We’ve talked about this before, and I don’t want to go too far down this tangent, but really low cholesterol can be a problem for hormones because, as I said, cholesterol is the precursor to pregnenolone, and pregnenolone is the mother of all hormones in the body.

Anyway, the enzyme that converts cholesterol to pregnenolone is limited, and it requires a lot of ATP, which is cellular energy.  It’s an energy-intensive process.  That means that the amount of pregnenolone we can make in the body is limited, and there’s something called the pregnenolone steal that I’m sure many of you have heard of, which describes a process where the majority of the pregnenolone that we produce on a daily basis is channeled into cortisol production, and this happens when we’re under a lot of stress because cortisol is one of the hormones that’s involved in the stress response.  So if you’re not sleeping well, you’re not managing your stress, you’ve got a lot of stuff going on in your life, and/or you have gut infections or you’re eating a poor diet or you’re dealing with any kind of chronic illness/injury/pain problem, that’s going to create a stress response in the body, and that in turn will divert pregnenolone into that cortisol pathway, and it takes it away from the DHEA pathway, and the DHEA pathway, if you go down that road, that’s where estrogen and testosterone are produced.  So if you have low DHEA levels on a lab, that’s often a sign of pregnenolone steal, and getting back to the replacement model, if you just give that patient more pregnenolone, it can actually make things worse because it just channels more raw material into that cortisol pathway.

The solution in this case is that you have to decrease stress physiology, so you have to address the underlying causes of the stress, whether it’s a gut infection or poor diet or lack of sleep or emotional/psychological factors.  You have to also address blood sugar issues because that can be a stressor on the body.  Insulin resistance can lead to elevated cortisol levels, and high cortisol levels can lead to insulin resistance.  And of course, you need to do all of the other things that we’ve talked about at length to manage stress, so making sure you’re getting enough sleep, doing some regular stress management, addressing any gut issues or any other chronic health issues that are causing a stress response in the body.

I think this is the thing that’s so hard for all of us to do.  You mentioned it in the beginning of the show, Steve.  It’s something I still struggle with.  Despite the fact that I’m keenly aware of how important it is and I take steps to manage it pretty regularly, it’s still something that I struggle with.  But what I can tell you in doing a lot of testing, treating well over a thousand patients now with these kinds of problems, almost every man or woman with a sex hormone issue, like in women they either have low progesterone and estrogen dominance or excess testosterone or men with low testosterone, I can tell you that virtually every single one of these patients that I’ve treated had an underlying HPA axis issue.  So I can’t emphasize this enough.  You have to address the adrenal side because if your pregnenolone levels are low or they’re getting diverted into cortisol because of stress, you just will not have enough raw material to make the sex hormones, and that can lead to infertility, it can lead to menstrual cycle issues, mood imbalances, low libido – all the classic hormone symptoms.

Steve Wright:  That’s the exact same thing that I’ve seen, and this piece right here seems to be the one complete neglection from the replacement model that seems to torpedo that model the most, in my opinion.

Chris Kresser:  Absolutely, and it’s the hardest thing to change, you know?  I’ve noticed that dietary changes, you know, they’re challenging for people, but a lot of people have an easier time doing that than making the changes to deal with stress management.

The next area of focus is the gut, and again, this is right up there with the HPA axis in terms of its importance.  Impaired gut function can mess with hormones in several different ways, so if you have a parasite or a fungal overgrowth or dysbiosis or leaky gut, that causes inflammation.  Inflammation suppresses the function of the hypothalamus and the pituitary in the brain, which produce the stimulating hormones, and then it also suppresses the function of the adrenals and the ovaries and the gonads in men that produce the actual hormones.  Inflammatory cytokines can also cause hormone resistance, which we talked about just now, where the levels of hormones may be fine but the receptors on the cells aren’t sensitive to those hormones, so you end up getting the same symptoms.  Dysbiosis has been shown to increase the activity of something called beta-glucuronidase, which reverses hormone conjugation in the liver, which means that you get a recirculation of deconjugated hormones like estrogen back into the circulation, and that can cause estrogen dominance.  Dysbiosis also increases the production of certain downstream estrogen metabolites like 4-OH and 16-OH, which are proliferative.  That means that they actually can contribute to breast and prostate cancer, and dysbiosis decreases the production of 2-OH, which is protective against those conditions.  I mean, this is just a tiny sliver of the ways that gut issues can affect hormone production.  We don’t have time to go into all of it, but suffice to say that healing your gut is a really crucial part of addressing hormone problems.

The next or number four issue is proper detoxification.  A while back I wrote a series called Paleo Diet Challenges and Solutions, which is now available as an eBook where I go into some considerable detail on the importance of detoxification, and one of the main things that I was talking about in that series and now eBook is that the liver and gallbladder play an important role in clearing excess hormone from the body.  Defects in hormone detox can cause hormones to be only partially metabolized, and I just gave an example of that with beta-glucuronidase and the recirculation of estrogens back into the blood and how that can cause estrogen dominance.  Partially metabolized hormones compete for receptor sites with active hormones, but when they bind to the receptors, they don’t have the same effect, so they actually block the receptors from the active hormones, and that ends up throwing off proper negative feedback that we talked about before, which is the way that hormones are regulated in the body, and the end result is you get a patient with symptoms of hormone imbalance but relatively normal labs or a patient that’s extremely sensitive to any drugs or supplements.  I’m sure you’ve seen people like this, Steve, where whatever supplement or drug you give them, they just react extremely.

Steve Wright:  Yes.  Yeah, it’s definitely a growing number of people.

Chris Kresser:  A growing issue, right, and there are some genetic mutations that predispose people to that, but those mutations generally won’t be activated epigenetically unless there’s some kind of issue here with impaired detox pathways.  Of course, the key here is to make sure those pathways are functioning well and to reduce the toxic burden that we’re exposed to.  We’re exposed to toxins in food, of course, with the standard American junk food diet, the flour, the seed oils, the excess sugar, the chemicals, preservatives, and things that are increasingly used in processed and industrially refined foods, but there are also environmental toxins like BPA and phthalates and the many other chemical agents that are introduced into our environment every year with very little regulation or concern for safety.  So using natural skincare and cosmetic products, shampoos, soaps, natural home cleaning products – all of this can help reduce the toxic burden and give our detox pathways a little bit of a break.  And then there are a lot of things that we can do to improve detox capacity, like improving our methylation status, improving our glutathione levels, etc., and I talk about that a little bit more in the eBook.

The last concern for hormone balance is fatty acid balance.  Fatty acids are precursors to compounds called prostaglandins, and prostaglandins, in turn, modulate hormone receptor sites and our response to hormones.  We’ve talked in the past, and if you’ve read my book or you’ve been following my blog for any length of time, you know that excess omega-6 fat can lead to a number of different problems, and one of the problems that this can cause is altered hormone receptor function.  Too much omega-6 and not enough omega-3, the long-chain omega-3’s like EPA and DHA, essentially ends up driving the production of prostaglandins that are proinflammatory.  So you have not enough omega-3 and too much omega-6, that leads to an inflammatory environment, but if you get sufficient amounts of omega-3 by eating cold-water fatty fish or taking fish oil, EPA and DHA, that promotes the conversion of the prostaglandins into less inflammatory substances or pathways.  And then EPA and DHA, the longer-chain omega-3’s, also improve insulin sensitivity and glucose tolerance.

What you’ve probably noticed with all five of these systems is they’re important to focus on in their own right, but they all are also interacting with each other.  Blood sugar problems can lead to adrenal and HPA axis issues and vice versa, gut issues can cause adrenal and HPA problems, and having chronic so-called adrenal fatigue can definitely make it more likely that you’re going to have gut issues.  Inflammation from fatty acid imbalance can affect the gut and the adrenals and blood sugar.  It just goes on and on.  If we put these five points on a piece of paper and we just started drawing lines between them, it would become like a big web, and that’s really the point of this show, this particular episode, that these are the five fundamental areas that you need to focus on to maintain proper hormone balance, and any approach you do, whether you’re taking replacement hormones or not, should include this focus.

Steve Wright:  Awesome.  Well, I love laying that content out.  I know that there are going to be a lot of questions in the comment thread because we didn’t dive into each one, and I think that’s going to be the beauty of these short formats, that we can let the listeners sort of ask some follow-up questions here about each one of these five areas and let us know, Chris, if we need to dive into each one in more detail.  Out of all the five, what’s the one that’s being missed the most by practitioners out there that the patients need to really, really educate themselves on?

Chris Kresser:  It’s hard to say because there is some difference from person to person, but I think the HPA axis issue is probably paramount.  But then if we ask what’s the thing that’s being missed most in terms of adrenal stuff, it’s the gut.  So as I said earlier, I’d have to say there’s a tie for first place with the gut and the adrenals.

Steve Wright:  Gotcha.  Awesome.  Well, we’ve kind of hit our limit for this show, so I want to thank everyone for listening.  Chime in in the comments like I said about this kind of a shorter format more in depth.  Let us know what you think about it and what questions you have about this current episode.

Chris Kresser:  All right, thanks for listening, everyone, and talk to you soon!

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Join the conversation

  1. It is a long article, but I learned so much while reading it. It is worthy of our time to learn more about hormone imbalance. I also believe, that if you have imbalanes hormone, something is not you. Better to know different methods to treat hormone imbalace.

  2. There are only 2 root factors which would prevent the body from recovering from a Chronic state of imbalance or Illness:

    1. An active autoimmune process/systemic inflammation. This can affect the endocrine system and other parts of the body (Endocrinopathy, Encephelopathy). The causes of Autoimmunity are several, some of which are:

    1. Long term systemic inflammation from viruses, bacterial infections, leaky gut/SIBO/SIFO/Stress.

    2. Resistance to endogenous hormones at the cellular level due to chronic metabolic issues or chronic stress (insulin resistance or cortisol resistance). Cortisol resistance from chronic stress is one predisposing factor that contributes to Autoimmunity.

    3. Underlying paraneoplastic processes yet to be identified. Basically brewing cancer that hasn’t yet grown large enough to be diagnosed.

    The best approach to be able to start recovery would be to shut down the inflammatory and/or autoimmune mechanisms which would immediately take the burden off the HPA axis (inflammatory cytokines interfere with the HPA axis). The liver detoxification processes would improve since inflammation slows the CYP metabolizing enzymes, and adrenal insufficiency further slows the liver’s detoxification ability.

    Shutting down inflammation also reduces the gut’s mucosal sensitivity and inflammation towards its own microbiota, which often causes symptoms of IBS.

    No matter how you look at it, chronic inflammation is a major cause of chronic illness and disease. Everyone should have a basic blood test done to check these inflammation markers:
    1. ESR
    3. Ferritin
    4. Fibrinogen
    5. LDH

  3. Hi, I’ve been getting the run around between endocrinologists, HRT doctors, etc for the last 5 years dealing with somewhat boarderline hypothyroid, but mainly symptoms that are often advertised by HRT clinics… What doctors in the South Florida area share the same ideals as your podcast- that treating these underlying issues are what’s important, and how to go about pinpointing those issues. Currently I’m being diagnosed based on the type of treatment the doctors specialize in and want to continue to see/charge me for… not helpful and potentially making things worse.

  4. Hi! I had a total thyroidectomy on 2/24/17. The path report, among other things, showed chronic lymphocytic thyroiditis. Since this is an automimmune disease, and I no longer have a thyroid for it to “reside” in, what happens to the disease? Should I expect to now have other autoimmune diseases? Or does it go away with the removal of the offending gland?