What Causes Hormone Imbalance?

Conventional medicine uses what we might call the replacement model of endocrinology. This is where you measure hormones — or not, in some cases — you see what’s low or you estimate that hormones are low, and then you replace them with that given hormone. The functional model of endocrinology is fundamentally different than the replacement model or the conventional model, in that we look at the underlying mechanisms that are causing the hormone imbalance in the first place. We’re going to the source of the problem and addressing it at that level instead of just dealing with the symptom, which is the hormone imbalance.

In this episode, we cover:

4:52  The underlying mechanisms that contribute to hormone imbalance
17:52  Four ways to balance your hormones

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Steve Wright: Good morning, good afternoon, and good evening. You are listening to the Revolution Health Radio Show. This episode of RHR is brought to you by 14Four.me. If you’re someone who has been listening to this show and you’re still trying to put together all the pieces of great health, maybe you’re still struggling with low energy, a little extra weight right now, digestive issues, acne, or anything like that, you know that Chris talks about the foundation of all health starts with four areas: diet, sleep, movement, and stress. These things can be very hard to create in your life. If you’ve ever tried to create multiple healthy habits at once, they are difficult, and what the 14Four program is, is a step-by-step way to integrate them all at one time. Whether you’ve fallen off the wagon or you want to get on the wagon for the first time, I’d really encourage you to check out 14Four.me and give it a try.

Chris Kresser: Hey, everybody, it’s Chris Kresser. Steve and I couldn’t sync up our schedules this week, so I’m going to be flying solo. This week we have a great question from Susan, so let’s give it a listen.

Question from Susan: Hi, Chris. I really enjoy your podcast, and I’d like to ask a question. This is regarding a 12-year-old girl who started her period and is having really bad menstrual cramps to the point where she can’t go to school and a lot of irregularity. She went to a physician, and they put her on birth control pills to help regulate her, and I’m wondering if there’s a better solution, something that’s not quite so, you know, added hormones or something more naturopathic. Anyway, thank you.

Chris Kresser: OK, thanks, Susan, for sending that in. This is yet another good example of how conventional medicine and functional medicine are fundamentally different. Conventional medicine uses what we might call the replacement model of endocrinology. This is where you measure hormones — or not, in some cases — you see what’s low or you estimate that hormones are low, and then you replace them with that given hormone. So if estrogen’s low, you give estrogen. If progesterone is low, you give progesterone. Likewise, if a particular hormone is high, you might give something to suppress that hormone, sometimes another hormone or sometimes something completely different.

In this situation, the symptom is dysmenorrhea or an irregular menstrual cycle, and in this conventional replacement model of endocrinology, what they’re doing is giving her hormones to regulate her cycle. There certainly may be situations where this is helpful, but here’s why I don’t think it’s a good idea: It doesn’t really fix the problem. And beyond that, it can actually make the problem worse because it suppresses the natural regulatory feedback mechanisms that lead to proper hormone production. And then, of course, there are also side effects that are associated with these drugs. Birth control pills are associated with numerous problems, some of which, ironically, are more likely to make hormone imbalance worse. For example, birth control pills can deplete zinc levels, magnesium, B6, and a whole bunch of other nutrients, especially when they’re taken over the long term.

But the most important question here is, what caused the hormone imbalance in the first place? That’s really important because hormones don’t just go out of balance for no reason. In a healthy, functioning person, hormones will be regulated and operating as they should, so the fact that they’re out of whack is a sign that something is not working properly. This is where we turn to the functional model of endocrinology, which is fundamentally different than the replacement model or the conventional model, in that we look at the underlying mechanisms that are causing the hormone imbalance in the first place. We’re going to the source of the problem and addressing it at that level instead of just dealing with the symptom, which is the hormone imbalance.

The Underlying Mechanisms That Contribute to Hormone Imbalance

I’m going to talk about four or five of the major underlying mechanisms that I see contributing to hormone imbalance in my practice and also in the scientific literature. And then at the end, I’ll make a few basic recommendations. Of course, if you understand the mechanisms that contribute to hormone imbalance, then you can pretty much figure out what to do about it by addressing all of the various mechanisms that I mention. If we went into great detail on all of that, it would take several hours instead of 25 minutes that we have, but hopefully this will be a good overview to get you started.

We’ll start with the gut, as we often do. You’re probably tired of hearing at this point about how the gut contributes to virtually every modern chronic health problem, but it’s true and this is no exception. There are several studies that tie, for example, the microbiome to hormone balance. There’s even a term that was recently coined called the estrobolome, which refers to the complete set of bacterial genes that code for enzymes that metabolize estrogen within the gut. In other words, your gut flora can either predispose you to having excess estrogen or estrogen deficiency, based on how certain species of bacteria in the gut metabolize estrogen.

Another mechanism would be that dysbiosis increases levels of certain estrogen metabolites that are inflammatory and proliferative. In women, they can increase the risk of breast cancer. In men, they can increase the risk of prostate cancer. And then dysbiosis would also decrease the more protective estrogen metabolites.

Dysbiosis, of course, can promote intestinal permeability, which in turns leads to inflammation, which then disrupts hormone balance in several different ways.

That’s just a really high-level overview. There are several more mechanisms, actually, within the rubric of gut pathology that we could talk about, but as you can see, just those alone could be a significant issue for many people.

The next group of mechanisms would be cortisol dysregulation and HPA axis dysfunction, so hypothalamic-pituitary-adrenal axis dysfunction. This is relatively easy to understand because the hypothalamus and the pituitary are the glands that regulate all hormone production in the body, including adrenal hormones and sex hormones. So if you have an imbalance in that axis, then, by definition, you’re going to have a problem with sex hormone production or adrenal hormone production or thyroid hormone production.

Cortisol, as I’m sure you know by now, is the hormone that’s produced in the stress response, and if we’re under a lot of stress or continual stress, that can lead to high cortisol levels, and high cortisol can cause hormone resistance. This is when the cellular receptors to hormones that are on the outside of all of our cells become less sensitive to the effect of that hormone, and then the hormone can’t activate the transcriptors and do what it’s supposed to do in the first place. The hormone levels in the body could be normal, but if the receptors are insensitive to those hormones, then there’s going to be a problem. I’m sure you’re familiar with this concept with insulin resistance. That’s where the cells become less sensitive to insulin, and then the body might make more insulin in order to try to overcome that, and you end up with a situation where insulin levels are high but the cells aren’t sensitive to it, so you get rising glucose levels.

Problems with the HPA axis and cortisol can also lead to intestinal permeability or leaky gut, which causes all of the problems that we just talked about in the gut.

When the stress response is active, pregnenolone, which is the precursor to all hormones in the body, gets channeled into the cortisol pathway and away from the production of sex hormones, like estrogen. This is something that’s often referred to as the pregnenolone steal in the functional medicine world, and that can lead to low estrogen levels over time.

Another mechanism would be insulin and leptin resistance and problems with blood sugar regulation. One of the primary causes of this, in turn, would be poor diet or lack of exercise, inadequate sleep, and these things are all a lot more common these days in 12-year-olds and preteens and teenagers. I’ve read some pretty disturbing studies lately about how little sleep kids of that age are getting, which is really sad because kids at that age need even more sleep than we need as adults. It’s a very important developmental time. But with the intrusion of electronic devices into the bedroom and sleeping area, kids having their phone by their bed and getting text messages all night, using devices like phones and tablets late at night before bed, which emit blue light and suppress melatonin production and interfere with their circadian rhythm, is leading to an epidemic of sleep problems in that age group, and I think we’re seeing a lot of health consequences as a result of that.

Insulin resistance can also lead to high cortisol levels, so that, of course, contributes to everything that we just talked about when we talked about cortisol and the HPA axis just now.

Insulin surges can upregulate the production of an enzyme called 1720-lyase, which in turn leads to higher testosterone levels. This is a very common phenomenon in the US and the industrialized world. It’s one of the common causes of PCOS in women and a common cause of infertility, but, of course, it can cause just garden-variety hormone imbalance and dysmenorrhea as well.

Liver detoxification is another important mechanism. The liver plays an important role in the detoxification of hormones. If phase 1 or phase 2 of the liver detox process is compromised, then hormones will be only partially metabolized or broken down. These partially metabolized hormones don’t activate the receptor sites or initiate the cellular response like the fully active hormones do, but they actually would compete with those active hormones for receptor binding sites and throw off the normal regulatory feedback pathways. So they’re kind of like “Frankenhormones” in the sense that they don’t do what they’re really supposed to do, but they look enough like normal hormones that they interfere with receptor binding of those hormones and the feedback pathways. So the end result is a patient that has hormone imbalance symptoms but labs that actually might appear to be somewhat normal.

All of the enzymes that are important in the various phases of liver detoxification require nutrients as cofactors, so nutrient deficiencies from a standard American type of diet, which is really high in calories but low in nutrients, could certainly impair detox capacity, but so can exposure to a wide range of environmental toxins like heavy metals, mold, volatile organic compounds, pesticides, and other chemicals, like BPA, which have become ubiquitous in the environment.

Methylation, which is something we’ve been talking about a lot recently on the show, is crucial for proper detoxification, and as you now know, impaired methylation due to genetic and environmental causes, diet and lifestyle factors, is somewhat common and a really important thing to address.

The last mechanism that I want to talk about is essential fatty acid metabolism. These are the polyunsaturated fats. Alpha-linolenic acid is the essential fat on the omega-3 side, and linoleic acid is the essential omega-6 fat, but then you have the longer-chain derivatives of these, EPA and DHA on the omega-3 side and arachidonic acid on the omega-6 side. The reason these are so important is that essential fatty acids influence prostaglandin production, and prostaglandins modulate hormone receptor site sensitivity and the proteomic response that happens when a hormone binds to the receptor. Too much omega-6, for example, can lead to altered hormone receptor function, and this omega-6 linoleic acid is found in industrially processed plant oils, like soybean and corn oil, safflower, sunflower. These are oils that are typically found in processed and packaged foods, chips, anything fried, a lot of restaurant foods, but certainly most foods that come in a bag or a box, which comprise a disturbingly large percentage of calories for the average American. And EPA and DHA are found primarily in cold-water fatty fish and shellfish, and a fairly large percentage of people are not eating enough of this preformed EPA and DHA.

Now, in theory, alpha-linolenic acid, the plant-based omega-3 essential fat, can be converted into DHA, but that conversion is very inefficient. Less than one half of 1% of alpha-linolenic acid gets converted into DHA in most people. And too much omega-6 fat in the form of all of these processed and refined foods that are so common in the standard American diet actually reduces the conversion of ALA, alpha-linolenic acid, to DHA. So what happens with all of that extra omega-6 is that when the hormone binds to the receptor site, the proteomic response that is supposed to happen is either diminished or exaggerated, and that can cause problems related to hormone excess or hormone deficiency.

If we tie this all back to another issue, which is blood sugar and insulin, it’s worth pointing out that insulin resistance decreases the conversion of alpha-linolenic acid to EPA and DHA.

So we’ve talked about five of these mechanisms, and as you can already see, they’re not separate. It’s kind of like a perfect storm. They all contribute to one another so that if you have cortisol and HPA axis issues, that’s going to interfere with insulin and leptin signalling, which in turn will make your gut lining more permeable and lead to inflammation in the gut, which in turn leads to higher cortisol production, which leads to more insulin and leptin resistance, which interferes with liver detoxification, which can lead to a buildup of excess hormones, which — You get the picture. It just goes on and on and on. This is why it’s so crucial to address these underlying problems because if you don’t, just taking hormones, as you can clearly see, is not going to address all of these issues, and it should be also somewhat obvious how it could even make them worse, which is unfortunately why we see a lot of women in the clinic who have been on birth control pills for a very long time, not necessarily for contraception, but to regulate their cycle, and are having a ton of side effects and symptoms related to that, and they want to get off the pill, but it’s extremely difficult to do so, and it can take many months, if not years, to fully unwind all of the pathology and symptoms that were caused by being on the pill for that long.

Four Ways to Balance Your Hormones

There’s more to look at and talk about here, but I don’t want to go on for too long. These are among the most important steps that we would look at in the clinic. And I know it’s a lot of information and fairly technical, so let me, again, boil it down into a few basic recommendations.

The first is something we always talk about, which is eating a nutrient-dense, anti-inflammatory diet. We talked about how the cofactors for enzymes in the detoxification process and also in conversion of the essential fatty acids into the longer-chain derivatives like EPA and DHA require certain nutrients, and it’s also true that for insulin and leptin signalling to work properly and the adrenals to function properly and the gut to function properly, we need those nutrients as well. So making sure we’re eating a very nutrient-dense diet and we’re avoiding some of the modern foods that can provoke oxidative stress and inflammation, like excess refined sugar, excess refined flour, some of the industrial plant oils could be inflammatory, some artificial ingredients and things like that, that’s a really good starting place. A paleo type of diet or a paleo-template type of diet is a great way to get started with a diet like that.

The second is to manage your stress. This is important not only for adults, but also kids. The methods might be different for a kid or even a 12-year-old versus an adult, but it’s really important. It’s a stressful time of life. There’s a lot going on, a lot is changing, and as we just discussed, problems with cortisol and the HPA axis are probably primary in a lot of these hormone imbalances, so it’s really important to do this sort of thing and talk about this with your children. It’s pretty fun. Both my wife and I are long-time meditators, and when we’re doing our meditation practice, sometimes Sylvie will just come and sit in our lap. She’s about 4 years old now, so she doesn’t sit for a long time, but I’ve been pretty surprised at times by how long she’ll sit there and just be quiet and sit with us. So I think these are things you can introduce to your kids. Certainly just spending time outdoors, having fun, laughing, watching funny movies, for example, taking walks on the beach, developing hobbies. A lot of the same stuff we talk about for adults is definitely relevant for kids, but I think it’s easy to overlook that with kids, and they’re so busy and so overscheduled these days that it can be hard to fit it in, but it’s really, really crucial.

Next would be getting enough sleep. We already talked about some of the threats and challenges in modern life to getting enough sleep, and this is, I think, especially dangerous for kids when they’re still developing. Their HPA axis is actually still developing, so the amount of sleep, as I said, that they need is even greater than adults. Most kids at that age around 12, I think, need about 10 hours of sleep ideally, and I think very few are getting that much, so that’s important.

And then exercise. You want to do just the right amount — not too much, not too little. Overtraining can certainly interfere with hormone balance, which is why amenorrhea, just lack of a menstrual cycle at all, is a common thing that you see among women who are training really, really hard. But not getting enough exercise, too much time sitting, which is pretty common now with kids sitting all day at school and then sitting at home doing homework, it’s really important to encourage them to move their bodies and create opportunities for them to do that that are fun so that they don’t look at it as just another chore.

These shouldn’t be surprising that the four kind of pillars of health that we often talk about, they’re the basis of my 14Four program, which you can check out at 14Four.me. We’ve actually had a lot of kids and teenagers go through the program and get a fantastic response. They really love it, and they seem to respond really well, so you could have her check that out as an entry point. But if these steps aren’t enough, I do think it’s worthwhile to seek out a functional medicine practitioner. They can do some testing to figure out where the source of the problem is. They can also prescribe herbs, botanicals, and other nutrients that can promote healthy estrogen balance. If you do a little research, you’ll probably come across herbs like vitex or chasteberry, which can definitely be useful in some situations, particularly for adults, but may not be a good choice for girls under the age of 18 because, as I said before, their HPA axis is still developing. We might be somewhat concerned about the effects that vitex might have on regulatory feedback, but I think it could be used in some cases under supervision.

Susan, I know that was a bit of a firehose of information, but I hope that some of that was helpful for you, and if you can implement those four steps that I talked about — the nutrient-dense diet, managing stress, getting enough sleep and exercise — hopefully that will do the trick, and if it doesn’t, maybe pay attention to some of the mechanisms that I talked about more specifically and seek out a good functional medicine practitioner that can help.

OK, everyone, thanks for listening. I’ll be back next week with Steve, and I’ll look forward to talking with you then.