Essentials: How to Optimize Female Hormone Health for Vitality & Longevity | Dr. Sara Gottfried

Key Takeaway

If vegetables are hard to eat consistently, make a smoothie three times this week and hide nutrient-dense additions inside a flavor you already enjoy. Dr. Sara Gottfried suggests frozen steamed broccoli because it has almost no flavor, plus greens or a green powder, blended into chocolate or vanilla-berry smoothies. This is a practical way to increase plant intake, support the microbiome, and address micronutrients that contribute to hormone production and estrogen metabolism.

Episode Overview

Dr. Andrew Huberman and Dr. Sara Gottfried discuss how female hormone health is shaped by genetics, stress, nutrition, metabolic health, exercise, and life stage. They cover hormone and micronutrient baselines, PCOS, constipation, oral contraceptives, perimenopause, brain metabolism, and cardiometabolic screening. The central theme is individualized, data-informed care rather than one-size-fits-all hormone advice.

Full Transcript

Transcript of Essentials: How to Optimize Female Hormone Health for Vitality & Longevity | Dr. Sara Gottfried from Huberman Lab. Auto-generated from episode audio; may contain minor errors.

Welcome to Huberman Lab Essentials, where we review past issues to find the most effective and efficient science-based tools for mental and physical health, as well as productivity . I'm Andrew Huberman, a professor of neurobiology and ophthalmology at Stanford School of Medicine. And now to my conversation with Dr. Sarah Gottfried. Dr. Gottfried, Sara, congratulations . Thank you. I am very happy to be here. Yes, I am very happy and look forward to the opportunity to ask you about a huge number of topics. You are an expert in many fields, including female hormones.

Is it useful for a woman, regardless of age, to know something about her mother's, or perhaps even her grandmother's, hormonal experiences? What conversations should women have with themselves and family members to understand what their specific needs might be? My work lies at the intersection of genetics and lifestyle, and I believe it is important to understand what your grandmother, and especially your mother, went through. I would start with trauma and intergenerational trauma, because I believe it has an extremely strong impact on the endocrine system, especially cortisol signaling.

There are also certain female conditions that have a very strong genetic component, most of which run in my family. These include, for example, endometriosis, fibroids, and polycystic ovary syndrome. Maybe we could go through the stages and say what biomarkers should be looked for in teenage girls who have already started puberty? Likewise for women in their 20s and 30s, perhaps we could look at it in decades, starting from puberty . In adolescence, I think it 's interesting to look at cortisol, but observing the interaction of estrogen and progesterone during these years is less useful because there is a lot of variability due to the immaturity of the system.

If someone has really regular periods, it might be better to take some measurements at that age, but in general I think it's best to do it in your 20s or 30s. Is n't the menstrual cycle irregular in duration when it is first established? In many women, it is irregular. And then there's the issue of oral contraceptives and other forms of contraception, which leave you completely unaware of what your normal cycle is. But going back to your original question about biomarkers by decade. In your 20s, it's time to establish baseline levels of estrogen, progesterone, and testosterone.

It often happens that estrogen dominates this “tango”. And when that happens, it increases your risk of developing fibroids and endometriosis. I would like to learn about DHEA and the entire androgen pathway in general. I would like to learn about estrogen metabolites, as some of them are protective and very beneficial. Others behave a bit like Homer Simpson. I mean, they just create a bunch of problems in your body. I would also like to know about their chair. So, I want to know about the microbiome. Regarding blood tests or other tests for these biomarkers, women need to have estrogen, testosterone, and other indicators taken at different stages of the menstrual cycle .

If they had to choose one day, either in the follicular or luteal phase of the ovulatory cycle, when would you recommend doing it? So, if you forced me to pick one, I would say probably 21-22 days for a woman in her 20s. Most women have a menstrual cycle that lasts an average of 28 days. That is, it is about a week before the start of menstruation. This is more difficult for women with irregular cycles . As women age, their cycles usually become slightly shorter. So, when progesterone production begins to decline, periods become more frequent.

In this case, it is worth taking the tests earlier, for example, on the 19th-20th day. A blood test is the cheapest option. It is usually covered by insurance. But I prefer a urine test to get metabolomics data in addition to hormone levels. And if I have to, I'll use a blood test. It's not that comprehensive, and as you know, it's just a quick snapshot while the needle is in the vein for about 30 seconds. Let me go back and say a few more things about biomarkers.

An important part of the testing I perform when phenotyping my patients is precision medicine. I like to start, essentially, by checking the nutrients. This may be helpful in your 20s and becomes less important with age as more micronutrient deficiencies occur, but micronutrients play a huge role in hormone production. Magnesium, for example, plays a huge role in how you get rid of estrogen. So the micronutrient testing that I usually do is a combination of blood and urine to look at all the micronutrients that can be measured based on clinical data, and polyphenol intake from vegetables is an important indicator of breast cancer risk in people aged 50 to 60 and older.

And the most important time is adolescence. If you had evidence that you could show a 17-year- old that she had a micronutrient deficiency, it would motivate her to eat differently at such a critical time, even if the results wouldn't be visible until 25 years later, when it would potentially change her life path. What to do with a young girl who doesn't like vegetables or for some reason can't or doesn't want to consume five colors of vegetables a day to support the microbiome? What other tools, behavioral or otherwise, are useful?

I'm trying to convince them to make smoothies. If you can get them to drink smoothies three times a week and add these vegetables to them, it will make a huge difference. We know that this really changes the microbiome. For example, I recommend using frozen steamed broccoli because it has almost no flavor. They can be added to a chocolate smoothie. You can add some greens. I like green powders, they are very convenient. So, combined with a flavor they like—whether it's chocolate, which most of my customers choose, or vanilla with berries, etc.—it'll work.

This can be a big help if you don't like vegetables. If that's not enough, I would recommend some supplements, but they are only a secondary option compared to smoothies. What is the best way to check the microbiome? In nutritional testing, I like to use a panel to check for antioxidants like vitamin A, vitamin C, alpha lipoic acid, and plant antioxidants because they can be measured in the blood. I like to look at key vitamins, especially the B vitamins, because as you probably know, certain genetic polymorphisms can make it harder for the body to absorb vitamin B9, folate, vitamin B12 , etc.

Returning to antioxidants, I also pay attention to glutathione, because I consider it a very important lever. I also look at the levels of some minerals. Magnesium is the most important, and we know that approximately 70-80% of Americans are deficient in it. This is the most obvious solution that lies on the surface. I would be interested to know, for example, regarding magnesium: if so many people are deficient, does this mean that they all need to adjust their diet in favor of magnesium-rich foods and/or take magnesium supplements?

And if so, what forms of magnesium are there? It is necessary to measure the magnesium level in red blood cells, as in whole blood. And in case of deficiency, it is interesting to observe the intake of supplements. For my patients who are prone to constipation, which is , frankly, about 80% of the women I treat. Seriously? Yes. Oho. I wonder why that is. Patriarchy. Rage. PINE system. Yes. Psychological, immunological, neural and endocrine factors together. This is Yes. And I would also mention another factor. Being a woman is a health risk.

We have twice the rate of depression and insomnia. We have a three to four times higher risk of multiple sclerosis. We have a five to eight times higher risk of thyroid dysfunction. So, if you look at that and mild preclinical thyroid dysfunction, a large number of my patients have thyroid problems that contribute to constipation. And if you go back to that control system, the hypothalamic-pituitary- adrenal-thyroid-gonadal -gut axis, they're experiencing a lot of stress along with this borderline thyroid function that conventional doctors don't consider a problem.

And then she has a problem with the balance between estrogen and progesterone, and she will be prone to constipation. Women suffer from constipation much more often than men . Women's intestines are about 10 feet longer than men's. And they have a much more common elongated ( dolichocolon) colon. You can find out about this during a colonoscopy. Women experience more trauma than men. This is a well-known fact . If you look at the ACE studies conducted by the CDC and Kaiser in 1998. We know that men, mostly middle-aged men, experience significant trauma, as defined by the ACE questionnaire, about 50% of the time.

For women, this figure is 60%, and this has been a fairly stable figure since 1998. They face various forms of violence, much more often sexual. They have a different hypothalamic- pituitary- adrenal axis response than men. Their perceived stress levels are usually higher, and I generalize to the entire population. So, if you look at a woman's physiology, I think that constipation and this need to control , to restrain, and to keep everything inside is part of the physiology. So, I'm stepping away from the science, but I think this is a very important signal that deserves close attention.

What tools do you recommend using to relieve constipation? It seems like reducing stress levels will be one of the most important. Yes. What are your favorite stress relief tools? Something that can really lower the baseline. So, I'm not a fan of simply "stress reduction." I am a proponent of reducing stress. I think we all need a broad menu of choices for the most effective methods. So what works for me now at my age is different from the TM I did as a student— transcendental meditation. I became a certified yoga instructor when I was in my 30s.

It's very effective for many people . I practice holotropic breathing. I think people are starting to realize that there are ways to relieve stress that aren't limited to just vacations . Really. and meditation. But I want to say that meditation is obviously a wonderful tool. It is certainly a great tool, and it has a solid scientific basis. But there is so much more to this menu of choices . Sex, orgasm, emotional connection, the feeling of being heard, seen, and loved. I want to take this opportunity to, first of all , remember this, coming back to a question that we did n't fully address earlier -- and that's my fault: It's now clear to me that a woman in her late teens or early 20s should know something about her testosterone, estrogen, thyroid, and cortisol levels.

She should at least start thinking about her microbiome. She should keep track of how many times a day she defecates and at what time. And I assume that what I just described is just as relevant for women in their 20s, 30s, 40s, 50s, and well into their 100s. Is this correct? That's correct, but I would say there are different possibilities depending on the decade. So I'm glad she came back to the topic of teenagers and testosterone, because I think if you know, for example, in adolescence, that you have high androgen levels and that you have this potential phenotype for the future that you may not even be aware of.

I mean, maybe you'll notice a few extra hairs on your chin or something like that. If you know that your testosterone or other androgen levels are elevated, it may change your approach to self- care. So, I think this can be very helpful during adolescence. At 20 years old, for people like me who are constantly under stress—like 27 years old on the UCSF ward—if I had known that I had such high cortisol levels, I think I would have acted differently. I would change my behavior. Your testosterone can start to decline as early as your 20s, depending on the stress your body is exposed to.

So in women it can start as early as 28 years old. Typically, your testosterone levels decline by about 1% per year. What level of testosterone would you like to see in a woman, say, after age 25? So, in podcasts, I usually describe it as the upper half of the normal range. I get asked a lot of questions about PCOS. Yes. So, PCOS is one of those conditions that is very poorly understood. It seems to go unnoticed until a woman wants to get pregnant or has another problem that forces her to see a doctor.

The problem is , it's a syndrome, right? So, polycystic ovary syndrome. Sometimes called polycystic ovary syndrome. And syndromes do not necessarily fit into clear diagnostic criteria. So in this case we are looking for three different criteria. These are ovarian cysts and clinical manifestations of hyperandrogenism. It could be hirsutism, acne, and other things. And also, as a rule, irregular menstruation. According to the latest criteria , it is defined as a menstrual cycle lasting 35 days or more. A typical cycle is 28 days, 35 days. You know, when a cycle is sometimes skipped.

So, these are the criteria we use to diagnose PCOS. There are about four different systems for diagnosing PCOS in the literature, which complicates the situation. There are women who do not have ovarian cysts, but have hirsutism and irregular menstruation. Can you explain what hirsutism is? Hirsutism is excessive hair growth, usually where you don't want it. In women, it can be, you know, masculine. They can spot it on their chest. We know that PCOS is not just a problem of irregular periods and difficulty conceiving. This is mostly a problem in your 20s, 30s, 40s, but it is also a huge risk factor for cardiometabolic disease with age.

Many people tend to think of PCOS as only a problem of reproductive age . We have to consider this throughout a woman's life. I would say it's even more important to think about this after age 50, because the average age of menopause is 51-52, because we know that elevated testosterone, high androgens, are probably the main cardiometabolic factor in women with PCOS. The threat we have n't talked about yet is the role of insulin and glucose. So, for some PCOS phenotypes, the problem is hyperinsulinemia, high levels of insulin in the blood, which causes theca cells in the ovaries to overproduce testosterone.

Are you a fan of continuous glucose monitors? The most ardent, biggest supporter of CGM. I have never seen a tool in medicine that changes behavior the way CGMs do. I think truly understanding what exactly is affecting your glucose control is critically important. Although, it's worth noting, this is also a kind of delayed effect. I mean, it's better to know your insulin levels. And we know from the Whitehall study that insulin , especially postprandial insulin, as well as fasting insulin, can change years before glucose levels change.

So, this is more about prediabetes and diabetes. The third is the democratization of data . One of the most promising and exciting things I see in healthcare right now is that we're moving away from patriarchal relationships where doctors hold the power and control the data, to a situation where patients and clients have much greater access to information about their own chemistry and biology. Teaching the patient to be his own doctor. For me, it is a cycle of kindness and wholeness that I believe is essential for building health.

We have a system for treating diseases. We need the democratization of data to become a healthcare system. If you had a magic wand, what two or three things would you advise not to do to maximize vitality and longevity? Let's focus on women first, but if this applies to men too, what wouldn't you want them to do? So, I would highlight sleep, alcohol, hyper-stress during sleep, eating the wrong foods, toxic relationships, and isolation. And sixth— insufficient mobility or lack of movement and exercises that really suit your body.

So, is this really it? Just because it is what it is , and then work in reverse. Yeah, well, I think for me, because I have a phenotype that produces a lot of insulin, depending on how fit I am, I have a lot of glucose. So I need to exercise more to use up this glucose. So, I think we need to move from medicine for the masses or general prescriptions to what works for the individual. One factor that I think is important, especially for people who do what I call chronic cardio, like I used to , is cortisol.

We know that runners, especially marathoners, people who do a lot of cardio and little strength training, usually have significantly elevated cortisol levels. You can balance this with vitamin C. Vitamin C can reduce the effect, but chronic cardio doesn't always benefit people. When I first started getting my hormone profile checked, I went to the doctor and said, " I'm 35. I've never been so exhausted in my life. I feel like I'm pushing a rock up a mountain. I've got belly fat that I don't like, and I don't want to have sex with my husband.

What can we do about it?" He offered me birth control pills and antidepressants. Oh, God. So I left him, got hormone tests done, and my cortisol was three times higher than normal. My insulin was over twenty. I was on a hunger strike. Glucose level was 105. My thyroid was slightly altered. My progesterone was low. It made me realize that the way I worked as a doctor, especially with women, didn't allow me to get to the root causes that are so important. I would say that we should have started with cortisol first.

At that time, I was running 4 miles three or four times a week. This increased my cortisol even more. So, it wasn't the kind of workload I needed. I needed more adaptive exercises. I started doing Pilates, more yoga. This helped lower cortisol levels. This prompted me to change my approach to stress, as well as change my supplement regimen. I want to make sure we get back to the topic of contraception. In particular, to oral contraceptives. What are your concerns? What do you like about oral contraceptives?

What do n't you like about them ? As for the benefits, I think that especially in the early days of it and even now, it gives women reproductive choice , and that's important. So I'm a big proponent of this, and we have a lot of data showing both the risks and the benefits. So, I'll talk about the benefits first, because I'm going to discuss the risks a little bit. We know that it reduces the risk of ovarian cancer. So, there is something about the very idea of continuous ovulation that is not beneficial for the female body.

So if you look , for example, at women who are nuns, who do not take oral contraceptives and have their periods every month throughout their reproductive lives, they have a higher risk of developing ovarian cancer. If you look at women who have had multiple children and had a period of pregnancy where they didn't ovulate and then breastfed for a while, they have a lower risk of ovarian cancer. Therefore, oral contraceptives help reduce ovulation and reduce risk. We know that taking oral contraceptives for about 5 years reduces the risk of ovarian cancer by 50%.

And this is important because we are very bad at diagnosing ovarian cancer in its early stages. In fact, there is no single truly effective method. We use CA 125 testing and ultrasound screening, especially in women at higher genetic risk, but even then we often diagnose the disease at a late stage. Perhaps this statement will highlight for many people the question of what are the very first symptoms that can be recognized without a blood test. So will ovarian cancer be accompanied by pain? The problem is that the symptoms are very vague and nonspecific.

One of the most common symptoms is bloating. We've already talked about constipation. We discussed that women have a longer gastrointestinal tract, so bloating is a very common occurrence for most women. There may be symptoms of fullness, a feeling as if the lower abdomen is bulging. The way we advise women to monitor this is to have regular gynecological checkups . For women who are at high risk, or if, for example, an ultrasound reveals a tumor that is of concern for some reason, there is a way to determine which test they need.

And it is in this situation that a blood test for CA 125 may be needed. Taking estrogen, which reduces the frequency of ovulation, reduces the risk of developing ovarian cancer. Would it be advisable for women, even those who are not sexually active— that is, they are not trying to get pregnant or avoid pregnancy—to periodically suppress ovulation with hormonal contraceptives simply to reduce the risk of ovarian cancer? This is a very rational question, and I would say that this is exactly what official medicine is guided by, recommending oral contraceptives not only to those who need to prevent pregnancy, but also for acne, painful menstruation—that is, almost at every opportunity.

They prescribe oral contraceptives. This is what I was talking about, and I think it's largely the influence of pharmaceuticals. An oral contraceptive consists of two hormones. These are ethinyl estradiol and progestin. So, this is not the normal progesterone that your body, your ovaries, and your adrenal glands produce. This is a synthetic form of progesterone, and it's the same progestin, similar, same class, that was found to be dangerous and provocative by the Women's Health Initiative. Therefore, I am not a fan of progestins. I don't recommend them to any woman unless they give them some freedom in some sense.

Like almost any pharmaceutical drug, oral contraceptives deplete certain micronutrients. Magnesium, certain B vitamins are depleted. It also affects the microbiome. This data is not so clear-cut, but there is some effect, and there is also an increased risk of inflammatory bowel disease and autoimmune conditions. It increases the level of inflammation. The studies I've seen show an increase in one of the markers of inflammation, high-sensitivity CRP, by about two to three times. It seems to make the hypothalamic- pituitary- adrenal axis more rigid. So you can't easily adapt to changes and regulate cortisol production the way you can without birth control pills.

This can affect thyroid function. When you take oral estrogen , it increases your levels of sex hormone-binding globulin. And you've already talked about this with other podcast guests, Kyle, I think. I think of sex hormone binding globulin as a sponge that soaks up free estrogen and free testosterone. So when you start taking birth control pills, you increase your levels of sex hormone-binding globulin. It absorbs, in particular, free testosterone. And for some women, this isn't a big problem. They don't notice much difference. But there is a specific phenotype, possibly related to CAG repeats in the androgen receptor, that is extremely sensitive to this reduction in free testosterone.

This opens up the opportunity to talk a little about testosterone in women. It is the most common, biologically most abundant hormone in the female body. It is very important for women. It is necessary for many things, not only for sex drive, muscle mass, and response to strength training, but also for confidence and a sense of self- efficacy. And therefore, in those women who are very sensitive to testosterone levels, high levels of sex hormone-binding globulin lead to a decrease in testosterone. They describe vaginal dryness, possibly a decrease in sexual desire; but there is also a broader issue related to confidence and agency, and even risk-taking, which, according to our research among MBA students, I believe is a serious problem.

Perhaps most importantly of all, it can shrink the clitoris by up to 20%. 20%. And if a woman comes to me who I do n't think should be on birth control pills—maybe she's on them for acne or because her periods have been a little painful—I say, "Let's use other ways to make your periods less painful." Let's take a look at your painful periods and see if they're related to your inflammation levels. And we'll give you fish oil and SPM, maybe some aspirin when you start your period.

So, let's find other ways to deal with this, instead of taking oral contraceptives, the side effects of which you were not informed about, including the fact that they can shrink the clitoris by up to 20%. This usually convinces most people to stop taking them. The data we have is limited. There is one woman, Claudia, who had her sex hormone binding globulin levels studied a year after stopping birth control pills, and it was still elevated. It wasn't as high as it was when I was taking the pills, but it was still elevated .

So to your question about reversibility—I don't know if we have an answer to that. What do you think about menopause? When should people start thinking about this? And I would suggest, based on everything you've said today, that there are women in their 30s who, even though they're still 20 years away from menopause, should probably be taking some steps now to prepare for it. The more you know about your phenotype, your hormonal phenotype at 30, the better prepared you are for what to do in the future.

This is especially true for things like your thyroid, estrogen, and progesterone levels, as you can revert to a youthful thyroid state . I usually don't get back to exactly the same estrogen and progesterone levels I had before, but we can get pretty close. So, having a baseline at 30 years old, I think, is very important. What's more interesting is to talk about perimenopause. So, perimenopause is the period of time before your last menstrual cycle . And in most women, depending on how attentive you are to the symptoms, it can last for 10 years.

So I'm still in perimenopause. This has been going on for about 20 years now because I track it so closely . It usually starts with your cycle becoming shorter. So, it could happen in your 30s or 40s. The cycle is shortened from 28 days to 25, something like this. You may notice this as increased anxiety, trouble sleeping, and it is likely related to estrogen receptors. So, there's this whole perimenopause period . What's most fascinating to me is that there are huge, just colossal changes happening in the female brain that people don't talk about enough.

If you look at the work of Lisa Mosconi from Cornell, from about the age of 40 there is a massive change in cerebral metabolism. You can do a PET scan with FDG, look at glucose uptake, and on average there is a 20% decrease from premenopause, up to about 35 years old, to peri- and postmenopause. Those who have the most symptoms during perimenopause and menopause—hot flashes, night sweats, difficulty sleeping—are the ones who have the most severe cerebral hypometabolism. It's almost like, I don't want to scare people with these words, but this is low-level or, let's call it, a kind of pseudodementia.

Yes, this looks like a phenotype that could then be linked to Alzheimer's disease , because this is Lisa Mosconi's research. She considers that Alzheimer's disease is not a disease of aging. This is a disease of middle age. What biomarkers can we identify to understand your risk level. My mother and grandmother had Alzheimer's disease. You can believe that I study this data in great detail. Insulin resistance and insulin sensitivity, which we talked about earlier, also seem to have something to do with this, and when this idea first came out, some people were skeptical, but then of course they got it, right?

The brain is an organ with extremely high metabolic needs. If you deprive neurons of fuel sources, or make them less sensitive to them, they start to die, they definitely start to work less actively. It makes perfect sense, and I think now, thanks to Lisa's work, the work that you've done and talked about a lot in your books and other sources. It really highlighted for people the fact that metabolism and metabolomics are going to be as important as genes and genomics when it comes to dementia. Perhaps especially in women.

Can we say that? I think so, because we think this system is regulated by estrogen. Therefore, the decline in estrogen levels, which begins around the age of 40-43 ( this is the average) , seems to be the main cause of cerebral hypometabolism. I explain this to my patients as a slowing of brain energy. You walk into a room and can't remember why. You simply notice that you can't handle tasks the way you used to. Everything happens a little slower. And when I tell women this, they say, "I have the same thing.

" "Help me." We have many women who are potentially moving towards an increased risk of developing Alzheimer's disease. And they have the opportunity to undergo hormone therapy at the age of 40 or 50. But they may not be offered it. Because the typical conventional approach based on the WHI is: “If you don’t have severe hot flashes and night sweats, I won’t give you hormone therapy .” I just want to draw attention to this. I would say, "No, that's not the approach to take." Today, conventional medicine believes that hot flashes and night sweats are just unpleasant symptoms that we can temporarily eliminate.

It doesn't matter that you're not sleeping anymore. Reduce the temperature in the room. This is wrong, because hot flashes and night sweats are a biomarker of cardiometabolic diseases. This is a biomarker of accelerated bone loss. This is a biomarker of changes in the brain. So many of the symptoms that occur during perimenopause are not caused by the ovaries. They are caused by the brain. I want to say that you have taught me an incredible amount of things. The amount of knowledge you have shared is vast and will be very useful and practical, especially for women.

Can I add one more thing that we have n't talked about because we haven't reached the 40-50 years on the biomarker list? If there was one thing women remembered today , it would be to get a coronary calcium index by age 45, or earlier if you have premature heart disease. How is this done? This is a CT scan of the chest. You can order it yourself. This kind of gives you a choice point on how carefully a woman should monitor her cardiometabolic health. It's so exciting because, you know, there are women who have zero, like me, but if you're 45 and it's starting to go up, or you have, say, PCOS or other biomarkers that point the way to a major killer, it gives you a real opportunity to start making changes.

And I think it's extremely important to know this data. Most regular doctors won't do this. So, if I went to my doctor and just said I wanted to get a cardiac calcium index test, that's what people should be asking for. Coronary artery calcium index, KIKA. Of course. There are certain people, they are extremely few, but you are exactly the kind of person who, when she speaks, just pours out knowledge, and it is incredibly useful and valuable knowledge, so thank you. Thank you.

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