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

0:00Andrew Huberman:Welcome to Huberman Lab Essentials, where we revisit past episodes for the most potent and actionable science-based tools for mental health, physical health, and performance. I'm Andrew Huberman, and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine. And now for my discussion with Dr. Sara Gottfried. Dr. Gottfried, Sara, welcome. Thank you. So happy to be here. Yeah, I'm delighted and very excited to ask you about an enormous number of topics. You are expert in so many things, female hormones in particular. Is it ever informative for a woman, regardless of age, to know something about her mother's, perhaps even her grandmother's experience vis-a-vis hormones?

0:42Andrew Huberman:What sorts of conversations should women be having with themselves and with family members to get a window into what their specific needs might be? So my work is really at the interface between genetics and environment. And I think it's essential that you understand what your grandmother went through, and especially your mother. So I would probably start first with trauma and intergenerational trauma, because I think that affects the endocrine system so hugely, especially cortisol signaling. And then there's certain female conditions that have a very strong component genetically, most of which run in my family.

1:25So that includes endometriosis, fibroids, and polycystic ovarian syndrome.

1:31Andrew Huberman:Maybe we could march through and just say, for a woman in her teens who's already hit puberty, what sorts of biomarkers should those young women be paying attention to? Likewise for women in their 20s, 30s. Maybe we could take it more or less by decade, starting at puberty. In your teenage years, what I think is really interesting is to look at cortisol. To look at the dance between estrogen and progesterone in those years is less helpful because I think there's a lot of variability due to the immaturity of the system. If you've got someone who's got really regular periods, it's probably better to do some benchmarking at that age.

2:06But generally, I find that benchmarking is best performed in your 20s or 30s.

2:11Andrew Huberman:Are periods not that regular in terms of duration of the menstrual cycle when the menstrual cycle first sets in? For a lot of women, they're not regular. And then there's the whole piece of oral contraceptives and other forms of contraception where you have no idea what the normal cycle is. But getting back to your original question, which is about biomarkers per decade. In your 20s, that's when you want to do some base casing with estrogen, progesterone, and testosterone. What happens a lot of the time is that estrogen dominates in that tango. And when that happens, it sets you up for greater risk of fibroids, endometriosis.

2:53I'd want to know about DHEA and sort of the whole androgen pathway. I'd want to know about the metabolites of estrogen because some of them are protective and very helpful. Others are a bit like Homer Simpson. I mean, they are just like causing all kinds of problems in your body. I'd also like to know about their stool. So I want to know about the microbiome.

3:15Andrew Huberman:In terms of blood testing or various tests for these other biomarkers, getting estrogen, testosterone, and other ratios, women will need to do it at different stages of their menstrual cycle. If they had to pick one, either in the follicular phase or in the luteal stage of their ovulatory menstrual cycle, when would you suggest they do that? So if you force me to pick one, I would say probably day 21 to 22 for someone in their 20s. So for most women, they've got a menstrual cycle date that averages out at 28 days. So this is about a week before they start their period. For women who are more irregular, it's harder to do that.

3:54As women get older, usually the cycle gets a little shorter. So as they start to decline in their progesterone production, their period gets a little closer together. At that point, you want to test sooner, like day 19, 20. Blood test is the cheapest thing. It's usually what's covered by insurance. But my preference would be to do dried urine so that I get metabolomics in addition to the levels of these hormones. And if I'm forced to, I'll use blood testing. It's not as comprehensive. And as you know, it's a quick little snapshot while the needle's in your vein for 30 seconds. Let me go back and say one other thing about biomarkers.

4:30A big part of the testing that I do in phenotyping my patients, I practice precision medicine. I like to almost start with nutritional testing. That would be potentially a helpful thing to do in your 20s. It becomes less important as you get older and you develop more micronutrient deficiencies. But micronutrients play a huge role in terms of hormone production. Magnesium is hugely involved in the way that you get rid of estrogen, as an example. So micronutrient testing, what I usually do is a combination of blood and urine. And so I'm looking at all of the micronutrients that we can measure that have some clinical scientific basis behind them.

5:09Intake of vegetables, polyphenols, is such an important predictor of future risk of breast cancer, like when you're 50, 60 plus. And the most important time is when you're a teenager. If you have evidence that you could show a 17-year-old that they've got micronutrient gaps, I think that would be a motivator for them to eat differently at a time when it's so critical. Even though it's 25 years in the future, that it's going to potentially change this arc that they're on.

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6:41Andrew Huberman:Right now, Element has a limited edition lemonade flavor that is absolutely delicious. I hate to say that I love one more than all the others, but this lemonade flavor is right up there with my favorite other one, which is raspberry or watermelon. Again, I can't pick just one flavor. I love them all. If you'd like to try Element, you can go to drinkelement.com slash Huberman, spelled drinkelement.com slash Huberman to claim a free Element sample pack with a purchase of any Element drink mix. Again, that's drinkelement.com slash Huberman to claim a free sample pack. What do you do for a young woman who doesn't like vegetables or is not somehow able or willing to get those five colors a day of vegetable to help support the microbiome?

7:26Andrew Huberman:What other sorts of tools, behavioral or otherwise, are useful? What I try to get them to do is have a smoothie. If I could get them to have a smoothie three times a week and to throw some of these vegetables in, that makes a huge difference. I mean, we know that makes a difference in terms of microbiome change. Like I have them do steamed broccoli that's in the freezer because it's got very little taste. They could do that in a chocolate smoothie. They could add some greens. I like greens. Powders are super convenient. So that with, you know, kind of a taste that they like, whether that's chocolate, which is what most of my clients want, or, you know, vanilla with berries and that sort of thing.

8:03So that can go a long way if you don't like vegetables. And short of that, I would say some supplements, but I would say that's a distant second to making a smoothie.

8:12Andrew Huberman:What is going to be the best way to test the microbiome? What I like to do with nutritional testing is run a panel that's looking at antioxidants. So like vitamin A, vitamin C, alpha lipoic acid, plant-based antioxidants, because you can measure that in the blood. I like to look at some of the key vitamins, especially the B vitamin range, because as you probably know, if you've got particular genetic polymorphisms, you might be less likely to be absorbing the right level of vitamin B9, folate, vitamin B12, etc. I'm also looking going back to the antioxidants at glutathione because I think that's such an important lever.

8:52And then I'm looking at some of the minerals. Magnesium is really the most important. And we know that somewhere around 70 to 80 % of Americans are deficient in magnesium. That's like the

9:01Andrew Huberman:lowest hanging fruit. I would be curious, for instance, like with magnesium, if that number of people are deficient, does that mean that that number of people should be targeting their nutrition towards foods that contain magnesium and or supplementing with magnesium? And if so, what forms of magnesium? You have to measure red blood cell magnesium, like whole blood. And with deficiency, it's interesting with supplementation. For my patients who tend toward constipation, and that's frankly about 80 % of the women that I take care of. Really? Yes. Wow. I'd be curious as to why that is. Patriarchy, rage, the pine system.

9:42Andrew Huberman:Right. Psychology, immunology, neural and endocrine factors combined. Is that? Yes. And then I would say there's another factor. Being female is a health hazard. So we have twice the rate of depression, insomnia. We've got three to four X increased risk of multiple sclerosis. We've got five to eight times the risk of thyroid dysfunction. So if you just look at that and you look at subtle preclinical thyroid dysfunction, a large number of the women that I take care of have thyroid dysfunction that's contributing to constipation. And if we go back to that control system, the hypothalamic, pituitary, adrenal, thyroid, gonadal, gut axis, and they have a lot of perceived stress together with this borderline thyroid function that no mainstream medicine doctor has told her is a problem.

10:32And then she's got a problem with the tango between estrogen and progesterone. She's going to tend toward constipation. Women have a lot more constipation than men. The gut is about 10 feet longer in women compared to men, and they are much more likely to have a torturous colon. And the way you know that is you get a colonoscopy. Women experience more trauma than men. This is well established. If you look at the ACE studies that were done by the CDC and Kaiser in 1998, we know that men, for the most part, middle-aged men have about, about 50 % of them experience significant trauma as defined by the ACE questionnaire.

11:09Women are at 60%. And that's pretty durable since 1998. They have different forms of abuse, much more likely to have sexual abuse. They have a different HPA response than men. Their perceived stress tends to be higher. And I'm generalizing for a population. And so if you look at the physiology of a female, I think that constipation and that need to control and restrain and hold things in, I think that's part of the physiology. So I'm veering away from the science, but I do think that it is a really important signal to pay a lot of attention to.

11:50Andrew Huberman:What sorts of tools do you recommend people use to relieve constipation? Sounds like reducing stress is going to be a huge one. Yes. What are your favorite stress reduction tools, things that can really lower the baseline? So I'm not a fan of lowering stress. I'm a fan of lowering perceived stress. I think all of us need an a la carte menu of what is most effective. So what works for me now at my age is different than the TM I did as a college student, Transcendental Meditation. I became a certified yoga teacher when I was in my thirties. That is very effective for a lot of people. I do holotropic breath work.

12:28Andrew Huberman:I think people are starting to appreciate that there are ways that they can relieve their stress that don't only fall under the categories of vacation and meditation. But I want to say that meditation is obviously a wonderful tool. Well, certainly it's a great tool and it's got such a scientific basis behind it. But there's so many things on this a la carte menu. Sex, orgasm, connection, feeling heard and seen and loved. I want to use this as an opportunity to A, keep this in mind as we turn to a question that I didn't close the hatch on earlier, and it's my fault, which is I'm now clear on the fact that a woman in her late teens, early twenties ought to know something about her testosterone, estrogen, thyroid, cortisol levels.

13:12Andrew Huberman:should start at least thinking about her microbiome, should be thinking about how many bowel movements and the timing of those bowel movements per day. And I'm assuming that what I just described is also true for women in their 20s, 30s, 40s, 50s, on up to hundreds. Is that correct? That's correct. But I would say that there are differential opportunities by decade. So I'm glad she circled it back to teenagers and testosterone, because I think if you know So, for instance, in your teenage years that you have high androgens and that you've got this potential phenotype way into the future that you may not even notice.

13:53I mean, maybe you notice you've got a few extra hairs on your chin or something. If you know that your testosterone is elevated or some other androgen, it might change the arc of how you take care of yourself. So I think that could be very helpful in your teenage years. In your 20s, for people who are a stress case like me, so age 27 on the wards at UCSF, if I had known that I was such a high cortisol person, I think I would have done things differently. I would have changed my behavior. your testosterone can decline starting in your 20s, kind of depending on how much stress your matrix is under.

14:30So for women that can start as early as 28, usually your testosterone declines by about 1 % per year.

14:37Andrew Huberman:What level of testosterone do you like to see in a woman once she's sort of post, let's say after age 25? So the way I tend to describe this on podcasts is the top half of the normal range. I get a lot of questions about PCOS. Yeah. So PCOS is one of those really poorly understood conditions. It kind of flies below the radar until a woman wants to get pregnant or she's got some other issue that drives her to a physician. The problem is that it is a syndrome, right? So polycystic ovary syndrome, sometimes polycystic ovarian syndrome. And syndromes don't necessarily fit together into a really clear diagnostic criteria.

15:19So in this instance, there are three different criteria that we look for. So cysts on the ovaries, having clinical manifestations of hyperandrogenism. So that could be hirsutism, acne, other things, and then usually irregular periods. And the way that that's defined, at least by the latest criteria, is having a period every 35 days or less. So typical cycle length, 28 days, 35 days, you know, you're skipping a period here and there. So those are the criteria that we use to diagnose PCOS. There are about four different systems out there in the literature for diagnosing PCOS, which is where it starts to get confusing.

15:58So there's some women who have gnosis on their ovaries, but they've got hirsutism and they've got irregular periods.

16:06Andrew Huberman:Could you define hirsutism? Hirsutism is increased hair growth, usually in places that you don't want it. So for women, it can be kind of male pattern. They might notice it on their breasts, on their chest. What we know is that PCOS is not just a problem in terms of irregular periods and then difficulty getting pregnant. So those are mostly problems in your 20s, 30s, early 40s. But it is a massive risk factor for cardiometabolic disease as you get older. So many people tend to pigeonhole PCOS as a problem of reproductive age. We have to be thinking of it over the entire female life cycle. And I would say it's even more important to consider it over the age of 50, you know, average age of menopause is 51 to 52, because we know that that elevated testosterone, the high androgens are probably the greatest cardiometabolic driver of disease for women with PCOS.

17:05The thread we haven't talked about is the role of insulin and glucose. So for some of the phenotypes of PCOS, the problem is hyperinsulinemia, high insulin in the blood, is driving those theca cells in the ovaries to overproduce testosterone.

17:23Andrew Huberman:Are you a fan of continuous glucose monitors? The hugest, most gigantic fan of CGMs. I've never seen any tool that I've ever used in medicine change behavior the way that CGMs do. Like I think really understanding what the mediators are of your glucose control is essential. Now, that said, it's also kind of a later effect. I mean, I'd rather know your insulin. And we know from the Whitehall study that insulin, especially postprandial insulin, fasting insulin too, can change years and years before you get a change in glucose. So that's more for prediabetes and diabetes. Third thing is it democratizes data.

18:05One of the most hopeful and exciting things that I'm seeing right now in the health space is that we're going from this patriarchal relationship where doctors hold the power and are the gatekeepers of data to patients and clients having much more access to that enchantment about their own chemistry and their own biology. teaching the patient to be their own clinician, to me, that is a loop of benevolence and integrity that I think is essential to creating health. We've got a disease care system. We need the democratization of data to become a health-based system.

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20:04Andrew Huberman:If you add a magic wand and you could give two or three don'ts to maximize vitality and longevity, let's focus first on female patients. But if it extends to male patients as well, what would you like to see them not do? So I would say sleep, alcohol, high perceived stress, eating the wrong foods, toxic relationships and isolation. And then number six, not moving enough or not moving and exercising in a way that really fits with your body. Can we start with that one actually? Sure. Just because it's such a, and then work backwards. Yeah. Well, I think for me, because I have a phenotype that produces a lot of insulin, kind of depending on how I'm on my game.

20:47I have a lot of glucose, so I have to exercise a lot more to dispose that glucose. So I think you then have to move from medicine for the population or prescriptions for the population to what works for the individual. One of the mediators that I think is important, especially for people who do what I call chronic cardio, which is what I did, is cortisol. So we know that runners, especially marathon runners, people who do a lot of cardio and don't do much resistance training, they tend to have much high cortisol levels. And you can buffer that with vitamin C. Vitamin C can decrease the effect, but chronic cardio doesn't always serve people.

21:28When I first started measuring hormone panels in myself, I went to my physician and I said, I'm 35. I've never been so exhausted in my life. I just feel like I'm pushing a rock up the hill. I've got this belly fat that I don't like and I don't want to have sex with my husband. What can we do about this? And he offered a birth control pill and an antidepressant. So I left him and I went to the lab and I ran a hormone panel and my cortisol was three times what it should have been. My insulin was in the 20s. I was fasting. My glucose was 105. My thyroid was mildly abnormal. My progesterone was low.

22:10And that set me on this course of realizing that what I was doing as a physician, taking care especially of women, was not getting to some of these root causes that are so essential. And I would say I had to start first with cortisol. at that time I was running four miles three times a week four times a week that was just raising my cortisol further so that was not the right exercise for me I needed more adaptive exercise I started doing Pilates more yoga that helped to lower my cortisol I mean it started me on changing the way I was managing perceived stress and it also changed my supplement regimen