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

1. 0:00 – 0:24

   Female Hormone Health

   1. AHAndrew Huberman0:00

      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.

   2. SGDr. Sara Gottfried0:22

      Thank you. So happy to be here.

2. 0:24 – 1:31

   Family History, Intergenerational Trauma; Endometriosis, Fibroids, PCOS

   1. AHAndrew Huberman0:24

      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? 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?

   2. SGDr. Sara Gottfried0:51

      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. So that includes endometriosis, fibroids, and polycystic ovarian syndrome.

3. 1:31 – 3:35

   Biomarkers by Decade; Teens & Cortisol; 20s & Sex Hormones

   1. AHAndrew Huberman1:31

      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, by decade. At, starting at puberty.

   2. SGDr. Sara Gottfried1:46

      In your teenage years, what I think w- 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, but generally, I find that benchmarking is best performed in your 20s or 30s.

   3. AHAndrew Huberman2:11

      Are periods not that regular in terms of duration of the menstrual cycle when the menstrual cycle first sets in?

   4. SGDr. Sara Gottfried2:19

      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. I'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.

   5. AHAndrew Huberman3:16

      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 and/or in the luteal stage of their ovulatory menstrual cycle, when would you suggest they do

4. 3:35 – 5:40

   Tool: Hormone Test Timing; Micronutrient Testing, Magnesium

   1. AHAndrew Huberman3:35

      that?

   2. SGDr. Sara Gottfried3:35

      So if you forced me to pick one, I would say probably day 21 to 22 for someone in her 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. As 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, you know, 30 seconds. Let me go back and say one other thing about biomarkers. A 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. 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. Intake 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.

5. 5:40 – 6:39

   Tool: Smoothies, Greens Powders & Microbiome

   1. AHAndrew Huberman5:40

      What do you do for a young woman who doesn't like vegetables, is, or is not somehow able or willing to, to get those five colors a day of vegetable to help support the microbiome? What other sorts of tools, behavioral or otherwise, are useful?

   2. SGDr. Sara Gottfried5:57

      What I try to get them to do is to 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.

   3. AHAndrew Huberman6:05

      Mm.

   4. SGDr. Sara Gottfried6:06

      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, 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. So 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

6. 6:39 – 8:01

   Nutrient Panels, Antioxidants, B Vitamins, Glutathione

   1. SGDr. Sara Gottfried6:39

      smoothie.

   2. AHAndrew Huberman6:39

      What is going to be the best way to test the, uh, microbiome?

   3. SGDr. Sara Gottfried6:42

      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, 'cause 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, et cetera. I'm also looking, going back to the antioxidants, at glutathione, because I think that's such an important lever. And 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, the lowest hanging fruit.

   4. AHAndrew Huberman7:30

      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?

   5. SGDr. Sara Gottfried7:44

      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

7. 8:01 – 10:17

   Constipation, Thyroid Dysfunction; Trauma & Female Physiology

   1. SGDr. Sara Gottfried8:01

      care of-

   2. AHAndrew Huberman8:01

      Really?

   3. SGDr. Sara Gottfried8:02

      Yes.

   4. AHAndrew Huberman8:03

      Wow. I'd be curious as to why that, that is.

   5. SGDr. Sara Gottfried8:06

      Patriarchy, rage, the PINE system.

   6. AHAndrew Huberman8:09

      Right. Psychology, immunology, neural, and endocrine factors combined. Is that-

   7. SGDr. Sara Gottfried8:14

      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 pre-clinical 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, and then she's got a problem with the tango between estrogen and progesterone, she's gonna 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. Women 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, um, constipation and that need to, like, 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.

8. 10:17 – 11:58

   Tools: Reduce Perceived Stress, Meditation, Yoga, Breathwork

   1. AHAndrew Huberman10:17

      What sorts of tools do you recommend people use to relieve constipation? Sounds like reducing stress is going to be a huge one.

   2. SGDr. Sara Gottfried10:25

      Yes.

   3. AHAndrew Huberman10:26

      What are your favorite stress reduction tools, things that can really lower the baseline?

   4. SGDr. Sara Gottfried10:30

      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 30s. That is very effective for a lot of people. I do holotropic breathwork.

   5. AHAndrew Huberman10:56

      I think people are starting to appreciate that there are ways that they can relieve their stress that, that don't al- only fall under the categories of vacation-

   6. SGDr. Sara Gottfried11:04

      Right

   7. AHAndrew Huberman11:04

      ... and meditation, but I want to say that meditation is obviously a wonderful tool.

   8. SGDr. Sara Gottfried11:09

      Well, certainly it's a great tool.

   9. AHAndrew Huberman11:10

      Yeah.

   10. SGDr. Sara Gottfried11:10

       And it's got such a scientific basis behind it. But there's so many things on this a la carte menu.

   11. AHAndrew Huberman11:15

       Mm-hmm.

   12. SGDr. Sara Gottfried11:15

       Sex, orgasm, um, connection, feeling heard and seen and loved.

   13. AHAndrew Huberman11:22

       I want to use this as an opportunity to, A, keep this in mind as we turn to a, a question that I didn't, uh, 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 20s ought to know something about her testosterone, estrogen, thyroid, cortisol levels, 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 100s. Is that correct?

9. 11:58 – 13:18

   Opportunities by Decade; Androgens & Testosterone Decline

   1. SGDr. Sara Gottfried11:58

      That's correct, but I would say that there are differential opportunities by decade. So I'm glad you circled it back to teenagers and testosterone, because I think if you know 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. I 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've done things differently. I would've changed my behavior. Your testosterone can decline starting in your 20s, kind of depending on how much stress your matrix is under. So for women, that can start as early as 28. Usually, your testosterone declines by about 1% per year.

   2. AHAndrew Huberman13:05

      What level of testosterone do you like to see in a woman once she's sort of post, let's say after age 25?

   3. SGDr. Sara Gottfried13:11

      So the way I tend to describe this on podcasts is the top half of the normal range.

   4. AHAndrew Huberman13:16

      I get a lot of questions about PCOS.

10. 13:18 – 15:38

    PCOS, Diagnostic Criteria, Hirsutism, Cardiometabolic Risk

    1. SGDr. Sara Gottfried13:18

       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. So in this instance, there are three different cri- 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 a 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. So there's some women who have no cysts on their ovaries, but they've got hirsutism, and they've got irregular periods.

    2. AHAndrew Huberman14:34

       Could you define hirsutism?

    3. SGDr. Sara Gottfried14:35

       Hirsutism is increased hair growth, usually in places that you don't want it. So for women it can be, you know, 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. The thread we haven't talked about is the role of insulin and glucose.

11. 15:38 – 16:34

    Insulin & Glucose; Tool: Continuous Glucose Monitors

    1. SGDr. Sara Gottfried15:38

       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.

    2. AHAndrew Huberman15:50

       Are you a fan of continuous glucose monitors?

    3. SGDr. Sara Gottfried15:53

       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, uh, the White Ha- Whitehall study that insulin, especially postprandial insulin, fasting insulin too, can change years and years before you get a change in glucose. So, um, that's more for pre-diabetes and diabetes. Third thing is it democratizes data. One of the

12. 16:34 – 17:19

    Democratizing Health Data

    1. SGDr. Sara Gottfried16:34

       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.

13. 17:19 – 20:00

    Longevity "Don’ts"; Chronic Cardio & Cortisol; Tool: Adaptive Exercise

    1. AHAndrew Huberman17:19

       If you had a magic wand and you could give, like, 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?

    2. SGDr. Sara Gottfried17:33

       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. So those-

    3. AHAndrew Huberman17:49

       Can we start with that one, actually?

    4. SGDr. Sara Gottfried17:50

       Sure.

    5. AHAndrew Huberman17:50

       Just 'cause it's such a... And then work backwards.

    6. SGDr. Sara Gottfried17:52

       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, I 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. When 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.

    7. AHAndrew Huberman19:05

       Oh, goodness.

    8. SGDr. Sara Gottfried19:06

       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've been. My insulin was in the 20s. I was fasting. My glucose was 105. My thyroid was mildly abnormal. My progesterone was low. And 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.

14. 20:00 – 21:41

    Oral Contraceptives, Benefits & Ovarian Cancer Risk

    1. AHAndrew Huberman20:00

       I'd like to make sure that we circle back to birth control, in particular oral contraceptive birth control. What are your concerns? What do you like about oral contraceptives? What do you dislike about them?

    2. SGDr. Sara Gottfried20:11

       In terms of benefit, I think that especially when they first came out and even now, it gives women reproductive choice, and that's essential. So I'm a big fan in that regard, and we've got a lot of data to show both the risks and also the benefits of it. So I'll speak f- first into the benefits because I'm going to get on a soapbox a little bit about the risks. So we know that it reduces the risk of ovarian cancer, so there's something about this idea of incessant ovulation that is not good for the female body. So if you look at, for instance, women who are nuns who don't take oral contraceptives and they have a period every single month of their reproductive lives, they have a greater risk of ovarian cancer. So if you look then at women who have several babies and they've got a period of time when they're pregnant that they're not ovulating and then they breastfeed for some period of time, they have a lower risk of ovarian cancer. So oral contrace- contraceptives help with reducing ovulation and reducing risk. We know that if you take the oral contraceptive for about five years, it reduces your risk of ovarian cancer by 50%. And that's significant because we're so poor at diagnosing ovarian cancer early. There's really no method that's really effective. We use CA-125 and ultrasound screening, especially in women who are at greater genetic risk, but even that, often we diagnose it, you know, in a later stage.

15. 21:41 – 23:04

    Ovarian Cancer Symptoms, Bloating, CA-125

    1. AHAndrew Huberman21:41

       Maybe just because that statement is going to highlight for a number of people, um, the question of what are some of the sym- earliest symptoms that people can recognize without a blood test? So is o- ovarian cancer, is it going to be pain?

    2. SGDr. Sara Gottfried21:54

       So the problem is the symptoms are so vague and they're so nonspecific. One of the most common symptoms is bloating, and we've already talked about constipation. We've talked about how women have this longer track, GI track, and so bloating is a really common experience for most women. You can have bulk symptoms, you know, feeling like your, your lower belly is kind of pressed out. The way that we inform women in terms of watching for this is to get regular gynecologic exams. For women who are at high risk where they have, for instance, an ultrasound for some reason and it shows a mass that we're concerned about, there's a way to triage that in terms of what kind of evaluation that they need, and that's the situation where you might get a blood test called the CA-125.

    3. AHAndrew Huberman22:38

       Taking estrogen and thereby re- reducing the frequency of ovulation lowers the risk of ovarian cancer. Should women that are, even women who are not sexually active, so they're not, they're not actively trying to get pregnant or avoid getting pregnant, but if they're not sexually active, would they be wise to suppress ovulation for periodically using hormone-based contraception just so that they can offset the risk of ovarian

16. 23:04 – 26:21

    Oral Contraceptive Risks, Progestins, Inflammation; SHBG & Testosterone

    1. AHAndrew Huberman23:04

       cancer?

    2. SGDr. Sara Gottfried23:04

       That's a very rational question, and I would say that's what mainstream medicine has had at its back to recommend oral contraceptives, not just for women who are seeking contraception, but for acne, for painful periods, for really kind of the drop of a hat they're prescribing oral contraceptives. That's what I was taught to do, and I think a lot of that is pharmaceutical influence. The oral contraceptive is two hormones. It's ethinyl estradiol, and it's a progestin. So it's not the normal, uh, progesterone that your body makes, that your ovaries make, and your adrenals make. It is a synthetic form of progesterone, and it is the same progestin, similar, same class that was shown to be dangerous and provocative in the Women's Health Initiative. So I'm not a fan of progestins. I do not recommend them for any woman unless it, it gives them some freedom in some way. So like with almost any pharmaceutical, the oral contraceptive depletes certain micronutrients. Magnesium, there's certain vitamin Bs that are depleted. It also affects the microbiome. That data is not as strong, but there seems to be some effect, and there's also an increased risk of inflammatory bowel disease, an autoimmune condition. It increases inflammatory tone, so the studies that I've seen increase one of the markers of inflammatory tone, high sensitivity CRP, by about two to three X. It seems to make the hypothalamic pituitary adrenal axis more rigid so that you can't kind of roll with the punches and wax and wane in terms of cortisol production the way that you can off the birth control pill. It can affect thyroid function. Anytime you take oral estrogen, it raises sex hormone binding globulin, and you've talked to other podcast guests about this, Kyle, I think.

    3. AHAndrew Huberman25:01

       Mm-hmm.

    4. SGDr. Sara Gottfried25:01

       Sex hormone binding globulin I think of as a sponge that soaks up free estrogen and free testosterone. So when you go on the birth control pill, you raise your sex hormone binding globulin. It soaks up especially free testosterone, and for some women it's not a big deal. They don't notice much of a difference. But then there's a phenotype maybe related to CAG repeats on the androgen receptor who are exquisitely sensitive to that decline in free testosterone. So this then opens the portal of talking a little bit about testosterone in women. It's the most abundant, biologically the most abundant hormone in the female system. It is so important for women. It is essential to so many things, not just sex drive and muscle mass and seeing a response to resistance training, but also confidence and agency. And so those women who are so sensitive to their testosterone level, they've got this high sex hormone binding globulin, their testosterone declines, what they describe is vaginal dryness, maybe a decline in sex drive, but there's also this bigger issue related to confidence and agency, even risk-taking from studies that we've done with MBA students, that I think is a serious problem.

17. 26:21 – 27:28

    Clitoral Shrinkage; Tools: Alternatives for Painful Periods

    1. SGDr. Sara Gottfried26:21

       Maybe the most important out of all of these things is that it can shrink the clitoris by up to 20%. 20%. And if I've got a woman that I think should not be on the birth control pill, and maybe she's taking it for acne or she's taking it 'cause her periods were a little painful, what I'm gonna do is say, "Let's leverage these other ways of making your period less painful. Let's take the message of your painful periods and figure out, okay, it's your inflammatory tone, and we give you some fish oil and ATMs, maybe a little aspirin when you've got your period. Like, let's find some other ways to deal with it than to take the oral contraceptive, which you have not received informed consent about, because it can shrink your clit by up to 20%." Now, that usually convinces most people to come off of it.

    2. AHAndrew Huberman27:06

       Is that reversible?

    3. SGDr. Sara Gottfried27:06

       The data that we have is limited. There's one woman who, uh, Claudia something something, who looked at sex hormone binding globulin a year out from stopping the birth control pill, and it was still elevated. It wasn't as high as it was when they were on the pill, but it was still elevated. So your question about reversibility, I don't know if we know the answer to that.

18. 27:28 – 29:00

    Menopause & Perimenopause; 30s Hormonal Baseline

    1. AHAndrew Huberman27:28

       What are your thoughts on menopause? When should people start thinking about it? And I'm guessing based on everything you've told me today that there are women in their 30s that while they may be 20 years out from menopause, probably should be doing things now in-

    2. SGDr. Sara Gottfried27:41

       Yes

    3. AHAndrew Huberman27:41

       ... anticipation of that.

    4. SGDr. Sara Gottfried27:42

       The more you know about your phenotype, your hormonal phenotype when you're in your 30s, you're set up in terms of what to do in the future, especially things like your thyroid, your estrogen and progesterone levels, 'cause you can replace to a state of youth thyroid. I don't usually go exactly back to where the estrogen and progesterone levels were, were, but we can get pretty close. So in your 30s, having a base case I think is really essential. What's more interesting is to talk about perimenopause. So perimenopause is the, the period of time before your final menstrual cycle, and for most women, depending on how attuned you are to the symptoms, it can last for 10 years. So I'm still in perimenopause. It's been, like, 20 years because I've been tracking it so carefully. It usually gets kicked off by having your cycle get closer together, so that can happen in your 30s or your 40s. You go from 28 days to 25 days, that sort of thing. You may notice it as more anxiety, difficulty sleeping, and that probably is related to the estrogen receptor. So there's this whole period of perimenopause, and what's most fascinating to me is that there is this massive, massive change that happens in the female brain that people are not talking about enough. And so looking at

19. 29:00 – 30:58

    Female Brain, Cerebral Hypometabolism & Alzheimer’s Risk

    1. SGDr. Sara Gottfried29:00

       the work of Lisa Mosconi at Cornell, starting around age 40, there is this massive change in cerebral metabolism. So you can do FDG PET scans, you can look at glucose uptake, and there's about on average a 20% decline from premenopause up to, like, age 35 to perimenopause to postmenopause. The women who are having the most symptoms in perimenopause to menopause, the hot flashes, the night sweats, the difficulty sleeping, those are the ones who have the most significant cerebral hypometabolism.

    2. AHAndrew Huberman29:35

       So it's almost like a, um... I don't, I don't want to scare people with this language, but it's, it's a low level or let's call it pseudo-dementia of sorts.

    3. SGDr. Sara Gottfried29:45

       Yes. It i- it seems to be a phenotype that you can then map to Alzheimer's disease, because that's Lisa Mosconi's work. She's looking at, okay, Alzheimer's disease is not a disease of old age. It is disease of middle age. What are some of the biomarkers that we can define that can tell you what your risk is? I've got a mother and a grandmother with Alzheimer's disease. You can believe I am all over this data.

    4. AHAndrew Huberman30:10

       And insulin resistance-

    5. SGDr. Sara Gottfried30:12

       Huge part of it

    6. AHAndrew Huberman30:12

       ... insulin insensitivity, as we talked about it before, um, seems to be somewhere in there, uh, which I think when that first, when that idea first surfaced, a few people were like, "Really?" But then of course, right? I mean, the brain is this incredibly metabolically demanding organ. You deprive neurons of fuel sources, they, or you make them less sensitive to fuel sources, they start dying. They, they certainly start firing less. It makes perfect sense, and I think now it's, thanks to Lisa's work, work that you've, that you've done and, uh, talked about quite a lot is, um, in your books and elsewhere, I think has really, you know, highlighted for people that metabolism and metabolomics is going to be as important as genes and genomics when it comes to-

    7. SGDr. Sara Gottfried30:53

       That's right

    8. AHAndrew Huberman30:53

       ... dementia, perhaps especially in women. Is it safe to say that?

20. 30:58 – 32:49

    Slow Brain Energy, Hormone Therapy; Hot Flashes as Biomarkers

    1. SGDr. Sara Gottfried30:58

       I think so because we believe that the system is regulated by estrogen. So the decline in estrogen starting around age 40, 43 is kind of the average, seems to be the driver behind cerebral hypometabolism. The way I describe it to my patients [laughs] is it's like slow brain energy. So you walk into a room, you can't remember why. Like, you just notice that you can't manage all the tasks the way that w- you once could. Like, things are just a little slower, and I say that to women, and they're like, "I have that." [laughs]

    2. AHAndrew Huberman31:31

       [laughs]

    3. SGDr. Sara Gottfried31:31

       Like, "Help me." We've got all of these women that are marching toward potentially a greater risk of Alzheimer's disease, and they have this opportunity in their 40s and their 50s to take hormone therapy, and they may not be offered it because the typical conventional approach based on WHI is to say, "Unless you're having hot flashes and night sweats that are severe, I'm not gonna give you hormone therapy." And I, I just wanna call that out. I would say, no, that is not the way to approach it. The concept right now in conventional medicine is that hot flashes and night sweats are these nuisance symptoms that we will take care of temporarily. Doesn't matter that you're not sleeping anymore. Turn down the temperature in your room. And that's not right because hot flashes and night sweats are a biomarker of cardiometabolic disease. They are a biomarker of increased bone loss. They are a biomarker of changes in the brain. So many of these symptoms that occur in perimenopause are not driven by the ovaries. They are driven by the brain.

    4. AHAndrew Huberman32:30

       I just wanna say you've taught me a tremendous amount. The amount of knowledge that you've shared is, is immense and is going to be very useful and actionable for women in particular.

    5. SGDr. Sara Gottfried32:42

       Can I just add one last thing?

    6. AHAndrew Huberman32:43

       Absolutely.

    7. SGDr. Sara Gottfried32:43

       'Cause I didn't talk about it since we didn't get-

    8. AHAndrew Huberman32:45

       Please

    9. SGDr. Sara Gottfried32:45

       ... to the 40s and the 50s-

    10. AHAndrew Huberman32:47

        Please, please

    11. SGDr. Sara Gottfried32:47

        ... in this list of biomarkers.

    12. AHAndrew Huberman32:48

        Please

21. 32:49 – 33:55

    Tool: Coronary Artery Calcium Score

    1. AHAndrew Huberman32:49

       do.

    2. SGDr. Sara Gottfried32:49

       If women went away with one thing today, it would be to do a coronary artery calcium score by age 45 and sooner if you've got premature heart disease.

    3. AHAndrew Huberman33:00

       How is that taken?

    4. SGDr. Sara Gottfried33:01

       So it's a CT scan of the chest. You can self-order it. It almost gives you this fork in the road in terms of how much you need to pay attention to cardiometabolic health as a woman. It's so fascinating because, you know, there's some women who have a zero, so my score is zero. But if you're 45 and you're starting to be elevated, or you've got, you know, maybe you've got PCOS, or you've got some other biomarkers tending you in this direction toward the number one killer, that allows you to really start to make changes, and I, I think it's essential to know that data. Most conventional doctors are not gonna do it.

    5. AHAndrew Huberman33:36

       So if I were to go to my doctor and I just say, "I want a, a cardiac calcium score," that's what people should ask for?

    6. SGDr. Sara Gottfried33:40

       Coronary artery calcium score.

    7. AHAndrew Huberman33:43

       Coronary-

    8. SGDr. Sara Gottfried33:43

       CAC.

    9. AHAndrew Huberman33:44

       Okay. There are certain people, they are exceedingly rare, but you are one such person that when they speak, knowledge just comes out of them, and it's incredibly useful and helpful knowledge, so. [upbeat music]

    10. SGDr. Sara Gottfried33:53

        Thank you.

    11. AHAndrew Huberman33:54

        Thank you.

Episode duration: 34:00