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

welcome to the huberman Lab podcast where we discuss science and science-based tools for everyday [Music] life I'm Andrew huberman and I'm a professor of neurobiology and Opthalmology at Stanford school of medicine today my guest is Dr Sarah gotfried Dr Sarah gotfried is an obstetrician gynecologist who did her undergraduate training in bioengineering at the University of Washington in Seattle she then completed her medical training at Harvard Medical School and she currently is a clinical Prof professor of Integrative Medicine and nutritional Sciences at Thomas Jefferson University she has also been a clinician treating men and women in

various aspects of Hormone Health and Longevity for more than 20 years she is an expert in not just traditional medicine as it relates to hormones and fertility but also nutritional practices supplementation and behavioral practices and combining all of that expertise in order to help women navigate every aspect and dimension of their hormones longevity and vitality ranging from puberty to Young adulthood adulthood perimenopause and menopause and nowadays she's also treating men across the lifespan in terms of longevity vitality and Hormone Health during today's discussion Dr gried shares an enormous amount of information and tools that women

can apply toward their Hormone Health fertility vitality and Longevity we discussed the gut microbiome which many people have heard about but Dr Godfrey points out the specific needs that women have in terms of managing their gut microbiome and the ways that that influences things like estrogen levels and Metabolism testosterone thyroid and growth hormone and much more we also discuss nutrition and exercise we touch on how the omega-3 fatty acids play a particularly important role in managing female hormone Health Dr gried points out why women have particular needs when it comes to essential fatty acids and

how best to obtain those essential fatty acids for Hormone Health we also discuss exercise and she offers some surprising information about the types ratios of resistance training to cardiovascular training that women ought to use in order to maximize their Hormone Health we also talk a lot about the digestive system this was a surprising aspect of the conversation I did not anticipate Dr gried shared with us for instance that women suffer from digestive issues at more than 10 times the frequency that do men and fortunately that there are tools specific to women that they can use

in order to overcome those digestive issues and that in overcoming those digestive issues they can overcome many of the related hormone issues that so many women face Dr gried also shares with you tremendous knowledge about the specific types of tests not just blood tests but also urine and microbiome tests that women can use in order to really get a clear understanding of their hormone status not just of present but also where the trajectory of their hormones is taking them so we have an avid discussion about puberty about young adulthood adulthood per menopause and how best

to manage and navigate per menopause and menop pause including a discussion about hormone replacement therapy in addition to her academic and clinical expertise Dr gotfried has authored many important books on nutrition hormones and supplementation as it relates to women and to people generally the two books that I'd like to highlight and that we' provided links to in the show note captions are women food and hormones and the hormone cure I read the hormone cure and found it to be tremendously interesting and informative not just in terms of teaching me about female hormone health and various

treatments for female hormone Health but also as a man trying to understand how the endocrine system interacts with mindset nutrition and supplementation more generally so I highly recommend the hormone cure for anybody interested in hormones and Hormone Health and women food and hormones in particular for women although again both books are going to be strongly informative for women wishing to optimize their Hormone Health vitality and Longevity before we begin I'd like to emphasize that this podcast is separate for my teaching and research roles at Stanford it is however part of my desire and effort to

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to be here yeah I'm delighted and very excited to ask you about an enormous number of topics you are expert in so so many things so uh the challenge for me is going to be to uh constrain this walk as it were but uh I'm hoping that we can touch on a great number of things today the first of which is really about hormones and female hormones in particular and I have a question which is is it ever informative for a woman regardless of age to know something about her mother's perhaps even her grandmother's experience

VIs V hormones not just pregnancy challenges with or um ease with pregnancy and child rearing child birth this sort of thing but you know 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 love this question so my work is really at interface between genetics and environment so your question gets to both and I think it's essential that you understand what your grandmother went through I'd even say your great-grandmother depending on longevity in your family so I grew up with my

great-grandmother I get that and especially your mother so I would probably start first with trauma an intergenerational trauma because I think that affects the endocrine system so hugely especially cortisol signaling but the broader Pine system Psycho imuno neuroendocrine System and then there's you know if I think about the stages the life cycle that a woman goes through if you think about puberty I think I don't know how genetically determined the age of puberty is certainly there's a lot of environmental influences like toxins can affect it but um pregnancy the age at which you start to

go through per menopause menopause many of those have a genetic component so with pregnancy I mean you can certainly think the shape of the pelvis your ability to have a vaginal birth some of that is genetically determined I mean you do have you know the the sperm donor affecting some of that but you know in my family for instance we have no cesarian sections so everyone goes through this process of a relatively easy national birth I was a forceps baby but you know for the most part um you can find out about that and then

there's certain female conditions that have a very strong component genetically most of which run in my family so that includes enmet trios fibroids I just had a hysterectomy I had a 50 plus fibroids and uh polycystic ovarian syndrome and of those three uh how fre are those and um maybe I can constrain the question a little bit by saying um today's discussion I imagine is going to be heard by men and women of all sorts of Ages so I um maybe I'll direct the question a little bit toward you know at what age should these

discussions start um you know we always imagine that uh women in their um 30s and 40s and 50s and onward should be getting certain tests and um addressing things like uh ovarian reserve and and other sorts of things but you know maybe we could March through and just say for a woman in her teens who's already hit puberty what sorts of biomarkers whether not their blood-based or per or um phenotyping you know the outward appearance of uh should those young women be paying attention to likewise for women in their 20s 30s maybe we could take

it a more or less by by decade at starting at puberty assuming that woman hits puberty sometime what between what is it now the average in the US is somewhere between 12 and 16 years years old do I have that right no you do not oh great I love to be wrong so so it used to be 12 to 16 I would say 50 years ago it's been moving younger and we think some of that is related to toxin exposure as I mentioned but I was 10 when I went through puberty so uh well I

should say menarchy and I started growing breasts much before that so I think now I'm going to step away from the science for a moment I'm going to do that pretty fluidly and I'll try to call it out I think there's also a huge influence from stress and like the development of the adrenal glands so going back to the science the issue in teenage years is that the hypothalamic pituitary adrenal axis and I like to think of it broader so stay with me I hypothalamic pituitary adrenal gatal over recent women testes and Men thyroid gut

axis so that to me is the control system so I'm kind of expressing my bioengineering side here well I think it's great to include the other organs and tissue systems of the body because as we both know that the narrow definition of just hypothalamic pituitary adrenal it can't be just that right no it can't right no yeah it doesn't tell the whole story so if you look at the the main sex hormones in a a young woman who's in her teenage years the hypothalamic pituitary adrenal gatal part of that is not fully mature so they're

more likely to skip periods especially under stress they have a lot of influences that really doesn't get well established until you're done with adolesence and I'm told that adolescence now is till like age 25 to 26 I heard that I was like I've got two daughters and I was thinking that's a really long time not just psychologically defined or bio psych mostly mostly psychologically defined I heard that from a psychologist so biomarkers you asked about 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 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 are periods not that regular in terms of duration of the menstrual cycle when the menstrual cycle first sets in it depends so I was like clockwork every 28 days until I had my hysterectomy in August same thing with my daughters

I've got two daughters one's 17 the other's 23 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 and I hope we'll have some time to talk a little bit about oral contraceptives because I think it is this is now opinion again and not science I think it is the number one endocrinopathy that is iatrogenic for women uh we will definitely talk about I get a lot of questions about oral contraceptives um in the

social media space and also questions about iuds quite a lot totally in particular copper iuds non non- hormonal iuds so we will definitely touch on that I'm an IUD Crusader so I just want to you know give you that warning you're you're a fan do I have that right or you're anti I'm a huge fan uhuh which iuds in particular so I like copper because it's non hormonal it's as effective as getting your tubes died who would have thought it's that toxic to the sperm Mobility is that how it works that's my understanding of it

is that that it that it basically it's like a uh more or less an electric fence to the the sperm cap and just that's it electric fence is a bit of a harsh analogy but I'll work with that but it's you know to have something that can last for 10 years so that you really have complete autonomy and sovereignty over your sexual life that's profound and to not get all those Downstream risks that are associated with birth control pill the other thing that's important to know about it I know this is a zore women who

use the copper IUD have the highest satisfaction rate of anyone on contraceptives the highest satisfaction rate and yet it is the least used of all forms of interception now my favorite is vasectomy but short of vasectomy I think the IID is a really great choice there are some risks associated with it I'm not saying it's risk-free but I love the ID and I love it for younger women too because it used to be that when I went through my training which was 30 years ago we were told you know don't put it in someone who

hasn't had a baby and that is patriarchal messaging but getting back to your original question which is about biomark per decade in your 20s that's when you want to do some base casing with estrogen progesterone and testosterone so I think it's really helpful to know about this this Tango you're from Argentina or your father I have Argentine lineage yes yeah my grandparents did Tango into their late 80s I I am I'm in my late 40s and I I still haven't started so I suppose there's time it might be time for you to that okay and

it might be a factor in their longevity do they have good health span not justan and my grandfather Smoked Cigarettes daily remained mentally sharp until he died in his late 90s but um almost burned down their apartment several times falling asleep with a cigarette in his mouth so I don't recommend anyone Smoke by the way uh but it was uh coffee mate red meat and cigarettes and they lived into their 90s so that side of my family has the genetic Advantage the other side less so um but in any event um Tango um is a

is a 2023 goal it has been every year um the uh I'm gonna hold you accountable to that okay we'll do and there no there will be no YouTube video of me doing thing at least not initially Tim Ferris actually a phenomenal podcaster as we know is a he's a badass he's a badass Tango Tango dancer I know this through various sources yes yeah I've seen yeah so this Tango between estrogen and progesterone is incredibly important you want to have the the right lead you want to have the right follow between the two hormones again

I'm stepping away from my science hat but what happens a lot of the time is that estrogen dominates in that Tango and when that happens it sets you up for a greater risk of fibroids enetri posis breast pain probably in association with the microbiome in the estrobolome oh can you familiarize me with the estrobolome I'm delighted know that I don't recognize the term yeah so the estrobolome is the set of microbes in and their DNA their DNA mostly in the gut microbiome that set of microbes in their DNA so it's in the if you look

at the totality the subset of particular bacteria modulate estrogen levels so a lot of this work was spearheaded by Martin Blazer and what we know is that there are some women who have an estrobolome that makes them have a greater risk of certain estrogen mediated conditions like breast cancer and amral cancer and in men prostate cancer so the estrom is incredibly important there's not a lot of attention paid to it but I always think in terms of my patients you know could this be someone who's got faulty estrobolome and we need to adjust it with

you know some of the microbiome uh modulating uh nutrients nutrical that we have so that they're less likely to have that that Tango that's not working with estrogen and progesterone so getting back to the biomarkers if if you gave me an unlimited budget which I kind of have with some of my um clients that I work with now what I would want to know is estrogen progesterone testosterone and I want the timing right for that 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 increasing the risk of Quinones like d damage and potentially an increased risk of breast cancer although that data I think is mixed I'd also like to know about their stool so I want to know about the microbiome so the best that we have right now is to look uh when we do stool testing and I do a lot of stool testing we can look at things

like beta glucuronidase are you familiar with BG I'm familiar with it as a term and so for those listening it very often not always when you hear an acea you're dealing with an enzyme so we can take a stab there and and it sounds like it's somehow involved in um glucose metabolism of some sort or is it glucuronidation so it's involved in when you produce estrogen in the body this is like the simplified version but when you produce estrogen you are meant to use it like send it to The receptors where it's meant to go

and then lose it like you don't want to keep recirculating estrogen like Bad Karma and that's what happens with people who have high bet beta glucuronidase so it's this enzyme that's produced by three bacteria in particular in the gut and I see a lot of men and women who have elevated beta glucuronidase and then they have some estrogen dominance related to that is that the total reason we don't really know but it's one of the drivers it's one of the levers and it can be detected from a microbiome AK stool sample that's right and terms

of blood testing or various tests for these other biomarkers getting estrogen testosterone and other ratios I I realize there are people have different means financial means but in general people wanting to do a blood test it sounds like they're going to need to do it what women will need to do it at different stages of their menstrual cycle if they had to pick one you know either in the follicular phase and or in the ludal stage of their ovarian menstrual cycle excuse me ovulatory menstrual cycle when would you suggest they do that if they had

to pick one so if you forced me to pick one I would say probably day 21 to 22 for someone in her 20s so we're focused right now on that decade 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 regular it's harder to do that as women get older and we'll talk about this in a moment usually the the cycle gets a little shorter so as they start to decline in their progesterone production

their period gets a little closer together like mine before August was about every 26 days so at that point you want to test sooner like day 19 20 and I'm not talking about a blood test so a blood test is the cheapest thing it's usually what's covered by insurance but my preference would be to do dried urine I like to use saliva for cortisol I like to use 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 and that's certainly the gold

standard for all of these hormones that we're talking about but um 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 yeah the salivary cortisol makes sense to me because my understanding is that you get free cortisol which is the active cortisol you said with urine you're also getting the metabolites that's right and then um for blood testing you're getting sort of a crude window into the averages a static total level so uh 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 so I I like to almost start with nutritional testing I don't think I've ever had a teenager I've got some NBA players that are 19 20 21 so maybe those count but uh those are men obviously but for 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 you know

the 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 if I could do that for a teenager I think it might be helpful because I recently gave a lecture on breast cancer RIS reduction another quick sidebar and I was sad to find that 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 now I have one daughter that eats vegetables she loves them and I have another daughter who eats food that's beige and it's very hard to get her to eat the volume of vegetables you know five colors a day which is what I do and 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 you know 25 years in the future that it's going to potentially change this Arc that they're on 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 you know are supplements a useful tool in that case um what other sorts of tools Behavioral or otherwise are useful such a good question so here I'm going to invoke Rob Knight at UCSD so I think his his uh his gut project has really

been helpful in terms of understanding what kind of modulators are going to be important so what I try to get that person to do and I don't see many teens anymore other than NBA players what I try to get them to do is to have a smoothie very hard to get them to have a smoothie every day but 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

she be blending up broccoli or kale cauliflower so cauliflower great even they're putting things into the Smoothie yeah I don't know if you can get a teenager to do that but they often will use like I have them do steamed broccoli that's in the freezer because it's got very little taste so that they could do that in a chocolate smoothie they could add some greens I like greens powders are was 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 smoothie I've got one patient that I have to mention because um he took this to the extreme so he's a retired physicist professor at UCSD he found out that his microbiome was a hot mess and um developed autoimmune disease and so he became hellbent like only a physicist could on changing his microbiome and he

dramatically shifted it by having a smoothie every day with 57 vegetables and fruits in it 57 independent 57 independent so I mean this just warms my heart the way that he did this but he would go to the farmers market he would just get a bunch of this a bunch of that and he would go home make the smoothie and then stick it in the freezer so he'd have a serving every day and he became a completely different person based on this microbiome change his uh autoimmune disease is in remission he um he dropped a

huge amount of weight he went from being you know kind of this phenotype that I know you know well of a professor High performing traveling around the world on so many boards so much Innovation so many great ideas super computer guy to being someone who gets up in the morning gets in his hot tub EX exercises for like 1 to two hours a day and then does a little work like he completely shifted the way that he lives and his microbiome shift you know who knows what what's the chicken and what the what's the egg

there but he had a huge change in his physiology glucose went from being quite high he had and he tracks all of this of course it's like on S after all right and retired I suppose might have had and he's retired but he's he's got the Longest Time series of anyone I know and he's tracked his glucose and Insulin going back 20 years so he can show you okay here's where I started having my smoothie and here's how my glucose and Insulin changed as a result of that I'd like to take a quick break and

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a year supply of vitamin D3 K2 again that's athletic greens.com huberman to get the five free travel packs and the year supply of vitamin D3 K2 is there a case for I'll say young women but young women and men um using over-the-counter probiotics as a way to enhance the microbiome this is something I hear about a lot I've heard that excessive doses of capsule probiotics can give a brain fog like condition um I personally don't use capsule probiotics unless I feel like my system is under a significant amount of stress in which case I might

add that in for brief periods of time or if I've just taken antibiotics for a period of time right uh do you ever recommend that the college student or the high school student that she or he take capsule probiotics assuming that they're getting let's say three to five servings of vegetables per day either in smoothie form or some other form what are your thoughts on on supplementing probiotics it sounds like such a simple question it is such a complex answer and I don't think we really have the answer so I'll tell you the way that

I approach it I look for randomized trials to support my use of probiotics and frankly I'm underwhelmed so I've seen some data if I invoke my um NBA players for a moment almost every player I've tested has increased intestinal permeability they just have such a high training load probably mediated by cortisol very high glucoses when they drain that they have increased intestinal permeability so those tight junctions in their intestine become loose they develop a lot of inflammation as a result of that and when you're a professional NBA player and you're making 20 million a year

like you don't want a lot of inflammation you want a little bit to like help your muscles recover but you don't want it to be um adding to problems when you develop an injury so this is leaky gut leaky gut I don't love that term but yeah we'll use it here so there's a there's a particular probiotic that is helpful in athletes with leaky gut so that's the kind of specificity and randomized trial that I'm looking for the rest of it I think there's support if you find help from it as you described if you

take a course of antibiotics I mean first of all I would question whether you need them but I try and avoid them there there have been instances where they've been prescribed and I took them mostly in the past I was in college they seem like they kind of gave them out you had a sinus infection they give you you know antibiotics you like yeah the worst treatment ever yeah so if you're coming off of antibiotics I think that's a good time to do what we call replacement dose Pro biotics I think what's far more interesting

is prebiotics I think the data is much better for prebiotics and um The Selective use of polyphenols how would a person in their teens and 20s or any age for that matter know what whether or not they have nutritional deficiencies what is the best way to analyze if one is getting enough magnesium um and for that matter what is going to be the best way to test the microbiome you said stool sample it and I'll come right back with the same question I asked about blood test what time of day when during the month um

to establish this a baseline so this would be prior to embarking on a you know 97 vegetables or how per day it's only 57 well I love the idea that you're telling us if I'm gathering correctly is that yes there's a case for probiotics but for the typical person regardless of age eating more vegetables or drinking more vegetables as as the case may be is going to be beneficial for the gut microbiome perhaps without the need to go test whether or not one is making a certain number of estrogen related metabolites or not just that

that's a great starting Place eat or consume more vegetables totally um but if one wants to analyze their gut microbiome are there good tests available to the general public this has been I'm not going to name companies but I've been tracking this over the years and it's never been clear to me that we know what constituents of the gut microbiome are are best you we know that dis is is bad and we know that diversity of the microbiome is good we hear this but no one's ever told me that you want a particular ratio of

one microbiota to another right in a way that has made any sense to me at least totally um I'm not a microbiologist but whereas with you know with testosterone and Men we hear okay you want your free testosterone to be about 2% of your total perhaps with women you women are going to have more testosterone than estrogen on average but still less than men when you look at testosterone it's ET Etc but you can kind and get some some crude measures but for the microbiome it just seems like long lists of microbiota for which um

I just get dizzy I just if you just wrote out a bunch of I's and L's and s's you'd kind halfway you getting a bit bit the same information I'm not trying to poke at that field it's a beautiful field but they haven't told me what to what I what my microbiota ought to look like like what's a healthy microbiome chart well that's because we don't know I mean the best we have is Rob nights work but even even that is limited in terms of you know can I tell you that a a woman in

her 20s should have this particular pattern with her microbiome no I can't so um let me go to your first question because I think you just asked about six your first question is about nutritional testing what I like to do with nutritional testing is run a panel that's looking at antioxidants so like vitamin A vitamin C Alpha lip IC acid um plant-based antioxidants CU 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 um

polymorphisms you might be less likely to be absorbing the right level of vitamin B9 folate vitamin B12 Etc um I'm also looking going back to the antioxidants at glutathione because I think that's such an important lever when it comes to detoxification which we haven't talked about yet 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 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 we've talked about mag 3 and eight SLE there's a magit there's so many forms can be a little bit of overwhelming to people so any any detail um in sourcing would appreciate it great so first in terms of testing what I prefer to do is to mention one more than one lab and more than one brand um and I can just I'm speaking mostly from

experience so uh for testing I do a lot of goova neutrals during the pandemic they developed an at home tests normally with a neutral you have to get your blood drawn and you have to do a urine sample so a lot of people can't do that the great thing about this test is your insurance usually pays for most of it and so the co-pay is about $150 so during the pandemic they developed another test called metabolomics which does much of the same testing but it's a finger prick so most of my patients prefer that in

fact they haven't gone back to the neutral second lab is Spectra cell I use Spectra cell occasionally I find it not quite as easy in terms of fitting into my practice but I've got friends and mentors like Mark Houston who does a lot of uh kind of precision um cardi metabolic Health he thinks spectrol is the best test out there so you asked about 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 that is um is it I I can guess uh diet stress um patriarchy rage so psychos psych so Pine the um the pine system right psych psych olog Immunology neural and endocrine factors combined is it yes and then I would say there's another factor which is being female is a health hazard so we've twice the rate of depression insomnia we've got 3 to 4X increased risk of multiple sclerosis we've got 5 to8 times the risk of thyroid dysfunction so if

you just look at that and you look at subtle preclinical thyroid dysfunction a huge number of the women that I take care of well let me back off 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 gatal gut AIS 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 going to tend toward constipation women have a lot more constipation than men the gut is about 10t longer in women compared to men we should talk about some sex and gender differences and Define those sure and they are much more likely to have a torturous colon and the way you know that is you get a colonoscopy and they tell you yeah it's really hard to like get in there do what we need to do as a brief tangent but I think this is the time to ask um what at what age now

do Physicians insists their female patients get colonoscopies uh for men I think the age used to be 50 now it's getting ratcheted back to 45 or 40 again these are recommendations not requirements but they're pretty strong recommendations from depending on where you live Etc um for women how early do you think they should get a colonoscopy to to explore for possible pops Andor colon cancer yeah it's a really good question I don't know the answer so what I've always operated with is 50 the way that I answer that is to go to the US preventive

task force rating to determine based on their synthesis of the data what age is the most appropriate has it changed as you just described for men from 50 to younger I don't know so we should fact check that all these um additional health hazards for women um you mentioned some some of the you broadly mentioned psychological impact right and and of course these things are all related psychology immunology and one of the I think wonderful things about neuroscience and Science in general and medicine is that there's now an an understanding that all the organs are

connected to one another it's a network it's a network and then the microbiome sits at at um at a key node within that Network um and I think most people accept that now yes you it that seems to be a theme that at least in the last 10 years is really wonderful because um certainly for Neuroscience it was thought that you know unless it's in the cranial Vault it's not neural which is ridiculous because there's lots of nervous system outside the the skull but in any case for can I interrupt for a second yes please

so I think you're right that there's an understanding about the network effect but I think that as much as I love mainstream medicine and I trained in it and I so grateful for my education I still think it is a silo based way of taking care of patients so even if there's an understanding of the network effect more at the science level or as you described in Neuroscience there's still you know if you are a woman who has constipation fatigue um maybe an autoimmune condition uh feel stressed out all the time feel like your hormones

are out of whack you get sent to the gastroenterologist for the constipation you get sent to the room dermatologist for your autoimmune issues you maybe get sent to an endocrinologist if you've got thyroid problems and there's very little collaboration between these groups so even though there's an understanding of the network effect in real life it's not happening let's um let's go deeper down that path because I you point out something really important and and you've mentioned constipation a few times can we view constipation as a serious enough symptom that it warrants an immediate intervention that

is does it flag or signal problems that are severe enough that that should be the issue that's dealt with uh for anybody that's experiencing it and I mean sort of an odd topic for many people because they think oh you know bowel movements and sort of you know there's that kind of um pre-adolescent humor around this but I think it's it's so important what you're what I'm hearing you say is that constipation is far more common in women and it signals a general set many problems occurring does that mean that women should address constipation and

if so what's the best way to address constipation yeah I love this question because you're doing can we have a quick little meta conversation so you're doing something that I knew you would do which is you're teaching me something and you're changing like there's this social genomics thing happening where you're changing my thought about this so I just wanted to acknowledge that thank you thank you well I think for me you know when I hear that there's a kind of you know you're talking about a phenotype constipation is a phenotype it's one that people generally

don't wear a t-shirt explaining it to people but that I'm guessing anything to do with sexual health um bowel Health Urology people just don't talk about right um for all sorts of reasons and those reasons are probably so obvious that they're not even worth discussing but because and also because we won't change them except by talking about them y so if you say um women are far more constipated and that's signaling a larger set of problems yes then my immediate thought is well we relieving constipation um pun uh intended retroactively um will that assist in

a great number of issues Andor will it get them down the road of thinking about those other issues more specifically like do I need more magnesium or should I be putting vegetables in my smoothie you know so I'm curious about constipation as a Target yeah for intervention that then opens up a bunch of other discussions because there are these certain nodes in the in the mental health physical health space that when someone like we talk a lot deliberate cold exposure do I think it's magic no but I think that if someone's getting themselves into a

cold shower once a day it opens up a number of questions about themselves and reveals a number of things to themselves like how do I buffer stress yeah what sorts of levels of control do I actually have and on and on so perhaps not the best example but um some of us hate cold exposure right which is we have we have like a gene that makes us stress out like you wouldn't believe C exposure which I would argue makes it um very likely that even 10 seconds of cold exposure gets you the effect that you

want as opposed to someone who adores cold exposure like a penguin needs a lot more cold exposure for it to have the the Adaptive response anyway that's my way of of guming through that uh quite you're you're you're quite correct um so so let's answer this question constipation issue yeah so this is how you're changing the way I think about this so you're asking okay instead of looking at constipation as a constellation of symptoms what about if you just used it on its own sort of a um a key indicator or signal of dysfunction with

pine Network or maybe something broader and I think that's right so it makes me think of a few things it makes me you're also changing this book that I'm writing on autoimmunity and Trauma so thank you for that so 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 um about 50% of them experience significant trauma as defined by the ace questionnaire women are at 60% and that's

pretty durable since 1998 so women have more they have different forms of abuse much more likely to have sexual abuse they have a different HPA response than men men their perceived stress tends to be higher and I'm generalizing for a population so I note you know in Precision medicine we don't do that we do medicine for the indiv individual not the population not medicine for the average 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 you know

tighten the anal sphincter 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 now you also asked about microbiome testing should we do that or do you yeah well I have one I have a couple more questions about constipation I never thought I'd ask this many questions about constipation but now I'm fascinated by the way also this morning I taught medical students at Stanford about the fact that we are basically a series of tubes

so you talked about the the anal sphincter we are a set of sphincters from one end to the other I mean we are tubes nervous system being one of those tubes and and I think in eastern medicine they talk about the various locks between those tubes and Chambers and it's not without coincidence there's some real wisdom there of course wait did you just talk about energetic Anatomy uh more or less I didn't say the word chakras but uh I might in passing it's the bondas the bondas right are the are the are the the the

sphincters right yes that's right uh thank you for for that the um so what defines constipation I mean in other words let's let's think about that healthy rather than thinking about the unhealthy let's how many bowel movements should um a woman or a man have per day assuming this is where it gets tricky because some people are doing time restricted feeding some people are eating more some people eating more fiber more bulk larger meal at the end of the day larger at the beginning of the day we will never um be able to sort out

all those variables but on average um how many bowel movements and is timing during the day for bowel movements at all uh informative well works for you um well when I'm asleep um generally I don't want a bowel movement so I'm going to be like most people right well sleep is primary for you right exactly um I'm I always assumed that morning time was a was a healthy time for B movements um and I think almost everybody babies included recognize the feeling of being lighter and more energetic when they've evacuated their colon totally um in

fact so much so that I'm I'm obsessed with jungian and fian psychology that the first thing we learn when we come into this world right is that we want something we we feel some sort of autonomic arousal stress whether or not it's food or warmth or the need to have a bowel movement one of the first things that parents learn is how to recognize that not by the odor coming from the diaper but by the look on the baby's face or their agitation agitation signals the need for some sort of relief right temperature relief food

relief um evacuating the bowel relief so my understanding is that as autonomic arousal increases in the early part of the day ideally after a good night's sleep that bowel movements become more likely unless that arousal becomes so great that then people feel so quote unquote locked up right um because of the the balance of the autonomic uh features so early day I'm guessing and again in the second half of the day and here I'm totally guessing um and certainly not having to wake in the middle of the night um yeah those are my best guesses

that's great so I would agree with that when I was at Harvard Medical School in UCSF or residency I was taught that constipation is having a bell movement less frequently than one every once every three days sorry I don't think I've ever laughed out loud on this podcast as a consequence of of uh textbook medical knowledge are you kidding me is that ridiculous well that sounds like and and here pun intended that sounds like the uh the conclusion of some very um cons emotionally and and and and in other ways con ated individuals and again

this might seem like an odd conversation but the the discussion around constipation is is present in psychological literature yes because of this relationship to the autonomic system well it's a metaphor in literature it's crucial so you you spoke to a number of different threads that I think are important here so that's the definition that I learned and I was I heard that and I was like hell no that doesn't work for me doesn't work for anyone I know and I spent a lot of time time especially in medical school and in my internship where you

rotate on medicine disimpacting women like older women who come in who haven't had a bowel movement in a month whoa and that let me tell you that is not nice for anybody well believe me I I became a scientist and not a physician for a number of reasons that's one both positive and negative that's one of them yeah so my definition of constipation as a western mostly White girl is that if you're not having a bowel movement every single morning and you have a feeling of complete evacuation anything less than that is constipation so that's

how I Define it if you're in India and you're eating food that's got a fair amount of microbes in it it's less you know sanitary I'm using that word um as carefully as I can generally they have about movement after every meal but they've got a different microbiome they're exposed to different microbes here in the US I would say one day you also spoke to something very important which is the balance between the parasympathetic nervous system rest and digest and poop versus the sympathetic nervous system kind of the on button you know fight flight freeze

spawn so I think for those of us who've got issues with autonomic balance it can lead to constipation and I like that constipation could be pulled out and kind of RIT larger as an important signal what sorts of tools do you recommend people use to um relieve constipation um in eating more fiber sounds like reducing stress is going to be a huge one yes what are your favorite stress reduction tools um I like to divide these into um realtime tools so big proponent of like physiological s real time you know these sorts of things but

um things that can really lower the Baseline on stress overall to facilitate constipation and other other um broad indicators of health so I'm not a fan of lowering stress I'm a fan of lowering perceived stress and I think the distinction is really important I learned when I was in my 30s that I was a massive stress case and I didn't know it it was just sort of I think I through residency through working 120 hours a week I just was so accustomed and sort of um that was 120 not under 20 folks yeah not unusual

in in medicine well they they've changed training so that you work no more than 80 hours a week now but that was before my time so I became accustomed to a massive amount of cortisol massive and I would say I've spent the past 20 years really working on perceived stress to find I think all of us need an all a cart menu of what is most effective so what works for me now at my age is different than you know the the TM I did as a college student trans Dental meditation it's different than the

I became a certified yoga teacher when I was in my 30s that is very effective for a lot of people it wasn't enough for my Matrix I do holotropic breath work um I didn't read it but I saw that she just had a paper in cell on your sign and um it kind of it made me think like teach me how to sigh teach teach me how to sigh like can you say a little bit about that like how do you do it yeah very briefly that study was we we wanted to find a minimal

effective dose intervention yeah I just wanted yeah so five minutes a day we need to figure out what people would do every day yeah and we were monitoring subjective mood Etc but also Biometrics remotely so it's kind of a nice study which Biometrics HRV HRV uh nighttime sleep cortisol uh I wish um so this was done during the pandemic more than 100 subjects the advantage was that we got data 24 hours a day because they're pinging us in their data uh wearing 24 yeah nice so that was nice resting heart rate um subjective mood we

would get in touch with them daily so when people were swapped between groups like any good study but five minutes a day of sort of standard if you will forgive me meditations so just sitting no instructions about how to breathe just focusing on um closing their eyes and focusing on focusing yep um another group did box breathing y inhale hold exhale hold for equal durations the duration of each of those inhales and holds was set by their carbon dioxide tolerance so somewhere between 3 and 8 seconds depending on how well they regulate carbon dioxide another

group did cyclic sighing so this would be double inhale through the nose so big inhale through the nose followed by it to lungs empty exhale that second inhale after the first big lung inhale through the nose is really important because it makes sure that all the collapsed avoli the lungs totally snap open and then the exhale you offload a lot of carbon dioxide that's very similar to holotropic breath work not yes not not um not unlike holotropic breath work little bit pranayama is um but the exhale is rather passive as opposed to active um and

then the fourth category was cyclic hyperventilation which is a lot like Tumo AKA Wim hofish breathing different than Wim Hoff breathing so this would be so very active inhales and exhales every 25 Cycles of inhale exhale that would be one cycle long exhale hold lungs empty 15 to 30 seconds then repeat for about five minutes everyone did that for five minutes and what we found was that the cyclic sighing led to the greatest improvements in mood Around the Clock not just around the the practice or during the practice as well as lowered resting heart rate

improvements in sleep Etc and you got to publish in cell we were very fortunate I I think um the the thankfully the reviewers and editors understood that these minimal intervention things uh hopefully are going to be of use to people so so useful to people I mean how often do you read a paper like that that could offer a behavior change that is so easy to implement I mean I love that question thank you so what about did you tell them not to drink because alcohol has such a huge effect on H yeah so in

this case we didn't tell them to alter anything else about their behavior hoping it background kind of across the same Al yes and some were Stanford students others were from the general population any Frat Boys we drinking heavily probably not well during the pandemic I think alcohol intake went way way up across the board um I mean is an if I had a magic wand I would I would ask that people either not drink or drink two drinks per week maximum at least that's my understanding of the literature um are you familiar with the whoop

data with alcohol no but we have a collaboration with whoop through that paper um and it certainly disrupts patterns of nighttime sleep in particular my understanding that first phase of sleep that's related to the massive growth hormone release that you we all really need and want in their measure growth hormone we did not no the second iteration of the study will certainly include free cortisol by saliva hormone panels well I'm beginning to think that we should also um be asking people how often they're going to the bathroom in what time of day yes I mean

this thing around constipation is uh is super interesting and I think that plus um BL blood markers and then I'm I'm very excited to learn that um that urine contains additional markers that could be informative so yeah it was a it was a fun study uh not easy study to do with that number of of subjects um takes a lot of training for your research assistance yeah it was a big group it was nine people in our group and three clinicians and a lot of lot of phone calls and a lot of back and forth

but you know and thank you to the subjects who served as the uh the real life guinea pigs so yeah I think that stress you know people's I think people are starting to appreciate that there are ways that they can relieve their stress that that don't all only fall under the categories of vacation right and meditation but I want to say that meditation is obviously a wonderful tool um it's just it's a it's a tool not unlike any other tool that is great for some people and less great for others 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 allart menu sex orgasm um connect ction feeling heard and seen and loved um yeah let's talk about that you know you mentioned earlier that all these stress factors you you said patriarchy right but I think what if I may um at risk of uh of just strengthening that uh statement I I mean that that to me it's is signaling a bunch of other factors around as you said like keeping keeping things in um what do you think explains let's

talk about that because I think that that's likely to have raised a certain flag in people's minds like what exactly is she talking about are you talking about less opportunity are you talking about less opportunity to um to vocalize are you talking about less opportunity to vocalize and be heard I mean I realize that there are an infinite number of variables but given that it sounds like a a really strong input to the system uh what I mean by that is that psychology is influencing biology and you're saying that that these uh that these po

power Dynamics structures and Dynamics are impacting I'd love let's hear your thoughts on that because uh I I hate to let a flag like that go by without fleshing it out and let never waste a good flag well and let's preface it by by just saying that like people will have different opinions on this and that's and I think that's healthy and and like with the discussion about constipation let's talk about what people aren't willing to talk about when it comes to health love it so we might need to talk about patriarchy on part two

but I'll give you some material that I've been working with I started I did not even understand the existence of patriarchy until I was a bio-engineering undergraduate at MIT I should mention which has always had a bit of a of a male um a skewed male in terms of faulty numbers well my my that's true at most universities true well my postto adviser was the late Ben Baris who was a female toale transition transgender first transgender member of the National Academy of Sciences one of my closest friends unfortunately died of of pancreatic cancer we were

very very close they're actually making a documentary about Ben but Ben this is interesting Ben went to MIT because he wanted to be around a lot of men yeah that's a lesser known fact but then he was a very strong advocate for women he went as Barbara when he was Barbara and um by the way he's given me permission to share all this prior to his death I recorded a lot of conversations with Ben um I only ever knew him as Ben by the way but when he was at MIT he was identified female and

he later talked about the intense um suppression oppression literally is how he described it um especially given that he was performing so well yes so you just defined patriarchy you did it yourself a couple things when I was in bioengineering I took a women's studies class and it was all about teaching under graduates about the existence of patriarchy which I would Define maybe at its simplest as power over I'm not saying men are patriarchy I'm saying something very different which is power over let me correct one thing that you said I didn't go to MIT

as an undergraduate so I'm from I was in Alaska and I went to the University of Washington for bioengineering in Seattle in Seattle okay I dropped out of a graduate program in bioengineering to go to the Harvard MIT program for Health Sciences and technology in Boston thanks for that clarification University of Washington also wonderful place I have many many many many many wonderful close colleagues there it's an incredible place especially for vision science it's especially good for engineering bioengineering but um yeah so my my MD is jointly between MIT and Harvard and it's the oldest

maybe largest although Harvard says this a lot program for biomedical engineers and uh MD phds physician scientist training program great thanks for that clarification I'm going to blame the internet for this one I am I think we need to send our our Wikipedia editors out I I think LinkedIn is correct okay great well w wikipedia uh editors note get out there and make the make the correction now you you heard it um so stress that is what you're really talking about is systemic stress in the body as a concept as a consequence excuse me of

systemic stress of environment that's right but there's you know there's particular forms of it I would say this also relates to White Privilege it relates to uh racism and when you look at you know kind of the way that systems including my beloved MIT the way that they're set up is that might Mak makes right and generally the people that are the strongest you know big men strong men they're the ones who tend to be the most successful so for people who are bipo for people who don't have white privilege for women it's a different

experience and so I'm using patriarchy as kind of a umbrella here but it connects to many other things I'd like to take AEF brief break and thank our sponsor insid tracker inside tracker is a personalized nutrition platform that analyzes data from your blood and DNA to help you better understand your body and help you reach your health goals I've long been a believer in getting regular blood work done for the simple reason that many of the factors that impact your immediate and long-term Health can only be analyzed from a quality blood test the problem with

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for you if you'd like to try insid tracker you can visit insid tracker.com huberman and get 20% off any of insid tracker's plans that insidetracker docomond to get 20% off I want to use this as an opportunity to a keep this in mind as we turn to 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 how many bowel movements and the timing of those bowel movements per day really 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 [Music] are differential opportunities by decade so I'm glad she 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 words 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 and I don't know because I didn't base case these but 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 you're testosterone declines by about 1% per year what level of testosterone do you like to see in a woman once she's sort of post let's say after age 25 what kind of range is healthy I know what the reference range is only because I know one could look it up I don't know it off

the top of my head admittedly but what what's a kind of a nice reference point there so the way I tend to describe this on podcast is the top half of the normal range great so that I think is a good benchmark you know for PCOS generally it's much higher than that you know I've seen patients with PCOS where their total testosterone is 100 to 200 do they always have peripheral manifestations of that a little bit of hair the the skin plaques I've heard about you know so dark and skin plaque regular periods regular periods

is that um you know I I get a lot of questions about PCOS yeah um and you're the first person we've had on this podcast that's really qualified to talk about PCOS in a real way um so here we're talking about too many androgens cysts on the ovary irregular ovarian me uh excuse me I keep saying that ovulatory menstrual cycle um what are some other indicators and do you recommend that women start taking Androgen blockers or or I mean how do seems to be a lot of PCOS out there I'm hearing about it a lot

so glad you asked about this so PCOS is one of those really poorly understood conditions that gets it kind of flows 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 criteria that we look for so cists on the ovaries having um clinical manifestations of hyperandrogenism so that

could be heroism acne other things and then usually irregular periods and the way that that's defined at least by the uh 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 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 nosis on their ovaries but they've got heroism

and they've got irregular periods could you define ha sism her sism 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 um um and then there's of course a a familial quality to that like I was just looking at a paper last night looking at ises and how much heroism they have and whether this is related to CAG repeats on the Androgen receptor do they get um not Israelis but um do women

who um who might have PCOS experience um endogenic alopecia so hair loss that sort of of the quote unquote male pattern baldness of course it's Androgen pattern baldness as opposed to male we're talking about testosterone DHD related sometimes you know this is where I'm going to invoke clinical experience rather than uh what I've seen in the literature women definitely can have some androgenic um alpia I tend to see it later in life but this is an important point because we think of PCOS as you know I was just talking about it in teenage years like

wouldn't it be nice to know that you have this phenotype and you're at risk for all the things that people are at risk for and we haven't talked about glucose and ins yet we should what we know is that pcus 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 cardom metabolic disease as you get older so many people tend to pigeon hole PCS is 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 cardio metabolic driver of disease for women with PCS wow now one other thing I want to mention and I still have my notes that we're going to talk about microbiome testing because that's such a fun subject what I was taught to do again saying this with so much

love for the people who have taught me how to do medicine what I was taught to do is that if you have a woman with PCOS you make the diagnosis you measure her testosterone you see if she has acne blah blah blah you asked that woman one question do you want to get pregnant or not so then you have these women with PCS who get started on a birth control pill if they don't want to get pregnant if they want get pregnant then you help them get pregnant by addressing some of these PCS issues like

maybe you give them Clomid or you do something to make them ovulate more frequently that is the way that most conventional medicine approaches this and it does women at gigantic disservice so one of the things I'm speaking into is the gender gap that exists so I my feeling is that the research money that goes into women's health is abysmal compared to what goes into Men's Health really and I think that's changing but there's also a huge lack of awareness of sex and gender differences when it comes to the way that we construct clinical trials and

other experiments well that's absolutely true I mean I sit on I've sat on NIH review panels for more than a decade now I'm a regular standing member which is only to say that I see the research as it's being proposed yes and now it's required no Grant will get funded without sex as a biological variable and here I'm I'm by the way folks this is sex biological sex the noun not sex the verb both are super interesting obviously but um when we say sex as a biological variable meaning even even if it's a study on

mice where did that start though that didn't start that long ago it must have been I think we can thank I don't want to misattribute here I think we can thank Francis Collins for insisting on this amen Francis and Bernardine hey Bernardine Healey has done so much to help us but you know she made the Women's Health Initiative which I hope we'll get to which just a hot mess like so confusing the data that came out of that and these trials are long and so the data are only now starting to emerge so just to

be clear I mean I have a a question that I don't think is going to take us off track but this is I'm going to posee this question as a hypothesis because I think it's likely to be uh a little bit of a of a not a barbed wire question but maybe like a prickly question when people first hear it but it's posed as a hypothesis you you mentioned some of the psychosocial stress issues based on at the organiz ational level institutional level societal level maybe right down to the family and and just life that

are biasing Health outcomes for the worse in female populations okay you refer to as the patriarchy I'm just trying to put make sure that we're both talking about the same thing and that's non-exhaustive I realize that's just a subset of the issues I'm also hearing there's a lot more PCOS which is hyper androgenization of the ovary in there we're talking about you mentioned you know excess testosterone which females naturally have more testosterone than they do estrogen anyway but we're talking about elevated levels here's a hypothesis one hypothesis would be that the increased androgens and the

P PCOS are a consequence of the psychosocial conditions that are I don't want to say forcing but are biasing the need for females to um think behav react act in certain ways to survive let alone Thrive is that a I don't say this for any kind of political correctness hypothesis this is a in my this would be a fun interesting and I think important study to run right depending on stress and the conditions the specific type of stress do females underproduce or overproduce androgens or is it a neutral effect does that make make sense I

love this question so let me just paraphrase the last part of it to make sure I got it it sounds like what you're asking is could PCOS or at least some phenotypes of PCOS be a response to what I'm calling patriarchy and then you had a second part to it which is do healthy women like what is their production of testosterone like is that right yes and and with the acknowledgement I mean you're the expert here um you're the physician clinician and expert in hormones and I'm not but with the understanding that absolute levels of

hormones are interesting but perhaps not as interesting as the ratios of testosterone to estrogen so when we're talking about excess testosterone we're really not talking about oh women making a lot of testosterone because frankly they already make a lot like then most people weren't aware of that I wasn't aware that women make more testosterone than estrogen right and so it's not saying that testosterone in women is bad or is always a reaction to the environment yes but when it becomes um super physiological or hyper elevated is I could imagine all sorts of social conditions that

would create that um so in males and females but here we're talking about PCOS and females in particular so I'd love for you to speculate um should we run the study we should totally run the study because I don't know the answer I suspect that you're on to something it may not explain all of the women with PCOS because as I metion there's a lot of different phenotypes but I think it could explain a significant portion and you know you're almost you're saying if we look at the gene environment interface this environmental influence of having

being someone who's got power over you if if pcus was a response to that the way that we treat it would be completely different so on the one hand I want to be careful not to dismiss the suffering and experience of women with PCOS I've got a lot of women with PCOS in my family and it is there's so much pain and suffering you know especially if you want to have a baby and you try for years and you just can't ovulate on the other hand I read a paper recently and maybe we could site

this that compares the phenotype of a woman with pcus to a man who is hypoandrogenic and I think that's a really interesting way to look at this because the thread we haven't talked about with PCOS is the the role of insulin and glucose so for some of the phenotypes of PCOS the problem is hyper insulin emia High insulin in the blood is driving those Thea cells in the ovaries to overproduce testosterone these women are insulin sensitive so more insulin is being cranked out and the cells in the ovary are therefore making more Androgen you don't

like to say insulin resistant oh I I can uh I don't have a problem saying resistance like the way I'm just I'm just a little bit outside the lane lines of my expertise so I I was trying to use it what what is the correct gnom en clature so that we can make sure everyone well what I like about insulin insensitive the way that you just said it is that I think that offers people a way in and I love to do that in terms of messaging insulin resistance starts to lose people cuz they don't

really get what that means at a receptor level I think I say insulin insensitive because when people hear insulin sensitive it almost sounds like a bad thing but that's actually what you want so I think I think that's how I defaulted to insulin insens what your insulin I don't know what I'm do for a blood test yes you are I'm doe for a blood test um I had blood work done about eight months um sure that'd be great I I uh I'm always um experimenting with different supplements and different behavioral regimens and I've kept charts

since I was 19 oh like my patient I been sort of Obsessed by this and I would say everybody if you can afford it and at the time actually I had to save up Insurance wouldn't cover it um get some basic blood work done so that you have a reference point do it as soon as possible because even you know the we've been talking about these women over the life cycle I wish I knew what my insulin was when I was a teenager I wish I wish I knew what my fasting insulin was I really

wish I knew my postprandial insulin like in my teenage years in my 20s in my 30s well I knew it in my 30s starting at 35 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 wow why do you think they are so effective at changing Behavior I've tried one and I really liked it I learned that in the sauna my insulin or my blood glucose goes up probably by a bit of dehydration

I learn what kind of foods work for me which don't um I I thought it was fascinating I learned how every Behavior you could possibly imagine use your imagination impacts blood glucose totally fascinating to me including how a two wake wake-ups during the middle of the night versus one versus none impacted blood glucose the next morning fascinating for a data junkie like me it was like I was in heaven um why do you think they are so effective in changing behavior is it because of that that people can see that real time control like scan

in and like oh that's the that's the sandwich I think it's many things I think it's generally the Enchantment of learning about your own chemistry and I love that and I think for me what I've seen you know I feel like doctors are basically marketers like the sacred marketing like our job as a physician is to convince people to do something that we think is good for them based on the best science but we can't just say here why don't you fill this prescription for a CGM you have to Market it you have to say

I think this completely changes the way that you approach your pre-diabetes I think this could dramatically affect your risk of Alzheimer's disease that you're so worried about that your mother has so our job as Physicians is to be that sacred marketer so cgms are one of my tools that I think are so crucial so enchantment number two yeah it's the real- time effect so if you go get your glucose and Insulin measured or maybe you do like a 2hour glucose challenge test where you look at glucose and Insulin at the fasting Point 1 hour later

2 hours later or more frequently that does not have the same kind of behavior effect as having continuous data where you can say okay I drove to see you Andrew from my place in Berkeley and it was stressful it was torrentially raining and I know my glucose was elevated like I think really understanding what the 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 head White Hall 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 so I think those are the main reasons why I think it's such an important tool third thing is it democratizes data which you do too I mean incredible how you do that with your podcast but I think one 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 having much more access to that enchantment about their own chemistry and their own biology so to me that is so exciting like for me to be able to I've got you know probably 100 patients that are in a data stream with me where we're looking at their glucose and I can I mean I'm on spaical so I'm not doing this so much anymore but I can call a patient be like why is your glucose so high like what did you do oh it was my birthday I had a piece of birthday cake

like that kind of collaboration that also is 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 Amen to that a million times over we share that uh sentiment can tell it at a deep level I I think the pandemic actually assisted in well it harmed many things but it assisted in people's understanding that um no magic fery nor the government nor any anyone

was going to arrive at their door with a kit of things to make them healthy that provide sunlight movement sleep and all the various aspects of nutrition no nothing nothing that it everyone has to have access to first and foremost and then Implement those things as best they can speaking of which and kind of circling back to this idea of people in their late teens 20s 30s and onward if you had a magic wand and you could give like two or three don'ts or to make it personal if you could go back in time and

erase certain behaviors what would the the don'ts category be um you can tell us more than two or three um but if the goal is to maximize vitality and Longevity and those are not always uh parallel to one another certainly not the same thing sometimes orthogonal but let's just say fertility being a proxy for vitality and Longevity I think people will sometimes forget this that fertility isn't just about people who want to conceive children it's also it's a it can serve as a proxy for vitality and Longevity so uh what would you like to see

patients let's focus first on female patients but um if it extends to male patients as well what would you like to see them not do yeah or do far less of I really like that so I would say a few things I'll just headline them and then we can go into detail number one sleep I do want to diverge from you a little bit on some things but sleep is probably not one of them oh well feel free I mean you're the one that worked 100 you're the one that worked 120 hours a week sleeping

much then's I can't imagine unless unless you lived in a different reality than I do um uh you and there are times in my career where I was pulling all nighters and sleep deprived there just it I don't recommend it but I did it hope you don't do that anymore no longer if I can avoid it but there were years many years where it was like all right here we go and I I'm quite um Adept at it for one cycle yeah but two nights I kind of start to fall fall apart totally yeah so

I would say sleep alcohol High perceived stress and I'd love to talk about maybe um the data on telr and what we know so you'd like to see people get enough sleep so don't don't just yeah not all of these are concordant so um not enough sleep too much alcohol too much perceived stress eating the wrong Foods toxic relationships and isolation and then number six um not moving enough or not moving and exercising in a way that really fits with your body we start with that one actually cuz it's such a and then work backward

um uh that's interesting I I I think nowadays people appreciate the need for quote unquote cardio I know that the the exercise physiologists cringe and and dissolve into a puddle of Tears when I say that but getting the heart rate up over some period of time longer than 10 minutes in order to generate cardiovascular health circulation so and resistance training of some kind maybe flexibility what what do you mean by Body phenotype or and exercise I'll speak from personal experience so what I did through I mean I gave up my 20s to medicine and during

that time I occasionally got to the gym you know at UCSF on pralis you could go to the gym and then as soon as your beer went off you're back into the hospital but I didn't exercise much I had um do you remember Nordic tracks I had a Nordic Track in my house and that was that was like it what I believe because for me the primary outcome that I'm interested in is cardiometabolic health so when it comes to exercise what I really feel if we're going to be at a population level I feel that

about a third cardio 2/3 resistance training is based on my synthesis of the literature the best combination and I think there's you know as you described with your s um study I think there's a minimal effective dose which for a population is about 150 minutes I think most of us need a lot more than that per per week per week but I think you know 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 I think that recommendation is fantastic um I think resistance training well let me put it this way I'm neither a trainer nor a physician but I've seen in family members that were doing I wouldn't say a lot of cardio but just cardio that when they add resistance training everything in terms including their biomarkers um have improved dramatically yes is in particular for female members of

my family well one of the 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 um 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 so quick personal example when I first started measuring hor panels in myself I went to my

physician and I said I'm 35 I've had one kid I want to have another kid 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 um I don't want to have sex with my husband so what do you think what could we do about this and he offered a birth control pill and an anti-depressant oh goodness 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 and that set me on this course of realizing that what I was doing as 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 Rising 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 you know changing the way I was managing perceived stress and it also changed my supplement regimen could we talk about that um what the moment you said lowering cortisol thought of the two supplements that come to mind are ashwagandha which I think can potently reduce cortisol but I've heard some recommendations about cycling it um and I've always wondered about time of day for ashwaganda intake because sort of quote unquote

want cortisol elevated in the early part of the day yes and we know this uh we know you do not want cortisol peaking later in the day no you do not interferes with sleep interferes with sleep um and then the other supplement is riola rosacea do I am I pronouncing that correctly yeah so riola is very effective it's been shown in multiple randomized trials to lower cortisol so that could be very effective what sort of dose I've started taking it recently by the way and I made a huge mistake I like to make the mistakes

first so then my audiences don't make them um as I was taking it I heard it was an adaptogen so I thought oh I'll take it before resistance training but of course you want the cortisol Peak during resistance training because that's going to set in motion the Adaptive response so I started taking it later in the day and it's really improved I would say my late day second half of the day cognition this is subjective to be fair I just feel like I'm in a more even plane of attention in the second half of the

day so you're describing an NF1 experiment which is anec data it well it is not anecdotal so I was taught at Harvard Medical School that the hierarchy of evidence starts at the lowest with expert opinion you know case studies then you've got cohort studies then you've got um observational data that's prospective then you have randomized trial but the highest quality evidence of all is the n of one experiment where you serve as your own control so what you're describing with riola I would frame that as n of one experiment where you have a wash out

period and you compare before and after and I'd like to measure some other metrics to see if there's an effect including your cortisol so rodial has been shown in multiple randomized trials to reduce cortisol the other thing that I think is super effective is phosph title searing PS for short fish oil also more modestly reduces cortisol ashwaganda is interesting so in my first book the hormone cure which I read by the way you did I did I was hoping that was the one you read I did I read it and it's spectacular and I thought

going into it I had this like you know let's just call it what it was it's kind of male bias like is there going to be anything in here for me because uh I'm I don't have ovaries and you know is this going to be and it was IM mely informative um so thank you yeah I have very fond Recollections of the the walks I took listening to it and then I own the print version too so I like to switch back and forth so thank you for that it's a it's a superb book for

anyone to read thank you I so appreciate that so in chapter 4 you may or may not remember that ashwagandha at least the time that I wrote that book ashwag ganda's data is not great but lack of proof is not proof against so with ashwag gandha most of the comes from thousands of years of using it in itic medicine and it's considered again not my science hat it's considered a double adaptogen so that it's potentially helpful when you are um a high cortisol phenotype like I was like I sometimes still am or low cortisol I

haven't found that in my patients although I'll give you one exception so ashwaganda is mostly based on animal studies there's not as much human data but it is used a ton in Integrative Medicine the um there's one supplement that I found to be incredibly helpful for people who tend to have high cortisol at night and that's called a cortisol manager it's by integrative Therapeutics I don't have a second um supplement manufacturer that makes something similar it's their number one selling supplement because it's so effective is it a cocktail of several things it's a combination of

phosph tile Serene and ashwaganda tell tell me more about tile Serene I I am familiar with it for it's been mentioned by some guests that were on the Tim Ferris podcast long ago for other reasons I think related to sleep yes um and maybe that's another reason why you like it um but before we move on from Rola is there a dosage of rodal or rosacea that you um so I would refer people to my book because the randomized trials and the doses that were used are in there so I can't remember with riola although

I took it this morning to prepare to be with you yeah we can look it up remember with phos sering I take that regularly so 400 to 800 m is the typical dose for PS and what's interesting is that in the randomized trials that were done 400 milligrams was more effective than 800 milligrams interesting I've found that for several supplements that the lower dose was more effective yes um yeah I won't it doesn't matter what those were and so when you say PS you were referring to by the way folks not PCOS just cuz scien

and clinicians are familiar with and Military very familiar with acronyms phospha tidal serin PS so 400 800 milligram 400 being more effective taken later in the day or early day does it matter it depends on when your cortisol is high so for me I tend to you know what's the pattern for cortisol typically it rises to its peak 30 to 60 minutes after you get up then it has this gradual kind of asmic decline until you go to bed so if you're someone like me who Peaks like way crazy high I don't do that anymore

but that's what I used to do I need a phosph Serene in the morning for people who are high at night who have what's known as a a flat cortisol pattern or a inverted pattern you want to take it at night and the flat pattern just quick sidebar is that that's associated with a number of conditions that most mainstream Physicians don't know about so a flat pattern where it's in the morning and it's high at night is associated with anxiety depression uh decreased survival from breast cancer that was studied at Stanford by David Spiegel that

he was my um coll close even collaborator even uh on the breath work study that we oh interesting yeah he's our associate chair of Psychiatry now a wonderful human being has has been a guest on this podcast and and I'm now fantasizing about a conversation that includes uh a panel of of of uh Incredible Minds like you and David from the clinical side so in any case um yeah the late shifted cortisol not good not good not good and it seems to have the worst immune Downstream issues of any of the cortisol patterns so that's

really important to know about because it then maps to things like um it's related to PTSD so that's the pattern we see like in vets who've got PTSD as well as others it maps to autoimmunity it maps to fibromyalgia I was told that one in 12 people um have our heterozygous so one mutant copy or hypermorphic for some some mutation in adrenal related Gene so congenital adrenal hyperplasia is that true and if so that means that one in 12 people walking around are cranking out far too much cortisol or not enough cortisol all or the

quol system is already skewed in a direction that makes life more challenging at the levels we're talking about um did I hear that correctly because that one in 12 is not a small number it's not a small number it fits with what I see clinically I mean I want to see that data just to see um what does that mean and could you modulate it with environmental influences but it certainly fits with what I see you know I was taught once again in mainstream medicine that in terms of adrenal function it's very binary how most

clinicians think about it you either have Addison's disease and you don't make enough cortisol or you've got Cushings or cushingoid pattern and you make too much cortisol and anything in the middle is normal and my experience is that hell no like there are those of us like me who make a lot of cortisol I don't have Cushings maybe I've got one of these I wouldn't call it a mutant Gene I would call it more of a um vulnerable Gene so maybe I have one of those maybe that's part of the reason why I make you

know two to three times what I should be I'm aware of certain groups of individuals from within the military sector that um have there's a more frequent occurrence of some mutation in C C congenital adrenal hypertension not necessarily two copies which will if people look that up they're going to go oh wow there's all these phenotypes and um but sort of hypomorphic type thing so you know less than or too much cortisol and they are very good at staying up multiple days per night right uh multiple nights in series so they can pull all nighters

very easily they can push harder when most people would quit and everyone thinks well that's a great phenotype to have but guess what it's because they hyper produce cortisol yep and um so that's interesting and I think if we were to panel medical students and graduate students and you were to look at you know who's pulling excessive long hours who's stressed out a lot even outside of Academia and medicine and pushing pushing pushing really hard I think the ability to push and not crash we think of it as adaptive but in some sense it's maladaptive

over a series of years which is sort what were you described earlier yeah it's such a good point because you know you in some ways you'd want to select for that in certain professions like in the military like in medicine um but I would wonder for those folks about the downstream consequences of producing so much cortisol no it's got to be detrimental for their health in the long run and and you see that but even the data shows that if you're someone like me who makes a lot of cortisol higher rates of depression like 50%

of people with major depression have high cortisol levels higher rates of suicide um much more metabolic dysfunction we know that trauma as an example maps to an increased risk of glucose metabolism issues and certainly High cortisol does that because it's one of the jobs of cortisol is to manage glucose and it's it kind of sets you up for um this one number five which is toxic relationships you know someone who hyper produces cortisol it's hard to live with someone like that it's also I would say people that have this um let's just call it biological

resilience um it's not always adaptive because you can stay in in bad circumstances longer the ability to to crash provided it's not suicide or life life destroying or you know long Arc of of of pause and the requirement to you know take two years off from work or school or something um the ability to keep pressing on is is a double-edged sword let's put it that way um I want to make sure in staying within this conversation uh because you mentioned fos serin we talked about Rola Rosa as we talked a bit about ashwagandha you've

also talked about Omega-3s and fish oil in particular I'd love to know your favorite sources of these I think nowadays there's more General acceptance that getting these essential fatty acids is important do you have a threshold level of sort of grams I I've encouraged uh um podcast listeners to consider depending on what they're eating to try and get a gram of EPA or more per day does that seem excessive um and what are the real data on epas because then the uh cardiovascular experts always hit back and say oh no you know it's not good

for cardiovascular health and then you go well it's better than anti-depressants and other studies and they go no so I feel like if you really want to make your life difficult if you want to raise your cortisol you go on Twitter and you say something positive about Omega-3s of fish oil and um and you learn a lot um what are your thoughts on Omega-3s I take a lot of them I've always been a big fan yeah so this is where I personalize I think some people need more than others and what I do is I

measure your level so this gets back to nutritional testing so for you I would suggest an Omega Quant or one of my favorite cardom metabolic panels is to do a Cleveland heart lab so I think they they give me the most reliable information not just for lipids and subclasses and you know NMR fractionation but it also gives me an insulin resistance score it gives me um levels of Omega-3s great we'll provide links to these different sites so people but one quick thing about that the whole story is not Omega-3s in taking fish oil so the

work of Charley Siran at the Brigham is showing that the way that we resolve inflammation our understanding of it is really I think in the learning to crawl stage and so if you look at the omega-3 6 pathway in the body fish oils can help you know kind of push the reactions in a particular direction but typically they're not enough for the resolution of inflammation now what most people do including my NBA players is they pop an ibuprofen or something like that when they've got inflammation that's got lots of other side effects that are not

so good for you and we know in terms of the resolution of inflammation that taking something like ibuprofen reduces the amplitude of inflammation by by about 50% but then it potentially blocks the complete resolution of inflammation so there's these new supplements that you may have heard of called specialized Pro resolving mediators there's a lot of different supplement companies that make them and that combined with fish oil seems to be the best combination and what I do for athletes who've got you know kind of the normal aches and pains of the training load they have is

all combine a little aspirin small dose just like um 81 Mig or two of those baby aspirin together with fish oil plus specialized Pro resolving mediators and there's some that are NSF they're certified for sports but the the dose I would say with my patients some of them only need 1,000 milligrams your Gram that you mentioned for the population some of them need six gram together with spms so I think it has to be personalized how young um is it okay for people to start taking Omega-3s um for instance young women in their teens people

in their 20s and their 30s young guys in their 20s and 30s should they take fish oil if just as a assuming they're not going to get anything tested I'm thinking about the college student who is really into biomarkers and that sort of thing we'll go do some of this um but many people won't but they want to do the right thing so they'll try and drink a little less hopefully hopefully they won't smoke or vape please please don't smoke or vape the idea that vaping is okay it's like we had a whole episode so

bad so bad for everything we're talking about let's end that chap exactly so just you know avoid they hopefully they'll try and avoid those things hopefully they'll avoid hard drugs um hopefully they'll avoid getting any STI if they do they'll resolve them quickly hopefully yes um so but they might say oh well okay I'm willing to you know take some magnesium or take some phosph sering buffer my cortisol eat some vegetables um should they considering fish oil as a kind of a cross theboard in ulatory thing so I'd like to rank order these I would

say fish oil yes I think a th milligrams as a general recommendation is good but I also have a food first philosophy so my preference would be that they're having salmon or some kind of Smash fish and they're getting that as the primary source of their Omega-3s and then the days that they don't have fish I recommend it probably twice a week that they take fish oil then I would put magnesium next since so many people are deficient then I'd probably put vitamin D what how many IU a vitamin D per day well you keep

asking me this like for the the population yeah well for the let me put it this way for the LA for the lazy person or and this is an or not an and um or the person who um just doesn't have the finances to go get measured levels measured because you know our audience is a huge range we've got people who can have tons of disposable income that list in the spot we have people with no disposable income so a th000 to 2,000 International you but my you know what I do is I dose to

a serum level that's between about 50 and 90 great and so I have a vitamin D receptor uh snip and so I need to take about 5,000 a day to get to what I need a lot of people don't need that and you know there's some supplements that I don't know if they need so you mentioned phosph tile sering for someone who's a college student and their cortisol is completely normal they're wasting their money on PS they don't need it they might need it later but they don't need it now I'd like to make sure

that we Circle back to birth control in particular oral contraceptive birth control and we should touch on iuds perhaps a little bit more but what are your thoughts on S pure estrogen birth control this is what I learned when I was in college is that birth control is basically tonic estrogen so constantly taking estrogen estrogen women are taking estrogen so that they don't get the estrogen priming of progesterone you're not getting any ovulation and I've known women that have been taking oral Contra or that took oral contraception as like estrogen pills basically for 5 10

15 years are there long-term consequences of this as it relates to pregnancy PCOS menopause what if so what are some of those consequences um what are your concerns what do you like about oral contraceptive what do you dislike about them I like how balanced you asked that question so women who take oral contraceptives as long as you're describing like 10 years or longer we call those Olympic oral contraceptive users 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 as you may

know our reproductive Choice has been declining recently 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 first into the benefits because uh I'm going to get on a soap box 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 uh don't take

oral contraceptives and they have a period every single month of their reproductive lives they have a greater risk of a brain cancer so if you look then at women who have uh 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 aaring cancer so oral Contra contraceptives help with reducing ovulation and reducing risk we know that if you take the oral contraceptive for about 5 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 ca125 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 maybe just because that statement is going to highlight for a number of people um the question of what are some of the Sy earliest symptoms that people can recognize without a blood test so is ovarian cancer is it going to be pain so the problem is the symptoms are so vague and

they're so non-specific 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 so the way that we inform women in terms of watching for this is to get regular gynecologic exams um for women who are at high risk where they have for instance an ultrasound for some reason 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 a situation where you might get a blood test called a ca129 ca1 25 the um yeah the problem is the symptoms are so vague it could be it depends on how big the tumor is how much bulk you have what it's pressing on so if if um taking estrogen and thereby 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 they're not actively

trying to get pregnant or avoid getting pregnant but if they're not sexually active then the probability of conceiving unless they go through some IUI or some other route is is very low as far as I know um that's what I was taught in high school anyway um would they be wise to suppress ovulation for periodically using hormone-based contraception just so that they can offset the risk of ovarian cancer that's a very rational question and I would say that's what mainstream medicine has had at its back to recommend oral contra cves 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 but there's so many consequences and I think the issue here is more about consent because in OBGYN and I started out as a board certified OBGYN and I now mostly see men but I was taught as an OBGYN to convince women to go on the oral contraceptive and I think a lot of that is pharmaceutical influence so maybe we could talk about the risks and why the answer

is no to your question um as we do that could I just ask is the um the so-called ring the new it used to be called the NOA ring maybe that's a brand name but it when I was in college there was all this discussion about the ring all right by both men and women for reasons that don't belong on the podcast um use your imagination folks so um is the the ring obviously it's not oral it's not oral hormone contraception but it's hormone-based right the ring is releasing estrogen locally as opposed to taking it

orally but would you would you slot it under what you're about to tell us in terms of the concerns so we have less data about the ring so the oral contraceptive is two hormones it's ethany estrad and it's a progestin so it's not the normal uh progesterone that your body makes 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 the consequence of not taking them is surgery or some other um you know unless it it gives them some freedom in some way so I don't like progestins the uh Nar ring is estrogen plus progestin but it's released transdermally through the vagina so given the the way that um it's delivered to the vagina the doses are lower than what's taken orally but in terms of some of the risks that I'm about to talk about we don't know about much of the data yeah we think that it's similar there's probably a

spectrum of risk and the ne ring is a little more towards the middle than you know what I'm talking about with oral contraceptives okay are you ready for that yeah I'm ready for the risks okay so like with almost any pharmaceutical the oral contraceptive depletes certain micronutrients so magnesium there's certain vitamin BS that are depleted uh 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 in 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 2 to 3x 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 Wayne in terms of cortisol production the way that you can off the birth control pill it can affect thyroid function I'm thinking of the slide that I have that has like 10 problems associated with oral contraceptive but that's what I can remember right now that's very helpful and it makes me wonder whether or not if on the

one hand oral contraceptives are protective in women against ovarian cancer but then they have these other issues yeah there's one another I want to mention please anytime you take oral estrogen it raises sex hormone B globulin and you've talked to other podcast guests about this Kyle I think 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 bill you raise your sex hormone binding globuline 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 exquisitly sensitive to that decline in free testosterone so this then opens the portal of talking a little bit about testosterone and women so we've mentioned already that it's the most abundant biologically the most abundant hormone in the female system even though men make almost 10 times as much or even more than 10 times 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 Bing 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 need agency even risk-taking from studies that we've done with MBA students that I think is a serious problem maybe the most important out of all of these things is that it can shrink the clitoris by up to 20% 20% and that includes the a

regression of the of the nerves that innervate the the clitoris is that I mean that's a very good question as a neuroscientist yeah I would think uh used to teach uh the neural side of of reproductive Health we need to do a series on Sexual Health maybe you would co-host that with me sure I we could certainly use your expertise I think um yeah that's a dramatic that's a dramatic number yeah but then let's go back to the sacred marketing if I've got a woman that I think should not be on the birth control pill

maybe she's taking it for acne or she's taking it because her periods were a little painful what I'm going to 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 is it your inflammatory tone and we give you some fish oil and spms maybe a little aspirin when youve gotch 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 trick your by

up to 20% now that usually convinces most people to the elevation in sex hormone binding globulin does not seem to go away when you come off the birth control pill to me that is the biggest problem problem with prescribing oral contraceptives now 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 wow okay um that's yeah that's a significant statement and something that for consideration related to this although this might seem not related it is how early do you recommend that women go get their follicle number assessed in other words to get a size a sense of the size of the ovarian reserve and their amh levels U measured um I'm going to I'm an amateur Outsider as I say this but we have an episode on infertility where I just describe the ovulatory menstrual cycle

yeah um and I'm not the best person to answer that yeah well we can I'm too far off from it okay well um I suppose then from taking the perspective of somebody who thinks about fertility in terms of at least congruent with vitality and Longevity would given that it's fairly non-invasive it's an ultrasound or a blood draw or amh or both is there any reason why a woman would not want to get her follicle number assessed or her amh levels assessed is there any reason why because I was shocked to learn that most women don't

do this until they're hitting their late 30s or early 40s and they haven't conceived or they suddenly decide that they want to conceive and I thought why doesn't every doctor insist that their female patients get have their amh level addressed so that if they need to freeze eggs it's cost yeah so I think if you've got the disposible income to do it go for it it's not included in a standard blood panel no wow the only way women in my practice who've had amhs done and have looked at their follicle count are women who want

to freeze their eggs or and that requires disposable income or they um are having trouble getting pregnant so they are in the reproductive Endocrinology system and they're getting an evaluation and then they're also um the women who have symptoms of early menopause so premature ovarian insufficiency which is before age 40 uh those are the women that I see getting attested and I think you're right that it should be offered more broadly it speaks to the democratization of data again and I think most women don't know that so you're doing a huge service I think to

be speaking into this one other point related to that is that what I see in conventional medicine is that when a woman asks for a hormone panel and she's not trying to get pregnant she usually gets told that hormones vary too much it's a waste of money you don't need it or if you're feeling hormonal why don't you go on a birth control Bill unless she's trying to get pregnant if she's trying to get pregnant suddenly those same tests are very reliable and they get you know their their testosterone their free testosterone their thyroid pain

they get their estrogen and progesterone maybe they get their cortisol they get their amh so there's a double standard between those who want to get pregnant and those who don't and that needs to end yeah I totally agree as I've learned more about um ovulatory cycle and amh and and the anal population of follicles all it's fascinating it just seems to me wow a relatively straightforward test one definitely invasive ultrasound but I don't consider that yeah not terribly invasive but invasive uh at least but the other one just pure blood test just seems like why

wouldn't why wouldn't this be offered a covered by insurance or or you know that anyone that wanted it but now now I understand why you mentioned menopause huge topic enormous topic uh we had a guest on the podcast who's not a clinician who said something in passing so I wanted I likely to get this wrong um but what they said was that the results of the large scale trials on hormone replacement therapy for women for menopause said something to the effect of if the hormone therapy was started early enough it was very beneficial for yes

vitality and health outcomes whereas if women went through menopause and then initiated the hormone therapy hormone replacement therapy that it could be detrimental to their health so first of all uh do I recall that statement correctly and then second of all what sorts of hormones are being replaced is it just estrogen and how is that done is it done through birth control so oral contraceptives nver Rings what are your thoughts on menopause when should people start thinking about it and what is the pallet of things available so that we can do an entire episode with

you on on this topic in the future but just to I you know I get a lot of questions about this and 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 anticipation of that yes so we haven't talked about the 30-some but I totally agree with you 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 because you can replace to a state of you thyroid whatever that is for you you can replace 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 so you spoke to the Women's Health Initiative which was published in 2002 and we went from a huge number of women taking hormone therapy to a very small percentage like in the range of 5% and

that means we've got millions millions of women who are suffering needlessly with things like insomnia difficult with their mood difficulty with sex drive um feeling like they are closing the store in terms of sex because they're not on hormone therapy I would agree with the statement that you made that hormone therapy particular forms that are similar to what your body always made when it's given judiciously at the right time typically within 5 to 10 years of menopause which is 51 to 52 that it is incredibly safe so it's a complicated study the women's health initiative

but it was the the wrong study in the wrong patients with the wrong medications and um with some of the wrong outcomes so it was powered to look at cardiovascular outcomes it was not powered to look at breast cancer it was stopped because of breast cancer risk but what happened in the control arm of the study was that they had an incredibly low rate of breast cancer and so as a result they ended up having this increased risk of breast cancer at 5 years and they stopped the study now the study was done with synthetics

it was done with conjugated equin estrogen known as Premarin and mroy progesterone acetate those were the so-called estrogen and progesterone those are uh synthetic hormones we think especially the progest is associated with the greater risk of breast cancer although the the subsequent re-evaluations of the data now 18 years out have shown that um this problem with the control group and no increased risk of breast cancer um and for the women who got estrogen only those who had a hysterectomy the Premarin they actually had a decreased breast cancer risk and decreased breast cancer mortality so there's

a lot to be said about this I'm trying to keep it really brief brief but if you look at the women 50 to 60 So within 10 years of menopause they're the ones who seem to have the greatest benefit so they had a decreased subclinical atherosclerosis so less cardiovascular disease they had an improvement in terms of um bone health um less progression to diabetes and then over the age of 60 they started to have greater risk of certain outcomes such as cardiovascular disease myocardial infection and so on you asked about um what do I do

and to me this problem is not just menopause what's more interesting is to talk about per menopause so per menopause is the the period of time before your final menstrual cycle and for most women depending on how attuned you are of the symptoms it can last for 10 years so I'm still in Period menopause 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 that you start sleeping more poorly because progesterone is so important you talked about that with Kyle you may notice it as more anxiety difficulty sleeping and that probably is related to the estrogen receptor so e Alpha is estrogen receptor Alpha is enio um it increases anxiety ER beta is associated with an angiolytic activity and then there's a total of about six estrogen receptors now there's the the G protein coupled estrogen receptors and those are mixed angiolytic angiogenic so um there's this whole period of paropa and what's Most Fascinating to

me and we've got to talk about this either today or another time 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 the work of Lisa mascone at Cornell from uh 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 Prem menopause you know up to like age 35 to per menopause to postmenopause the women who are having

the most symptoms in per menopause menopause The Hot Flashes the night sweats the difficulties sleeping those are the ones who have the most significant cerebral hypo metabolism 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 lowlevel or let's call it pseudo dementia of sorts yes it it it seems to be a phenotype that you can then map to Alzheimer's disease because that's Lisa musc'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 and insulin resistance ins sensitivity as we talked about it before um seems to be somewhere in there which I think when that first when that idea first surfaced a few people are 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 you've done in a 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 right dementia perhaps especially in women is it safe to say that I think 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 hypom metabolism the way I describe it to my patients 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 you once could like things are just a little slower and I say that to women they're like I have that like help me so this is then circling back to Whi where women are scared to death of taking hormone

therapy and 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 going to give you hormone therapy and I I just want to call that out I would say no that is not the way to approach it further 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 maybe with a little bit of estrogen progesterone or birth control pill because it's given a lot or that they pass this idea you know suck it up suck it up doesn't matter that you're not sleeping anymore you know turn down the temperature in your room and that's not right because hot fleshes 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 yeah it's the the bidirectional cross talk between the body and the brain keeps you know I think is this resounding theme uh we had Chris Palmer on here a psychiat who's talking about ketogenic diet for treat mental health I know you we could have a whole other discussion and we will I hope if you'll agree to it about nutrition and as it relates to hormones um specific diets and so forth but the and that's a question too

whether this problem of cerebral hypometabolism could we solve it with estrogen Andor increase metabolic flexibility so I just wanted to footnote that sorry to interrupt you no please uh please interrupt um uh I I know you're as long as we're there I know you are a fan in some instances of intermittent fasting time restricted feeding Andor ketogenic diet yes um to get cells sensitive to insulin which is not to say if I understand correctly which is not to say that women need to stay on the ketogenic diet for long periods of time or intermittent fast

by only time restricted feeding for 8 hours or 6 hours a day but that by increasing you said met abolic flexibility excuse me but by increasing cells sensitivity to insulin and then maybe returning to a more typical eating pattern and periodically switching back and forth that might actually benefic be beneficial do I have that right yeah I love the pulse so I feel like it's much more physiologic than say going on a ketogenic diet and staying there for years all of the data that we have on the ketogenic diet it's pretty Limited in terms of

duration you know the the longest players that we have in terms of the data are the folks with epilepsy and that's just a different phenotype so I think in terms of microbiome effects diversity disbiosis some of those issues we really don't know in terms of long-term effects so I prefer with a ketogenic diet that it's used as an nof one experiment and that you do it for four weeks maybe you measure biom merkers before and afterwards maybe look at your stool before and afterwards and we still haven't talked about stool tests yet but you could

measure you're fasting insulin and your glucose you could just start there do four weeks of Keto clean keto including vegetables doesn't have to be 57 a day and then measure it again afterwards since you measure mentioned stool testing yes um what what is your recommendation about stool testing so my recommendation this is again in the the field of if you have the disposable income so I usually start with goova because they've got a good co-pay system with insurance that's what I typically use so I usually do their one day stool test where you have to

go digging through your stool and send it off to this lab that's in North Carolina I usually do the one day unless I'm concerned about parasites in that case I tend to do three days I do that for people who travel a fair amount and go to places where there's greater risk or they just have gut symptoms another test that I do a lot is um cuz I was like to mention two Labs is a test by longevity and this is much more of a data wonk uh type of test because it's powered by AI

it was designed by um a guy who's got inflammatory bowel disease and he is a um he's a PhD deep phenotyping bioinformatics guy who wanted to make this really easy so the test is is under the umbrella of thorn and um they used call it gut bio they might have another name for it and they just improved it so that it's a a wipe instead of digging through your stool and so my athletes will do it now they were not so into digging through their stool before is anybody really no one is I don't want

the answer I know the answer I prefer to that question but that's a super interesting test because it's you get much more dense data the issue is um um with apologies to my friends at Thorne the issue is that their recommendations end up being Thorn supplements so that can be very easy for people who want to you know connect the dots that's not always the way that I like to do it uh first of all three things um you've shared with us an immense amount of knowledge uh and in that first statement I also want

to apologize because I threw you the entire lifespan of uh female lifespan reproductive Health contraception diet uh microbiome so many things but um I first I just want to say you've taught me a tremendous amount um including I think something that most people including myself have not thought about enough which is the psychosocial impact on things that we're all familiar with constipation bowel movements what we eat what we avoid I have to say really a huge thank you for that because it's not something that's been discussed on this podcast before sort of know that brain

communicates with body psychology and biology are linked but I think this is the first time that anyone's ever directly linked circumstances and biology and psychology in such a concrete way so that's the that's the first thing and I I speak for many people on that second of all we barely scratch the surface of your know knowledge and um which is both uh frustrating for me because uh it I always want to learn more and I know many other people do as well but also very very exciting because uh with uh hopefully without much persuasion we

can have you back on to talk about pers at all like men uh I know you're working with men now Men's Health um some particulars around per I think there's more for us to explore in terms of PCS menopause contraception and all of the above but then something that you and I were talking about off camera um before started which I think is a really important factor that ties back to this issue of of trauma and stress and the bidirectional relationship between biology and psychology hopefully someday we won't even separate those two um which is

the use of specific medicines including plant medicines yes and how that can influence overall health which no doubt will include Hormone Health so I say all of that for two reasons first of all to queue up the we won't even call it a part two but a equal to to this which um I'm gratified to hear that you you'll join us for that and then also to just really extend a huge thank you the amount of knowledge that you shared is is immense and uh is going to be very very useful and actionable for for

men in terms of their thinking and their actions and for women in particular today's discussion in particular for women in terms of how to think about their health and biology how to think about their psychology and the environment that all of that embedded in so I just want to say an enormous thank you thank you Andrew I so appreciate that and I so appreciate what you offer to the world in terms of a way in a way to understand physiology and how to craft a architect a better life um can I just add one last

thing because I didn't talk about it since we didn't get to the 40s and the 50s in this list of biomarkers to so I feel like if people 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 how is that taken so it's a CT scan of the chest you can self-order it like I think at Stanford Hospital you can self-order it last time a patient checked it was $250 so again disposable income but it it tells

you 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 and it's 45 for men too so if you haven't had one have you had one no you need one insulin cortisol CAC great so I'll run all that by you it's really essential and it's um yeah it's it's so fascinating because you know there's some women who have a zero so my score is zero and that's great so often you can just keep doing what you're doing 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 really eight to nine out of the top 10 killers in the US that allows you to really start to make changes and I I think it's essential to know that data it's not it's probably not going to be offered by your doctor certainly Peter AA is going to offer it but most conventional doctors are not going to do it and then the last thing I

want to say before you mention so if I were to go to my doctor and I just say I want a a cardiac calcium score that's what people coronary artery calcium score CAC okay so everyone hear that and know that if you're 40 or older and maybe if you're 45 or older get get it so the last thing is and this for men and women is your a score so adverse childhood experiences knowing your a score is so essential in terms of a baseline for how much trauma your system your Pine system endured when you

were a kid and we know that childhood trauma whether it's abuse or neglect or you know having an alcoholic parent that maps to disease in middle age and it can give you so much Insight I'll give you an example I've got a patient who had an elevated coronary artery calcium score who does everything right with her food I think it was her trauma that elevated her C when she was 45 so I think an a score knowing your a score starting as a teenager like knowing it and knowing how to work with that is really

essential there are certain people they are exceedingly rare but you are one such person that when they speak knowledge just comes from comes out of them and it's incredibly useful and helpful knowledge so thank you I'm going to get both of those things good um and I highly recommend everyone else pursue ways that they can get those or if they can't get them that they you know earmark those as things to get at the point where they they can obtain sufficient uh disposable income sounds like that the health uh the detriments to health that those

can offset would be well worth the cost totally thank you thank you for joining me for today's discussion all about female hormone Health vitality and Longevity with Dr Sarah gotfried if you'd like to learn more about Dr gotf Freed's work please check out her social media channels we've provided links to those in the show note captions in addition please check out one or all of Dr G reads excellent books that she's written about nutrition supplementation and various treatments for Hormone Health longevity and vitality we've linked a two of those notably women food and hormones and

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newsletter and you can find it at hubman lab.com during today's episode and on many previous episodes of The hubman Lab podcast we discuss supplements while supplements aren't necessary for everybody many people derive tremendous benefit from them for everything from sleep to focus to hormone regulation the ubberman Lab podcast is happy to announce that we partnered with momentus supplements because momentus supplements are of the absolute highest quality also they include many single ingredient formulations which is essential if you wanted to design a supplement regimen that is both cost- effective and the most biologically effective supplement regimen

that's very hard to do with blends of supplements it's very straightforward to do with single ingredient formulations also momenta supplements ship internationally which is important because we realize that many of you reside outside of the United States if you'd like to see the supplements discussed on the hubman Lab podcast you can go to Liv momentus spelled ous so that's liv.com huberman thank you once again for joining me for today's discussion all about female hormone Health vitality and Longevity with Dr Sarah gotfried and last but certainly not least thank you for your interest in science [Music]