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 life

I'm Andrew huberman and I'm a professor

of neurobiology and Ophthalmology at

Stanford school of medicine today my

guest is Dr Sarah Gottfried Dr Sarah

Gottfried 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 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 Gottfried 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 discussed

nutrition and exercise we touch on how

the omega-3 fatty acids play a

particularly important role in managing

female hormone Health Dr Gottfried

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 and 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

Gottfried 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 Gottfried 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 perimenopause

and how best to manage and navigate

perimenopause and menopause including a

discussion about hormone replacement

therapy in addition to her academic and

clinical expertise Dr Gottfried has

authored many import 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've 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 from my teaching and

research roles at Stanford it is however

part of my desire and effort to bring

zero cost to Consumer information about

science and science related tools to the

general public in keeping with that

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huberman and now for my discussion with

Dr Sarah Gottfried Dr Gottfried Sarah

welcome thank you so happy to be here

yeah I'm delighted and very excited to

ask you about an enormous number of

topics here we are expert in so so many

things so uh the challenge for me is

going to be to constrain this walk as it

were but 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-a-vis

hormones not just pregnancy

challenges with or

um ease with pregnancy and child rearing

childbirth 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 the 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

psychoimmunuroendocrine 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 determine 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

perimenopause 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 cesarean sections so everyone goes

through this process of a relatively

easy vaginal 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 endometriosis

fibroids I just had a hysterectomy I

added 50 plus fibroids

and polycystic ovarian syndrome

and of those three uh how frequent are

those and 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 uh 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 women

in their 30s and 40s and 50s and onward

should be getting certain tests and

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 or not

they're 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 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 U.S is somewhere between

12 and 16 years old do I have that right

no you do not oh great so that's 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 hypothalamic pituitary

adrenal gonadol a recent women testes

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 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

gonadal part of that is not fully mature

so they're more likely to skip periods

especially under stress they have a lot

of influences it really doesn't get well

established until you're done with

adolescence and I'm told that

adolescence now is still like age 25 to

26. I heard that and I was like I've got

two daughters and I was like that's a

really long time and not just a

psychologically defined or bio

psychosocial 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 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 is 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 it 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 IUD 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 am a

huge fan which iuds in particular so I

like copper because it's non-hormonal

it's as effective as getting your tubes

dyed who would have thought right I mean

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

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

it's 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 they're associated with

a birth control pill the other thing

that's important to know about it I know

this is a sidebar

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 contraception

now my favorite is vasectomy

but short of vasectomy I think the IED

is a really great choice there are some

risks associated with it I'm not saying

it's risk-free but I love IUD 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 biomarkers 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 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 okay and it

might be a factor in their longevity did

they have good health span 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 uh 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 uh Tango

um is a 2023 goal it has been every year

um the uh I'm gonna hold you accountable

today okay we'll do and there no there

will be no YouTube video of me do at

least not initially Tim Ferriss actually

a phenomenal podcaster as we know is uh

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 us and progesterone is

incredibly important you want to have

the right lead do 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

greater risk of fibroids endometriosis

breast pain

probably in association with the

microbiome and the estrobolume can you

familiarize me with the estrobloom yeah

I'm delighted to know that I don't

recognize the term yeah so the

estrobolume 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 Glaser

and

what we know is that there are some

women who have an estrobolume that makes

them have a greater risk of certain

estrogen mediated

conditions like breast cancer

endometrial cancer

and a men prostate cancer

so the estrobulum 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 a faulty a strobe and

we need to adjust it with you know some

of the microbiome

modulating

uh nutrients nutraceuticals that we have

so that they're less likely to have that

that Tango that's not working with

estrogen 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 Anderson 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're just like

causing all kinds of problems in your

body increasing the risk of Quinones

like DNA 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 I do a

lot of stool testing we can look at

things like beta glucoronidase

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 ace ASE 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 clickeronautation 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 the estrogen like Bad

Karma and that's what happens with

people who have high blade beta

gluconidase 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 AKA stool sample

that's right and in terms of blood

testing or various tests for these other

biomarkers getting estrogen testosterone

and other ratios 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 luteal 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 in that

decade

so for most women they've got a

menstrual cycle Dave that averages out

at 28 days so this is about a week

before they start their period

for women or more irregular it's harder

to do that as women get older and we'll

talk about this in a moment

usually 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 1920 and I'm not talking about

blood tests 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 it

it's sort of a crude window into the

averages ecstatic 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 a 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 risk reduction

another quick sidebar

and I was sad to find that

intake of vegetables polyphenols is such

an important predictor a future risk of

breast cancer like when you're a 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 our 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 should be blending

up broccoli or kale cauliflower so

cauliflower is 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 super

convenient so that with you know kind of

a taste that they like whether that's

chocolate which is what most 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 us to the extreme so he is a

retired physicist professor at UCSD he

found out that his microbiome was a hot

mess

and developed autoimmune disease and so

he became hell-bent 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

farmer's 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 exercises for like one 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

Jupiter after all right and retired I

suppose might have had and he's retired

but he is 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

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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 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

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

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

glucosis 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 MBA 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

yeah 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 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 to give you Pro you know

antibiotics using 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

probiotics I think what's far more

interesting is

prebiotics I think the data is much

better for prebiotics and

um a 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 and for that matter

what is going to be the best way to test

the microbiome you said stool sample and

I'll come right back with the same

question I asked about a blood test

what time of day when during the month

um to establish a baseline so this would

be prior to embarking on a you know 97

vegetables or how many years per day 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 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

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 we know that

dysbiosis is bad yeah and we know that

diversity of the microbiome is good we

hear this yeah 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 I'm not a microbiologist but

whereas with you know with testosterone

in men we hear okay you want your free

testosterone to be about two percent of

your total perhaps with women you women

are gonna have more testosterone than

estrogen on average but still less than

men when you look at testosterone etc

etc but you can kind of get some some

crude measures but for the microbiome it

just seems like long lists of microbiota

for which I just get dizzy I just if you

just wrote out a bunch of I's and L's

and s's you'd you can go halfway 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 Knight's

work but 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 lipoic acid

um plant-based antioxidants because you

can measure that in the blood

I like to look at some of the key

vitamins especially the B vitamin range

because as you probably know if you've

got a particular genetic

um polymorphism so you might be less

likely to be absorbing the right level

of vitamin B9 folate vitamin B12 Etc

I'm also looking going back to the

antioxidants at glutathione because I

think that's such an important lever

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 788 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 three and eight for Sleep

there's a Mexican there's so many forms

it can be a little bit overwhelming to

people so any any detail 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 Genova neutrals

during the pandemic they developed an

at-home test normally with a neutral

valve 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 copay is about 150 dollars

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

nutribal

second lab is spectracell

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

kind of Precision

cardiometabolic Health he thinks

spectrosol 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 percent 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 diet stress

um patriarchy

rage

to psychosis so Pine the um the pine

system right

psychology Immunology neural and

endocrine factors combined is that yes

and then I would say there's another

Factor

which is

being female is a health hazard

so we have twice the rate of depression

insomnia

we've got three to four x increased risk

of multiple sclerosis

we've got five to eight times the risk

of thyroid dysfunction

so if you just look at that and you look

at subtle pre-clinical thyroid

dysfunction

a 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

Canal gut axis

and they have a lot of perceived stress

together with this borderline thyroid

function that no mainstream medicine

doctor has told her is a problem and

then she's got a problem with the Tango

between estrogen and progesterone

she's going to tend toward constipation

women have a lot more constipation than

men

the gut is about 10 feet longer in women

compared to men

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 and do what we need to do as a

brief tangent but I think this is the

time to ask

um at what age now do Physicians insist

their female patients get colonoscopies

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 polyps and or 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 U.S

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 of the

you broadly mentioned psychological

impact right 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

understanding that all the organs are

connected to one another it's a network

it's a network and that the microbiome

sits at had um at a key node within that

Network

um and I think most people accept that

now yes yeah 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 skull but in any case 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'm 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

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

rheumatologist 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 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 yeah 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 when you're

what I'm hearing you say is that

constipation is far more common in women

and it signals a general 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 a 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 yep 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 will relieving constipation

um pun uh intended retroactively

um will that assist in a great number of

issues and or 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 you know like we

talk a lot of 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 nun 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

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 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 gumbing through that uh

quite uh you're you're quite correct

um so so let's answer those questions

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 as sort of a

um

a key

indicator or signal

of dysfunction with my 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 in 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

their perceived stress tends to be

higher and I'm generalizing for a

population

side note you know in Precision medicine

we don't do that we do medicine for the

individual individual not the population

not medicine for the average

and so if you look at

the physiology of a female

I think that 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 yeah well I have

a couple more questions about

constipation I never thought I'd ask

this many questions about concentrating

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 a set of tubes a

nervous system being one of those tubes

and well 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 but I might in

passage it's the bondas right are the

are the are the the sphincters yes yes

that's right uh thank you for for that

the um so what defines constipation I

mean in other words let's think about

the healthy rather than thinking about

the unhealthy let's how many bowel

movements should 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 eat more fiber

more bulk larger meal at the end of the

day a larger meal 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 his

timing

during the day for bowel movements at

all informative what 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 always assumed

that morning time yeah was a was a

healthy time for bowel movements um and

I think almost everybody babies included

recognize the feeling of being lighter

and more energetic when they've

evacuated totally colon totally um in

fact so much so that I'm obsessed with

jungian and Freudian 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 balance of the

autonomics of 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 for residency I was taught that

constipation is having a bowel movement

less frequently than whenever once every

three days

so 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 constipated personally

and and and and in other ways

constipated individuals and again this

might seem like an odd conversation but

the the discussion around conservation

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 it doesn't work for

anyone I know

and I spent a lot of 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 yeah believe me I

became a scientist not a physician for a

number of reasons 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 a bowel movement

after every meal

but they've got a different microbiome

they're exposed to different microbes

here in the U.S I would say Wednesday

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 writ 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

real-time tools so a big proponent of

like physiological sign real time you

know these sorts of things but things

that can really lower the Baseline on

stress overall to facilitate

constipation and other other 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 in 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 Transcendental

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 it she

just had a paper and sell on your sign

and

um it kind of it made me think like

teach me how to 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 do every day yeah and we

were monitoring

subjective mood Etc but also Biometrics

remotely so it's kind of a nice

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 HRV 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 are 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 yep

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 three and eight seconds

depending on how well they regulate

carbon dioxide

another group did cyclic signs 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

long inhale through the nose is really

important because it makes sure that all

the collapsed abiola 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 we're a

little bit pranayama-ish but the exhale

is rather passive as opposed to active

and then the fourth category was cyclic

hyperventilation which is a lot like

Tumo AKA Wim Hof ish breathing different

than Wim Hof breathing so this would be

so very active inhales and exhales

every 25 cycles of inhale exhale that'll

be one cycle long exhale hold lungs

empty 15 to 30 seconds then repeat for

about five minutes now the info everyone

did that for five minutes and what we

found was that the cyclic sign 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 it publish and sell yeah

we were so amazing we're very fortunate

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 HRV yeah so in this case we didn't

tell them to alter anything else about

their behavior just hoping it was

background kind of across the system yes

and some were Stanford students others

were from the general population any

Frat Boys that were drinking heavily

probably not well during the pandemic I

think alcohol intake went way way up

across the board

um I mean isn't 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 through that paper

yeah um and it certainly disrupts

patterns of nighttime sleep in

particular from my understanding that

first phase of sleep that's related to

the massive growth hormone release that

you all really need and want in

different measure growth hormones we did

not no the second iteration of this

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 and what time of

day yes I mean this thing around

constipation is uh is super interesting

and I think that plus um 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 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 assistants yeah it was a

big group it was nine people in our

group and three clinicians and a lot of

a 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 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 a la

carte menu sex orgasm

um connection

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 yeah 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 is is signaling a bunch of other

factors around us 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 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 power 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 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 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

bioengineering undergraduate at MIT I

should mention which has always had a

bit of a of a male

um askewed male in terms of Faculty

numbers well my my that's true at most

universities true well my postdoc

advisor was the late Ben Barris who was

a female to male transition transgender

interest first transgender member in the

National Academy of Sciences were my

closest friends unfortunately he 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 yeah

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 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

undergraduates 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 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 there I think

LinkedIn is correct okay great well

Wikipedia editors note get out there and

make that make the correction now 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

you know there's particular forms of it

I would say this also relates to

White Privilege it relates to

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 make us 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 bipoc 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

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get twenty percent off I want to use

this as an opportunity to a keep this in

mind as I return to a question that I

didn't close the hatch on earlier and

it's my fault which is I'm now clear on

the fact that a woman in her late teens

early 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 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 your testosterone

declines by about one percent 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's

off the top of my head immediately but

what what's a kind of a nice reference

point there so the way I tend to

describe this on podcasts 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 darkened skin

irregular periods regular periods is

that

um you know 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

excuse me I keep saying that ovulatory

slash menstrual cycle

um

what are some other indicators and do

you recommend that women start taking

Androgen blockers or so 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

this is on the ovaries having

um clinical manifestations of

hyperandrogenism so that could be

hirsutism acne other things and then

usually irregular periods and the way

that that's defined at least by the uh

latest criteria is having a period every

35 days or less

so typical cycle length 28 is 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

gnosis on their ovaries but they've got

hirsutism and they've got irregular

periods could you define haircitism here

statism 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

and then there's of course a familial

quality to that like I was just looking

at a paper last night looking at

Israelis and how much hair statism they

have and whether this is related to CH E

repeats on the Androgen receptor

do they get um not Israelis but um do

women who

um who might have PCOS experience um

androgenic alopecia so hair loss that's

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 DHT

related sometimes you know this is where

I'm going to invoke clinical experience

rather than what I've seen in the

literature women definitely can have

some androgenic alopecia

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 Insulin yet we should

what we know is that

PCOS is not just a problem in terms of

irregular periods and then difficulty

getting pregnant so those are mostly

problems in your 20s 30s early 40s but

it is a massive risk factor for

cardiometabolic disease as you get older

so many people tend to pigeonhole PCOS

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 51-52 because we know that

that elevated testosterone the high

androgens

are probably the greatest cardio

metabolic driver of disease for women

with PCOS 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 was 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

you ask that woman one question

do you want to get pregnant or not

so then you have these women with PCOS

who get started on a birth control pill

if they don't want to get pregnant if

they want to get pregnant then you help

them get pregnant by addressing some of

these PCOS 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 mental 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 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 is a biological

variable meaning even if it's a study on

mice how did that start though that

didn't start that long ago it must have

been I think we can think

I don't want to miss attribute here I

think we can thank Francis Collins for

insisting on this amen Francis

Bernadine Healy has done so much to help

us but you know she made the Women's

Health Initiative which I hope will get

to

which is a hot mess like so confusing

the data that came out of that yeah so

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 pose this question as a hypothesis

because I think it's likely to be 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 mentioned

some of the psychosocial stress issues

based on at the organizational 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 it 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

pieceo PCOS are a consequence of the

psychosocial conditions that are

I don't say forcing but are biasing the

need for females to

um think behave 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 under produce

or over produce 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 add 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 acknowledgment I mean

you're the expert here

um you're the physician clinician an

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 that weren't aware of that I

wasn't aware that women make more

testosterone 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 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 onto something

it may not explain all of the women with

PCOS because as I mentioned 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 PCOS 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 cite this

that compares the phenotype of a woman

with PCOS 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

thika cells and ovaries to overproduce

testosterone these women are insulin

insensitive so

more insulin is being cranked out

and these 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 okay

I'm just a little bit outside the lane

lines of my expertise so I was trying to

use it what is the correct nomenclature

so that we can make sure well what I

like about insulin insensitive the way

that she 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 because

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 what's your insulin

I don't know what I'm due for a blood

test yes you are I'm due for a blood

test um I had blood work done for eight

months um sure that'd be great I uh I'm

always

um experimenting with different

supplements and different behavioral

regimens and I've kept charts since I

was 19. oh you're like my patient I I've

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 you

have a reference 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 learned what kind

of foods work for me which don't

um I thought it was fascinating I

learned how every Behavior you could

possibly imagine use your imagination

impacts blood glucose totally totally

fascinating to me including how a

two-way 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 I think it's many things I

think it's

generally the enchantment

of learning about your own chemistry and

biology I love it 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 I wanted to

fill this prescription for a ctm 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

two hour glucose challenge test where

you look at glucose and Insulin at the

fasting point one hour later two 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 hat white Hall study

that insulin especially postprandial

insulin vascular insulin 2 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 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 sabbatical 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 sentiment I can tell it at a

deep level I I think the pandemic

actually assisted in well harm to many

things but it assisted in people's

understanding that um no magic fairy nor

the government nor any anyone was going

to arrive at their door with a kit of

things to make them healthy right that

provide sunlight movement sleep and all

the various aspects of nutrition no

nothing nothing that 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 right

they're 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 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.

120 hours a week sleeping much then I

can't imagine unless unless you lived in

a different reality than I do

um uh you know and there are times in my

career where I was pulling all-nighters

and sleep deprived there's just it I

don't recommend it but I did it yeah I

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'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 date on telomeres 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 so we start with that one

actually just because it's such a and

then work backwards um uh that's

interesting 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 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 Parnassus

you could go to the gym and then as soon

as your beeper 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

two-thirds 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 sign

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 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 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

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 hormone 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 can we do about

this

and he offered

a birth control pill

and an antidepressant 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 a physician taking

care especially of women was not getting

to some of these root causes that are so

essential and I would say I had to start

first with cortisol

at that time I was running four miles

three times a week four times a week

that was just racing 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 Richmond

can we talk about that and what the

moment you said lowering cortisol

thought of the two supplements that come

to mind are

um ashwagandha which I think can

potently reduce cortisol but I've heard

some recommendations about cycling it

and I've always wondered about time of

day for ashwagandha 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 uh

rhodiola rosacea do I am I pronouncing

that correctly yeah so radiola is very

effective it's been shown in multiple

randomized trials to lower cortisol so

that could be very effective what sort

of doses 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 start 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 right which is organic data

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

and you've got

observational data that's prospective

then you have randomized trial but the

highest quality evidence of all is the

end of one experiment where you serve as

your own control

so what you're describing with rhodiola

I would frame that as an end of one

experiment where you have a washout

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 radial has

been shown in multiple randomized trials

to reduce cortisol

the other thing that I think is super

effective is phosphatidylserine PS for

short

fish oil also more modestly reduces

cortisol

ashwagandha is interesting so in my