Female Hormone Health, Fertility & Vitality | Dr. Natalie Crawford

1. 0:00 – 1:40

   Dr. Natalie Crawford

   1. AHAndrew Huberman0:00

      (uptempo music) 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. My guest today is Dr. Natalie Crawford. Dr. Natalie Crawford is a medical doctor specializing in obstetrics and gynecology, reproductive endocrinology, and infertility. She also holds a degree in nutrition science. Dr. Crawford runs a clinical practice, seeing patients daily, as well as being actively involved in public education, both through social media and through her popular podcast entitled As a Woman. Today, Dr. Crawford teaches us about all aspects of female hormones and hormone health and fertility, beginning as far back as in utero, when we were still in our mother's womb, and extending as far forward as menopause. We discuss topics such as the timing of puberty and what the timing of puberty in girls means for their fertility, and we discuss birth control, both hormonal and non-hormonal forms of birth control, and how birth control may or may not relate to long-term fertility and different aspects of female health. We also talk extensively about measuring fertility, that is, egg count. We also talk about egg retrieval, AKA freezing one's eggs, as well as in vitro fertilization. And we also take a deep dive into the popular and important topics of nutrition and supplementation as they relate to fertility, as they relate to pregnancy, but also how they relate to female hormone health generally. Indeed, Dr. Crawford provides us with a masterclass on female hormones and fertility, one that I know that all women ought to benefit from and that men would benefit from listening to as well.

2. 1:40 – 4:59

   Sponsors: Maui Nui Venison & Helix Sleep; The Brain Body Contract

   1. AHAndrew Huberman1:40

      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 theme, I'd like to thank the sponsors of today's podcast. Our first sponsor is Maui Nui Venison. Maui Nui Venison is the most nutrient-dense and delicious red meat available. I've spoken before on this podcast, in solo episodes and with guests, about the need to get approximately one gram of high-quality protein per pound of body weight each day for optimal nutrition. Now, there are many different ways that one can do that, but a key thing is to make sure that you're not doing that by ingesting excessive calories. Maui Nui Venison has the highest density of quality protein per calorie, and it achieves that in delicious things like ground meats, venison steaks, jerky, and bone broth. I particularly like the ground venison. I make those into venison burgers probably five times a week or more. I also like the jerky for its convenience, especially when I'm traveling or I'm especially busy with work and know that I'm getting an extremely nutrient-dense, high-quality source of protein. If you'd like to try Maui Nui Venison, you can go to mauinuivenison.com/huberman and get 20% off your first order. Again, that's mauinuivenison.com/huberman to get 20% off. Today's episode is also brought to us by Helix Sleep. Helix Sleep makes mattresses and pillows that are tailored to your unique sleep needs. Now, sleep is the foundation of mental health, physical health, and performance. When we are sleeping well and enough, mental health, physical health, and performance all stand to be at their best. One of the key things to getting a great night's sleep is to make sure that your mattress is tailored to your unique sleep needs. Helix Sleep has a brief two-minute quiz that if you go to their website, you take that quiz and answer questions such as, do you tend to sleep on your back, your side, or your stomach? Do you tend to run hot or cold in the middle of the night? Maybe you don't know the answers to those questions, and that's fine. At the end of that two-minute quiz, they will match you to a mattress that's ideal for your sleep needs. I sleep on the Dusk, D-U-S-K, mattress, and when I started sleeping on a Dusk mattress about two years ago, my sleep immediately improved. So if you're interested in upgrading your mattress, go to helixsleep.com/huberman, take their two-minute sleep quiz, and they'll match you to a customized mattress for you. And you'll get up to $350 off any mattress order and two free pillows. Again, if interested, go to helixsleep.com/huberman for up to $350 off and two free pillows. I'm pleased to announce that we will be hosting four live events in Australia, each of which is entitled The Brain Body Contract, during which I will share science and science-related tools for mental health, physical health, and performance. There will also be a live question-and-answer session. We have limited tickets still available for the event in Melbourne on February 10th, as well as the event in Brisbane on February 24th. Our event in Sydney at the Sydney Opera House sold out very quickly, so as a consequence, we've now scheduled a second event in Sydney at the Aware Super Theatre on February 18th. To access tickets to any of these events, you can go to hubermanlab.com/events and use the code HUBERMAN at checkout. I hope to see you there, and as always, thank you for your interest in science. And now for my discussion with Dr. Natalie Crawford.

3. 4:59 – 13:27

   Female Puberty & Growth Characteristics, Height

   1. AHAndrew Huberman4:59

      Dr. Crawford, welcome.

   2. NCDr. Natalie Crawford5:00

      Thank you so much for having me. I'm honored to be here.

   3. AHAndrew Huberman5:03

      Well, I've been paying attention to your content for a long time, and I find it to be incredibly clear, informative, and for many people, actionable. So today, I'd like to talk about both fertility and, of course, hormones. But as we both know, fertility is not limited to a discussion about hormones and actually relates to things like behaviors-

   4. NCDr. Natalie Crawford5:24

      Yes.

   5. AHAndrew Huberman5:25

      ... sex behaviors, and other behaviors, nutrition, supplementation. So we'll get into all of it, but if we could just back up developmentally and talk a little bit about female puberty, because I think pretty much everything we'll talk about today is related to what happens puberty forward, mostly in females, but we will also discuss male fertility and hormones a bit. And the question I have is, is there anything about a woman's timing or let's just say patterns of puberty, right, how frequently they menstruate early on, what the timing of menstruation is, uh, in terms of their age, et cetera, that provides hints or maybe even...... facts or directives about her future fertility or how long her fertility might last?

   6. NCDr. Natalie Crawford6:17

      This is a great question, and I think defining some terminology before we begin is helpful. So if we go all the way back to when you're a fetus inside your mom, so when there's a female fetus inside your mom, you have the most eggs you're ever going to have at about 20 weeks gestation. You have about six to seven million eggs. By the time you're born, you've already lost more than half of those, and you continually lose eggs all the time. So the analogy that I always use, and you do too, is imagining that there's a vault inside the ovary where all your eggs are kept, and every single month since the moment you have an ovary, you lose a group of these eggs, and when there's more inside, you're losing more. So you're losing all of these eggs throughout early fetal development and then up until the time period even of puberty. When you reach puberty, you have a lessening of the number of eggs in your ovary to the point where it can start to respond to the signals from the brain. So when we think about puberty onset in females, first we have really thelarche, which is the development of breasts. So that happens about two years on average before you have menarche, which is your period starting. So what happens is the brain, as we know from the hypothalamus, sends out GnRH, and then we have FSH coming out, which really starts to stimulate those follicles. So FSH, or follicle stimulating hormone, well-named hormone for the female. Of course, men have it too, and it's less well-named for them. But it starts to get those follicles, which house the eggs, to grow and make estrogen. Women have about two years of estrogen exposure alone, so unopposed estrogen, with no progesterone because they're not yet ovulating, and that's when you start to see breasts budding and you start to see the development of some of those secondary sex characteristics before you actually have a period.

   7. AHAndrew Huberman8:06

      What are some of the other secondary sex characteristics that precede menarche? Um, so you said, uh, breast bud development and then breast development, uh, on average about two years before-

   8. NCDr. Natalie Crawford8:14

      About two years before.

   9. AHAndrew Huberman8:15

      ... menarche.

   10. NCDr. Natalie Crawford8:16

       You have sexual hair development. So actually andrenarche is one of the first, usually comes right before at the same time with breast buds, so two to three years before you'll see your period. And then you-

   11. AHAndrew Huberman8:25

       So genital hair, underarm hair typically.

   12. NCDr. Natalie Crawford8:27

       Exactly. Yeah, genital hair usually first-

   13. AHAndrew Huberman8:28

       Okay.

   14. NCDr. Natalie Crawford8:28

       ... and then underarm hair.

   15. AHAndrew Huberman8:29

       Okay. Um, and, uh, we're getting right down into the weeds here-

   16. NCDr. Natalie Crawford8:32

       (laughs)

   17. AHAndrew Huberman8:32

       ... which is good. Um, you know, a goal of this podcast is to normalize all aspects of health, including sexual health and, and reproductive health. Um, is that commensurate also with, um, the development of body odor?

   18. NCDr. Natalie Crawford8:46

       Yes.

   19. AHAndrew Huberman8:47

       You know, 'cause as a young boy who eventually hit puberty and became a young man and now I suppose I'm in middle age, um, 48, um, I can tell you that the, the locker room smelled a lot different, um, be- before and after middle school, right?

   20. NCDr. Natalie Crawford9:00

       Right.

   21. AHAndrew Huberman9:01

       Right? Like the, in other words, uh, boys start to smell stinky. Um, (laughs) right? And, and-

   22. NCDr. Natalie Crawford9:06

       They do, yes, and that's usually around that same time of sexual hair development is when you start to have those glands around the hair making some of those odors that start to produce stink, for lack of a better-

   23. AHAndrew Huberman9:16

       Do they reflect hormones themselves?

   24. NCDr. Natalie Crawford9:20

       Not the s-, like the smell, the actual smell-

   25. AHAndrew Huberman9:22

       Mm-hmm.

   26. NCDr. Natalie Crawford9:22

       ... doesn't actually reflect levels of hormones or anything like that. It is just that your body, your gonads, whether it is testes or ovaries, are now starting to respond to those brain signals. The brain is turned on. They're starting to respond, and your body is starting to mature in a way to get to the point where it can support reproduction.

   27. AHAndrew Huberman9:40

       The reason I ask that question is not to get people thinking about, um, stinky smells, but, um... And by the way, some people love the musty smell of, of their own bod-

   28. NCDr. Natalie Crawford9:48

       (laughs)

   29. AHAndrew Huberman9:48

       ... uh, armpits or others.

   30. NCDr. Natalie Crawford9:50

       To each their own, to each their own.
4. 13:27 – 17:31

   Eggs & Ovulation, Harvesting Eggs, In Vitro Fertilization (IVF)

   1. AHAndrew Huberman13:27

      me to a, uh, a, um, a very specific question. Um, if puberty arrives, let's, again, define this menarche, um, for sake of d- our discussion right now. If puberty arrives early in a girl, does that mean that her fertility will shut down earlier as well?

   2. NCDr. Natalie Crawford13:44

      Great question. It does not. So the age of which you start the onset of your period does not impact how long you're going to have a reproductive lifespan. And that's because you have the eggs inside that vault. You're losing them every month no matter what.

   3. AHAndrew Huberman14:00

      Mm-hmm.

   4. NCDr. Natalie Crawford14:00

      So you lost them all those years before your period started, no matter if your period came at 10 or at 15. It's just about when did they start allowing your body to ovulate determined by being able to carry a baby. Your, your body now thinks you can be pregnant.

   5. AHAndrew Huberman14:15

      I think this is so important to highlight, because it puts together what you said earlier about the loss of eggs even in, um, as a fetus. Um, I think most people sort of assume that the reduction in egg count is due to ovulation and the fact that, you know, one egg ovulates typically, but that other eggs are deployed in that ovulatory cycle, and then those, those basically are taken out of the vault and out of the opportunity for fertilization. But what you're saying is that the eggs are constantly being culled from the vault starting from early t-

   6. NCDr. Natalie Crawford14:49

      Yes.

   7. AHAndrew Huberman14:49

      ... embryonic development. And that ovulation is a, a distinct step, in some sense, unrelated to-

   8. NCDr. Natalie Crawford14:56

      To the loss of eggs.

   9. AHAndrew Huberman14:56

      ... to the, to the loss of eggs.

   10. NCDr. Natalie Crawford14:58

       Correct.

   11. AHAndrew Huberman14:58

       I think this is going to be very important for our discussion later about potential egg harvest-

   12. NCDr. Natalie Crawford15:02

       Yes.

   13. AHAndrew Huberman15:03

       ... because I think some people have it in mind that-

   14. NCDr. Natalie Crawford15:05

       There's a lot of misconceptions-

   15. AHAndrew Huberman15:06

       Yeah.

   16. NCDr. Natalie Crawford15:06

       ... that you're losing eggs from your vault, and that's not the case. You're just accessing the ones outside.

   17. AHAndrew Huberman15:11

       So you're not, um... So we can just answer this now perhaps. It seems, if I understand correctly, that if one were to harvest eggs for IVF or for embryogenesis in a dish, to set them aside later or freeze them for later, um, if they want to use them, eggs or, or fertilized embryos, that one is not reducing their total number of eggs any more than they would had they just let their, their cycles proceed naturally.

   18. NCDr. Natalie Crawford15:36

       Exactly.

   19. AHAndrew Huberman15:36

       Oh, that's such an important point. I think there, I think a lot of people believe the opposite. They think-

   20. NCDr. Natalie Crawford15:40

       It's probably the number one thing that patients fear when they come talk to me about egg freezing or going through IVF, is, "I don't want to harm my future fertility. I don't want to cause myself to run out of eggs earlier or go into menopause earlier." And it's explaining this process to them that your ovaries are on a pathway that you can't change. Those eggs are coming out of the vault regardless of if you're on birth control pills, you're pregnant, we do IVF. What we're modifying is one's not going to ovulate and have the rest of them die. We're going to try to give you medication to get them all to grow so we can take all of the ones that have been released from the vault that month and give them a chance for later. And the next month, you'll have another group come out.

   21. AHAndrew Huberman16:21

       So IVF is not about stimulating hyper-release or excessive release of eggs. It's about stimulating the growth of the ones that have been released so that they can be frozen at stage either for later fertilization or fertilized in a dish and then frozen as embryos. Is that right?

   22. NCDr. Natalie Crawford16:36

       Ex- exactly, and we just use the hormones that your body normally makes in a different way. The medications we use are FSH and LH to get the eggs to grow. So people will say, "I don't want to take all these weird hormones or strange medications," but we're just manipulating that normal process that happens in the natural menstrual cycle in order to say, "Hey, this month, let's get all these eggs to grow. Let's try to improve the efficiency of finding which eggs are going to be normal or not and help you along this process."

   23. AHAndrew Huberman17:03

       I think a good number of people are now going to, uh, head to the IVF clinic. I, I think that, again, I really want to highlight this. I, I think most people that I've spoken to assume that the process of harvesting eggs for freezing, for fertilization then or later is going to diminish their fertility because they're basically pulling more out of the savings account, so to speak.

   24. NCDr. Natalie Crawford17:24

       Right.

   25. AHAndrew Huberman17:24

       Okay, so we-

   26. NCDr. Natalie Crawford17:25

       You're making the withdrawal no matter what.

   27. AHAndrew Huberman17:27

       Right, well, um, such an important point for, for people to know and, and propagate.

5. 17:31 – 21:39

   Endocrine Disruptors, Fetal Development

   1. AHAndrew Huberman17:31

      Um, getting back to puberty, uh, a little bit later on, I wanted to get into endocrine disruptors and things of that sort. But since you brought it up, um, you know, I've heard things such as, okay, things like evening primrose oil. If mom is putting evening primrose oil on or is, has it in her shampoo, that I've heard of young males getting, um, precocious breast bud development. Uh, keep in mind, folks, that some transient breast bud development is, um, characteristic of some normal puberties in males. It sometimes shows up and goes. I knew some kids like that in the neighborhood. They got teased a little bit, and then they stopped getting teased. Hopefully nowadays, they don't tease other kids. But when I was growing up, those kids got teased, not by me, but by other people. But it was normal, and it passed for, for some, right? It occurred, um, normally and then passed. But I've heard that things like exposure to evening primrose oil, maybe even just through contact with mom, can, um, increase the e- the frequency or degree of that male breast bud development. Is it also true that young girls can undergo precocious puberty, or let's just say accelerated or exacerbated puberty, um, through contact with things like evening primrose oil, which is a, I think has some pseudo estrogen-like properties?

   2. NCDr. Natalie Crawford18:41

      It's important to differentiate that the secondary sex characteristics we see, like breast bud development, are from estrogen, but it's not really puberty being initiated when it's from an endocrine disrupting chemical. So taking...... you know, being exposed to evening primrose or lavender or tea tree oil in a male isn't going to cause him to start to go into puberty, but it is going to expose him to estrogen when his body is not, and therefore stimulate some breast bed development. Same thing can happen in young girls, meaning they could show some of those secondary sex signs earlier than they normally would, and this is why, if that's happening at a really young age, kids should go to a pediatric endocrinologist who are gonna check things like bone age and see if you've really started the puberty process or not, or is it an outside exposure which is causing it? Interestingly, about the young child exposure and development, the other thing to say that's really interesting and relevant in my field is that when we think about how many eggs are in the vault, and everybody's born with this different number, and I'm sure we'll talk about ovarian reserve, what we now know is that the vault, your ovaries are most susceptible to whatever your mother does when she's pregnant with you, and that that epigenetic, that programming which is happening, is predisposing young women to probably having, some of them, low ovarian reserve, some of them having diseases we associate with infertility, like PCOS or endometriosis. And we haven't yet characterized what all they are, but if we look at the incidents of some of these disease that we see now, what we do know is that the time period of which these people were pregnant, the '80s and '90s, was not the healthiest time when it comes to endocrine disruptors and plastic exposures and chemicals and all of this processed stuff, let's just say, that people have been exposed to, that we're really seeing that those, that ovarian susceptibility to egg quality and quantity happens in that fetal development period.

   3. AHAndrew Huberman20:49

      It's interesting, uh, because there's some, uh, parallels to male fetal development, like the, the fact that you have these or- early organizing effects of hormones like dihydrotestosterone, which essentially stimulate the growth of the penis, but also then establish a, a propensity for hormones during puberty to activate growth of the sex organs, but also activate the brain areas that are responsible for a host of different things. So, uh, I only mention that because, uh, what I'd like to kind of illustrate in the background here is that, um, basically our reproductive health begins really prior, prior to conception, really. It's, uh, dependent on mom and dad, but, um, certainly to a great degree on, on mom, um, but then fetal development is going to be important, so short of, um, us, uh, being able to pick our parents-

   4. NCDr. Natalie Crawford21:38

      Yeah.

   5. AHAndrew Huberman21:38

      ... um,

6. 21:39 – 25:13

   Lavender, Tea Tree & Evening Primrose Oils, Scents, Diapers

   1. AHAndrew Huberman21:39

      I, I do have a couple questions about lavender, tea tree oil, and evening primrose oil. I was aware that evening primrose oil, oil, excuse me, can, um, somehow bind estrogen receptors. It m- or mimic, uh, some of the estradiol or something similar to it. I wasn't aware of tea tree oil or lavender. Um, here, are we talking about oils? What about aromas? And how concerned do people have to be about this stuff, because I mean, you know, you'll go into a restaurant bathroom, there'll be potpourri, uh, some people wear perfume. I mean, uh, we don't want to set up paranoia-

   2. NCDr. Natalie Crawford22:11

      No, no.

   3. AHAndrew Huberman22:12

      ... but, but I, but I think people should know about this stuff. Tea tree oil is in a lot of those, um, natural shampoos-

   4. NCDr. Natalie Crawford22:17

      A lot of the shampoos.

   5. AHAndrew Huberman22:17

      ... the ones, the ones that burn.

   6. NCDr. Natalie Crawford22:18

      Yes, the one that tingle your scalp. So p-

   7. AHAndrew Huberman22:20

      Yeah, I don't like those.

   8. NCDr. Natalie Crawford22:20

      Some people love them though.

   9. AHAndrew Huberman22:21

      Yeah, yeah.

   10. NCDr. Natalie Crawford22:23

       Constant exposure is very different than a one-time handwashing in the bathroom, and I think that's the big difference for everything when we talk about chemicals or toxins or exposures in the world. You can't live in a toxin-free world, but choosing what you put in and on your body on a regular basis does set the tone for certain physiologic changes. And so, you know, using unscented products, especially with children, is a really important thing, because we want to make sure that their lifetime exposure to some of these things, especially during critical times, is much less. And so you'll see people recommend things like your laundry detergent, you know, what scents are in your laundry detergent. The shampoo and conditioner are a big one, and the soaps that you use on a day-to-day basis in your house, or the oils you put on your body. Lavender's huge because there's this whole community of people, they want to rub lavender oil on their baby's feet and help them sleep, but really, we can see, and if somebody goes and shadows a pediatric endocrinologist for a day, they'll see some kids come in and this will be the reason why.

   11. AHAndrew Huberman23:29

       Hmm. Uh, what about cloth diapers versus non-cloth diapers? I've, I've heard, you know, that you have your, like, very strong cloth diaper proponents, right? And that because they seem to, um, feel or believe that, um, non-cloth diapers somehow contain things that can get into baby's skin, and, and maybe there's a bigger question here. Is baby skin more permeable than adult skin?

   12. NCDr. Natalie Crawford23:52

       Well, I guess I don't know that baby skin is more permeable or not.

   13. AHAndrew Huberman23:54

       I don't either. I just, uh, to me, it seems-

   14. NCDr. Natalie Crawford23:56

       I think it's pro-

   15. AHAndrew Huberman23:56

       ... it seems like it'd be hard to imagine it is, but, but babies do seem to have this incredible skin, right? Their skin is so smooth and-

   16. NCDr. Natalie Crawford24:02

       It's very soft.

   17. AHAndrew Huberman24:02

       ... and you want to squeeze their cheeks and all this kind of stuff, but, um, yeah, the idea they would be more permeable.

   18. NCDr. Natalie Crawford24:08

       I think it's more that their development is, this time is very important in setting the stage for a lot of what happens later, versus in adulthood, those stepwise developmental processes have already happened, so I think that's why we pay so much attention to what happens in the, you know, childhood period of time, because we're now learning about those later consequences of what you're exposed to. It's not that, you know, regular diapers versus cloth, whatever we want to say, one's necessarily better than the other. It's more honestly a personal preference. Babies are exposed to them a lot, and there's been a lot of attention to that, but similarly, somebody could use cloth and wash it with a detergent that then, you know, has certain chemicals in it. So, there hasn't been a study shown that this one thing is an exposure for a baby that somebody needs to be worried about. There's definitely companies now which are promoting and talking about, you know, traditional diapers that-... they are making sure have less toxins in them. And I always think anytime you can decrease toxin exposure to a child is going to be very important.

7. 25:13 – 26:04

   Breast Milk vs. Formula & Fertility

   1. NCDr. Natalie Crawford25:13

   2. AHAndrew Huberman25:13

      Is there any evidence for, um, you know, breast milk versus formula in terms of e- impact on future reproductive development of, or r- reproductive status of, of a child?

   3. NCDr. Natalie Crawford25:25

      That's a complicated question, because breast milk exposure, at least for the first six months of a child's life, certainly helps with the immune system development, and we know that poor immune development can lead to higher risk of autoimmune disease later, what people call leaky gut, and some of those diseases certainly are correlated with fertility. So, I wouldn't say we've gone so far to say that if you don't breastfeed your child, they're going to have fertility issues, but we do know that there's an in-between correlation with things that breastfeeding is protective against, and how those diseases themselves may relate to fertility in the female later on.

8. 26:04 – 34:08

   Menstruation Cycle & Hormones, Timing

   1. AHAndrew Huberman26:04

      Okay. Okay, so if we're, um, thinking about a young girl/woman, 'cause we're talking about puberty, right?

   2. NCDr. Natalie Crawford26:10

      Sure.

   3. AHAndrew Huberman26:10

      So, I, I don't know what the exact nomenclature is there. You know, m- my experience is, I'll, I'll offend, and, um, somebody no matter what.

   4. NCDr. Natalie Crawford26:17

      (laughs) .

   5. AHAndrew Huberman26:17

      Um, but, a girl who undergoes puberty, right? So, a young woman, um, w- who's maybe 13 or so, so she's early teens, um, undergoes puberty and, therefore, is continuing to lose eggs from the vault, um, but now, is undergoing, uh, presumably roughly every 28 days, menarche. But let's talk about this 28 days thing, because I think a lot of people-

   6. NCDr. Natalie Crawford26:40

      Yeah, yeah.

   7. AHAndrew Huberman26:40

      ... think that, um, quote-unquote, "Normal menstruation is always 28 days," and, and we know that's not true. So what is the, the range of n- uh, normal, uh, durations between, um, menstruation's, uh, cycles, or duration of the menstruation cycle? And let's also define when the menstruation cycle starts. Probably for the males mostly in the audience, right?

   8. NCDr. Natalie Crawford27:03

      Sure, sure. So let's think through the cycle. We'll do a quick one over, and then answer the questions. So, what we think of as cycle day one, or when you're going to say this starts, is going to be the day that you start bleeding. So that's actually shedding the endometrial lining from what grew the last time.

   9. AHAndrew Huberman27:18

      So any spotting, even, would be considered day one?

   10. NCDr. Natalie Crawford27:20

       Yeah, mm-hmm.

   11. AHAndrew Huberman27:21

       Okay.

   12. NCDr. Natalie Crawford27:21

       So, it is ... we can get back to it, but there's problematic if you have a lot of spotting before that full flow starts. A day or so can be really normal, just as the body's adjusting to the drop in progesterone. But let's just start at the beginning. Day one, you have a period, a menses. This is when you're actually bleeding. At this time period, we like to think about all of those new eggs being out of the vault, being susceptible to that FSH, which, of course, is that well-named hormone, because it stimulates a follicle to grow, and each egg is in a follicle. That egg starts to grow, and makes estrogen. That estrogen stimulates the proliferation of the lining of the uterus in preparation for potentially that pregnancy that may come. And also, that estrogen makes you feel really great, right? That's the follicular phase, named so because that follicle is growing, and it's an FSH dominant phase, where you have a lot of estrogen. Whe-

   13. AHAndrew Huberman28:11

       And people feel b- great when they have a lot of estrogen?

   14. NCDr. Natalie Crawford28:14

       Yep.

   15. AHAndrew Huberman28:14

       B- c- because?

   16. NCDr. Natalie Crawford28:15

       Women feel good with estrogen.

   17. AHAndrew Huberman28:16

       Because of the relationship between estrogen and other neuromodulators, like dopamine and serotonin? And, and is that happening in parallel, or are they somehow related? Like is estrogen controlling the release of serotonin somehow, and vice versa? Or are they just kind of coincidentally happening in parallel?

   18. NCDr. Natalie Crawford28:31

       We definitely think that there's s- more of a correlation/causation than just coincidence, because we know there's time periods where people are more depressed within your cycle, correlating with those low estrogen levels, and we know that when you go into menopause, or you run out of eggs, and you're now in a low estrogen phase, we see a lot more of a depressed mood, and, you know, anhedonia. Lack of response to things which would normally give you pleasure happens more frequently. The female brain loves estrogen, and it's protective against things like dementia. So, this is a time period where women are going to be more energetic, they're going to have more energy, more focus. This is the estrogen dominant phase of the cycle. And when you have seen that estrogen at its high levels, which it's only made from a mature follicle, and it's very specific, 200 picograms per milliliter for 50 hours. That's the brain's clue, "Okay, we must have a mature egg." And it can send out that surge of LH, or luteinizing hormone. And now you ovulate. And when you ovulate, the follicle opens up, releases, closes back, and then it's the corpus luteum, and we've entered the luteal phase.

   19. AHAndrew Huberman29:37

       And the corpus luteum, as the name suggests, a corpus, it's like a body that's basically the, it's, it's base-

   20. NCDr. Natalie Crawford29:42

       A fatty body, yeah.

   21. AHAndrew Huberman29:42

       ... it's basically the, the corpse of, of what, uh-

   22. NCDr. Natalie Crawford29:45

       It's the dead follicle, yes. Mm-hmm.

   23. AHAndrew Huberman29:47

       ... essentially ensheath- yeah, ensheathed the egg before, um, and it ... Wh- what I find so amazing, I mean, biology is so beautiful, right? It, instead of just taking that tissue and saying, "Okay, like, let's just discard this," or, um, that becomes the trigger for the next phase of the, of the-

   24. NCDr. Natalie Crawford30:01

       It is essential for life, right? The corpus luteum, which makes progesterone, opens and closes the implantation window. It is what allows somebody to get pregnant, and for our species to continue. And so, it's extremely fascinating. And that corpus luteum gets stimulated to produce progesterone, and pulses throughout the entire luteal phase, because it's still controlled by the brain, unless you get pregnant. And then in that luteal phase, progesterone is fascinating. It's trying to protect you from things which could potentially harm your baby. So suddenly now, you have less energy, you want to sleep more, you want to eat more, you maybe do not want to have sex as much, because your body is suddenly saying, "Let's just protect this potential implantation that you're going to have." If that pregnancy doesn't come, the corpus luteum can only live 12 to 14 days. It has a very distinct lifespan. And then it dies. Your estrogen and progesterone both drop. You bleed starting over the next cycle, and a new group of follicles comes out to be released. And the reason why walking through that-... very succinctly, but is important when you're asking, "How long is the normal cycle?" Because the luteal phase is pretty set at 12 to 14 days. The follicular phase can vary in person to person, and what we know, though, is for one individual, if your menstrual cycle, your reproductive hormones are working right, it should be relatively constant for you. And so, if your periods are every 24 days, but they've always been every 24 to 25 days, then that's not concerning. And if your periods are every 33 days, but they've always been every 33 days, then that's not concerning. But we do get concerned when there's a change in your period, or we get concerned when people have what I like to say is irregularly regular periods. Because what you'll see textbooks tell you is that your periods could be as short as 21 days, as long as 35 days, and that can all be normal. But people will hop between them, and they'll have one cycle that is 24 days in length, from day one to the last day before the next day one. Then the next cycle's 32, and then it's 26, and then it's 34, and that's not normal. That's too irregular, and that can be a sign that something is not communicating correctly within your reproductive hormones. So, what I tell patients is, "In general, your periods should be less than 35 days apart, and you should be able to look at a calendar and with your finger, put a finger on the date, and within a couple days of accuracy, be able to predict when your period's coming. And if you can't, there could likely be something that is interfering with the hormonal signals between the brain and the ovary." And one of the biggest, really one of the only things we see as women start to have fewer eggs in the vault is a shortening of their cycles. So, you have a regular period, and suddenly now, you have less eggs in the vault, so less are coming out each month, and when the brain sends out that FSH signal, now there's fewer eggs, so it's not getting as dilute and you have one starting to respond sooner. So, suddenly, you're ovulating shorter, faster in your cycle. You're ovulating on cycle day nine instead of 14. Your luteal phase is still set. But the person who comes to see me and says, "My periods have always been 28 to 30 days, but now they're every 24. I just figure it's no big deal," I am- I have red flags going off everywhere, because I'm now really concerned that potentially their ovarian reserve has dropped to a point where we are starting to see clinical changes. Now, of course, things like thyroid and prolactin and other hormones can also cause such changes, but that's why you'll hear most reproductive endocrinologists say, "Your period's a vital sign." And what we really mean is the regularity at which it comes and the predictability of it is telling us if your hormones are all communicating in a normal fashion, or if something could potentially be off.

9. 34:08 – 35:59

   Sponsor: AG1

   1. NCDr. Natalie Crawford34:08

   2. AHAndrew Huberman34:08

      As we all know, quality nutrition influences of course our physical health, but also our mental health and our cognitive functioning, our memory, our ability to learn new things and to focus. And we know that one of the most important features of high-quality nutrition is making sure that we get enough vitamins and minerals from high-quality, unprocessed or minimally processed sources, as well as enough probiotics and prebiotics and fiber to support basically all the cellular functions in our body, including the gut microbiome. Now, I, like most everybody, try to get optimal nutrition from whole foods, ideally mostly from minimally processed or non-processed foods. However, one of the challenges that I and so many other people face is getting enough servings of high-quality fruits and vegetables per day, as well as fiber and probiotics that often accompany those fruits and vegetables. That's why way back in 2012, long before I ever had a podcast, I started drinking AG1. And so I'm delighted that AG1 is sponsoring the Huberman Lab Podcast. The reason I started taking AG1 and the reason I still drink AG1 once or twice a day is that it provides all of my foundational nutritional needs. That is, it provides insurance that I get the proper amounts of those vitamins, minerals, probiotics, and fiber to ensure optimal mental health, physical health, and performance. If you'd like to try AG1, you can go to drinkag1.com/huberman to claim a special offer. They're giving away five free travel packs plus a year's supply of vitamin D3 K2. Again, that's drinkag1.com/huberman to claim that special offer. Let me see if I have this correct. Um, we've got this thing that we call the menstrual cycle, or the ovulatory cycle. The- there's two phases, a follicular phase and a luteal phase.

   3. NCDr. Natalie Crawford35:50

      Mm-hmm.

   4. AHAndrew Huberman35:50

      Follicular precedes the luteal phase. The luteal phase tends to be, if I heard correctly, um, fairly fixed, about 14 days.

   5. NCDr. Natalie Crawford35:56

      Mm-hmm.

   6. AHAndrew Huberman35:57

      Um, the follicular phase

10. 35:59 – 38:08

    Estrogen, Progesterone & Menstrual Cycle

    1. AHAndrew Huberman35:59

       can vary in duration, maybe 10 to 14 days, maybe even 10 to 18 days.

    2. NCDr. Natalie Crawford36:03

       Yeah.

    3. AHAndrew Huberman36:03

       Depending on-

    4. NCDr. Natalie Crawford36:04

       The person.

    5. AHAndrew Huberman36:05

       ... som- something about their brain to ovary communication. For those that, um, aren't familiar with this, um, the- I always learned that estrogen primes progesterone is kind of the, the really basic top contour description of the ovulatory cycle that, you know, estrogen is going to slowly climb toward the, the point of ovulation, and then there's a, there's a peak and then a drop, and then progesterone is going to dominate in the luteal phase, the second half. You said that estrogen, um, is associated with, both at a psychological level and a physiological level, more energy, um, feelings of vitality, and some of that estrogen increase is actually coming from the one egg that got stimulated the most, the-

    6. NCDr. Natalie Crawford36:47

       Mm-hmm.

    7. AHAndrew Huberman36:47

       ... one that got selected, right? So picked for the team-

    8. NCDr. Natalie Crawford36:50

       (laughs)

    9. AHAndrew Huberman36:50

       ... um, potentially for the team, but got picked, uh, potentially for fertilization, and that egg sheds its corpus luteum, uh, which is this-... piece of the, of the egg that then triggers the progesterone that dominates the luteal phase. Do I have that right? Um-

    10. NCDr. Natalie Crawford37:05

        Mostly, mostly.

    11. AHAndrew Huberman37:06

        Okay, yeah, please correct me where I'm wrong.

    12. NCDr. Natalie Crawford37:07

        The follicle in which the egg grows, right, when you ovulate, it ruptures. Y- the cyst bursts. A follicle's a cyst, a cyst is a fluid-filled structure, follicle's a fluid-filled structure that holds an egg, so when you ovulate and you get that LH surge, the cyst bursts. It opens up and the egg comes out of it, and then it re-heals and becomes the corpus luteum.

    13. AHAndrew Huberman37:27

        Got it.

    14. NCDr. Natalie Crawford37:27

        So just a little bit different in timing. And you're right with estrogen primes progesterone, but really, we think about it the layer of the uterus, because estrogen stimulates the growth of that lining, and then progesterone stabilizes it and allows implantation to occur. But the sequence of events of when you're estrogen dominant and progesterone deficient, which is the follicular phase, and people will come in having labs drawn randomly, and they're all concerned that they don't have progesterone, and when you talk to them about where they are in their cycle, you say, "You're not supposed to have progesterone. That's your follicular phase. This is perfectly normal."

    15. AHAndrew Huberman38:04

        Okay, great. Thanks for that clarification.

11. 38:08 – 42:42

    Hormonal Birth Control & Ovarian Reserve, AMH Testing, Fertility

    1. AHAndrew Huberman38:08

       I get a lot of questions about birth control-

    2. NCDr. Natalie Crawford38:10

       Mm-hmm.

    3. AHAndrew Huberman38:10

       ... but on my social media handles. Um-

    4. NCDr. Natalie Crawford38:12

       Don't we all? Don't we all? (laughs)

    5. AHAndrew Huberman38:14

       Uh, to be clear. Um, there's, it's a vast topic for exploration, but along the lines of what we're talking about now, I've heard, and I suspect it may not be true, but tell me, is there any evidence that taking birth control can disrupt the process that you just described? And when we talk about birth control, we should probably define what we're talking about. So there are, um, hormone-based birth controls, AKA the pill. There are also hormone-based birth controls that are not in pill form. Um, there are IUDs. There are copper IUDs. There are other IUDs. Let, let's just talk about hormone-based contraception in females.

    6. NCDr. Natalie Crawford38:54

       Okay.

    7. AHAndrew Huberman38:54

       Uh, if, which, many of them, as I understand, are estrogen mimics or estrogen themselves, that suppress ovulation. Do they diminish or increase the number of eggs that are taken from the vault?

    8. NCDr. Natalie Crawford39:07

       Fantastic question. Let's talk about what people say is the pill. So let's specifically talk about combined oral contraception, the pill which has ethinyl estradiol and some type of progestin. No. Contraception does not change the release of eggs out of the vault. They are occurring at the same process and the same pathway. You're not ovulating because that estrogen does prevent FSH from coming from the brain, so you have the group of eggs still come out of the vault. There's no FSH. They just all die. The next group comes out. So when you are saying, "Are you going to run out of eggs faster? Is it going to harm your fertility? Does birth control impair the process?" The answer's no. But there's a couple important caveats. One is that the birth control pills, especially if you take them continuously or for a prolonged period of time, the, the body's smart, and the ovaries start to say, "Well, we're not really doing anything," and one of those markers of ovarian reserve we have is AMH, and that's anti-Mullerian hormone. And AMH is made from the granulosa cells or the cells that surround every follicle. So in the shortest way possible, more eggs in the vault, more come out every month, higher AMH. Fewer eggs in the vault, fewer come out, lower AMH. If your AMH is being suppressed because of the birth control pill, because it's decreasing the activity of those granulosa cells, you might get a low AMH value when you've been on the birth control pill for a long time. That is completely reversible, but it can be significant. So if somebody is wanting to get an AMH level, let's say somebody comes to my clinic, they're not trying to get pregnant, and they're on the pill, and they're considering freezing their eggs, so we're going to check their ovarian reserve. If we draw it, I always say this, "AMH may be up to 30% lower in somebody who is on the birth control pill." So we can still draw it, and if it comes back in the normal range, we feel good. But if it does come back low, we're going to have to make a decision. Are we going to stop the birth control pill for a period of some months, use alternative contraception if you don't want to be pregnant, and then repeat this test to see if this is a true low? Because we do see that young women do have low ovarian reserve sometimes. Or was this just suppressed because you were on the birth control pill? So we see it impact some of the hormone testing that we can do, and I think that's an important distinction, and we can see that the longer you take it, that potentially it might actually improve your fertility if you had underlying endometriosis or some medical conditions that we see associated with infertility. So prolonged pill users can potentially improve their fertility versus people who are trying to get pregnant that same age who were not on the pill. Those studies are complicated, right, because of selection bias, because if you've been on the pill for 10 years, you're a little bit older, so is it that they were preventing pregnancy and the other group potentially had some exposure, so they were inherently more infertile than the group that was on the pill? But we do know that the pill doesn't cause infertility, and I use it all the time. All the time in IVF cycles, we put people on the birth control pill because we can actually synchronize that group of eggs that comes out of the vault to grow together, because your body doesn't want to have 20 babies at one time, right? And what we're trying to do with IVF, get 20 eggs to grow, if that's what's out of the vault, really goes against the check and balance of the human body to not have 20 babies at once.

12. 42:42 – 46:11

    Spermatogenesis & Testosterone; Heat: Ovaries vs Testes

    1. NCDr. Natalie Crawford42:42

    2. AHAndrew Huberman42:42

       Why is it that males who take testosterone, synthetic testosterone, it shuts down their own testosterone production and sperm production, but females who take estrogen in the form of birth control pills, it doesn't shut down estrogen production by the ovaries?

    3. NCDr. Natalie Crawford42:56

       So I love this question. You know the answer, so I like it extra because I know you're asking.M- spermatogenesis is a constant and ongoing process, right? So in women, you're born with all the eggs you're ever going to have, and what we're talking about is if we stop FSH at that moment, we're just impacting the ability to ovulate at that time, but we're not changing this constant loss throughout the vault. Spermatogenesis, right? The sperm is made every single day, you're making brand new sperm, so 72 days for the sperm to be created in the testes and 18 days to find their way out the ejaculatory system, and so exposures that you have that stop the production of FSH and LH inhibit the development, the creation of new sperm. So somebody who's been on testosterone will tell the brain, the brain doesn't know as from you're taking it, it says, "Hey, we have plenty of sperm, we're good, we don't need anymore." So the brain then gets suppressed and doesn't make that FSH and LH, therefore not stimulating both further testosterone production, 'cause you don't need that, but testosterone production and sperm production go hand-in-hand, so therefore you're no longer making new sperm. And in fact the longer you're on testosterone, the harder it may be to get sperm production to come back and in 25% of people, they may not get it back if they've been on prolonged testosterone exposure. So it's really because of what women will sometimes say is unfair, which is the fact that you're born with all these eggs and you run out of them. They accumulate, the wear and tear of your life, right? We see egg quality being a huge issue in female reproduction, yet men get to have new sperm every 90 days. They get to wash away whatever bad deeds they did and can change their lifestyle and their exposures and have very different sperm. But because of that same process, things that shut off the production of FSH/LH really impact sperm quite significantly.

    4. AHAndrew Huberman44:50

       You mentioned bad deeds, um, for sperm, um, not by sperm, I said-

    5. NCDr. Natalie Crawford44:56

       (laughs)

    6. AHAndrew Huberman44:56

       ... for sperm, um, and you know, we, we know that heat is, is a, uh, you know, a pretty dramatic insult to the, um, to the spermatogenesis cycle, um, saunas and hot tubs and whatnot, I, I did receive the question as to whether or not, um, heat exposure, saunas, hot tubs, et cetera, are they detrimental to ovulation or egg production in any way? I mean, obviously things are more internal in females, the ovaries are internal, but is there any evidence for that? I mean, the body does heat up.

    7. NCDr. Natalie Crawford45:24

       Yeah, there's no... It doesn't harm the ovulatory period or the ovaries, and just like we know, the reason why the testes are so susceptible is because they're supposed to be at a cooler temperature, that's why they're in the scrotum outside the body, that's why the testes are so susceptible to heat changes. But the ovaries being inside the body, they're not in the same way. Now when somebody's pregnant, important distinction, right, we know that the development, especially organ development of an embryo can be more sensitive to certain things and that heat exposure at that time, whether it's hot tub use or extreme fevers even can make a difference in development of a fetus. But when it's coming to the ovulatory cycle or hormone production, heat in the female doesn't make any difference.

13. 46:11 – 48:56

    Period & Pregnancy, Conception Window

    1. NCDr. Natalie Crawford46:11

    2. AHAndrew Huberman46:11

       Well, I want to be clear before I ask the next question that I don't want to r- be responsible for any unwanted pregnancies-

    3. NCDr. Natalie Crawford46:15

       (laughs)

    4. AHAndrew Huberman46:15

       ... but when I was in high school-

    5. NCDr. Natalie Crawford46:17

       (laughs)

    6. AHAndrew Huberman46:18

       ... they told us that women can get pregnant even while they have their period. Is that true? Seems like a lie based on everything you're saying. But I don't want anyone to run out and, um, test that hypothesis without having the facts first.

    7. NCDr. Natalie Crawford46:32

       So in general, if somebody has extremely regular cycles, then that's a complete lie. You can't get pregnant on your period. The reason why they tell us this is one, especially when you're younger, your period cycles tend to be irregular, they're not s- your body hasn't fully matured to have that regularity, and that we know that sperm do live in the reproductive tract for much longer than the egg does, so sperm can live there for up to five days. So if somebody did have a shorter period window, let's say their normal periods are going to be 24 days, they're ovulating on cycle day 10. If they have a regular period that's five or six days, they could potentially have intercourse the end part of that period, the sperm could live for five days and be right there when you have the egg en route. So it's not the most fertile time for sure, and in most people that is considered a time when you're not going to get pregnant, but especially when you're younger and you have more irregularity or in people who have a short cycle window, that might not be the case.

    8. AHAndrew Huberman47:37

       So by extension, um, can we conclude then that the most fertile time is going to be when sperm meets egg, let's, uh, save timing of intercourse for, uh-

    9. NCDr. Natalie Crawford47:47

       Yep.

    10. AHAndrew Huberman47:48

        ... uh, for the time being, but 'cause there's, can be a delay there, uh, when sperm meets egg, um, on obviously day of ovulation or day, uh, day after?

    11. NCDr. Natalie Crawford47:58

        Day of.

    12. AHAndrew Huberman47:59

        Day of?

    13. NCDr. Natalie Crawford47:59

        The egg lives for 24 hours. So the egg can only be fertilized for 24 hours while it's in the fallopian tube. Once the egg has entered the uterus, it can't be fertilized anymore. So it has this very short window of time where it will allow sperm to enter it. Now sperm can live for five days, so we'll say the fertile window is this five-day period ending on the day of ovulation. You will hear a lot of us, a lot of doctors say the day after ovulation because do you really know exactly what time you ovulated on and if the egg has 24 hours, then that extra day could potentially be helpful? But really, it's five days ending on the day of ovulation, and people with very regular cycles or who can track them and they know when that ovulation is happening, the day before and the day of ovulation, those are the two top-hitting days. So if you're kind of not in the mood to have lots of sex, those are going to be the days you target to have the highest chance of conceiving.

14. 48:56 – 51:33

    Estrogen, Libido & Ovulation; Mittelschmerz

    1. AHAndrew Huberman48:56

       And what is the relationship between estrogen, libido, and ovulation in females?

    2. NCDr. Natalie Crawford49:00

       The higher your estrogen is, the m- increased libido that you're going to have, and of course you see those peak estrogen levels which are going to trigger that LH surge. So the body is made to get pregnant. You're going to have that peak estrogen, that peak libido right before and right at that ovulatory time period so that hopefully you also want to have intercourse and get pregnant.

    3. AHAndrew Huberman49:23

       I've heard before, let's just say-

    4. NCDr. Natalie Crawford49:25

       (laughs)

    5. AHAndrew Huberman49:25

       ... that some people (laughs) have to be careful here-

    6. NCDr. Natalie Crawford49:27

       (laughs)

    7. AHAndrew Huberman49:28

       ... um, uh, can sense the, literally the deployment of the, of the egg, the o- the ovulation. They, they report that they can feel-

    8. NCDr. Natalie Crawford49:36

       Yeah.

    9. AHAndrew Huberman49:36

       ... that this, let's just say, the, the departure of the, of the, uh, egg. Um, is that an imaginary thing?

    10. NCDr. Natalie Crawford49:44

        No, no, no. That's very real.

    11. AHAndrew Huberman49:45

        I mean, it's like I always liked, I always liked that image that people can know when that happens, right?

    12. NCDr. Natalie Crawford49:48

        It's so real, it has a name.

    13. AHAndrew Huberman49:48

        I mean, after all, men generally know when, when their, um, when their sperm are, are leaving their body. Let's hope they do. Um-

    14. NCDr. Natalie Crawford49:55

        (laughs)

    15. AHAndrew Huberman49:55

        ... but, um, why wouldn't th- there be an internal sense for, for women also o- of what's going on? I mean, we have interoception. There's a ton of nerve enervation of that area, but-

    16. NCDr. Natalie Crawford50:06

        It doesn't communicate to the brain excellent as far as tracking to where that sensation is. But you're right. I already said ovulation is the rupture of a cyst, right? It is rupturing, and the egg is being released, and those follicular fluid is also exiting and going into the peritoneal cavity. And so there is a group of women who can feel that, especially people who are very in tune with their body, and it has a name. It's called mittelschmerz. The pain almost feels like a crampy pain that happens in the middle of the cycle, and that is your ovulatory pain.

    17. AHAndrew Huberman50:41

        Oh, interesting. What is it called?

    18. NCDr. Natalie Crawford50:42

        Mittelschmerz.

    19. AHAndrew Huberman50:43

        Okay, we'll put that in the show note captions-

    20. NCDr. Natalie Crawford50:45

        Yeah.

    21. AHAndrew Huberman50:45

        ... and whoever does it is going to have to s- uh, get-

    22. NCDr. Natalie Crawford50:47

        (laughs)

    23. AHAndrew Huberman50:47

        ... the spelling right. Mittelschmerz. Amazing. Amazing. Um, amazing and foreign to me, but for obvious reasons, uh, but amazing. Uh, I'm always a- astonished in the, um, how incredibly well-orchestrated this whole process is. It's a, it's just a, such an incredible feat of biology. Just, I mean, the number of things that have to be timed correctly and the use, and I don't want to say reuse, but the, the repurposing of tissues for different things, and like, it's, what a, what an incredible dance. It's just amazing.

    24. NCDr. Natalie Crawford51:19

        It's beautiful. I mean, I'm so nerdy because I just love how everything has to communicate just perfectly. It makes you in awe of all the pregnancies that just happen, just all the time, because really things have to synchronize really at the wonderful time period.

15. 51:33 – 55:03

    Tool: Intercourse Timing & Conception; Artificial Insemination, IVF

    1. NCDr. Natalie Crawford51:33

       And even though this isn't what we're talking about, I've heard you say this, so I want to say this. People always ask every single day, "Well, how much sex should you have? When should you have sex? Is there too much sex?" And what we know is that you definitely should not decrease your sexual intercourse interval. So if you are in a relationship and you are sex everyday people, have sex every day. You will 100% hit intercourse throughout your entire fertile window on the day that you ovulate. You're depositing the same sperm there because you're not generating new sperm. It's whether the load went half and half and half and half, or if it went in, you know, one big group. But if you're constantly putting more sperm out there, you have a higher chance. And so studies go back and always say daily intercourse is associated with the highest chance of fecundability, especially during the fertile window. However, for couples who are not sex everyday people, that idea can cause a lot of stress. Stress, of course, impacts the system in a lot of different ways. It can also cause sexual burnout where they no longer feel like being intimate or having sex on the day they're actually ovulating because they've been doing it this whole time leading up. And that's where the time period of saying have sex every other day throughout the fertile window, so starting five or six days before you think you're going to ovulate, and then try to target having intercourse on the day before and the day of ovulation. And the reason why people said every other day or a few days prior, to kind of get some sperm exposure there in case you ovulated early, but really to try to prevent some of that increased stress that can happen when you're trying to conceive, especially if you have programmed or timed intercourse that needs to happen on an everyday interval. But the odds of getting pregnant by saving up sperm for two or three days, that's not higher.

    2. AHAndrew Huberman53:26

       I'm curious then why if, let's just say hypothetically, someone is, um, donating or freezing sperm or doing IVF, why they instruct the male to, um, not ejaculate for 48 to 72 hours prior to, um, let's just say depositing sperm. It's such a funny word, um-

    3. NCDr. Natalie Crawford53:43

       It is.

    4. AHAndrew Huberman53:43

       ... but it works, so.

    5. NCDr. Natalie Crawford53:46

       Two points. One, if we're doing a semen analysis, now we're trying to evaluate the sperm, and any test has certain normal parameters, and these are all based on a 48 to 72 hour abstinence period. So yes, if you ejaculate more frequently, you're going to have less sperm, and that can be very normal. But if we're looking at a test with set normal parameters that are based on two to three days of not having intercourse, that's why we want you to do it for that. If we're doing, let's say, IUI or intrauterine insemination, also known as artificial insemination, or where we take the sperm and put it in a catheter and put it in the uterus, we're trying to get more players further down the field. In that case, I know when you ovulate because I'm timing it perfectly, and I am trying to get as many possible in this process, because we're not just having them deposited in the vagina. We're trying to get them further. So we want more because that's part of that treatment process. And similarly with IVF. I want to have as many sperm as possible to sort through and pick out the best looking, the most modal, the most normally shaped ones, so we're trying to get just a better sample, and by having these normal guidelines, we're able to judge this is low for what it should be, which can also be a clue to other problems.

16. 55:03 – 1:02:20

    Egg/Sperm Quality, Cigarettes, Vaping, Cannabis & Alcohol

    1. AHAndrew Huberman55:03

       I definitely want to talk about chemistry, both, um, sort of interpersonal chemistry and literally, uh, ejaculate and vaginal chemistry. But before we do that, um, I'm curious whether or not we can just touch on a few of the things that a lot of people wonder about in terms of egg quality, and if they touch on sperm quality, maybe we can also just mention that. Um, but for instance, um...... does cannabis, either by edible or by smoking cannabis, impact ed quality in either direction? Uh, alcohol would be the next. And then, I'm going to assume, and I have to do this, uh, strictly because of what I understand about, you know, drugs of abuse like cocaine and amphetamine, methamphetamine, that none of those can be good for systems of the body because they provide, they create so much stress for the body. Um, but let's just say alcohol and cannabis. Um, I read a statistic when researching the episode on cannabis that shocked me, which is that 15%, 1-5, percent. Not 1.5. 15% of American women, s- at least in this one study survey, reported having consumed or smoked cannabis during known pregnancy, which is wild.

    2. NCDr. Natalie Crawford56:19

       Wild.

    3. AHAndrew Huberman56:20

       Unless, of course, I'm just naive and THC is not harmful to the fetus, but I have a hard time believing that. So what gives? I mean, we, here we're t- and, and there I actually just threw in fetal development.

    4. NCDr. Natalie Crawford56:34

       (laughs)

    5. AHAndrew Huberman56:34

       So is cannabis, is alco- alcohol bad for egg quality?

    6. NCDr. Natalie Crawford56:39

       So they're different things and they're the same thing in one, so let's answer them each individually. So we'll go with the one that everybody knows and has accepted now that they wouldn't have accepted 40 years ago, right? Smoking cigarettes. So that's obviously bad. Decreases the number of eggs you have in the vault. Smoking cigarettes actually gets into your vault, decreases the number that you have. You have a higher chance of going into menopause earlier, and it increases the risk of having abnormal chromosomes, which is what we really think about when we think about egg quality, right? Impacting those meiotic spindles inside the eggs which hold the chromosomes in their perfect position. They are associated, they get wear and tear from things that cause inflammation or are toxic. So cigarette smoke, we know decreases egg quality, egg quantity, increases miscarriage, and then of course has fetal impacts.

    7. AHAndrew Huberman57:25

       Could I just ask you-

    8. NCDr. Natalie Crawford57:26

       Yes.

    9. AHAndrew Huberman57:26

       ... because, uh, when we talk about s- um, s- there's nicotine, which itself is not carcinogenic, and then there's the smoking process which brings in a bunch of other things. The, the question I know is burning in everybody's mind is vaping.

    10. NCDr. Natalie Crawford57:38

        Yeah, let's-

    11. AHAndrew Huberman57:38

        Right? Because vaping is f- I, I'm, I'm very bullish on this. I mean, it's very clear that the chemicals associated with vaping are just oh so bad for everybody's health. But it's distinctly different from saying that nicotine is bad-

    12. NCDr. Natalie Crawford57:51

        Correct.

    13. AHAndrew Huberman57:52

        ... for one's health. And it can be, but, um, without doing too much of a deep dive, is, are there any data that show that vaping is bad for egg quality?

    14. NCDr. Natalie Crawford58:00

        Of course there's not as much data because it just hasn't been around as long. But yes, vaping definitely has chemicals that looks like it's associated with poorer success rates in IVF cycles. And that's really kind of one of the most finite measures of egg quality we can see, because we're really testing the egg at a level in a lab versus just, are you getting pregnant naturally?

    15. AHAndrew Huberman58:21

        And s- sorry to interject again, but any time a conversation like this comes up, especially between two people in the health science space, um, there are these shouts, 'cause I hear them, literally, where people say, "Well, listen, I vaped-"

    16. NCDr. Natalie Crawford58:34

        Oh, yes.

    17. AHAndrew Huberman58:34

        "... every day and I've had three healthy babies." And I think that my response is always, "Okay, there's going to be a distribution of responses. And then of course, how much healthier could your babies have been-"

    18. NCDr. Natalie Crawford58:45

        Have been.

    19. AHAndrew Huberman58:45

        "... had you not vaped during pregnancy or vaped prior to pregnancy or?"

    20. NCDr. Natalie Crawford58:48

        Well, sure, at least-

    21. AHAndrew Huberman58:48

        I mean, I think these are the, the key issues that, like, you can't, you can't rewind the clock, as far as I know, right? In the absence of a time machine, you can't rewind the clock. So, um, I mean, basically everything you're saying is that smoking cigarettes or vaping nicotine just can't be good for egg quality.

    22. NCDr. Natalie Crawford59:04

        We know that.

    23. AHAndrew Huberman59:04

        Okay.

    24. NCDr. Natalie Crawford59:05

        We know that it's not good for getting pregnant. We know that it's not good for sperm, and therefore we also know it's going to impact pregnancy rates. You know, things like cannabis, right, decreases sperm production, decreases sperm motility, changes sperm morphology, the shape of it, changes the DNA, in- increases the fragmentation of the DNA. If your partner uses cannabis and you get pregnant, you have a higher chance of miscarriage because of the sperm association with the cannabis. Now-

    25. AHAndrew Huberman59:34

        Edible cannabis as well as smoke cannabis-

    26. NCDr. Natalie Crawford59:35

        I don't know, right?

    27. AHAndrew Huberman59:36

        Yeah.

    28. NCDr. Natalie Crawford59:36

        Because you can't study something that's illegal, so a lot of this data is just more new and a lot of it's going to be observational.

    29. AHAndrew Huberman59:43

        And in states like Colorado and California where, you know, cannabis is essentially legal-

    30. NCDr. Natalie Crawford59:47

        Mm-hmm.
17. 1:02:20 – 1:03:29

    Sponsor: InsideTracker

    1. NCDr. Natalie Crawford1:02:20

    2. AHAndrew Huberman1:02:20

       I'd like to take a quick break and thank our sponsor, InsideTracker. InsideTracker 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 assessed with a quality blood test. The problem with a lot of blood and DNA tests out there, however, is that they'll give you information about certain lipid markers or hormone markers, but no information about what to do with all of that data. InsideTracker makes it very easy to look at your levels of hormones, metabolic factors, lipids, et cetera, and then to assess what sorts of behavioral, nutritional supplementation, or perhaps other interventions you might want to use in order to bring those numbers into the ranges that are optimal for your health. InsideTracker's ultimate plan now includes three new hormone markers that are critical to measure during a woman's reproductive and menopausal years. These are estradiol, progesterone, and thyroid-stimulating hormone. If you'd like to try InsideTracker, you can go to insidetracker.com/huberman to get 20% off any of InsideTracker's plans. Again, that's insidetracker.com/huberman to get 20%

18. 1:03:29 – 1:10:00

    Intrauterine Device (IUD), Depo-Provera & Fertility

    1. AHAndrew Huberman1:03:29

       off. When we were talking about birth control, I unfortunately moved us forward and, and forgot to ask about IUDs.

    2. NCDr. Natalie Crawford1:03:37

       Oh, yeah.

    3. AHAndrew Huberman1:03:37

       So, uh, my understanding is that the copper IUD works by creating a sort of, um, not actually electric, but a kind of a electric, um, fence that kills sperm. Like, sperm don't like copper-

    4. NCDr. Natalie Crawford1:03:49

       I love that analogy. Yeah, I love that one.

    5. AHAndrew Huberman1:03:50

       (laughs) Sperm don't like copper, copper likes to kill sperm. Um, there, there's some interesting, uh, history. I've been reading a lot on the history of medicine of, um, people who, you know, for whatever reason were forced into or chose to be in the, the sex trade, pro- prostitutes using, um, inserting copper coins into their vaginal tract to try and, uh, kill sperm-

    6. NCDr. Natalie Crawford1:04:09

       Kill sperm.

    7. AHAndrew Huberman1:04:09

       ... but to varying degrees of success. Uh, obviously, there's a whole, um, socioeconomic landscape around that, so, um, I think it's obvious what I'm referring to. But, um, very interesting, but that's just one form of IUD.

    8. NCDr. Natalie Crawford1:04:21

       Yeah.

    9. AHAndrew Huberman1:04:21

       Right? There, there are some other, other IUDs, and then there's of course the ring. We didn't talk about that, so maybe we can just touch on a few of those in, within the context of whether or not it alters egg quality and/or future fertility when one takes the ring out, takes the IUD out.

    10. NCDr. Natalie Crawford1:04:36

        This is a great question because a lot of people don't know this, and, and I'll roll through a few of the top birth control methods in just thinking through. Copper IUD, as you already said, no hormonal involvement. It causes inflammation and a toxic environment inside the uterus, isolated. Does cause sometimes heavier periods, but they should still be regular. If they are irregular, that's a sign of a hormonal issue because you still ovulate with the copper IUD.

    11. AHAndrew Huberman1:05:00

        Is it literally a copper wire woven into the tissue of the uterus?

    12. NCDr. Natalie Crawford1:05:03

        Yeah, well, the, so the IU- well, the IUD is a, is a little T-

    13. AHAndrew Huberman1:05:04

        Mm-hmm.

    14. NCDr. Natalie Crawford1:05:05

        ... and the arms are, have copper wires wrapped around them.

    15. AHAndrew Huberman1:05:08

        And they, and those are, they grow into the uterine lining?

    16. NCDr. Natalie Crawford1:05:11

        They don't grow into the uterine lining. The IUD just sits in there, and just the presence of that copper causes that inflammatory reaction and that toxic environment.

    17. AHAndrew Huberman1:05:19

        And is it toxic to the environment in ways that are detrimental to the woman or just to sperm?

    18. NCDr. Natalie Crawford1:05:25

        Both. I mean, implantation is not going to occur likely, right? I mean, no, nothing is 100% successful, but it's much harder for an embryo to implant within that highly inflammatory environment.

    19. AHAndrew Huberman1:05:36

        To me, amazing that people figured this out before the advent of, like-

    20. NCDr. Natalie Crawford1:05:39

        Oh, it's fascinating.

    21. AHAndrew Huberman1:05:40

        ... laboratories, right? (laughs)

    22. NCDr. Natalie Crawford1:05:42

        Right? Let's just put some copper in some uteruses and see what happens.

    23. AHAndrew Huberman1:05:45

        Right, and, uh, you know, it, uh, it really speaks to the, the urgency that must have existed to preventing pregnancy and the, the just how costly biologically and-

    24. NCDr. Natalie Crawford1:05:53

        A pregnancy is, right?

    25. AHAndrew Huberman1:05:53

        ... financially a pregnancy is.

    26. NCDr. Natalie Crawford1:05:55

        And pregnancy's not health neutral, so it is something that somebody needs to be in, of right health or it can be a deadly circumstance. When we get back to other IUDs, so IUDs that more people are more familiar with are the progesterone-based IUDs. This is going to be Mirena, Kyleena, Lileta. They have a bunch of different names based on the amount of progesterone and how long they last for. These work mostly by thinning out the uterine lining. As we already said, progesterone compacts the uterine lining to prepare it for implantation in a normal cycle, but if you have constant exposure to progesterone, what is going to happen is it's going to prevent the uterine lining from growing, and it gets it very, very thin. Not all IUDs, in fact, most of them don't prevent ovulation. Only in about 50% of people do they actually prevent ovulation, so their main mechanism of action is this endometrial effect. When you remove the IUD, especially if you're already ovulating, no problem. The problem we do see in some people with progesterone IUDs that maybe isn't talked about as much is that this prolonged progesterone exposure, because people are putting IUDs in for five to seven years and not having a period for that length of time because the endometrium has become so atrophic or nonexistent that you're no longer bleeding despite the fact that you may be ovulating. It can take a while for that lining to grow back, and so it's not uncommon to have an IUD in place, and if you have no period, you're going to say, "This is great. I don't have a period. Wonderful." You get it removed, and now your period hasn't come back, and that leads people to sometimes be concerned that the IUD's causing them not to ovulate or they have this...... infertility caused by the IUD, but really what it is, is that the linings become so, so thin that it can take many months of that unopposed estrogen exposure in the follicular phase to get it thick enough to finally bleed when you're ovulating. So, I do tell people if they have a progesterone IUD to get it removed three to six months before they want to get pregnant, use some other form of contraception, but give their body time to make sure they have that regular period pattern back. Important distinction, if you're still ovulating and having a period on an IUD, then this is going to be less of a concern, because if you're growing enou- enough of a lining to then shed it, we're less worried about it. But if you are amenorrheic or have absence of your periods with an IUD, we need to think about removing it for a period of time before you get pregnant so that your body can grow that lining again. When it comes to some of the other things that you mentioned, one I- you didn't ask that I want to mention is the Depo-Provera shot. The Depo-Provera shot is a high dose of progesterone, high enough to actually prevent ovulation. So in that circumstance, you are not ovulating and therefore, if you don't ovulate, you're not going to get pregnant. Depo-Provera is proven to prevent ovulation for three months. So when you take it, you need to get it every three months to have a proven contraceptive benefit. However, it can last in your system for 18 months and prevent ovulation for up to 18 months. So I will see people who liked that option for contraception and now they haven't had a period in a long time, but their last Depo shot was six months ago, and they're all frustrated by the fact when I tell them, "Well, you still may not have another period for a year plus because this high level of progesterone that you've already injected into your system can last a substantial amount of time." So, that is a contraceptive option that I tell people to discontinue a year and a half to two years before they want to get pregnant, which sometimes people don't know that yet. And so that's something that can be a contraceptive option for if you're very remote from wanting to have a child, but in people who are in their childbearing years contemplating family building soon, that is not my favorite option.

    27. AHAndrew Huberman1:09:59

        So,

19. 1:10:00 – 1:19:39

    Birth Control Risks & Benefits, Cancers, Polycystic Ovarian Syndrome (PCOS)

    1. AHAndrew Huberman1:10:00

       you haven't mentioned, because I haven't asked, um, any negative consequences of birth control of any kind. A- and I'm not encouraging you to if you don't believe in them, I know they-

    2. NCDr. Natalie Crawford1:10:11

       Oh.

    3. AHAndrew Huberman1:10:11

       ... this is a very controversial, um, topic, but, um, you know, one of the more popular studies discussed on social media is one that I- I've spent some time with the paper, um, and a few of the papers that stemmed from it. Um, not a huge study, but describing that how women rate the faces of men as either more... Essentially what happens is there- there seems to be, at least in this study, a, uh, there was a, uh, statistically significant, um, bias, uh, for women to select particular male faces as attractive and those male faces tended to be of the more, you know, square jaw, A.K.A. masculine features, right? I- in air quotes, right? This is what the study, um, found, um, but that when women were on oral contraception, presumably estrogen, progestin type oral contraception, that that effect, um, was smeared. They had a, not a statistically significant tendency to, uh, choose the quote unquote more masculine faces. I have to be very careful with my language here because, you know, it's easy to get description of a study like this wrong. And that has led a lot of people to think that birth control is gonna throw off their partner choice. Um, now of course, it is a small study. Um, studies like it are, are not always so well controlled. Um, but is there any evidence that birth control, oral- oral estrogen, progestin based birth control, just to keep it specific, can increase rates of cancers, can decrease rates of cancers, can lead to, um, any sorts of disruptions in, um, bodily, uh, function or health? Th- that's really like a rock solid result that's been seen by multiple studies, clinical trials, um, or are we still just in the dark about a lot of this stuff?

    4. NCDr. Natalie Crawford1:12:00

       Okay, so nothing is without risk. Getting pregnant is not without risk, taking the birth control pill is not without risk. We do see that there's been a lot of not informed consent in people who are taking the birth control pill, meaning maybe they weren't educated about what all of their options were, the positives and the negatives about each one of them. If we're gonna reference the convo to the pill, estrogen, progesterone pill, important to understand that neither the estrogen nor the progesterone are the same estrogen, progesterone that your ovaries make, right? It's ethinyl estradiol, which your brain interprets as an estrogen, but other parts of your body may not. And then it's various types of progestins, some of which have even androgenic or male hormone-like properties, and some of which do not. So there's a ton of variation, even the amount of ethinyl estradiol that each pill has with your low-low and your low pills having less, and even with the modern day average pill having a lot less estrogen than it used to. When you're on the birth control pill, your ovaries aren't making estradiol, and that estradiol is important in growing the uterine lining, but also for the genital structures. And so we think about vaginal health and vulvar health, we certainly see that especially with continuous use. So if we distinguish you take the pill for 21 days and you have a seven day break where you might bleed, or you take sugar pills and then you take them again, a lot of people now are taking continuously where you have exposure to these-... compounds every single day.

    5. AHAndrew Huberman1:13:36

       Ah, so in the, in, like, the, the, um, the wheel, the little-

    6. NCDr. Natalie Crawford1:13:40

       Yeah.

    7. AHAndrew Huberman1:13:40

       ... little pouch with the wheel of different colored pills, um, may have seen these on the, on the counter shop in previous relationships. So they, (laughs) um, and then there's th- the ones that sometimes people just opt not to take.

    8. NCDr. Natalie Crawford1:13:50

       Yeah.

    9. AHAndrew Huberman1:13:50

       Because those are the pl-

    10. NCDr. Natalie Crawford1:13:51

        The placebos.

    11. AHAndrew Huberman1:13:51

        Not the placebo.

    12. NCDr. Natalie Crawford1:13:52

        They are. They're sugar pills.

    13. AHAndrew Huberman1:13:53

        They're the sugar pills. So like that, there's no need to take estrogen during that phase.

    14. NCDr. Natalie Crawford1:13:56

        Right.

    15. AHAndrew Huberman1:13:56

        And then, and then they repeat. Is that-

    16. NCDr. Natalie Crawford1:13:58

        Exactly.

    17. AHAndrew Huberman1:13:58

        Okay. But some people are taking estrogen all-

    18. NCDr. Natalie Crawford1:14:00

        Continuously.

    19. AHAndrew Huberman1:14:01

        ... all the way around the dial.

    20. NCDr. Natalie Crawford1:14:01

        It's very common right now.

    21. AHAndrew Huberman1:14:02

        Yeah.

    22. NCDr. Natalie Crawford1:14:02

        So people ... And they're not wrong. They say, "Oh, well, why have a period and these little breaks? It's not really a reflection of my hormone status," which is accurate, and so they're taking them continuously. You also have less pill failure pregnancies. So if you're using the pill for contraception, that can be a great strategy. But the longer you take them, we do see some vaginal vulvar changes, right? And so atrophic vaginitis, people who notice increased sensitivity, decreased elasticity, increased discomfort with intercourse, increase in, like, yeast infections, that can sometimes be seen because that environment is different. Now, that's just one thing that can c- come from the pill. We also see the pill be life-saving for other people. They have terrible, you know, PMS or premenstrual dysphoric syndrome where their mental health when they change from high to low estrogen, it's always the change in estrogen that interferes, can cause some people to really have mental health issues that are so severe that having that stable hormone level is helpful. And so the pill can be extremely beneficial for some people when it comes to mental health, it can be beneficial for people who have issues with very heavy periods and anemia. Instead of getting blood transfusions, you know, taking the birth control pill might prevent the lining of the uterus from growing so much that they bleed so much. Same thing with fibroids, people with PCOS. PCOS is polycystic ovarian syndrome. If we want to put it very simply, you have a lot of eggs in your vault, so you release a lot of eggs every month, and what this does is the FSH signal gets diluted and so you're not responding to the normal signal and you don't ovulate. And because the ovary is a hormone-making factory, it gets really bored when it can't make estrogen, 'cause that egg's not growing, so it starts to make testosterone. So you start to see this androgen dominant environment associated with lack of ovulation and having a lot of follicles inside the ovary that are not really responding.

    23. AHAndrew Huberman1:16:00

        And the androgyniza- excuse me, androgenization of other tissues like, like body hair-

    24. NCDr. Natalie Crawford1:16:07

        Yeah.

    25. AHAndrew Huberman1:16:07

        ... deepening of voice.

    26. NCDr. Natalie Crawford1:16:07

        Body hair. Typically, the level of testosterone made in PCOS isn't truly deepening voice. It can if there is an ovarian tumor making testosterone or certain other conditions, but typically with PCOS you see increase in body hair, increase in acne, and you can see some even, like, male pattern balding, some temporal balding of women. So some hair loss.

    27. AHAndrew Huberman1:16:29

        Temporal balding.

    28. NCDr. Natalie Crawford1:16:30

        Yeah.

    29. AHAndrew Huberman1:16:30

        So like the wi-

    30. NCDr. Natalie Crawford1:16:30

        Yeah. Like right in the-
20. 1:19:39 – 1:24:50

    Blood Clotting & Birth Control Pill; Health Screening

    1. NCDr. Natalie Crawford1:19:39

    2. AHAndrew Huberman1:19:39

       Can I just, uh, interrupt there?

    3. NCDr. Natalie Crawford1:19:41

       Yeah, yeah, yeah. Go.

    4. AHAndrew Huberman1:19:41

       You know, I'm aware, um...... that a, a fair- fairly high percentage of people have, um, mutations in Factor V Leiden, uh, a clotting factor. Um, fewer people are, as we say, homozygous, have two deficient copies, uh, or mutant copies, I should say. Um, but there are many people out there that have one mutant copy of Factor V Leiden, and my understanding is that oral contraception in females, um, can really exacerbate the Factor V Leiden mutation. Do you suggest that people get, um, get their Factor V Leiden, um, genetics analyzed? I mean, it's pretty inexpensive to do, right? I think on a standard blood test you can just ask for the Factor V, um, analysis and it- it's not like a, a really in-depth thing. You don't have to fly to some esoteric-

Episode duration: 3:27:33