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Speaker A: 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 Doctor Natalie Crawford. Doctor Natalie Crawford is a medical doctor specializin... |
Speaker B: Thank you so much for having me. I'm honored to be here. |
Speaker A: 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 actua... |
Speaker B: 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... |
Speaker A: What are some of the other secondary sex characteristics that precede menarche? So you said breast bud development, and then breast development, on average, about two years before. |
Speaker B: About two years before you have sexual hair development. So actually, adrenarche 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. |
Speaker A: So genital hair, underarm hair, exactly, yeah. |
Speaker B: General hair, usually first and then underarm hair. |
Speaker A: And we're getting right down into the weeds here, which is good. A goal of this podcast is to normalize all aspects of health, including sexual health and reproductive health. Is that commensurate also with the development of body odor? Cause as a young boy who eventually hit puberty and became a young man, ... |
Speaker B: Right. |
Speaker A: In other words, boys start to smell stinky. |
Speaker B: 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. |
Speaker A: Do they reflect hormones themselves? |
Speaker B: Not the smell. The actual smell doesn't actually reflect levels of hormones or anything like that. It is just that youre 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 ma... |
Speaker A: The reason I asked that question is not to get people thinking about stinky smells, but, and by the way, some people love the musty smell of their own armpits or others. You know, we're referring to adults, by the way. But the reason I ask is that there's a wealth of data in animal models, including nonhuman... |
Speaker B: So there's mild evidence, and it's murky, because we also know that anything that could be an endocrine disruptor, which a lot of scents or fragrances are, also can accelerate the onset of puberty by disrupting part of this system. And so we know that toxins and, you know, scents and a lot of the world that ... |
Speaker A: How much younger? I've seen the various graphs for different countries, but can we say that ten years ago, on average, girls in the United States and northern Europe were hitting menarche at about, what, twelve to 13 years of age? |
Speaker B: We'll use menarche for the purpose of this. So having your period ten to 20 years ago, you will see most data would say, oh, 13 to 15 would have been the average age. Now we're really seeing it shift to be starting at ten to eleven and completing by 1314. Most girls are definitely going through the puberty c... |
Speaker A: That earlier puberty means that your growth spurt in terms of height is going. |
Speaker B: To be truncated, not the same. And you probably most men will say, oh, but I had my growth spurt after I started having some of the puberty change that happened, but because it is this estrogen related process in women that we see that growth spurt, really, your final height is within that year of when your ... |
Speaker A: Interesting. Yeah. This discussion is certainly not about me, but I was one of these. What I thought was kind of an odd duck. I hit puberty about 1314. Let's just say I knew I did, but I didn't shave until I was after college. My growth spurt between freshman and sophomore year, I grew a foot, right? So I wa... |
Speaker B: 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. So you lost them all those years before your peri... |
Speaker A: I think this is so important to highlight because it puts together what you said earlier about the loss of eggs. Even as a fetus, I think most people sort of assume that the reduction in egg count is due to ovulation and the fact that one egg ovulates typically, but that other eggs are deployed in that ovula... |
Speaker B: To the loss of eggs. |
Speaker A: To the loss of eggs. I think this is going to be very important for our discussion later about potential egg harvest, because I think some people have it in mind. |
Speaker B: There's a lot of misconceptions that you're losing eggs from your vault, and that's not the case. You're just accessing the ones outside. |
Speaker A: Gosh, so you're not. 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, freeze them for later if they want to use them, eggs or fertilized embryos, that one is not reducing their total n... |
Speaker B: Exactly. |
Speaker A: That's such an important point. I think a lot of people believe the opposite. |
Speaker B: That'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 going to menopause earlier. And it's explaining this process to them that your ovar... |
Speaker A: 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 addition than frozen as embryos. Is that right? |
Speaker B: 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 ... |
Speaker A: I think a good number of people are now going to head to the IVF clinic, I think, again, I really want to highlight this. 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 bas... |
Speaker B: Right. |
Speaker A: Okay. |
Speaker B: You're making the withdrawal no matter what. |
Speaker A: Great. Well, such an important point for people to know and propagate. Getting back to puberty a little bit later on, I wanted to get into endocrine disruptors and things of that sort. But since you brought it up, you know, I've heard things such as, okay, things like evening primrose oil, if mom is putting ... |
Speaker B: 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 m... |
Speaker A: It's interesting because there are some parallels to male fetal development, like the fact that you have these early organizing effects of hormones like dihydrotestosterone, which essentially stimulate the growth of the penis, but also then establish a propensity for hormones during puberty to activate growt... |
Speaker B: A lot of the shampoo. |
Speaker A: The ones that burn. |
Speaker B: Yes, the ones that tingle your scalp. Some people love them, though. Constant exposure is very different than a one time hand washing 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, b... |
Speaker A: What about cloth diapers versus non cloth diapers? I've heard that you have your very strong cloth diaper proponents, and that because they seem to feel or believe that non cloth diapers somehow contain things that can get into baby's skin. And maybe there's a bigger question here. Is baby skin more permeabl... |
Speaker B: I don't know that baby skin is more permeable. |
Speaker A: I don't either. To me, it seems like it'd be hard to imagine. It is. But babies do seem to have this incredible skin. Their skin is so smooth, and you want to squeeze their cheeks and all this kind of stuff. The idea they would be more permeable. |
Speaker B: I think it's more that their development is this time is very important and 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 childhood period of time, beca... |
Speaker A: Is there any evidence for breast milk versus formula in terms of impact on future reproductive development or reproductive status of a child? |
Speaker B: 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 dise... |
Speaker A: Okay, so if we're thinking about a young girl woman. Cause we're talking about puberty, right? So I don't know what the exact nomenclature is there. You know, my experience is I'll offend somebody no matter what. But a girl who undergoes puberty, right? So a young woman who's maybe 13 or so, so she's early t... |
Speaker B: 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. |
Speaker A: So any spotting even, would be considered day one. |
Speaker B: Okay, 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 immense. This is when you're ... |
Speaker A: When they have a lot of estrogen. |
Speaker B: Women feel good with estrogen because of. |
Speaker A: The relationship between estrogen and other neuromodulators, like dopamine, serotonin. 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? |
Speaker B: We definitely think that there'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 lo... |
Speaker A: The corpus luteum, as the name suggests, a corpus. It's like a body that's basically the. It's basically the corpse of what unsheathed the egg before. And what I find so amazing, I mean, biology is so beautiful. Instead of just taking that tissue and saying, okay, let's just discard this, or that becomes the... |
Speaker B: 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 impulses throug... |
Speaker A: I'd like to take a quick break and acknowledge one of our sponsors, athletic greens. Athletic greens, now called ag one, is a vitamin mineral probiotic drink that covers all of your foundational nutritional needs. I've been taking athletic greens since 2012, so I'm delighted that they're sponsoring the podca... |
Speaker B: Mostly. |
Speaker A: Mostly, yeah. Please correct me. |
Speaker B: Where I'm from, the follicle in which the egg grows, when you ovulate ruptures, the cyst bursts. A follicle is a cyst. A cyst is a fluid filled structure. Follicle is 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 ... |
Speaker A: Got it. |
Speaker B: 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 y... |
Speaker A: Okay, great. Thanks for that clarification. I get a lot of questions about birth control, but on my social media handles. |
Speaker B: Don't we all? Don't we all? |
Speaker A: To be clear, 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 prob... |
Speaker B: 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 ethanyl 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 t... |
Speaker A: 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? |
Speaker B: So I love this question. You know the answer. So I like it extra, because I know you're asking. 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... |
Speaker A: You mentioned bad deeds for sperm. Not by sperm. I said for sperm. And we know that heat is a pretty dramatic insult to the spermatogenesis cycle. Saunas and hot tubs and whatnot. I did receive the question as to whether or not heat exposure, saunas, hot tubs, et cetera, are they detrimental to ovulation or ... |
Speaker B: 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. B... |
Speaker A: I want to be clear before I ask the next question, that I don't want to be responsible for any unwanted pregnancies. But when I was in high school, they told us that women can get pregnant even while they have their period. Is that true? It seems like a lie based on everything you're saying, but I don't want... |
Speaker B: 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 your body hasn't fully matured to have that regularity. And that we kno... |
Speaker A: So by extension, can we conclude then that the most fertile time is going to be when sperm meets egg, let's say timing of intercourse for the time being? Cause there can be a delay there when sperm meets egg. On obviously, day of ovulation or day, day after day of day of, the. |
Speaker B: 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 fer... |
Speaker A: And what is the relationship between estrogen libido and ovulation in females? |
Speaker B: The higher your estrogen is, the 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... |
Speaker A: I've heard before, let's just say that some people, to be careful here, can sense, literally, the deployment of the egg, the ovulation. They report that they can feel, let's just say, the departure of the egg. Is that an imaginary thing? |
Speaker B: No, no, that's real. |
Speaker A: I always liked that image that people can know when that happens. |
Speaker B: It's so real. It has. |
Speaker A: I mean, after all, men generally know when they're. When their sperm are leaving their body. Let's hope they do. But why wouldn't there be an internal sense for women also, of what's going on? I mean, we have interoception. There's a ton of nerve innervation of. |
Speaker B: That area 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 ... |
Speaker A: Oh, interesting. What is it called? |
Speaker B: Middleschmirtz. |
Speaker A: Okay, we'll put that in the show. Note captions, and whoever does it is going to have to get the spelling right. Mendelschmirtz. Amazing. Amazing. Amazing and foreign to me, but for obvious reasons, but amazing. I'm always astonished in how incredibly well orchestrated this whole process is. It's just such a... |
Speaker B: 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. And even though this isn't what we're tal... |
Speaker A: I'm curious then, why, if, let's just say hypothetically, someone is donating or freezing sperm or doing ivf, why they instruct the male to not ejaculate for 48 to 72 hours prior to, let's just say, depositing sperm. It's such a funny word. It is, but it works. |
Speaker B: Two points. One, if we're doing a semen analysis now, we're trying to evaluate this sperm. And any test has certain normal parameters. And these are all based on a 48 to 72 hours abstinence period. So, yes, if you ejaculate more frequently, you're going to have less sperm, and that can be very normal. But if... |
Speaker A: I definitely want to talk about chemistry, both sort of interpersonal chemistry and literally ejaculate and vaginal chemistry. But before we do that, 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 quali... |
Speaker B: Wild. |
Speaker A: 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, here we and there, I actually just threw in fetal development. So is cannabis, is alcohol bad for egg quality? |
Speaker B: 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 i... |
Speaker A: Could I just ask you, because when we talk about there's nicotine, which itself is not carcinogenic, and then there's the smoking process, which brings in a bunch of other things, the question I know is burning in everybody's mind is vaping, right? Because vaping is. I'm very bullish on this. I mean, it's ve... |
Speaker B: 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 poor success rates and 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 th... |
Speaker A: And sorry to interject again, but anytime a conversation like this comes up, especially between two people in the health science space, there are these shout, because I hear them literally, where people say, well, listen, I vaped every day and I've had three healthy babies, and I think my response is always,... |
Speaker B: We know that. 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... |
Speaker A: Now, edible cannabis, as well as smoking. |
Speaker B: Right. 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. |
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