Dr. Peter Attia
speaker
5,258 appearances
36 recordings
6 series
first heard Jan 2024
last heard Jun 2025
Dr. Peter Attia’s voice in public audio — every appearance, attributed to the second.
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So maybe to extend the analogy, part of the reason why a woman during this period of time can experience these enormous surges of estradiol is if you think that there's, say, a kink in the gas line and you really, really want to squeeze the lever to get as much gasoline as you can in the car, sometimes you overshoot and just you get a whole bunch extra in there because there's volatility in the follicle release.
Yeah, no, I love it. The one other thing I want to talk about, because it's going to come up later when we get to HRT, is do you buy the argument, which is the argument I have found most appealing, as to why women have varying degrees of sensitivity to the dramatic reduction in progesterone that they experience in the last quarter? quarter of the cycle once the lining sheds.
So we talked about how, of course, during the luteal phase, we're building up. Progesterone levels are rising. We're building up the endometrial lining in preparation for pregnancy. Most of the times that's not going to happen. Lining sheds, progesterone crashes. This is what's referred to as PMS. And some women are somewhat unfazed by that. And other women, that's a big deal.
And so the question is, is this about central receptors of progesterone and varying degrees of sensitivity?
Okay, so we've established now what's happening. We've established that during the period of perimenopause, the one consistent thing that's happening is inconsistency. At some point, we get to the place where the consistency returns, but now it's a new norm. And that new norm is you don't make estrogen. You don't make progesterone.
The signal from your pituitary FSH and LH begin monotonically rising, rising, rising. And so if you were to do the blood work of a woman in her 60s who had never been placed on HRT, you would see a very high FSH, a very high LH, usually above the lab's cutoff for measurements, and then estradiol and progesterone non-existent.
Let's talk about all the reasons why that woman that I just described in her 60s, who is now 10 years out of any hormones, what are the risks to her physical health, mental health, emotional health, the whole picture of her health, cognitive health, everything? What is she worse off for at that period of time?
We talked about obviously the risk of dementia. We talked about the risk of osteoporosis, cardiovascular disease, colon cancer. All of these are risks that are pretty clearly going up in the absence of hormones. So do you want to talk about the history of HRT? I mean, it was a largely normal practice in the 1960s. They certainly had some fits and starts.
They initially were just replacing estrogen. figured out pretty quickly, i.e. within a few years, that if you only gave a woman estrogen, you were going to run the risk of endometrial cancer going up because the endometrial lining just continued to get bigger and bigger and bigger, and you eventually developed hyperplasia, which presumably became metaplasia and ultimately cancer.
We figured out pretty quickly how to combat that. If you just oppose the estrogen with progesterone, keep the endometrial lining in check, And this largely became the standard of care through the 1980s and into the 1990s. And this was largely validated by epidemiologic observations, which showed that women who took hormones did significantly better.
Now, people who listen to this podcast are well aware of how critical I am of epidemiology, and it's certainly very easy to make the case that in the 1980s, women who were taking hormones had a healthy user bias.
These are women that probably had better access to healthcare, they were probably more health conscious, and as a result, they were probably doing many more things to improve the quality of their health. The NIH did something that I think made a lot of sense. It was the right thing to do, which was they said, look, we can't rely on this epidemiology. We need to do a randomized control trial.
And they did it through something called the Women's Health Initiative, which had two components, a nutritional component that was asking a question about low-fat diets, and then a component that was looking at the HRT.
Would you like to pick up the story as to how the study was designed, maybe talk about some of the potential pitfalls of it, and ultimately how the results of that have been misunderstood and misinterpreted for so long?
So, Rachel, I don't know how good you are at sensing a person's blood pressure from across the room, but if you were able to sort of project your vision into my carotid artery... I see it bulging. Yeah, you'd notice that my blood pressure is up. I'm probably at 180 over 120 right now. First off, I think that was a remarkable, succinct summation of the WHI.
I'm only going to repeat a few things, not because I didn't think you did a great job. You did. But because sometimes hearing it twice highlights the egregiousness of this study.
Truthfully, I have friends, female friends, and I have patients who to this day are paranoid about hormones, and I just want to offer yet another opportunity for them to sort of understand what's going on. So this was a study that had two parallel arms, one where women without a uterus were just randomized to either this synthetic or equine-based estrogen or
versus a placebo, and then one where if you had a uterus, you got MPA, a synthetic progesterone, and the estrogen. As you pointed out, the elephant in the room here, the one finding that got all of the attention was that in the women with uterus group, If you got the synthetic progestin and estrogen, you had an increase in your incidence of breast cancer.
It turned out it didn't actually lead to any change in mortality from breast cancer, but there was an increase in the incidence. The number is really scary if it's given in relative terms. It was a 24% increase in the incidence. Incidence, for the listener, meaning getting breast cancer. You had a 24% higher chance of getting breast cancer if you took the two hormones.
On the surface, that sounds devastating, but again, as people who listen to this podcast know, we always need to think in terms of absolute risk. And relative risk doesn't mean that much if you don't understand absolute risk.
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