Dr. Peter Attia

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.

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.

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.

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?

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.

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.

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?

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.

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.

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.

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.