Dr. Anna Cabeca explains the critical window theory of hormone replacement therapy, which suggests timing matters for how HRT affects cardiovascular health, bone density, and brain function. The Women's Health Initiative study shaped how doctors prescribe hormones, but newer research challenges those conclusions.
So there's a theory called the critical window theory of hormone replacement therapy. And I'm going to go through the exact science and where your doctors may be getting this information wrong. So the reality is we have to start with the Women's Health Initiative. So prior to the Women's Health Initiative, which was issued in 2002, hormone replacement therapy for women in menopause was standard of care. We're talking from the 50s, 60s, 70s, 80s and 90s and, and in fact, in most westernized countries, depending on the country you look at, between 40 and 70% of women were given hormone replacement therapy as standard of care through the menopause transition. Now, the Women's Health Initiative was a very poorly constructed study. The average age of the woman was 63. They were looking at long term cardiovascular risk and wanted to identify if hormone replacement therapy would reduce the risk of heart attack and stroke. So here's the thing, in order to do that, they must have enough time to show women going through a heart attack and stroke. So when they constructed this study, they picked women who were older. On average, the average age was almost 63 years old. These women were also smokers and ex smokers already had several cardiovascular risk factors that increased indicated they already had cardiovascular disease. They had high blood pressure, they had obesity, metabolic syndrome and diabetes. They inc actually went out and excluded healthy women from the study. Now this is important to know. If you're looking at hormone replacement therapy and the only people in the study already have cardiovascular disease, it is hard to pull apart how much the hormones had actions within the study and the actual participants themselves. So here's what the data really showed is they had three arms to the study. One group did nothing at all, no hormones. Another group actually did estrogen therapy only with a form of estrogen called Premarin. And the other group did a form of hormone replacement therapy called Premarin and medroxyprogesterone, which is a symptom, synthetic progestin. That's really important because it's the synthetic progestin that increased the stroke and heart attack risk in women over 65 or average age of around 63 that already had cardiovascular disease. And what they found was the women in the group that were taking medroxyprogesterone and the Premarin had a slight increased risk of stroke. That stuck stopped the study. Now what was true is the women that were actually on hormone replacement therapy showed a reduced risk of breast cancer, particularly in the group that was the women that were taking estrogen alone. Now, in the group that were on the medroxyprogesterone and the estrogen actually showed a slight, but not statistically significant increased risk of breast cancer. So here's the stats. What did it come to? All women at that age group have a 4 in 1,000 people chance of getting breast cancer. That's just the facts. Now, in that group that was on the medroxyprogesterone, they showed a 5 in 1,000 risk, not really statistically significant and could have easily been to chance. However, that's what happened in the media. That's what women were told. And overnight women were told that hormones were going to cause cancer or give them a stroke and stop hormone therapy, despite the fact that every single study prior to that showed hormone therapy to be protective and that it was standard of care for decades. And it was also considered treatment for things like osteoporosis. So one study, poorly done, ripped hormone therapy away from women. Now then we started looking at Thomas Therapeutic Window, and it's because we use the data in the Women's Health Initiative that we have a lot of confusion here. The reality is there are some real true science about starting hormone therapy earlier in the process. And actually it's better to start it before you're completely in menopause. And here's the reason why estrogen affects the entire body. It is a full body effect. Every single cell but two have estrogen receptors. So when we go through menopause and lose all of our estrogen, we actually see an increase in vascular. So this is your blood vessel inflammation, overall inflammation, metabolic changes that increase your risk for obesity and diabetes. We also see the loss of bone mineral density and bone bone strength because estrogen actually stimulates your bones to build. And probably even more importantly, we also see a radical change in the brain at this time. When we go through menopause, our brain actually increases the receptors for estrogen. So think of that as keyholes for the hormone estrogen to click into and think of that as the key. So that means the brain is so looking for estrogen that actually increases the number of estrogen receptors. So the brain is actually looking for that. But when you don't have estrogen on board, what happens is the brain starts to shrink. And the very important highways that go to the frontal lobe, which is where we have our deepest thought and also memory and critical thinking, those highways start to pull away from the frontal lobe. That's why you can't remember where your keys are. You can't remember the girl that you worked with for 20 years and you sat next to each other in the cubicles, but now you can't remember her name. You know what I'm talking about, right? It's because the brain remodels and, and so it is because of this process that we came up with a critical window theory. And like I said, it's not all theory. So the idea is, is the earlier you start hormone replacement therapy, particularly with estrogen, But I'm going to give you in the next segment why progesterone is so very important when we start that hormone therapy to support where your ovaries are no longer making enough. What we do is we stop the loss of bones by continuing to support your bone building efforts and reducing the bone reabsorption efforts, which are controlled significantly by estrogen. It also supports the brain to not shrink and lose some of those very important pathways to the memory and attention and focus centers of the brain. And it helps reduce inflammation and support, support the arteries and blood vessels which make us protected against cardiovascular disease. And actually women, until we go through menopause, are protected against heart disease compared to men. But within five to ten years of menopause, we actually age match men. So our risk actually exponentially goes up when we lose our hormones. So the critical window of best opportunity, this is really important, is going to be in that window of perimenopause to menopause or within a few years, because we get the best, most important benefits from it. However, that doesn't mean you can't start it later. Progesterone, which is the other hormone that's made by our ovaries when we're actually cycling, is on a steady decline from our, you know, late 20s, 30s, and is on a massive decline in our 40s. And by mid-40s, usually it is almost non existent. Right. That's why we have a hard time getting pregnant in our 40s because progesterone is no longer available. Now progesterone is really important. It helps the receptors so the keyholes in your brain for a, a neurotransmitter called gaba. So it is our natural anti anxiety neurotransmitter. So it's really important. So it helps keep you relaxed, it helps you sleep and get better, deep sleep. So progesterone is also really important to the brain and the body and even helps other parts of the body because it affects your cortisol and adrenaline as well. It is somewhat of the same pathway. And so progesterone is also equally important. So the next most important thing to understand is when do you start these? How do you know the biological impact and the actual timing for you individually? Because it's not one size fits all.
