Good News for Your Menopause Brain: What Research Is Revealing

Transcript:

Jamie Forward:  Dr. Horst, you wrote a review paper in an OB-GYN Journal recently. Can you tell us a little bit about that paper and what you learned?

Dr. Karen Horst:  Absolutely. So, I was the lead author. I had two other authors, a colleague of mine who’s also a reproductive psychiatrist, and then also a gynecologist whose specialty is midlife women’s health. And the review article was entitled “Menopause and Mental Health,” and it was to help the OB-GYN community learn about how to meet their midlife women patients’ mental health needs. And so, there’s significant neuroscience, so it reviewed the latest neuroscientific findings regarding why women have such profound mental health changes during the menopause transition.

And those include, let’s see, on a cellular level, there’s a change in how our brain cells use energy, and there’s a change from using glucose to using ketones.

There is also just reorganization of the white matter and towards refinement, not necessarily loss. But my big message is the brain is under renovation during the menopause transition due to hormone change, and the hormone change most significant is the decrease in estrogen levels. Progesterone levels also are lower during the menopause transition, and those also impact things like anxiety and sleep, those changes.

But estrogen is very busy in the brain. There are estrogen receptors throughout the brain and estrogen modulates mood through modulating serotonin activity. It also modulates focus and executive functioning through its impact on dopamine and norepinephrine.

It also affects everything from temperature regulation – we all know about that because the most common symptom of the menopause transition is the vasomotor symptoms, and that is actually a brain phenomenon, the same neuron that is involved in the feedback loop between the ovaries and the brain, because the brain is what tells the ovaries how to ovulate, basically.

So, the brain sends hormones to the ovaries that then get the ovaries to go through a cycle of developing a follicle for ovulation. Those follicles and the ovary then produces estrogen and progesterone that is in the bloodstream, goes back to the brain through the bloodstream, and these specific neurons called KNDy neurons are the ones that are involved in this feedback loop.

Those KNDy neurons have a completely different job in thermoregulation, and so, they do double duty. So, when estrogen levels go down, and estrogen actually downregulates those neurons, when estrogen levels go down, these neurons get hypertrophic and overly stimulated, and they do too good of a job of regulating a temperature.

And that’s what leads to hot flashes and night sweats, because people are more sensitive to any temperature change.

Jamie Forward:  Wow. That’s very interesting.

Dr. Karen Horst:  Yeah, so that’s a fun fact. So, that’s just one thing about how important the brain is in menopause. And I say that because historically we thought menopause was a gynecological issue. We thought it’s about vaginal dryness, genitourinary syndrome, stopping having periods, heavy bleeding, that kind of thing. That’s what the medical community was focused on. And over the last 20 years, there’s been a ton of neuroscience research and psychiatric research that has really highlighted that early in the menopause transition, there are a lot of mood, cognitive sleep changes.

And those are actually early in the menopause transition way before a woman is having those classic later menopause, perimenopause, early post-menopause symptoms having to do with their cycles or even hot flashes.

And so, my heart or what I’m passionate about is educating the medical community and everyone that early in the menopause transition, as our ovaries start being unable to ovulate regularly because they’re literally running out of follicles that are ready to go, you have dysregulation of that feedback loop between the ovaries and the brain, and you have symptoms coming out of kind of chaotic peaks and troughs of estrogen and progesterone.

Peaks and troughs of estrogen, low progesterone. And those can occur in a woman’s early 40s. And I see a lot of patients in my clinic who have been referred because their gynecologist says, “It’s not menopause; you need to go talk to a psychiatrist.”

Jamie Forward:  Sure. Well, everything that you just explained sure is affirming, isn’t it? Well, thank you for that. So, in your review of this, did you find anything surprising?

Dr. Karen Horst:  Honestly, the most surprising thing is the history of the Women’s Health Initiative and how poorly it was interpreted by the researchers at the time, and how their decision to stop the study early because of signals they perceived that were actually non-statistically significant for the biggest one we now know of, which is a concern for hormone therapy, estrogen therapy specifically, and an increased chance of breast cancer diagnosis, they stopped the study and science basically froze for about 20 years.

There were other studies looking at impact of estrogen in – there was a big cardiovascular study in Europe, for example, that stopped when the WHI stopped.

And the biggest shocker is that the research looking at the outcomes of the women in the WHI 18 years later showed that there was actually a lower incidence of breast cancer and a lower incidence of all-cause mortality in women given estrogen therapy. And that goes against a dogma that is kind of – it’s so thought to be such a fact that I have to keep going back to the research to make sure I’m not making something up, because so many people think estrogen therapy increases your risk for breast cancer, and it’s way more nuanced than that.

Jamie Forward:  Yeah, wow, very illuminating.

Dr. Karen Horst:  Yeah. And the reason I get excited about that is because the most effective treatment for menopause-related symptoms is hormone therapy. There are other treatments and for women for whom hormone therapy is not an option out of choice or because of a personal history of breast cancer, specifically estrogen receptor-positive breast cancer. Not everyone needs hormone therapy and it’s not a fountain of youth either. But hormone therapy does address the mood changes. We’re still trying to figure out how effective it is for the cognitive changes. It helps just the myriad of symptoms that we talk about with perimenopause that you can look up, and it’s somewhere between 30 and 50 symptoms people can have because estrogen is a very busy hormone in the entire body.