The peri-menopause in a woman’s life: a systemic inflammatory phase that enables later neurodegenerative disease, 2020, Raval et al

Andy

Andy

Senior Member (Voting rights)
The peri-menopause or menopausal transition—the time period that surrounds the final years of a woman’s reproductive life—is associated with profound reproductive and hormonal changes in a woman’s body and exponentially increases a woman’s risk of cerebral ischemia and Alzheimer’s disease. Although our understanding of the exact timeline or definition of peri-menopause is limited, it is clear that there are two stages to the peri-menopause. These are the early menopausal transition, where menstrual cycles are mostly regular, with relatively few interruptions, and the late transition, where amenorrhea becomes more prolonged and lasts for at least 60 days, up to the final menstrual period. Emerging evidence is showing that peri-menopause is pro-inflammatory and disrupts estrogen-regulated neurological systems. Estrogen is a master regulator that functions through a network of estrogen receptors subtypes alpha (ER-α) and beta (ER-β). Estrogen receptor-beta has been shown to regulate a key component of the innate immune response known as the inflammasome, and it also is involved in regulation of neuronal mitochondrial function. This review will present an overview of the menopausal transition as an inflammatory event, with associated systemic and central nervous system inflammation, plus regulation of the innate immune response by ER-β-mediated mechanisms.
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Open access, https://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-020-01998-9
 
"This review will present an overview of the menopausal transition as an inflammatory event, with associated systemic and central nervous system inflammation..."

"Wearily I sit here, pain and misery my only companions. Why stop now just when I’m hating it?” –Marvin

FML. Me, Female, aged 45.
 
Neuroscientist Lisa Mosconi: ""For every man suffering from Alzheimer's, there are two women. So why is that?"

Great TED talk here.

Men have more testosterone, women have more estrogens. But what really matters here is that these hormones differ in their longevity. Men's testosterone doesn't run out until late in life, which is a slow and pretty much symptom-free process, of course.

Women's estrogens, on the other hand, start fading in midlife, during menopause, which is anything but symptom-free. We associate menopause with the ovaries, but when women say that they're having hot flashes, night sweats, insomnia, memory lapses, depression, anxiety, those symptoms don't start in the ovaries. They start in the brain. Those are neurological symptoms. We're just not used to thinking about them as such. So why is that? Why are our brains impacted by menopause?

Well, first of all, our brains and ovaries are part of the neuroendocrine system. As part of the system, the brain talks to the ovaries and the ovaries talk back to the brain, every day of our lives as women. So the health of the ovaries is linked to the health of the brain. And the other way around. At the same time, hormones like estrogen are not only involved in reproduction, but also in brain function. And estrogen in particular, or estradiol, is really key for energy production in the brain.

At the cellular level, estrogen literally pushes neurons to burn glucose to make energy. If your estrogen is high, your brain energy is high. When your estrogen declines though, your neurons start slowing down and age faster. And studies have shown that this process can even lead to the formation of amyloid plaques, or Alzheimer's plaques, which are a hallmark of Alzheimer's disease.
 
Is there evidence that women develop Alzheimers younger than men do? I thought the greater number of women suffering this had more to do with more men dying younger of other things before they get a chance to get Alzheimers. Maybe I'm wrong.
 
@Mithriel did you take any hormone replacement?

@Mij I've had to take Progesterone since I was 38 because I stopped making it, possibly because of taking the contraceptive pill.

Only by using bio identical progesterone cream could my insane periods be controlled.

I've wondered if I'll avoid the horrors of menopause because I'm already using a treatment which is now the preferred hormone treatment of informed doctors for menopausal women.

They don't give estrogen at all.

This research isn't reassuring. It's a pain in the... Brain, I suppose. Which is quite inflamed enough already.

Why stop now, just when I'm hating it? - Marvin.
 
Trish said:
Is there evidence that women develop Alzheimers younger than men do? I thought the greater number of women suffering this had more to do with more men dying younger of other things before they get a chance to get Alzheimers. Maybe I'm wrong.
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From what I can see in the literature you are probably right. Incidence at a given age seems to be the same for men and women overall, although studies in different countries vary (one in the UK put incidence higher in men). There are a lot of papers talking about reasons for dementia being skewed differently for men and women but I am unclear how good the evidence is and it does not affect the fact that the risk looks to be much the same for both sexes.
 
Squeezy, I never took anything like hormone replacement as I felt my ME was worse when I was taking a contraceptive.

However, I have taken clonidine to help my ME for many years and women are given it to help with hot flushes so that might have made a difference.

I hope it all goes well for you :)
 
Mij said:
And estrogen in particular, or estradiol, is really key for energy production in the brain.
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Maybe that explains why I have no energy and a rapidly deteriorating brain. I had my estradiol measured last year and it was so low that it was just reported as < 18 pmol/L - Range < 100 pmol/L. I got the impression they couldn't measure any more precisely than that when levels were so low.
 
the menopausal transition as an inflammatory event, with associated systemic and central nervous system inflammation, plus regulation of the innate immune response by ER-β-mediated mechanisms.
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I've had what seems to be ME/CFS for around 7 years, with the last two also going though the perimenopause (aged 53, 54). I find it hard to separate out symptoms into ME/CFS and menopause buckets. Really, the only thing I have noticed that I would say is definitely menopausal is that it's easier to put on weight, especially around the middle, and probably some hot flushes. I know some women have many more symptoms.

But, what I wanted to say is that I have not noticed any change in my ME/CFS symptoms. Things have not been noticeably worse. Actually, possibly I now get fewer migraines, as I'd typically get a migraine with my period. Sample of one, of course. But, if the menopausal transition is indeed an inflammatory event with central nervous system inflammation, that particular inflammation does not seem to impact on the illness I have. I also note that my CRP levels have been mildly elevated - in the 10 to 20 range - throughout the 7 years of my ME/CFS illness. My latest CRP measurement, just a month or so ago when I had an infection, was only 8. So, if CRP is an indicator of the kind of inflammation the authors are thinking of, perimenopause has certainly not elevated it.

I think the menopausal transition is an interesting natural ME/CFS experiment - how it changes ME/CFS, if at all, may perhaps shed some light on what is, and is not related to causal factors. So, it's worth thinking about it and talking about it. A longitudinal study of peri-menopause in women with ME/CFS may not be the highest priority research, but it would be a lot more useful than much of the ME/CFS research we currently see.
 
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I’ve found sage supplements to be of enormous help in dealing with hot flushes, I’m reluctant to take HRT for health reasons but I was seriously considering it because the hot flushes were so sever and exhausting and as I’m already very ill they were definitely having an impact on my ME. I started taking the sage and although it took about 3 weeks to work for me, it has completely eliminated them for which I’m incredibly grateful!

it also works for night sweats generally, my daughter takes it and it’s stoped hers entirely and has also helped another friend of mine who’s post menopause but was struggling with hot flushes again years after they’d stopped. Sage is also an anti inflammatory which is interesting given the subject of this thread. Thought I’d mention it just in case it helps someone else.
 
Amw66 said:
at the other extreme - given one of the female spikes for incidence is puberty - does the rise in estrogen in puberty have some significance re immune function that may contribute to onset?
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It wouldn't surprise me if there were some hormonal connection, even if it's not straightforward or universal.

Another N=1, of course, but my ME symptoms were always twice as bad in the week before my period, and my overall function been significantly better since menopause.
 
Hutan said:
I've had what seems to be ME/CFS for around 7 years, with the last two also going though the perimenopause (aged 53, 54). I find it hard to separate out symptoms into ME/CFS and menopause buckets.
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I've had ME since the age of 29 and I can definitely tell the difference since starting meno 5 years ago (53). Reduced stamina, immune system going haywire, weakness in my hands/wrists, full stop weakness when I climb stairs, mood swings etc. I would describe the weakness and loss of stamina with meno as being quite different from ME.
 
Squeezy said:
I've wondered if I'll avoid the horrors of menopause because I'm already using a treatment which is now the preferred hormone treatment of informed doctors for menopausal women.

They don't give estrogen at all.
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This depends on the individual. In the UK at least. They are certainly cautious about oestrogen especially in women particularly at risk of certain side effects.

Progesterone only won't cut it for some ladies.

Here's a useful website for the curious -
https://www.menopausematters.co.uk
 
Mij said:
Interesting. I'm the complete opposite!
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My periods were a nightmare from the day they started to the day they stopped, as an unexpected but very welcome 45th birthday gift.

Life used to come to a halt completely for the first two days of the cycle, as I'd faint from the pain if I tried to stand up. The build-up beforehand with a huge ME flare went on for about eight days, so basically I got to decent weeks out of every four! It might have helped if I'd been diagnosed with endometriosis at the time instead of at age 58 during a lower endoscopy (they found lots of adhesions), but I doubt treatment would have resolved it completely.

Even though I did get menopause symptoms for a few years in my late 50s, life's been a joy since! I'm able to live on a completely even keel, with the only negative effect being a noticeably worse memory. My hair's thinner, but that's no bad thing; it used to take ages to cut, style, and dry.
 
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