#1

A British study. HRT affect on Alzheimer’s only affects those with ApoE4 gene.

Alzheimer’s Disease (AD) is typically characterised by the build-up of abnormal proteins in the brain, including beta-amyloid (Aβ) and tau. A study conducted by Liverpool John Moores University (LJMU) found that average levels of a biomarker - phosphorylated tau by amyloid beta-42 - were similar across both HRT users and non-users.

However, alarmingly, they discovered that women using HRT who carried at least one APOE e4 gene had levels of the same biomarker over 60 per cent higher. The researchers concluded that these elevated biomarker levels likely indicate an increased risk of developing Alzheimer’s-related pathology, and thus dementia, in these women.

Interestingly, HRT was not linked to higher biomarker levels in the absence of the APOE e4 gene. LJMU suggests that if their findings are confirmed in further studies, it would imply that women with the APOE e4 gene variant should be advised against using HRT.

Counterpoint: Dr Marie Anne Ledingham, a consultant clinical adviser to NICE, commented in November: “The risks (of dementia) are very low in the population, and HRT can provide huge benefits at a very difficult point in many women’s lives.”

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#2

Alarming finding but –

No specifics about the study’s design, such as sample size, duration, type of HRT (e.g., estrogen-only vs. combined), or how biomarkers were measured.

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#3

How timely to see this. Last night my doc and I were discussing possible strategies to address my osteoporosis, and potentially increasing my estrogen was listed as a possibility.

I have one copy of ApoE4

He said more estrogen might be good due to my 2mm uterine lining blah blah blah (the rest sounded Greek to me). I don’t understand it at this point, but we will eventually be discussing this in more detail.

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#4

You want to have a thin uterine lining for postmenopausal women to reduce
Endometrial polyps/hyperplasia risk.

Once you start HRT, your lining may become thicker, but aiming for a thickness of less than 4 to 5mm is safer. @DrFraser ?

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#5

So you are right that HRT will cause some increased thickness in the endometrium, which is good, it may be as little as 2-4 mm in a postmenopausal woman not on HRT. The concern of being in the 4-8 mm range is in women not on HRT, as this is abnormal with no estradiol. However, during a normal cycle, premenopausal, the average is in the 8-10 mm, and late in the cycle commonly 15-16 mm.

So I’m not concerned with a 4-8 mm in a woman on HRT, if it were more than this, we’d either decrease the estradiol dose or increase the progesterone dose.

Additionally, on this topic, here is the link to the actual paper.
The data seems a bit murky and messy as a good number had use of conjugated horse estrogen and synthetic progestin instead of estradiol topically and micronized progesterone.

We have data that looks concerning for conjugated estrogens started late, but we have encouraging data for estradiol started early. There is lack of data on what most of us are prescribing now, but this data will grow and we’ll have to keep an open mind. Their outcome data also was biomarker based and not actually demonstrating an increased rate of dementia or MCI, which is what our real concern is.

I disagree with the point that Dr. Ledingham makes above - the % is huge both in those with ApoE4’s and if you live a bit longer, for ApoE3’s.

I tell women on HRT that I have no evidence it will lengthen or shorten their life, but we do know on average it improves quality of life.

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#6

Well said, @DrFraser. This meta-analysis (as well as those by Lisa Moscone’s well-funded team) often pull in and mix together studies of women using wildly heterogenous formulations of both E and P, many of which aren’t used today.

As I see it, HRT meta-analyses should clearly tease out implications for women on “modern” formulations in use today (which generally don’t show associations with cognitive harm).

Because they don’t, subsequent media reports tend to gloss over this important nuance, with the headline takeaway for laypeople being, “HRT is bad for cognitive health.”

This reminds me of the debacle where the Women’s Health Initiative was incorrectly interpreted to imply that HRT posed a serious breast cancer risk. Many years later, this false conclusion remains hard to overcome. What a shame.

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#7

Would spotting be a good sign or a bad sign then for postmenopausal women on HRT? There are advocates for women on HRT to have their period again.

Felice Gersh, MD, is the most aggressive one.

#8

@AVS You are absolutely right on what you’ve said, and the WHI, in my opinion caused significant harm to women - well more accurately, the doctors who looked at the data and didn’t understand the nuance, panicked and stopped Rx’ing HRT.
Horsey estrogen (e.g. Premarin) was the primary form of estrogen utilized (from Mare Urine) and that has significantly more potency than estradiol and cannot be compared. Also getting rid of oral use of estradiol is an important step with 100% of my patients being on patches or very rarely Biest (E2/E3) topically.
I don’t see any reason to induce periods with menopausal women, easy to do, but don’t see a risk reduction of anything with doing this.
Bleeding in post menopause without being on HRT warrants and ultrasound and endometrial biopsy.
When I’m adjusting hormones and getting the balance right, bleeding can occur, and if it does I simply increase the estradiol/progesterone ratio in what I’m prescribing (either with increasing the estradiol or decreasing the progesterone).

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#9

Could there be benefit to iron dumping from inducing a period?

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#10

Only if ferritin with paired with a low CRP is higher than ideal. Also need to not be consuming much alcohol as that artifactually bumps up the ferritin. It could be harmful if one has low iron stores.

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#11

I’ve got one gene variant for hemochromatosis which makes me a carrier without getting the disease. Still my iron is supposed to trend higher than without that variant all things equal. Which is why I wonder what will happen once my period stops.

#12

My experience on this is that it is very rare to get iron overloaded in that situation in women. Someone HFE gene heterozygous may very slowly build up their stores, but typically entering menopause women are on the lower range on ferritin and do gradually build up a bit.

It is rare for menstruating women with hemochromatosis homozygous to have values that lead to diagnosis until they stop menstruating and then it builds up gradually.