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[Ana21]

Gilla999,

You wanted clarification on the statement: "Estradiol levels can underestimate estrogen exposure due to how hormones are metabolized, making estrogen seem low when it is not."

I can give you an example. After menopause, the majority of endogenous estrogen is produced by transformation of androstenedione (secreted by the adrenal cortex) to estrone in the peripheral tissues. Both estrone and its sulphate conjugated form, estrone sulphate, represent the most abundant estrogens found in postmenopausal women.

When you have a blood test to measure your estrogen level, you are only measuring estradiol.  That doesn't give you the complete picture of the estrogen in your body.  It doesn't take estrone into account.

Being overweight is a risk factor for breast, endometrial, ovarian, and some other cancers.  Simply put, fat cells make estrogen (estrone) and more fat cells mean more estrogen in the body.  That's why weight matters when prescribing MHT.

I take oral estradiol.  It's metabolized into estrone and estrogen conjugates such as estrone sulfate, estrone glucuronide, and estradiol sulfate, etc, prior to entering circulation.  An estradiol blood test would not tell you anything about my estrogen exposure.

Hope that helps.

[Gilla999]

Thanks for sharing Ana, yes I'm aware of Estrone and its conversion from oral Estradiol etc. I might be wrong, but I don't think this is what is being referred to when people talk about blood tests under representing Estradiol levels - I think it is something to do with Estrogen stored in the tissues and receptors which isn't necessarily represented in plasma (which is why for example saliva tests can sometimes show much higher levels than plasma, and there is a debate about which is a more accurate/valid representation). I just haven't seen much in depth studies/analysis into it and would like to, out of interest!

[joziel]

I've seen a lot of blood tests in US FB groups from women who ARE getting estrone tested along with estradiol. However, estrone is a pro-inflammatory unhealthy form of estrogen. It's not a substitute for estradiol. I have no idea why the body would convert estradiol to estrone either...

As for topical vs systemic HRT for GSM, systemic HRT can definitely help GSM symptoms alongside topical and, when at higher doses, many women find they no longer need local E. That's not a reason to use higher doses by itself, just a fact... By extension, if someone is slathering themselves with local E and still suffering GSM, it would make sense to try adding in systemic HRT as well - as long as there are no contraindications.

As for the article itself, I've had 4 years of absolute hell on lower E dosages/levels. I have finally begun to be able to sleep better on higher dosages (currently 200mcg patches plus 6 pumps of gel). So doctors can come out with all these cautions and warnings and 'this isn't provens' they like, but my lived experience counters that - and I know I'm not the only woman out there in my situation. And as for the 'investigate other things', I spent 4 years doing exactly that - at huge expense, psychological stress and zero benefit to myself. I don't know what my serum estradiol is yet, I will test that in a few weeks. I do know that it was around 330pmol on both 6 pumps and 12 pumps of gel: I was not absorbing any extra gel for those extra 6 pumps.

I'm also on 300mg utrogestan continuously and I usually increase to 400mcg the week before my period as I find this helps sleep more.

The option of higher doses of E should absolutely be available, perhaps only with hefty doses of P and blood tests and then (only if tests show high levels) scans to check things.

[Ana21]

joziel,

Thanks for the info.  Interesting to hear some women are testing for both estrone and estradiol in the US.

We know that both oral and transdermal estradiol are partly converted to estrone.  And we know, due to the first-pass effect, oral estradiol causes much higher estrone concentrations than transdermal estradiol.  I'm curious about the outliers, such as those women who convert more transdermal estradiol to estrone.  We know that the body can convert estrone back to estradiol.  Estrone is both a precursor and a metabolite of estradiol.

Sorry, I don't want to seem fixated on estrone, but I'm curious about what "non-absorber" really means and estrone is something we can measure.  I'm a non-absorber.  I've always wondered what happens to the estradiol that I apply to my skin.  On transdermal estrogen, my estradiol levels are too low for measurement on immunoassay.  I've asked my doctors about this and they say they don't know.  They never say I am not absorbing it through my skin.  It makes me wonder whether I metabolise transdermal estradiol is a non-typical way.


It would be so interesting to have your blood tested by mass spectrometry, profiling estrogens and their metabolites.  Curious to know how your body is metabolising transdermal estrogen.  I haven't been able to find any good information on this.  Any help appreciated.

[joziel]

What transdermal estrogen doses have you tried Ana21? Have you tried higher doses as well?

It seems I do absorb, just not well/much. I have very dry skin, which might be part of it. I'm afraid to moisturise it where I apply gel/patches, in case that is then a barrier which only further stops the estrogen getting in.

[Ana21]

joziel,

The highest dose of transdermal estrogen I've tried is 3 pumps of estrogel.  And my doctor was hesitant to prescribe a dose that high.  I'm in Canada and recently turned 60.  We're more conservative in our MHT dosing.  I would never be permitted to experiment with the higher doses that women are prescribed in the UK.  That's why I've been following your posts with interest.

I knew I had an absorption problem when I was testing the 3 pumps of estrogel, so I did not use moisturizer on hands or body.  I used a residue free body wash and I did not use rinse-out hair conditioner in the shower.  Like you, I was afraid of creating a barrier to absorption.  I applied the estrogel with a silicone spatula to avoid absorbing the gel through my hands and ensure the full dose was applied to the target area.

[joziel]

Yes, I also use a silicone spatula to apply it. I am feeling great on my current dosage and trying to keep anxiety at bay after Panorama-gate. I am on tons of utrogestan as well. It will be interesting to see what my serum levels are, in a few weeks.

[laszla]

Couple of thoughts in haste about this article. Something about its tone and content struck me as very off (starting with who on earth calls their own article a 'masterclass'). I went on to learn that this doctor is virulently, and I mean virulently, anti Louise Newson, has accused her of malpractice etc. Something to bear in mind.

As for some of the things she says - and I will look at more carefully at some point - I totally disagree that blood testing is pointless and as for the estrone/estradiol distinction - in an ideal world perhaps both could be measured but I am vastly more interested in E2 which is a lot more potent and beneficial than estrone which as Joziel mentions is considered pro inflammatory and as I've also read possibly the cause of occasional negative effects of "estrogen".

And if the following is true (and I do agree with this):

"being overweight is a risk factor for breast, endometrial, ovarian, and some other cancers.  Simply put, fat cells make estrogen (estrone) and more fat cells mean more estrogen in the body.  That's why weight matters when prescribing MHT."

then in the case of someone being underweight, as is my case, and therefore quite possibly almost totally deficient in estrone, that would be even more reason to absolutely need to check that at least my hrt is topping up my estradiol.

[Ana21]

Hi Laszla

In the article, Jen Gunter says she would do blood testing in certain circumstances:

"But to be a poor absorber, we need a definition. Do we say that someone with an estradiol level of 70 pg/ml (257 pmol/L) on a 100 mcg patch is a poor absorber, or are they just at the low end of the bell curve (because someone has to be at the low end of the bell curve, that is how distribution curves work)? It's impossible to say without studies of so-called poor absorbers matching levels with symptoms. 

If someone were in menopause, meaning no period for the past 12 months and on a 100 mcg patch and is still having terrible hot flashes or sleeping poorly (nocturnal hot flashes might be under recalled) or symptoms I would expect to resolve with estrogen, I would consider doing a one-time estradiol level to make sure it’s at least around 50 pg/ml. If it’s lower, she may be a poor absorber, but because absorption can be erratic and the test results have a margin of error, I would not give her more of what she isn’t absorbing; I’d likely suggest switching to a different transdermal system or to oral therapy. If her estrogen level were in an expected range, I’d look for other causes of her symptoms and other therapies. I still might even suggest a different estrogen delivery system to see if that worked better because, as I already noted, levels may not tell us what is happening at the cell level."

***END QUOTE


I was floored to learn that I had been prescribed a drug with a known potential for non-absorption and I had not been given a blood test when I failed to respond to treatment.  For 1.5 years, on top of the menopausal symptoms, I experienced constant bleeding which my doctor attributed to estrogen.  He wanted to reduce my estrogen dose and I begged him not to.  During that time, I had two biopsies and numerous scans.  Even when my endometrial thickness went down to 0.4 mm, my doctor didn't question whether I had a problem with absorption.  He said a thin endometrium is normal in menopause.  If I wasn't happy about the bleeding, I could have a Mirena.  He didn't provide me with any other options.

It wasn't until my hair fell out and he could see my scalp that he said I looked like my estrogen was low and ordered a blood test.  He was supposed to be a menopause specialist.  It was the first time I questioned the competency of my treating physician and felt unsafe. 

In hindsight, the bleeding was due to the lack of estrogen absorption.  I had been taking progesterone for a year and a half.  While all of this was going on, I was on the waiting list of a menopause clinic.  I had to wait 18 months for an appointment.

My new doctor wanted me to try a different transdermal regimen.  Blood tests confirmed I was not absorbing.  Fortunately, the experiments only lasted 4 or 5 months.  But during that time, I didn't get more than 5 hours sleep per night, waking from multiple episodes of night sweats.

I think I've spent most of my time on MHT not absorbing estrogen.  I worry that my bones have suffered as a result.  I had a DEXA scan in August and I have an appointment in November to go over my results.

In terms of costs to the healthcare system, it would have been cheaper to give me a few blood tests than the multiple biopsies and scans I received. 

The system may work for the majority of woman, but the rest of us suffer needlessly.

[Gilla999]

Ana this just makes me so angry and sad to read. I'm sorry that you've had such an appalling level of care, and I hope you're in a better place now. And I know you're not alone in experiencing it either. And then they question why we go elsewhere?! I too have experienced multiple examples of the same kind of thing - both with GPs and so-called meno specialists - as have my friends. It seems to be the norm rather than the exception. I eventually got referred to an NHS menopause doctor who has been just as good as any private people I've seen - she's very open to trying things outside of the NICE guidelines (within reason). The difficulty is that I only get to see her once or twice a year, but I take what I can get.

On blood tests, I can only say in my personal journey that they HAVE played a role and been very useful. But I do agree that there is more research needed into absorption of Estrogen - both poor and high absorbers, how it gets metabolised in different people, and is it fully reflected in plasma levels etc. No one seems to be doing this kind of research, I guess because like others have said, there is no potential financial gain at the end of it.

Joziel I saw on your other post you mention about anxiety as a result of the Panorama programme and that made me feel sad too. I hope you're doing ok!

[bombsh3ll]

I think the problem is when the discussion becomes very polarised, and I don't agree with blanket policies such as everyone should be on body identical hormones, or nobody should have above a certain dose.

I also believe there is a role for testing blood levels, to check absorption, to ensure a therapeutic dose for the indication eg osteoporosis prevention for which levels have been established, and also identifying a level at which an individual feels well.

For example I know that I feel good close to 400pmol/L. I therefore know what to aim for when I change from Zoely to licenced MHT.

Multiple good quality studies have been published measuring plasma estradiol in women taking oral estradiol, and if it is good enough for them, it's good enough for me.

Estradiol conversion to estrone is bidirectional, and the people with the highest level of estrone are young women, so I'm not concerned about this.

It is probably less healthy when older, heavier women have only or mostly estrone, which isn't going to be my situation anyway.

[Sage 🍃]

Couple of thoughts in haste about this article. Something about its tone and content struck me as very off (starting with who on earth calls their own article a 'masterclass'). I went on to learn that this doctor is virulently, and I mean virulently, anti Louise Newson, has accused her of malpractice etc. Something to bear in mind.

At least her 'MasterClass' is free unlike Dr Newson's.

https://newson-health.teachable.com/p/dr-louise-newson-menopause-masterclass

Calling a Dr 'virulently anti Louise Newson' without presenting the facts is completely irrelevant. I wonder if testosterone has a role in these heated reactions. After all it seems that hormones are the main cause and remedy for all things menopause.

[Ana21]

I'm in a good place now. I'm at the menopause clinic of a teaching hospital.  It has an excellent women's health unit, which includes a POI clinic, currently the only clinic of its kind in Canada.  It also has a vulvar dermatology clinic, a urogynaecology clinic (pelvic floor disorders affecting vagina, bladder, anus and rectum), and a pelvic pain (neuropelveology) clinic, etc.  I was on a wait list for 1.5 years.  The wait list is now 2 years.

Decisions regarding my care are now made in discussion with a team, not at the discretion of a sole practitioner as was previously the case.  I'm presented with options and answers to my questions.  I've found a regimen that works for me. 

My previous doctor felt challenged when I asked questions.  After the blood test indicating I was a non-absorber, he switched me to an oral estrogen, Premarin, a conjugated equine estrogen (CEE).  You'll be familiar with it from the WHI trials.  When I asked why Premarin and not micronized estradiol, he said:  "I like Premarin."  Given his tone of voice, he was essentially saying:  Because I said so.  It was extremely dismissive.  He had been prescribing Premarin for decades and was comfortable with it.  He eventually allowed me to switch to oral estradiol but only because I had continued bleeding on Premarin at various doses.

Personally, I would not use a private clinic.  I do not want a doctor who is trying to sell me something, even if it is their time.  I'm in Canada and the situation is different here, although it is evolving.  I appreciate that many women in the UK and elsewhere are well served by private doctors.  All women, regardless of means, should have access to quality care.  You can tell a lot about a society by its treatment of women at all stages of life.

[joziel]

Newson has a free online course because I did it... It was aimed at doctors but nothing to stop anyone signing up for it. It's called the 'Confidence in the Menopause' course.

Not to mention her free Balance website, free app, free podcast... where do I stop...