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[Kathleen]

Hello ladies

I wonder if any of you can answer this question which is probably stupid but here goes.

I understand that there are different types of Oestrogen, namely Estrone, Estriol and Estradiol. From the information on BeaR's recent post about the Guardian article it seems that only Estrone is produced by post menopausal women, the other two being concerned with pregnancy and reproduction respectively. I've looked on my packet of gel and note that it supplies Estradiol ( using the alternate spelling of Oestradiol ).

Is it a silly question to ask why post menopausal women aren't offered Estrone instead of Estradiol to relieve symptoms?  Surely this version of the hormone would be better tolerated. Also, could post menopausal women be struggling with Estradiol because they have lost the relevant receptors and their bodies are now being flooded with a hormone that they are unable to process. If all HRT is based on Estradiol does this mean that peri menopausal women will do better as they will they have the  appropriate receptors initially, indeed a constant flow of Estradiol may be maintaining those receptors. However if they decline in number as the menopause continues then symptoms may reappear  because the body is now getting the wrong hormone.?

I think that Estrone can convert to Estradiol in certain circumstances but is this what we really want when we are post menopausal?  It may not be possible to deliver Estrone in any way but could phytoestrogens in food help with increasing this version of the hormone and that is why some experts insist that specific diets and supplements can help.

In summary is Estradiol the correct hormone to be giving women to treat their menopause symptoms or is Estrone more appropriate for those who are post or approaching post menopause.menopause.

 It's pretty obvious that I'm not a scientist and there's likely a fundamental error in my thinking but I would be interested to hear anyone's comments on the subject.

Take care ladies.

K.

[MicheleMaBelle]

Hi Kathleen. I believe that Estrone is the less powerful version and isn't as effective as estradiol

[bear]

Hi Kathleen,

No question is stupid, don't be daft. 

1. Estrone is the predominant type of oestrogen in postmenopausal women, but not the only one, we still produce the other two.
2. Estradiol is the predominant oestrogen throughout the fertile years and estriol is predominant during pregnancy.
3. If estrone levels are high in postmenopausal women, I don't think there would be any reason to offer them more estrone, but...
4. Estrone has very little binding affinity to oestrogen receptors, compared to estradiol.
5. There's no evidence that postmenopausal women lose oestrogen receptors.
6. Perimenopausal women don't do better, not in my case! Estradiol levels can be quite high during perimenopause and the ups and downs cause most of the nasty effects.
7. Estrone can be converted to estradiol in peripheral tissues, but it is not accumulated in target tissues, unlike estradiol and estriol.

I think there may be a reason why estrone levels are kept high in postmenopausal women, that is a very interesting subject.

Estradiol is the most potent oestrogen, so if you want to achieve biological responses, estradiol is the 'correct' hormone.

You have raised a very interesting question though, what if estrone could be an option if given at large doses, so it could be converted to estradiol in target tissues, not only the obvious ones, breast, uterus, but also bones, brain and endothelium, so estradiol could exert its beneficial effects, without accumulating and potentially increasing the risks of breast and endometrial cancers?

BeaR.

[Kathleen]

Hello again ladies.

MicheleMaBelle - thank you for responding.

BeaR -  thanks for your very detailed reply.  It would be great if sometime in the future we could have a more tailor made treatment for our hormonal woes. We live in hope I guess!

Wishing you well ladies.

K.

[bear]

Hi again Kathleen,

I have just posted this bit from Oestrogel leaflet on another thread and I thought it might be interesting to post it on this one as well. Estrone is mentioned and at least for me this is new info.

'Pharmacokinetic properties

Absorption

Pharmacokinetic studies indicate that, when applied topically to a large area of skin in a volatile solvent, approximately 10% of the oestradiol is percutaneously absorbed into the vascular system, regardless of the age of the patient.

Distribution

Daily application of 2.5 g or 5 g Oestrogel over a surface area of 400-750 cm2 results in a gradual increase in oestrogen blood levels to steady state after approximately 3-5 days and provides circulating levels of both oestradiol and estrone equivalent in absolute concentrations and in their respective ratio to those obtained during the early-mid follicular phase of the menstrual cycle.

Oestrogel was administered to 17 postmenopausal women once daily on the posterior surface of one arm from wrist to shoulder for 14 consecutive days.

Maximum serum concentrations (Cmax) of oestradiol and estrone on Day 12 were 117 pg/ml and 128 pg/ml, respectively.

The time-averaged serum oestradiol and estrone concentrations (Caverage) over the 24hour dose interval after administration of 2.5 g of Oestrogel on Day 12 were 76.8 pg/ml and 95.7 pg/ml, respectively.

Biotransformation

Metabolism of oestradiol takes place mainly in the liver under oestriol, estrone and their conjugated metabolites (glucuronides, sulphates). These metabolites also undergo enterohepatic recirculation.

When treatment is stopped, oestradiol and urinary conjugated oestradiol concentrations return to baseline in about 76 hours.

Elimination

Oestriol is the major urinary oestradiol metabolite. However, glucuronide and sulphate metabolites of oestradiol and oestrone are also found in urine and bile. Metabolites excreted in bile undergo enterohepatic recirculation or are excreted in the faeces.'

Pay attention that both estrone and oestrone are used 

BeaR.

[Alicess]

Thank you, BeaR. Very informative. Especially the absorption of Oestrogel. Do you know of any research regarding the absorption of transdermal
patches?

[bear]

Hi Alicess,

There are many studies regarding the absorption of estradiol patches, most of them were published in the 80-90's and some comparing them to estradiol gel after 2000. I have chosen some interesting ones for you. Many are pay-per-view, I do have access to some of them if you're interested.

https://link.springer.com/article/10.2165/00003495-199040040-00006
https://www.sciencedirect.com/science/article/abs/pii/S0002937801531658
https://www.ncbi.nlm.nih.gov/pubmed/11306208
https://www.dovepress.com/clinical-efficacy-of-estradiol-transdermal-system-in-the-treatment-of--peer-reviewed-fulltext-article-RRTD
https://journals.sagepub.com/doi/full/10.2217/whe.15.64
https://www.degruyter.com/view/j/hmbci.2019.37.issue-2/hmbci-2018-0033/hmbci-2018-0033.xml
https://journals.viamedica.pl/ginekologia_polska/article/view/GP.a2017.0018/37562
https://patents.google.com/patent/US9314470B2/en
https://www.tandfonline.com/doi/abs/10.3109/13697139909038084
https://accp1.onlinelibrary.wiley.com/doi/abs/10.1177/00912709922008470
https://journals.lww.com/drug-monitoring/Abstract/1997/02000/Comparative_Serum_Estradiol_Profiles_from_a_New.6.aspx
https://link.springer.com/article/10.2165/00002512-199202060-00005
https://www.sciencedirect.com/science/article/abs/pii/S0378512203001890

BeaR.

[Alicess]

Thank you! I don't have much time to read them at the moment but, for now, I really appreciate your effort 🌷

[Bobidy]

Thanks BeaR, I've been searching for research papers relating to oestogel and couldn't find much at all so thank you for these x

[Hurdity]

Hi Alicess,

There are many studies regarding the absorption of estradiol patches, most of them were published in the 80-90's and some comparing them to estradiol gel after 2000. I have chosen some interesting ones for you. Many are pay-per-view, I do have access to some of them if you're interested.

Wow bear that's a humongously impressive compilation of refs! Most of us don't have the time to trawl through and subscribing to journals on the offchance of a juicy ref  is v expensive so if you are able to distill the essence and can extract any brief salient pertinent or relevant juicy nuggets which doesn't involve us wading through nor pasting reams of extraneous guff and would help to answer Kathleen's point we would all be grateful!

Hurdity x

[Hurdity]

Do you know of any research regarding the absorption of transdermal patches?

I don't have much time to read them at the moment

Alicess I tend to have one or two “go to” review papers that I refer to when I want to look up stuff which doesn't involve so much time! What is it that you are specifically wanting to know or are interested in? I may be able to point you in the right direction without having to do the trawl (however interesting!)....(can't promise though!).

Hurdity x

[Kathleen]

Hello again ladies

Bear - thank you so much for your heroic efforts! You have uncovered a lot of information there.

 Maybe science does have the answers we are looking for, but it's a mission to find them. Still, it gives me hope that 'the truth is out there'.

Wishing you well.

K.

[Hurdity]

Hello ladies

I wonder if any of you can answer this question which is probably stupid but here goes.

I understand that there are different types of Oestrogen, namely Estrone, Estriol and Estradiol. From the information on BeaR's recent post about the Guardian article it seems that only Estrone is produced by post menopausal women, the other two being concerned with pregnancy and reproduction respectively. I've looked on my packet of gel and note that it supplies Estradiol ( using the alternate spelling of Oestradiol ).

Is it a silly question to ask why post menopausal women aren't offered Estrone instead of Estradiol to relieve symptoms?  Surely this version of the hormone would be better tolerated. Also, could post menopausal women be struggling with Estradiol because they have lost the relevant receptors and their bodies are now being flooded with a hormone that they are unable to process. If all HRT is based on Estradiol does this mean that peri menopausal women will do better as they will they have the  appropriate receptors initially, indeed a constant flow of Estradiol may be maintaining those receptors. However if they decline in number as the menopause continues then symptoms may reappear  because the body is now getting the wrong hormone.?

I think that Estrone can convert to Estradiol in certain circumstances but is this what we really want when we are post menopausal?  It may not be possible to deliver Estrone in any way but could phytoestrogens in food help with increasing this version of the hormone and that is why some experts insist that specific diets and supplements can help.

In summary is Estradiol the correct hormone to be giving women to treat their menopause symptoms or is Estrone more appropriate for those who are post or approaching post menopause.menopause.

 It's pretty obvious that I'm not a scientist and there's likely a fundamental error in my thinking but I would be interested to hear anyone's comments on the subject.

Take care ladies.

K.

Kathleen - it is sad that you feel your questions might be stupid! The best discoveries can be made by people who look at things with fresh eyes! That is a fair question and one that has been raised before.

My GP gynae specialist told me that there are over 30 different oestrogens – and she was in favour of replacing others – although they are not widely known about nor occur in sufficient quantities. Estradiol is the major one with receptors all over the body and although it is a crude way of mimicking our pre-menopausal hormonal mix – it is probably the best we can do at the moment. Estriol is a strange one as it can't be reconverted to estradiol but nevertheless as you know is used widely for vaginal preparations where it binds preferentially to one of the estrogen receptors (either alpha or beta can't remember!).

This is not answering your questions directly but in fact there used to be a hormonal preparation containing a mix of those three oestrogens called Hormonin but was discontinued. I never looked into this particularly but there will be a reason it is not more widely used. I suspect it is not the norm for HRT because in fact estrone is an integral part of estradiol metabolism (this is not big news!) so no need to replace it – and there are interconvertible ( by this I mean the body converts one to the other depending on various factors and in different tissues). Estradiol taken as HRT is partly metabolised to estrone and this is notable for oral preparations, where it is metabolised extensively in the liver to estrone ( ?and estrone sulphate) and then reconverted to estradiol elsewhere in the body (not sure which tissues). From what I understand with oral HRT due to the liver “first pass effect” (the hormone has to go through the liver before entering the bloodstream)  the proportion of estrone to estradiol is way greater than occurs naturally which is apparently not ideal whereas transdermally the ratio is closer to that which occurs normally. This is from memory so can't remember what the disadvantage of having excess estrone is – but my main point is – you don't need to replace it because it is made in the body!

As far as I understand the hormones exist in the body in some sort of dynamic equilibirum ( ie re estrone/estradiol) and would not be confined to peripheral tissues (eg fat etc) as it will be transported around the body where it will exert its effects. The details are hazy so this garbled reply is off the top of my head - I've read odd bits but not enough to remember and don't have the time to spend my days researching hormones!!!

Estradiol seems to do a pretty good job for most women - provided you get the right dose of the right product and delivery method - and most important - the right progestogen which doesn't give such dreadful side effects!

Just a few random thoughts but do keep asking questions!

Hurdity x

[bear]

Hello again ladies

Bear - thank you so much for your heroic efforts! You have uncovered a lot of information there.

 Maybe science does have the answers we are looking for, but it's a mission to find them. Still, it gives me hope that 'the truth is out there'.

Wishing you well.

K.

Hello Kathleen,

You're welcome. Absolutely, many current articles are about recovering the overwhelming amount of data available online and trying to make sense of them.

Most of those links are from summaries, so you really don't need much time to read them. I personally think it's very important to know  as much as I can about everything, not just hormones, but they are a fascinating subject, not to mention they rule my life!

BeaR.

[Charliegirl@]

Hi Hurdity, I wish I had your GP!x