What explains high estrone but low estradiol?

IVILA

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Why would estrone be at a high end of the reference range whereas estradiol be at the low end while prolactin is low? Is it due to aromatase conversion or what?
 

meatbag

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Why would estrone be at a high end of the reference range whereas estradiol be at the low end while prolactin is low? Is it due to aromatase conversion or what?
"Estrone may be a weak estrogen but it is the main estrogen produced peripherally by both men and women (mostly in fat tissue). Its synthesis grows with age due to the high expression in aromatase in fat tissue, and it is the main "reservoir" of estrogen in the organism as it can easily be converted to estradiol and estriol as needed.
Estrone - Wikipedia
"...Estrone is an estrogen, specifically an agonist of the estrogen receptors ERα and ERβ.[1][4] It is a far less potent estrogen than is estradiol, and as such, is a relatively weak estrogen.[1][4][5] Given by subcutaneous injection in mice, estradiol is about 10-fold more potent than estrone and about 100-fold more potent than estriol.[6] According to one study, the relative binding affinities of estrone for the human ERα and ERβ were 4.0% and 3.5% of those estradiol, respectively, and the relative transactivational capacities of estrone at the ERα and ERβ were 2.6% and 4.3% of those of estradiol, respectively.[4] In accordance, the estrogenic activity of estrone has been reported to be approximately 4% of that of estradiol.[1] In addition to its low estrogenic potency, estrone, unlike estradiol and estriol, is not accumulated in estrogen target tissues.[1] Because estrone can be transformed into estradiol, most of the estrogenic potency of estrone in vivo is actually due to conversion into estradiol.[1] As such, estrone is considered to be a precursor or prohormone of estradiol.[3]"

As such, estrone, and especially its long-lived version estrone sulfate (E1S), are reliable gauges of total body estrogenic load and predict quite reliably mortality from both breast and prostate cancer.
https://raypeatforum.com/community/threads/test-for-estrogenic-activity-and-prostate-cancer.7886/

So, while it is indeed preferable to have higher as opposed to lower ratio of estrone/estradiol, having high levels of estrone and especially of E1S is by no means benign."
from haidut from thread:
-Why DHEA Must Be Taken In Small Doses Only
 

Michael Mohn

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High estrone means high aromatase activity converting testosterone into estrone. Estradiol is produced by men in the testis but apparently can be converted from estrone too. Where and how would be interesting to know.
 

5a-DHP

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Jun 23, 2020
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It's usually from the stress-induced rise in ACTH -> high DHEA-S output -> peripheral DHEA aromatization -> estrone.
Serum estradiol is mainly an indicator of intratesticualr testosterone production, so it's not surprising it's low in the case of elevated estrone, which along with prolactin is a better indicator of systemic estrogen load.
 

Michael Mohn

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Seems like every tissue in the body can convert estrone sulfate into estrone and estradiol.


 

IVILA

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It's usually from the stress-induced rise in ACTH -> high DHEA-S output -> peripheral DHEA aromatization -> estrone.
Serum estradiol is mainly an indicator of intratesticualr testosterone production, so it's not surprising it's low in the case of elevated estrone, which along with prolactin is a better indicator of systemic estrogen load.
High estrone means high aromatase activity converting testosterone into estrone. Estradiol is produced by men in the testis but apparently can be converted from estrone too. Where and how would be interesting to know.
I don't think so. Since estrone is formed from the conversion of androstenedione, I have read that people who have a high level of estrone but a low level of estradiol have a genetic issue with the enzymes so their body prefers the left side of the conversion of DHEA into androstenedione followed by estrone. This may also mean that their testosterone may be lower than optimal in this case since the DHEA is not converting to testosterone. Not sure what can fix this as some say that the use of 7-keto-DHEA would help with this.
 
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