While Estradiol Falls, Estrone Rises With Age And Is Much More Relevant For Estrogen-driven Diseases

haidut

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I posted a few studies in the past demonstrating that estrone (E1) and especially its long-lasting derivative estrone sulfate (E1S) are reliable biomarkers of both breast and prostate cancer progression/prognosis. However, for some reason the medical industry is obsessed with estradiol and since its levels plummet after menopause this has allowed doctors to declare menopause a life-stage characterized by estrogen "deficiency". E1 and/or E1S are almost never measured and many endocrinologists do not consider those steroids relevant for health/disease. While the estrones are indeed weaker estrogens than estradiol, both of them easily convert into estradiol or estriol in tissues and exert tissue-specific effects - a process known as "intracrinology". If E1 and E1S are measured, together with estriol and estradiol (and preferably prolactin as well), it becomes apparent that total estrogen reserves RISE with age instead of falling as the doctor claim. Thus, menopause and its associated diseases are driven by estrogen excess and not deficiency.

Well, the study below may finally change this attitude. It found (unsurprisingly) that estrone is elevated in post-menopausal women and its levels correlated well with age - i.e. the older the woman the higher her estrone levels. It also makes the direct claim that unless estrone is also measured as part of a the hormone panels often done for women, using only estradiol as a diagnostic/treatment biomarker is next to meaningless.

Higher testosterone level may confer ‘survival advantage’ in older women

"...Researchers found that women aged 80 to 84 years had estrone levels that were on average 9.2% higher vs. women aged 70 to 74 years (P = .001); women aged at least 85 years had estrone levels that were on average 11.7% higher vs. women aged 70 to 74 years (P = .01). When stratified by BMI, excess weight further influenced sex steroid levels, the researchers wrote, noting that older women with obesity had estrone levels that were on average 34.1% higher vs. women with normal weight (P < .001). The increasing proportion of women with unmeasurable [estradiol] in the older groups most likely reflects different effects of age on the enzymatic pathways essential for the biosynthesis of these hormones,” the researchers wrote. “Regardless, a key message from the findings is that studies investigating the association between estrogens and diseases of aging in postmenopausal women must measure [estrone] in order to provide meaningful findings.”
 

sweetpeat

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Is it possible the estrone levels are rising to compensate for the lower circulating estradiol levels of postmenopausal women?
 

haidut

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Is it possible the estrone levels are rising to compensate for the lower circulating estradiol levels of postmenopausal women?

It is an enticing proposition but I think the more likely explanation is increased fat mass carried by older woman (and men). They say in the study that older, obese women had the higher estrone levels. Estrone is mostly produced by fat cells, estradiol is mostly produced by ovaries (in women) and testicles (in men). Prolactin is the giveaway that estrogen signalling does not decline but rises with age. Prolactin is higher in postmenopausal women and its levels correlate well with age. Estrogen is the primary driver of prolactin secretion, followed by serotonin and cortisol.
 

sweetpeat

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That kind of confirms what I'm suggesting. Menopausal women are know to gain adipose tissue at the same time E2 levels are falling. The adipose tissue then is used to produce the estrone to compensate where the ovaries are falling short.
 

haidut

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That kind of confirms what I'm suggesting. Menopausal women are know to gain adipose tissue at the same time E2 levels are falling. The adipose tissue then is used to produce the estrone to compensate where the ovaries are falling short.

The gaining of fat is due to declining metabolism. Those extra electrons the body cannot pair up with oxygen have to go somewhere so synthesizing fat or storing dietary fat is a suboptimal way of handling the excess NAD(H). The extra fat then contributes to more estrone synthesis. It is virtually impossible to become deficient in estrogen as pretty much any cell/tissue can synthesize it. Finally, total estrogen reserves rise with age. Why would an older woman need to produce more estrogen than a younger one? It's not like she needs it for estrus considering the ovaries are failing.
 

LeeLemonoil

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Is it possible the estrone levels are rising to compensate for the lower circulating estradiol levels of postmenopausal women?

Compensation is definitely a wrong conceptualization, since the word transports the meaning of equivalent replacement.

I don’t think the body ever „tries“ to compensate nor can it be successful with an alleged try.
The system deteriorates from a better to a worse condition with worse mechanisms.
 

lampofred

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I think if doctors measured prolactin it would be much more accurate for diagnosing estrogenic activity & measuring risk of prostate cancer/breast cancer/similar issues. It wouldn't have the blood level vs cellular level issue that estrogen has because it unequivocally rises with age with a sharp spike at menopause.
 
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