Some aromatase inhibitors (AI) are estrogenic

haidut

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I have long suspected this considering the peculiar side effects of some AI drugs, but was not able to find concrete evidence...until now. The study below demonstrates that one of the most widely used AI - anastrozole - is a potent estrogen receptor activator/agonist, and at low concentrations too. At higher concentrations, the estrogenic effects seem to disappear but those concentrations are not achievable with clinically used doses. As such, for most people taking anastrozole in the clinically-approved 1mg-2mg (or lower) doses daily, the drug is a potent estrogen activator, which likely negates most of the benefit of inhibiting aromatase. While the closely-related analog letrozole apparently did not have estrogenic effects, structurally the drugs are very similar and produce very similar side effects. As such, I suspect letrozole also has at least partial estrogen agonism. The steroidal AI exemestane did not display estrogenic effects, and it also happens to not produce the side effects associated with the *zole drugs. Several studies have demonstrated that exemestane metabolizes into the potent androgen 17-beta-OH-6-methylene-boldenone, and that metabolite has anti-estrogenic effects similar to other androgens such as testosterone, DHT, Masteron, etc., all of which have been successfully used in the past for treating breast cancer. IMO, this androgenic property makes steroidal AI drugs such as exemestane, formestane, and atamestane less risky than the *zoles, especially if the steroidal AI are combined with endogenous anti-estrogens such as progesterone.

Anastrozole has an Association between Degree of Estrogen Suppression and Outcomes in Early Breast Cancer and is a Ligand for Estrogen Receptor α - PubMed

"...Results: Women with E1 ≥1.3 pg/mL and E2 ≥0.5 pg/mL after 6 months of AI treatment had a 2.2-fold increase in risk (P = 0.0005) of an EBCE, and in the anastrozole subgroup, the increase in risk of an EBCE was 3.0-fold (P = 0.001). Preclinical laboratory studies examined mechanisms of action in addition to aromatase inhibition and showed that only anastrozole could directly bind to estrogen receptor α (ERα), activate estrogen response element-dependent transcription, and stimulate growth of an aromatase-deficient CYP19A1-/- T47D breast cancer cell line. Conclusions: This matched case-control clinical study revealed that levels of estrone and estradiol above identified thresholds after 6 months of adjuvant anastrozole treatment were associated with increased risk of an EBCE. Preclinical laboratory studies revealed that anastrozole, but not exemestane or letrozole, is a ligand for ERα. These findings represent potential steps towards individualized anastrozole therapy."

"...However, in CYP19A1 KO T47D cells, only anastrozole at 0.1–10 nM resulted in increased cell proliferation, with a decrease in cell proliferation when anastrozole concentrations increased to 100–500 nM (Fig. 2B). In CYP19A1 KO T47D cells, treatment with exemestane or letrozole at the same concentrations (0.1 to 500 nM) did not affect cell proliferation compared with vehicle-treated cells (Supplementary Fig. S8B)."
 

Frankdee20

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I use a liquid Blue Sky product Examastane and I cannot report any issues from it.... Don’t know about any benefits either, who the hell knows if it’s even a real product
 

TheBeard

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I use a liquid Blue Sky product Examastane and I cannot report any issues from it.... Don’t know about any benefits either, who the hell knows if it’s even a real product

What were you looking to achieve with an AI?
 

hei

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Why do men who take anastrozole experience "low estrogen" symptoms like joint problems and libido loss?

I use a liquid Blue Sky product Examastane and I cannot report any issues from it.... Don’t know about any benefits either, who the hell knows if it’s even a real product
It's in OP:
The steroidal AI exemestane did not display estrogenic effects, and it also happens to not produce the side effects associated with the *zole drugs.
 

Frankdee20

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Why do men who take anastrozole experience "low estrogen" symptoms like joint problems and libido loss?


It's in OP:
Nice ! Also, Examastane does not cause rebound estrogen symptoms because it is an irreversible inhibitor, unlike the others... That allows the enzyme to slowly come back rather than being blocked and up regulating... but I am not sure if Blue Sky products contain what they say they do ... I can see white particles that settle to the bottom, so must be something in there
 

Frankdee20

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What were you looking to achieve with an AI?
Just to increase my T levels from baseline 470, but also to prevent Pansterone from building Estrogen... I was also taking it in conjunction with Clomid and Pansterone.... I also drink alcohol on a regular basis so my aromatase is probably abundant anyway... On prior tests, never saw my E2 go higher than 30 perhaps
 

ilhanxx

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I used letrozole (letrol brand), I didnt have any joint or low sex drive issue.
 

rei

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Why do men who take anastrozole experience "low estrogen" symptoms like joint problems and libido loss?


It's in OP:
Because they are "low estrogen symptoms" so nothing at all to do with estrogen.

It's like saying progesterone causes "low progesterone symptoms" like abortion when synthetic versions are used as contraceptive. It's just a narrative designed to confuse you and invert reality.
 

TheBeard

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Because they are "low estrogen symptoms" so nothing at all to do with estrogen.

It's like saying progesterone causes "low progesterone symptoms" like abortion when synthetic versions are used as contraceptive. It's just a narrative designed to confuse you and invert reality.

So when I take Exemestane and within 4 days my joints hurt and my libido tanks, and this scenario has happened the exact same way around 10 times every single time I take Exemestane, what is the cause of my cracky joints and low libido?
 

Razvan

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Maybe y
So when I take Exemestane and within 4 days my joints hurt and my libido tanks, and this scenario has happened the exact same way around 10 times every single time I take Exemestane, what is the cause of my cracky joints and low libido?
Maybe you have high prolactin.
 

5a-DHP

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Maybe y
Maybe you have high prolactin.
Joint pain and low libido following the use of an aromatase inhibitor the by-product of elevated prolactin?
Every paper that investigates the effect of AI on prolactin demonstrates a significant decrease. If you don't understand the mechanism by which a drug works or the effects it produces, why do you feel qualified to provide an answer? Some people take what they read here at face value; misinformation has consequences.
 

5a-DHP

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So when I take Exemestane and within 4 days my joints hurt and my libido tanks, and this scenario has happened the exact same way around 10 times every single time I take Exemestane, what is the cause of my cracky joints and low libido?
I agree with your view that low estrogen is the cause of exemestane-induced joint pain and reduction in libido.

Many on this forum who carelessly throw out advice re: hormones have no actual understanding of endocrinology. Their entire thinking is based upon the assumption that because X hormone produces undesirable outcomes in excess and/or within certain context, excessively reducing said hormone can/will only produce desirable outcomes, and any negatives effects associated with such decline cannot possibly be related to the hormone you're tanking. Then comes the mental gymnastics, whereby people try to scapegoat the negative effects of high dose AI on bs like in-vitro data demonstrating minute alterations to progesterone receptor expression in cell lines treated with anastrozole, instead of the 90%+ drop to estrogen - a hormone that, whilst detrimental in excess, still has a function to fulfil in the body.

Contrary to the belief here, you can have too little estrogen, cortisol, serotonin, prolactin, etc, because hormonal health is found in balance, not extremes.
 

rei

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So when I take Exemestane and within 4 days my joints hurt and my libido tanks, and this scenario has happened the exact same way around 10 times every single time I take Exemestane, what is the cause of my cracky joints and low libido?
some side effect of the drug. Imbalanced estrogenic effects in some places but not others? This is how progestins compare to progesterone, if not in more ways.

It should give you some clue how far out medicine is when progestins are used as contraceptive, when progesterone is essential for pregnancy. Yet progestins are almost universally talked about as "progesterone", even in scientific literature. Sometimes you need to dig DEEP to see that a progesterone study actually used a progestin, as it is not in any way indicated in the study itself, you need to go dig patent filings based on the product name given.... Most of medicine is corrupt TO THE CORE
 

Gustav3Y

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It should give you some clue how far out medicine is when progestins are used as contraceptive, when progesterone is essential for pregnancy. Yet progestins are almost universally talked about as "progesterone", even in scientific literature.
Progestins are also given to females that had previous spontaneous miscarriage, I know two females in this situation, the doctors did not prescribe progesterone because it is not even sold anymore in pharmacies, at least around here they aren't.
 

Razvan

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I agree with your view that low estrogen is the cause of exemestane-induced joint pain and reduction in libido.

Many on this forum who carelessly throw out advice re: hormones have no actual understanding of endocrinology. Their entire thinking is based upon the assumption that because X hormone produces undesirable outcomes in excess and/or within certain context, excessively reducing said hormone can/will only produce desirable outcomes, and any negatives effects associated with such decline cannot possibly be related to the hormone you're tanking. Then comes the mental gymnastics, whereby people try to scapegoat the negative effects of high dose AI on bs like in-vitro data demonstrating minute alterations to progesterone receptor expression in cell lines treated with anastrozole, instead of the 90%+ drop to estrogen - a hormone that, whilst detrimental in excess, still has a function to fulfil in the body.

Contrary to the belief here, you can have too little estrogen, cortisol, serotonin, prolactin, etc, because hormonal health is found in balance, not extremes.
I was referring to low libido only. In my experience if you lower estrogen too much and have higher prolactin you will experience low libido. You need to use something man, as i can see from your response you are a degenerated prick. Talking with me without knowing what I do or how I am. I help a lot of people and I'm not a prick behind a computer like you. I talk from experience and i help a lot of people daily. Don't reply to me with stupid sentences.
 

5a-DHP

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I was referring to low libido only. In my experience if you lower estrogen too much and have higher prolactin you will experience low libido. You need to use something man, as i can see from your response you are a degenerated prick. Talking with me without knowing what I do or how I am. I help a lot of people and I'm not a prick behind a computer like you. I talk from experience and i help a lot of people daily. Don't reply to me with stupid sentences.
Didn't even address any of the points I made, instead resorting to aggression and personal insults that are unrelated to the point of contention. Why are you so quick to anger? Not a good look, my man.
Regardless, the message you're responding to wasn't even aimed at you - otherwise I'd have @'d, so chill tf out and we'll revert back to having what was previously an objective discussion where all can benefit.
 
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