Proviron Is Curing My PFS Symptoms But Need Some Help

[benaoao]

He is partially right. While it's true that DHT itself is estrogen antagonist, it won't powerfully kill estrogen like an AI. But it's still a decent estrogen antagonist.

But I don't think that "estradiol can continue to build up" (WTF?) If you don't have a really high estrogen/prolactin problem, you don't need AIs too.

Many studies show a rise of e2 when taking SERMs. An AI prevents the buildup.

 

[Wagner83]

Proviron and Andractim block estrogens at receptor site only and by no means deactivate aromatase.

So yes, there is an E2 build-up inthe background while taking DHT derivatives, hence the E2 flare up some users experience upon DHT discontinuation without using an AI.

@haidut It would be interesting to have your opinion on this.

 

[vulture]

Proviron and Andractim block estrogens at receptor site only and by no means deactivate aromatase.

So yes, there is an E2 build-up inthe background while taking DHT derivatives, hence the E2 flare up some users experience upon DHT discontinuation without using an AI.

Where is such background? serum? then it should be serum E2 increase on DHT

 

[Arrade]

Wouldn't it be best to try to increase dht naturally? Creatine and weightlifting, perhaps other supplements that increase testosterone.

 

[Arrade]

I know DIM & Vitamin K supplements naturally reduce estrogen, plus idea labs has estrogen lowering scompunds.
Sorry about the TSH man, I'm working on fixing my hypo myself

 

[haidut]

@haidut It would be interesting to have your opinion on this.

The studies posted in the androsterone thread below strongly disagree. All 5-AR endrogens seem to inhibit aromatase and DHT seems to be pretty potent at that. I don't know if the same applies to Proviron as it is a modified molecules and I am not familiar with its aromatase inhibition effects.
Androsterone - A Potent Steroidal Aromatase Inhibitor

Also, even if those androgens were just blocking estrogen at the receptor (which may result in estrogen buildup) their antagonism of the ER increases its expression, so when you discontinue there should be a decline in estrogen synthesis due to the increased receptor density as the body adjusts estrogen synthesis according to the receptor density/sensitivity. Glucocorticoid antagonists like RU486 work the same way - they increase serum cortisol while you take them but when you stop the body should downregulate cortisol synthesis due to the increased receptor density/sensitivity. Emodin achieve the same thing but through a different mechanism - it lowers cortisol synthesis and this results in increased GR density/sensitivity, so when you stop taking emodin the body keeps cortisol production low since the GR is upregulated from the chronic low cortisol caused by emodin.
Just my 2c.

 

[RisingSun]

The studies posted in the androsterone thread below strongly disagree. All 5-AR endrogens seem to inhibit aromatase and DHT seems to be pretty potent at that. I don't know if the same applies to Proviron as it is a modified molecules and I am not familiar with its aromatase inhibition effects.
Androsterone - A Potent Steroidal Aromatase Inhibitor

Also, even if those androgens were just blocking estrogen at the receptor (which may result in estrogen buildup) their antagonism of the ER increases its expression, so when you discontinue there should be a decline in estrogen synthesis due to the increased receptor density as the body adjusts estrogen synthesis according to the receptor density/sensitivity. Glucocorticoid antagonists like RU486 work the same way - they increase serum cortisol while you take them but when you stop the body should downregulate cortisol synthesis due to the increased receptor density/sensitivity. Emodin achieve the same thing but through a different mechanism - it lowers cortisol synthesis and this results in increased GR density/sensitivity, so when you stop taking emodin the body keeps cortisol production low since the GR is upregulated from the chronic low cortisol caused by emodin.
Just my 2c.

That goes against what I have seen in my daily practice, just as it is the case with most studies.

Your view on hormone receptors is fallacious as you identify their mechanism to that of neurotransmitters.

The reality is different: an increase in plasma levels of a given hormone will increase its target receptor density, a decrease in plasma levels of a given hormone will decrease its target receptor density.

Men supplementing with testosterone see an increase in androgen receptor density, not a down-regulation.

A decrease of plasma E2 by use of an AI will work in the way of decreasing E2 target receptors density.

 

[Ron J]

I'm sure I've seen comments about aromatase inhibitors having adverse/estrogenic effects on the brain; is it all AI's or are there exceptions?

 

[Arrade]

I'm sure I've seen comments about aromatase inhibitors having adverse/estrogenic effects on the brain; is it all AI's or are there exceptions?

I think you’re referring to SERMs, not AIs. SERMs blocks estrogen in breast tissue but act as estrogen agonists in the brain.
AIs should universally downregulate estrogen expression, to my best knowledge.

 

[haidut]

Men supplementing with testosterone see an increase in androgen receptor density, not a down-regulation.

Agreed on the androgens. Nowhere in my posts did I say that androgens downregulate AR.
However, the agonist-driven downregulation or antagonist-driven upregulation has been shown to be true for other receptors. For example, if you have (chronically) elevated cortisol that will result in GR downregulation and ultimately "cortisol resistance" so that ever higher levels of cortisol are needed to maintain the same genomic effects through GR. Cushing syndrome is a very good example of how chronic stress and thus elevated cortisol can downregulate GR and cause issues. That is why GR antagonists like RU486 or chemicals like emodin (that lower cortisol synthesis by inhibiting 11b-HSD1) result in GR upregulation, and restore sensitivity to cortisol so that when they are discontinued endogenous cortisol levels go back to normal (unless there is actual tumor somewhere producing ACTH or cortisol).
Emodin opposes chronic unpredictable mild stress induced depressive-like behavior in mice by upregulating the levels of hippocampal glucocorticoid ... - PubMed - NCBI
"...Our results indicated that 6 weeks of CUMS exposure induced significant depression-like behavior, with high, plasma corticosterone concentration and low hippocampal GR and BDNF expression levels. Whereas, chronic emodin (20, 40 and 80 mg/kg) treatments reversed the behavioral deficiency induced by CUMS exposure. Treatment with emodin normalized the change of plasma corticosterone level, which demonstrated that emodin could partially restore CUMS-induced HPA axis impairments. Besides, hippocampal GR (mRNA and protein) and BDNF (mRNA) expressions were also up-regulated after emodin treatments. In conclusion, emodin remarkably improved depression-like behavior in CUMS mice and its antidepressant activity is mediated, at least in part, by the up-regulating GR and BDNF levels in hippocampus."

Same with estrogen - just like cortisol does with the GR, estrogen (strongly) downregulates ER(alpha). Since estrogen is antagonist on AR, it would be expected to increase AR expression, and this also seems to be the case.
Differential hormonal regulation of estrogen receptors ERα and ERβ and androgen receptor expression in rat efferent ductules
"...A slight recovery of AR was also observed after estrogen replacement. ERα expression was decreased to nearly undetectable levels after estrogen replacement. On the other hand, ERβ did not show evident effects following any of the treatments, suggesting a constitutive expression of this receptor. This differential modulation of the steroid hormone receptors highlights the importance of maintaining a physiological androgen-estrogen balance to regulate the structure and function of efferent ductules in the male."

Now, the picture is actually more complicated and seems to be tissue-dependent. For example, progesterone - a PR agonist and ER antagonist would be expected to downregulate PR and upregulate ER. But the effects largely depend on the tissue apparently.
Tissue specific effects of progesterone on progesterone and estrogen receptors in the female urogenital tract - ScienceDirect
"...The effect of progesterone administration on progesterone and estrogen receptors in the uterus, vagina and urethra of rabbits was studied. After 24 h of progesterone treatment the concentration of cytosolic progesterone receptors decreased to about 25% of the control value in the uterus, whereas no significant change in receptor concentration was observed in the vagina or the urethra. The concentration of the nuclear progesterone receptor did not change in any of the three tissues studied. The apparent dissociation constant (Kd) of nuclear progesterone receptor increased after progesterone treatment in all three tissues. Although the Kd of the cytosolic progesterone receptor also increased in all tissues, the difference was significant for only the vagina and urethra. The concentration of cytosolic estrogen receptors in the uterus decreased significantly (P < 0.001) after progesterone treatment whereas the Kd value increased slightly (P < 0.05). In vagina or the urethra, there was no change in either estrogen receptor concentration or Kd values after progesterone treatment. These data clearly showed that the reduction by progesterone of progesterone and estrogen receptor concentrations occurs only in the uterus and not in the vagina or the urethra."

As far as DHT, it seems to be some mix of a structural/functional antagonist - i.e. binds ER and causes its translocation to the nucleus but without the subsequent estrogen-driven transcription effects. Since it causes the ER to translocate to the nucleus, DHT would actually lower ER concentrations, appearing to work like an ER agonist, but it is in fact a functional antagonist due to the displacement of estrogen from binding to the ER and causing inactive steroid-receptor complex to move to the nucleus.
Androgen on the estrogen receptor. I - Binding and in vivo nuclear translocation. - PubMed - NCBI
"...Androgens appeared to behave as some synthetic antiestrogens (such as Mer 25), which displayed a very weak affinity for RE but were able to translocate RE to the nucleus (8). The nuclear translocation of RE induced by DHT also appeared to be correlated with the in vitro (20) and in vivo (Garcia and Rochefort, in preparation) effect of DHT on uterine protein synthesis. In this respect, DHT might be classified with other partial agonists and antiestrogens such as dimethylstilbestrol and estriol (21)."

 

[Wagner83]

The studies posted in the androsterone thread below strongly disagree. All 5-AR endrogens seem to inhibit aromatase and DHT seems to be pretty potent at that. I don't know if the same applies to Proviron as it is a modified molecules and I am not familiar with its aromatase inhibition effects.
Androsterone - A Potent Steroidal Aromatase Inhibitor

Also, even if those androgens were just blocking estrogen at the receptor (which may result in estrogen buildup) their antagonism of the ER increases its expression, so when you discontinue there should be a decline in estrogen synthesis due to the increased receptor density as the body adjusts estrogen synthesis according to the receptor density/sensitivity. Glucocorticoid antagonists like RU486 work the same way - they increase serum cortisol while you take them but when you stop the body should downregulate cortisol synthesis due to the increased receptor density/sensitivity. Emodin achieve the same thing but through a different mechanism - it lowers cortisol synthesis and this results in increased GR density/sensitivity, so when you stop taking emodin the body keeps cortisol production low since the GR is upregulated from the chronic low cortisol caused by emodin.
Just my 2c.

For those who are curious there are similar thought and other things here: Haidut Email Advice Depository .
Is there anything inherently bad with having higher level of hormones circulating in the body? For example if one has high estrogens but low sensitivity then would it be worse than having low estrogens with super high sensitivity? Don't estrogens need to be active in the body, activate their "receptors" in order to be (partly) detrimental?
Why would the body suddenly be successful at handling a proper balance once sensivity is higher (btw, there are external estrogenic compounds everywhere)?

 

[Ron J]

I think you’re referring to SERMs, not AIs. SERMs blocks estrogen in breast tissue but act as estrogen agonists in the brain.
AIs should universally downregulate estrogen expression, to my best knowledge.

Hopefully. I may try aromasin(seems to be the safest from what I've read here). Thanks.

 

[Arrade]

Hopefully. I may try aromasin(seems to be the safest from what I've read here). Thanks.

Yeah, In terms of lipid profile it’s the safest. It also increases free test levels.

 

[haidut]

For those who are curious there are similar thought and other things here: Haidut Email Advice Depository .
Is there anything inherently bad with having higher level of hormones circulating in the body? For example if one has high estrogens but low sensitivity then would it be worse than having low estrogens with super high sensitivity? Don't estrogens need to be active in the body, activate their "receptors" in order to be (partly) detrimental?
Why would the body suddenly be successful at handling a proper balance once sensivity is higher (btw, there are external estrogenic compounds everywhere)?

As I mentioned before, circulating steroids are indicative mostly of gonadal function and not much else. An exception is estrone sulfate (E1S), which seems to reflect total estrogen stores and as such is a good biomarker of estrogen excess. Menopausal women are very good example of very low serum estrogen and very high tissue estrogen.
I think functional results are usually more important than serum levels, so surrogates for tissue levels and activity of androgens, estrogens and progesterone are preferable. Prolactin is a good surrogate for estrogenic tone, kidney/prostate/genital size are good surrogates for androgenic tone, temps and pulse are good surrogates for thyroid/progesterone tone, etc. Serum levels only become relevant if they are really low (gonadal failure) or really high (endocrine tumor somewhere).

 

[Wagner83]

As I mentioned before, circulating steroids are indicative mostly of gonadal function and not much else. An exception is estrone sulfate (E1S), which seems to reflect total estrogen stores and as such is a good biomarker of estrogen excess. Menopausal women are very good example of very low serum estrogen and very high tissue estrogen.
I think functional results are usually more important than serum levels, so surrogates for tissue levels and activity of androgens, estrogens and progesterone are preferable. Prolactin is a good surrogate for estrogenic tone, kidney/prostate/genital size are good surrogates for androgenic tone, temps and pulse are good surrogates for thyroid/progesterone tone, etc. Serum levels only become relevant if they are really low (gonadal failure) or really high (endocrine tumor somewhere).

This is interesting, I have wondered about the relevancy of a number of hormonal blood tests for some time and it sounds like most practitioners and bro-scientists could be working with quite inadequate markers. Not to mention the fact that having particular hormones high in serum could mean they are low in tissues

 

[Mito]

As I mentioned before, circulating steroids are indicative mostly of gonadal function and not much else.

What about the steroid metabolites like a DUTCH test? Doesn’t the presence of hormone metabolites indicate the the hormone was in the tissue?

 

[RisingSun]

Hopefully. I may try aromasin(seems to be the safest from what I've read here). Thanks.

Be really careful with the dosage you’re going to use.

Exemestane as a standalone protocol is VERY detrimental for the brain, joints, mood, libido (not because of the compound itself, but because of lowered estrogen levels).

If you are going to do it anyways, I would advise against using it in the typical dose of 25mg/day, but rather 6.25mg every 4 days at most

 

[Arrade]

Be really careful with the dosage you’re going to use.

Exemestane as a standalone protocol is VERY detrimental for the brain, joints, mood, libido (not because of the compound itself, but because of lowered estrogen levels).

If you are going to do it anyways, I would advise against using it in the typical dose of 25mg/day, but rather 6.25mg every 4 days at most

Dry painful joints are the best indicator of lowered estrogen. I do miss crying for no reason and having no emotion :p

 

[haidut]

What about the steroid metabolites like a DUTCH test? Doesn’t the presence of hormone metabolites indicate the the hormone was in the tissue?

Yes, that could help but it is not enough on its own. Some people could have very slow or very fast steroid metabolism/excretion and that would skew the results. For example, having high levels of 3a-androstanediol-glucuronide (3a-ADG, which is commonly used as indication of tissue DHT levels) could be due to upregulated activity of 3a-HSD (which degrades DHT) and not high DHT levels. In fact, this is very common in obese people who degrade DHT much faster then lean people or in people who take SSRI (which upregulate 3a-HSD). So, on a DUTCH test the 3a-ADG could be elevated leading doctors to conclude you have high androgen tissue levels but in fact it could be due to increased degradation and in reality you could have LOW androgen tissue levels. Same with low 3a-ADG - most doctors could conclude that you have low DHT levels in tissues but people who smoke have low 3a-ADG due to nicotine inhibiting 3a-HSD, yet they have high tissue DHT levels (confirmed in countless human studies) due to decreased degradation.
As you can see, testing for tissue steroid levels is not easy, short of taking a biopsy. Hair/nail testing is akin to tissue biopsy but even that could be unreliable because it is a very unique tissue that may have special steroid requirements and its steroid contents may not be indicative of the systemic levels. Unfortunately, there are no large controlled studies looking at correlation between hair/nail and tissue levels and until that happens I would take even those tests with a grain of salt. I guess a person could do serum test, hair/nail test and a DUTCH test. The combination of all three should show a decent picture of what is going on with hormone metabolism but most insurance companies won't cover this extensive battery of tests and good luck convincing a doctor to even consider it.
This is why I always gasp at PCP and endocrinologists who do a simple blood test and make life and death decisions based on it like it is the gospel. A blood test has very limited use, and if it is done only once and by itself then it is next to worthless unless it shows extreme abnormality that leaves no doubt about some pathology happening. Maybe this is the reason of the abysmal performance of ALL of modern medicine except ER - most decisions are based on basically flipping a coin (once).

 

[RisingSun]

The combination of all three should show a decent picture of what is going on with hormone metabolism[...] ALL of modern medicine except ER - most decisions are based on basically flipping a coin (once).

Or you could trust a doctor that makes decisions based on how the patient looks and feels instead of gauging numbers, and who adjusts based on how the patient reacts to treatment.