Are we significantly overlooking the potential importance of estradiol/estrogen with regards to androgenization?

In a post I made earlier today I postulated that perhaps a clomid/zinc combination was able to temporarily restore my penis size via its effect on the estrogen receptor:

After reflecting on the potential reasons why there might be a potential link to estrogens, it led me to make a couple of interesting connections as to why the possible stimulation of the estrogen receptors/estrogen manipulation may have caused me to temporarily regain my penis size. First of all, I want to post this study:

This is a long and winding study, and frankly I dont have the time to go through the whole thing with a fine tooth comb nor do I have the scientific background to fully understand everything that was being discussed, that being said my general understanding was that estrogen plays some role in potentiating the androgen receptors in the brain. This excerpt seems to sum up the effect of estrogens with regards to androgen receptors:

In support of a permanent sex difference in the capacity to produce AR are studies of gonadectomized male and female rats, in which androgen binding levels in some brain regions remain higher in males despite the lack of circulating hormone (36). However, female mice, when treated with testosterone, express AR at levels equivalent to males (37); it is possible that, as in mice, female rats retain the ability to produce male-typical levels of androgen receptor in response to testosterone, particularly if estrogen receptors participate in this regulation in adulthood.

Subsequently after reading this I suddenly recalled a factoid that I had heard a long time ago regarding racial differences in estrogen (estradiol levels). I was able to find the study and have posted it below:

Contrary to the postulated racial difference, testosterone concentrations did not differ notably between black and white men. However, blacks had higher estradiol levels. Mexican-Americans had higher testosterone than whites but similar estradiol and SHBG concentrations. Given these findings, it may be equally if not more important to investigate estradiol as testosterone in relation to diseases with racial disparity.

I dont know about perceptions in the rest of the world but here in the US blacks are generally perceived as being more physically and psychologically masculine. Assuming that there is some truth to this stereotype then its plausible that blacks are indeed more masculine and this is due to their higher estradiol levels which would more greatly potentiate their androgen receptors, which incidentally supports or is at least related to the conclusions of the first study I posted about the mice.

Finally after making this connection I came across this study which details how estradiol (in spite of being a “female” hormone) actually plays an important role for males as well.

Traditionally, testosterone and estrogen have been considered to be male and female sex hormones, respectively. However, estradiol, the predominant form of estrogen, also plays a critical role in male sexual function. Estradiol in men is essential for modulating libido, erectile function, and spermatogenesis. Estrogen receptors, as well as aromatase, the enzyme that converts testosterone to estrogen, are abundant in brain, penis, and testis, organs important for sexual function. In the brain, estradiol synthesis is increased in areas related to sexual arousal. In addition, in the penis, estrogen receptors are found throughout the corpus cavernosum with high concentration around neurovascular bundles. Low testosterone and elevated estrogen increase the incidence of erectile dysfunction independently of one another. In the testes, spermatogenesis is modulated at every level by estrogen, starting with the hypothalamus-pituitary-gonadal axis, followed by the Leydig, Sertoli, and germ cells, and finishing with the ductal epithelium, epididymis, and mature sperm. Regulation of testicular cells by estradiol shows both an inhibitory and a stimulatory influence, indicating an intricate symphony of dose-dependent and temporally sensitive modulation. Our goal in this review is to elucidate the overall contribution of estradiol to male sexual function by looking at the hormone’s effects on erectile function, spermatogenesis, and libido.

Is it possible that by using clomid for a few weeks I was able to increase estrogen/estradiol levels and then by taking 100 mg of zinc I was able to suddenly drop estradiol levels which subsequently shocked the estrogen receptors in the penis thus causing me to temporarily regain my size?

Assuming that this is the case, would it be possible that I could achieve a more streamlined version of this by simply supplementing estradiol and then taking zinc intermittently/once a week?

More importantly, has anybody seriously tried looking into the manipulation of estradiol or the estrogen receptors for treating PFS? I feel like most PFS guys want to shy away from things that INCREASE estrogens (understandably), but I cant help but wonder if maybe for some (not all) PFS guys they would actually benefit by raising their estradiol or by manipulating the estrogen receptors in some way. In a similar fashion to how some PFS guys respond better to androgen boosters and others respond better to anti-androgens, maybe some PFS guys respond better to anti-estrogens and other PFS guys respond better to estrogen boosters. In fact there may even be an inverse relationship where guys that respond well to androgens respond poorly to estrogen boosters while guys that respond well to anti-androgens respond well to estrogen boosters (this is pure conjecture on my part)

What are the potential implications for the causes of PFS? Is there some mechanism which we have overlooked in which using a 5ari has somehow caused dysregulation with the estrogen receptor as well? I strongly suspect that this is the case and if it is then this opens up an entirely new world of ways to potentially treat PFS



Has any evidence been presented which has demonstrated estrogen receptor upregulation?

None to my knowledge, however this is because nobody has ever thought to look at estrogen receptor upregulation. That being said, my theory regarding possible estrogen upregulation is extremely speculative, its more of a mental exercise than anything. My main point is that I think we should consider the possible role that estrogen receptor dysregulation/insensitivity may play, if any. Previously I was completely unaware of how significant estradiol was for proper androgen functioning, so I can imagine that many others here are probably equally unaware as well.

*btw I decided to delete the post because I feel like it was far too speculative and it detracts from the points I was trying to make in the OP

I think there maybe something to your theory. I always have more libido the day after after a heavy drinking session and alcohol is known to increase oestrogen. There’s also PAS guy on one of the other forums (the forum mostly about HTMA) called willylong who had to raise his estrogen massively over range to regain his libido. He’s on testosterone for body building purposes.

1 Like

Could it be that be taking MediHerb Tribulus: Update: still completely recovered, raging libido for the last four years

During the taking some of the patiets have explained that they feel a lack of estrogen action, as it is supressed… maybe the creator of the thread was right and during every cycle of tribulus the receptors were increased (by lack of estrogen action) and thats why he declares that after every cycle he was getting better and better? Just an idea.

Alcohol does a whole lot more than just increasing estrogen.

Agreed, it also increases dopamine which might be where the effect is coming from, but at least it’s a different angle to come at this from that hasn’t really been looked into.

@chapman can you provide a link to the guy talking about massively raising his estrogen? I would really like to read this; maybe its possible that instead of solely attempting to raise DHT alone, we should also concurrently supplement estradiol as well; this of course is assuming that we dont have issues at the receptor level as well, which is most likely the case. But still, I feel like trying to raise both androgens and estrogens at the same time is something that maybe we havent really tried before; I feel like most PFS guys try to only raise androgens and try to get estrogens as low as possible, which as we now understand may be counterproductive

@Belikewater thanks for sharing that thread, I thought it was really interesting. I might have to try that protocol soon

1 Like

The site is private and banned on here haha so you’ll have to request access. Basically he states he injects 250mg of test a week with no AI, he has to keep his estrogen double the reference range of the labs he uses. If it drops back into the normal range he loses libido.

1 Like

This is really interesting …

It’s something we should be looking at more closely.

What site are you talking that this guys story can be found on? That’s banned here ?

Seeing that several PFS guys get worse from inhibiting estrogen this seems like it could be a clue to a mechanism of PFS

I’m thinking estrogen receptors down regulate or lack 3b-diol binding to them?
Now we need more estrogen to feel better ?

I suppose if that’s true more estrogen would mean temp fix. And we would want to up regulated estrogen receptor to fix.


@Chapman oh thats unfortunate, nonetheless thats fascinating and valuable information.

I also have a massive libido boost the morning after even moderate drinking

even after getting PFS I used to experience this somewhat but I dont experience it anymore. I have no clue why

lol k

1 Like

did you try to replicate that once again?