Testosterone, DHT, Estrogen Balance

[docj077]

He's referring to the estrogen receptor subtypes.

Then what was that bit about "all estrogen is not created equal"?

If you look hard enough, you'll find websites that discuss different types of estrogens. Some have beneficial effects on the body while others have almost deleterious effects. Studies have demonstrated this phenonemon, however, science still has absolutely no idea how the different steroid hormone subtypes interact in the nucleus, so it's really fruitless to base one's opinion on that area of cellular genetics and interactions. So, in reality, such websites are useless.

The body's response to estrogens is completely individual and it is somewhat concerning if a person desires to remove all estrogens from their body. Afterall, your body absolutely requires estrogen for normal development and maintainence of sexual characteristics (ESPECIALLY, libido). Without estrogen, you don't get epiphyseal closure, maintainence of bone density, or normal libido.

But, if you desire to inhibit both DHT and estrogen production via a 5AR inhibitor and an aromatase inhibitor, you'll simply shuttle testosterone in pathways that result in the formation of inactive metabolites; androsterone and etiocholanolone. Of course, that is until you saturate the enzymes that mediate that process.

 

[Bryan]

Actually, what I was interested in is the following specific statement he made which seems highly confused to me:

The biggest thing here is that all estrogen is not created equal, studies showing that it is good involves the Beta while studies showing it is bad shows the Alpha.

I want to know what he means by "Alpha" and "Beta". If he's referring to the two different types of estrogen receptors, then what does that have to do with the fact that "all estrogen is not created equal"? If he's implying that all estrogen molecules consist of either an "Alpha" version or a "Beta" version, then I want him to document that for me, because I've never heard of such a thing. That's why I asked him what the Sam Hell he was talking about!

 

[harold]

In looking for info on the relative strengths of various antiandrogens I was interested to see that estrogen actually has a pretty decent affinity for the androgen receptor and is actually capable of eliciting a fair bit of response from the androgen receptor.

Yeah, but that depends on what you mean by "response". Do you mean a true ANDROGENIC response, or something else?

In the study I read it elicited transcription of the same genes when given in high enough dose. So yeah i guess it would be termed a true androgenic response. Though in a male you would probably never see such a situation physiologically due to the androgen/estrogen ratio.

As are powerful antiandrogens such as cyproterone acetate. It has forced me to think of these hormones/compounds as weaker stimulators of the AR rather than as antagonists. Which is not really news but I guess I was shocked to see that if you had no androgens in your systm and you then added a whole bunch of cyproterone acetate or even estradiol in all probability you would be worse off than if you had none.

I can't really quite go along with that. It seems to me that it shows a true biphasic effect, not an overall weak androgenic effect. Some of these "antiandrogens" like cyproterone acetate (and possibly other ones like flutamide and RU58841) do have ANTI-androgenic effects at low-to-moderate concentrations, but begin to show a PRO-androgenic effect at much higher concentrations.

I guess thats exactly what I was saying though. The biphasic effect is only due to them being much less effective agonists so that when they are around to compete with DHT the effect is one of much less androgenic activity. The biphasic effect and weak androgenic effect go hand in hand.

Interestingly flutamide seemed to have no ability to stimulate androgenic transcription whereas the far more potent antiandrogen hydroxyflutamide did in high enough doses. The problem is that you need about 30 times as much flutamide to get the equivalent effect of a given amount of hydroxyflutamide. The upshot being that you are probably better off having a drug which is a weak to moderate agonist of the AR but has a high binding affinity than a pure antiandrogen with a weak affinity at the end of the day.

Well, the relative concentrations of the two would be an important factor, too.

True.

All of this makes sense when you consider that men on finasteride can usually maintain pretty much all their hair with more testosterone in their scalp and less DHT. Even testosterone could be viewed as a "weak antiandrogen" when compared to DHT.

You know, that was actually the rationale that Durk Pearson & Sandy Shaw used in their book "Life Extension" to justify the use of topically-applied testosterone to fight male pattern baldness!

Now that is very interesting! I suppose it could work if you saturated the 5 alpha reductase enzymes and then completely blew out the local THT ratio. Might just be crazy enough to work!

If all this is true then it is interesting to see just how much AR activity is needed to have a significant impact on hairloss and that it seems hair is actually quite resistant to at least some stimulus. Maybe.

Good point, although I also suspect that the timing of the androgen suppression or withdrawal is important, too. I think stopping it well before balding starts to get advanced requires less androgen reduction than waiting untill balding is well on its way.

I think I agree. With the recent study showing that balding dermal papillae were more susceptible to environmental stress and the converging stufff (IMO at least) about oxidative damage I think that if you could catch it early or nip it in the bud then you can deal with a bit of low level androgenic activity a lot better than if your follicles are mostly at the prematurely senescent stage. to say nothing of collagen deposition and its possible relation to "slick-bald" areas - the "end game" of the balding process.
hh

 

[RaginDemon]

doesnt injecting estrogen give one man boobs and limp dick?

 

[eddy_simpson]

Bryan I am surprised that you are unaware that by alpha estrogen he is referring to estradiol, as opposed to estrone and estriol, which are said to be the two weaker estrogens.

Since the three estrogens compete for the same receptor sites, the greater the levels of the weaker estrogens, the lesser the ability of estradiol to reap it's 'feminine effects'.


It is my understanding that phytoestrogens also weakly bind to receptor sites, again preventing estradiol from doing so, thus exerting a similiar effect to estriol and estrone.

To cut a long story short, I understand that:

Estradiol = bad.
Estriol, estrone and phytoestrogens = good.

 

[docj077]

Bryan I am surprised that you are unaware that by alpha estrogen he is referring to estradiol, as opposed to estrone and estriol, which are said to be the two weaker estrogens.

Since the three estrogens compete for the same receptor sites, the greater the levels of the weaker estrogens, the lesser the ability of estradiol to reap it's 'feminine effects'.


It is my understanding that phytoestrogens also weakly bind to receptor sites, again preventing estradiol from doing so, thus exerting a similiar effect to estriol and estrone.

To cut a long story short, I understand that:

Estradiol = bad.
Estriol, estrone and phytoestrogens = good.

"Alpha estrogen" is not 17beta-estradiol. When he says alpha and beta, he is referring to the different estrogen receptor subtypes for which 17beta-estradiol has pretty much equal affinity. Estrone binds preferentially to the alpha receptor while estriol typically binds to the beta receptor. Phytoestrogens can usually bind to either type of receptor, as well, but their action is far weaker. The binding of 17beta-estradiol likely mediates the inhibition of the telogen-anagen transition through the binding of estrogen receptor alpha. This binding also increases keratinocyte proliferation in the basal layer of the epidermis which also causes thickening of the epidermis. There are alpha estrogens like 17alpha-estradiol, etc., but their binding and biological effects are far less when compared to their beta molecules.

Those "feminine" effects that you speak of are the reason why women don't typically encounter hair loss until menopause.

You NEED estradiol as a man (even in the little concentrations you have) for various physiological maintenance processes.

 

[Bryan]

Bryan I am surprised that you are unaware that by alpha estrogen he is referring to estradiol, as opposed to estrone and estriol, which are said to be the two weaker estrogens.

"Alpha estrogen" is not 17beta-estradiol. When he says alpha and beta, he is referring to the different estrogen receptor subtypes for which 17beta-estradiol has pretty much equal affinity.

Well, as I pointed out in an earlier post in this thread, none of us really know FOR SURE what the hell he meant when he talked about "alpha" and "beta" estrogen. I've asked him more than once to clarify that, but he still hasn't done it.