Estradiol+DHT relieves PSSD in rats

[namaste]

I know this topic technically belongs in the studies sub-forum but I thought I'd post it here for more visibility. In late 2014 a study was published showing a complete relief of PSSD symptoms in rats treated with an antidepressant at birth. To date, this is the only journal reference I can find of this kind.

Hormone replacement with 17β-estradiol plus dihydrotestosterone restores male sexual behavior in rats treated neonatally with clomipramine
https://www.ncbi.nlm.nih.gov/pubmed/25449595

In the study, rats were given clomipramine neonatally, which induced severe PSSD-like symptoms that persisted through adulthood (almost zero interest in sex being one of them). Through blood tests it was found that the adult rats had normal levels of testosterone and estradiol. When treated with a course of estradiol+DHT, the symptoms were completely reversed.

Why might this have worked? Well, one theory is that PSSD is caused by persistent 5HT1A receptor desensitization. SERT is probably involved in this, along with sex steroids upstream of that. The following article shows a link between estradiol and SERT density.

Estradiol-17 beta increases serotonin transporter (SERT) mRNA levels and the density of SERT-binding sites in female rat brain
https://www.ncbi.nlm.nih.gov/pubmed/9105666

[mention]gbolduev[/mention] has already mentioned how this fits under his progesterone theory. I was curious if anyone else has thoughts on this topic, as it might influence how we go about our trials moving forward. Unfortunately I am unable to find the full journal article at this time, which would likely include dosing information for the estradiol+DHT.

 

[Snell1234]

He also says he doesn't think it will stick for us though.

 

[TeslaFan]

Quoting [mention]gbolduev[/mention]

"Taking DHT will only work with taking estrogen at the same time."

...in the context of PFS, and from the following saved post:

http://www.hackstasis.com/viewtopic.php?f=20&t=21&p=747#p747

 

[wuf]

Quoting @gbolduev

"Taking DHT will only work with taking estrogen at the same time."

...in the context of PFS, and from the following saved post:

http://www.hackstasis.com/viewtopic.php?f=20&t=21&p=747#p747

@gbolduev told it could be effective only while on it and it shoul not stick.

 

[Jaxx]

It indeed did not stick with this person and the effects declined while on it. But there were apparently significant benefits. Trial was very messy though with other drugs and as far as i know was tried by 1 person only.

Good to put here imho to build on the theory

 

[namaste]

It indeed did not stick with this person and the effects declined while on it. But there were apparently significant benefits. Trial was very messy though with other drugs and as far as i know was tried by 1 person only.

Good to put here imho to build on the theory

Yup, my point was not to suggest this as a potential remedy that people try. It's clear through gbold's comments that estradiol+DHT just acts as a band-aid. I think there is much to learn by analyzing the results of this study, though.

 

[IHateFin]

if activating prog receptors lowers estrogen and DHT then the inverse should be a "cure" so DHT plus Estrogen should tank progesterone no? thats probably why this works i would assume. only issue is once you withdraw exogenous hormones you have to let your body get back to producing them on its own which is the tricky part.

 

[Flynn]

Quoting [mention]gbolduev[/mention]

"Taking DHT will only work with taking estrogen at the same time."

...in the context of PFS, and from the following saved post:

http://www.hackstasis.com/viewtopic.php?f=20&t=21&p=747#p747

Can anyone briefly explain why this is? why will DHT have no effect on say sex drive etc. unless in conjunction with estrogen. I know this is just a temporary fix. But one thing that has always confused me. Is when I took exogenous testosterone, it had no effect on my sexual sides etc. is this because I never used estrogen as well? @gbolduev @TubZy

 

[ruprmurdoch]

Can anyone briefly explain why this is? why will DHT have no effect on say sex drive etc. unless in conjunction with estrogen. I know this is just a temporary fix. But one thing that has always confused me. Is when I took exogenous testosterone, it had no effect on my sexual sides etc. is this because I never used estrogen as well? @gbolduev @TubZy

1.As far as I know, people tahe Proviron (DHT derivative) without Estrogen, and it rasise their libido and sperm quality. But those people do not have PFS.

2. DHT + Estradiol is for Case #2 - antagonized receptors- Highish progesterone

3.DHT is Opposition for Estradiol and vice versa. I think this is the main reason why you have to take both when you are in case #2 PFS - to upregulate dht and estradiol receptors.

4. Exogenous testosterone almost always rise testosterone and estradiol. There is aromatase enzyme in body that convert testosterone to estradiol. Many people who take exogenous testosterone take proviron with it to counterbalance estradiol.

 

[Flynn]

1.As far as I know, people tahe Proviron (DHT derivative) without Estrogen, and it rasise their libido and sperm quality. But those people do not have PFS.

2. DHT + Estradiol is for Case #2 - antagonized receptors- Highish progesterone

3.DHT is Opposition for Estradiol and vice versa. I think this is the main reason why you have to take both when you are in case #2 PFS - to upregulate dht and estradiol receptors.

4. Exogenous testosterone almost always rise testosterone and estradiol. There is aromatase enzyme in body that convert testosterone to estradiol. Many people who take exogenous testosterone take proviron with it to counterbalance estradiol.

Ok, I was under the impression that DHT + estrogen worked for everyone. Surely increasing DHT and estradiol would downregulate their receptors rather than upregulate. I think it is something to do with opposing progesterone. But I don't fully understand. Note that proviron is an aramotase inhibitor so it has an anti-estrogen effect.

@TubZy said that most people use 11-keto-DHT I think versus proviron but I may be wrong. I feel more confused than when I started haha.

 

[TubZy]

Ok, I was under the impression that DHT + estrogen worked for everyone. Surely increasing DHT and estradiol would downregulate their receptors rather than upregulate. I think it is something to do with opposing progesterone. But I don't fully understand. Note that proviron is an aramotase inhibitor so it has an anti-estrogen effect.

@TubZy said that most people use 11-keto-DHT I think versus proviron but I may be wrong. I feel more confused than when I started haha.

Hey, I just kinda answered this in the other thread RANDOM QUESTIONS

But, I hate proviron honestly, it is basically a synthetic DHT, I would not use it in any circumstance. I tried it so many times in the past with no luck. If you are going to use DHT, use bioidentical DHT (either 11 keto DHT, DHT gel, androsterone (precursor to DHT) etc.) and use it with progesterone or cortisol (see other thread)

Estrogen makes DHT sensitive that is why it could help activate DHT again when they are supplemented together. But like you said, this is just a patch not a cure since you are just fixing the tail end of it.

 

[stefoo2]

Hey, I just kinda answered this in the other thread RANDOM QUESTIONS

But, I hate proviron honestly, it is basically a synthetic DHT, I would not use it in any circumstance. I tried it so many times in the past with no luck. If you are going to use DHT, use bioidentical DHT (either 11 keto DHT, DHT gel, androsterone (precursor to DHT) etc.) and use it with progesterone or cortisol (see other thread)

Estrogen makes DHT sensitive that is why it could help activate DHT again when they are supplemented together. But like you said, this is just a patch not a cure since you are just fixing the tail end of it.

What's your reason for not liking proviron? Is it only because its synthetic?

I tried taking it about a year ago but I only lasted 3 days because it made me feel extremely dehydrated

 

[TubZy]

What's your reason for not liking proviron? Is it only because its synthetic?

I tried taking it about a year ago but I only lasted 3 days because it made me feel extremely dehydrated

Never felt good on it, I got some of the physical effects, but just made me feel weird. Any of the synthetic AAS are only going to put you worse off in the long run because they will down regulate DHT even further. It is legit an AAS not a prohormone. A prohormone like androsterone for example is something that already exists in the body to convert into something else (DHT in this case). So rather than stimulate the pathway you are shutting it down even further with proviron. It also acts different than normal endogenous DHT as well, it binds much stronger to SHBG.

Proviron is already active given it is already 5 alpha reduced plus the fact that it is methylated.

Mesterolone - Wikipedia

"Mesterolone, also known as 1α-methyl-4,5α-dihydrotestosterone (1α-methyl-DHT) or as 1α-methyl-5α-androstan-17β-ol-3-one, is a syntheticandrostanesteroid and derivative of DHT.[14][15][1] It is specifically DHT with a methyl group at the C1α position.[14][15][1] Closely related AAS include metenolone and its estersmetenolone acetate and metenolone enanthate.[14][15][1]The antiandrogenrosterolone (17α-propylmesterolone) is also closely related to mesterolone.[16]"

"Uniquely among AAS, mesterolone has very high affinity for human serum sex hormone-binding globulin (SHBG), about 4.4-fold that of DHT.[13][1] As a result, it may displace endogenous testosterone from SHBG and thereby increase free testosterone concentrations, which may in part be involved in its effects.[1]"

 

[Ghost]

I think that the main thing with E2 here is that it's protecting SERT in the POA. That will decrease 5-HT activity and stop the 5-HT dampening of Dopaminergic activity.

 

[ruprmurdoch]

Hey, I just kinda answered this in the other thread RANDOM QUESTIONS

But, I hate proviron honestly, it is basically a synthetic DHT, I would not use it in any circumstance. I tried it so many times in the past with no luck. If you are going to use DHT, use bioidentical DHT (either 11 keto DHT, DHT gel, androsterone (precursor to DHT) etc.) and use it with progesterone or cortisol (see other thread)

Estrogen makes DHT sensitive that is why it could help activate DHT again when they are supplemented together. But like you said, this is just a patch not a cure since you are just fixing the tail end of it.

and what type of estrogen you recommend ?

 

[tanedout]

Guess resveratrol (for estrogen) and R-andro (for DHT) would do it? Anyone tried that combo?