Can someone explain if/how neurosteroids are affected and what it means?

General Discussion
#142

Very interesting. So in your case, initially Finesteride works by basically selectively blocking one, several or all 5AR to stop the conversion of T to DHT to prevent hair-loss. This has disrupted/retarded the AR signalling and 5AR activity.

At this point to me it seems there is only one reliable way but to reactivate those two components; the AR in the tissues and thus in turn the 5AR and thus T/DHT conversion… but going through your theory, it seems you think there is a tri-dependent relationship between AR, 5AR and the T to DHT conversion. I wonder if activating one as a tinder can act as a spark to jump start the other two…

I wonder that is probably way people on this site were so drawn to the creatine as it instantly metabolises T to DHT and gives them instant relief. I’m wondering if creatine at low doses (say half a teaspoon every second day for an example) can give a stimulatory effect to activate 5AR and thus the T/DHT conversion which will slowly awaken the down regulated AR in parts of the body over a sustained period of time. Slowly increasing circulating 5AR in the body may stimulate the AR is just my thought. In turn, the AR will be stimulated to produce more DHT, thus stimulating 5AR and thus the tri-dependent relationship starts working again.

This combining with a 5AR supportive diet and resistance exercise which I believe will stress/urge and demand the body to restart this tri-dependent relationship. Exercise is likely to deplete DHT, and thus when depleted will demand the body to produce more through the tri-dependent relationship - this is where the 5AR will need alot of support through 5AR support foods, low dose supplementation (as it has been selectively damaged blocked from Finesteride).

In my case though, I have not selectively blocked 5AR but just damaged the tri-dependent relationship thought exogenous DHT (disrupting the signalling of AR and 5AR). In which case, I believe the same approach as above (for me) is worth a shot.

#143

I have not looked into creatine. I will try to read about it.

In general, whenever you have a self-regulatory system which is propped up by an exogenous supplementation, the challenge is how do you avoid crashing the system when you withdraw the exogenous element. I guess slow withdrawal is better but would it be sufficient - I don’t know.

The AR is upregulated in PFS. The reason for this, I believe, is that AR is negatively regulated by DHT. When DHT is low, AR gets upregulated. Notice that my theory is based on the assumption that it is the opposite with 5ar2 - there is a positive regulatory effect of DHT. There are papers that show this for 5ar2 but not for 5ar1. In any case, things are definitely more complicated than this simple model.

I don’t think it is correct to say that DHT gets depleted from exercise. It is indeed increased by exercise though through upregulation of 5ar. Interestingly, AR is also increased by exercise. So the entire system is forcibly put into overdrive by exercise to increase androgen signal.

NB!

I hope I will write a separate post about this but I have already noticed the effects of resistance exercise on increasing DHT in the muscles/joints. My joints/muscles are DHT insufficient and as a result there is inflammation, which results in extreme joint pain (I have provided a paper about this in the thread above). I control the pain with exogenous DHT.

Since I have started exercising, the pain has gone down significantly and I require a lot less DHT. I have lowered my DHT to less than half what I needed before to remain pain-free. I don’t know yet if this effect will be permanent but I guess I would have to do this for longer.

While I have no doubt this is working in muscles/joints, the question is can it also work in peripheral tissues such as pudendal nerve, penis, prostate, etc? From what I have seen in the literature it can but the effect on 5ar there might be smaller, so it might require a bigger exercise load/full body effort, plus might take much longer.

#144

Yeah you are right. My guess is not to rely on creatine as a means of reliance but to stimulate 5AR and in turn the AR - as well as stress the body to demand the creation of DHT (and in turn further stimulating AR signalling and 5AR).

Yes not depleted by DHT but stimulate the demand for it through exercise - or any activity that will require the body to produce DHT in general (watching porn?) without masturbation?

#145

Shit, thats complicated. So you got a see-saw, inverse relationship…where you can fix one but not the other and vice versa.

Does Finesteride target all 3 5AR?

#146

It probably targets all 3 but with different affinity. Type 2 is affected the most. They used to think type 1 is not affected but now they know it is, just less. It might be interesting to observe how people with PFS from finasteride vs. dustasteride differ. 5ar1 may have a different regulatory mechanism than 5ar2 so it might be more resistant to crashing. It’s possible.

In your case, even though you did not take a specific 5ar inhibitor and you just had a sudden drop in DHT, your 5ar silencing may still be concentrated in the type 2, since that may be more sensitive to drops in DHT.

There is a paper about the sensitivity of the different types of 5ar to DHT. Will try to remember where I can find it.

#147

@provironabuser Do you have changes in urinary function as well - reduced pressure, slower urinary flow, urinary drip, incomplete emptying of the bladder, etc?

#148

Yes. I attributed this to having an enlarged prostate due to the exogenous DHT (Proviron) but it could also be due to the new veins (varicose) in the penis?

It could also be due to the structural size change of the tissue due to decreased size of the penis (due to low DHT)

If you fix the entire issue, I am pretty sure this issue will go away.

#149

DHT is what makes men, men. So it is more a Testosterone (T) to produce DHT issue than a Testosterone issue. Focus of effort must be in assisting and supporting the Androgen Receptors (AR) and 5 Alpha Reductase Enzymes (5AR) to support the conversion of T to DHT. Although boosting T will also indirectly stimulate AR and 5AR to assist in the conversion. Sorry just a brain dump of what I have learnt being on this forum to address my issue.

Insights;

#150

If you have PFS, urinary problems are likely due to lack of DHT in prostate and other pelvic muscles, not to enlarged prostate. The prostate requires DHT to function. Lack of DHT may also lead to prostate inflammation (similar as in joints), and of course to shrinking of the prostate. Most people with PFS don’t have and have no reason for an enlarged prostate since they never had high levels of DHT.

#151

Yeah you are probably right. I didn’t start have urinary problems until after a few months after discontinuing proviron.

One also needs to focus on liver health like a detox since T to DHT conversion is done in the liver (via 5AR)

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#152

caffeine acts as a catalyst to the 5-alpha reductase enzyme.

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#153

This is a good point. Thanks Sibelio. It explains why your recent exercise is helping certain parts of your body.

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#154

Likely. Probably need to exercise your penis by watching porn without masturbating. Maybe repeat exposure may stimulate your AR in that region just like you have with your other muscles/joints. Or get blowjobs, even despite it not working.

#155

Hello, just an update on this. I took Milk Thistle in moderately high doses after discontinuing Proviron. I am more inclined to think now my PFS symptoms are more likely from the Milk Thistle as opposed to the discontinuation of the Proviron (whereas they both likely have contributed to my current state).

Came across this which has made me think this;

Having said that, I am still having bad side effects.

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#156

Most likely milk thistle caused PFS in your case then, I don’t think I’ve found any stories of people crashing from proviron permanently. But I wonder if you would still respond to Proviron if you were to go back on it again.

#157

Yes I am very much inclined to think so. I am now following this guy’s posts who crashed from Milk Thistle too; https://forum.propeciahelp.com/u/invictus/activity

#158

hi @sibelio just wanted to check how you got your dht cream compounded? how do you go about this? I dont think the all saints clinic compound this any more. btw topical application of dht cream is one of the treatments prescribed by goldstein with apparently effective results

you may be on to something

#159

In this study we demonstrate the cancer protective potential of silibinin, a flavolignan derived from the fruits of Silybum marianum, which down-regulates the co-activator of the androgen receptor, the prostate epithelium-derived Ets transcription factor (PDEF) and consequently the secretion of PSA [22].

#160

Does anyone know more about PDEF and secretion of PSA?

It seems milk thistle down regulates the co-activator of the AR as stated above, the co-activator being PDEF - prostate epithelium-derived Ets transcription factor

#161

The down-regulation of basal as well as DHT stimulated PDEF and PSA by silibinin demonstrates the antiproliferative potential of this agent. These effects underline the possible therapeutic use of silibinin in the management of prostate cancer.

Silibinin = Milk Thistle

Note to self;

Milk Thistle; Androgen Receptor down-regulates the co-activator of the androgen receptor, the prostate epithelium-derived Ets transcription factor (PDEF) and consequently the secretion of PSA.

Androgen Receptor seems to be blocking DHT/T and current T/DHT levels being produced by body is not fully being utilised. Androgen Receptor severely BLOCKED.

It is unknown if increasing the density and/or activation of current Androgen Receptors (i.e. via Tribulus etc) will undo the inhibition of the co-activator of the androgen receptor, the prostate epithelium-derived Ets transcription factor (PDEF).