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

All the evidence I have seen so far - in the literature and in real life, my own data included - points in the direction of malfunctioning 5a-reductase. The benefit of this theory, as of any theory that is a candidate of being a true theory, is that it explains all the available evidence - including the low neurosteroids, and including the physical changes - shrunken dick, etc.

I have written more about this in this post and in the last post of the same thread. Tribulus stopped working. What else works?


How do you explain that taking exogenous DHT (proviron) doesn’t even provide minor improvement, or even makes symptoms worse, in the vast majority of cases? That’s the reason why no one believes in this theory.

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Serum DHT levels are a poor predictor of tissue-specific DHT levels. So proviron may boost serum DHT levels, but this may well not translate to tissue-specific levels. This has been shown.


I agree with the fact that they are poor predictors however for me the theory cannot be true because if the cause were androgen deprivation then you would notice at least slight improvement. How is it possible that not even a few molecules of proviron can enter the affected area and bind to the AR? If the cause of persisting side effects were androgen deprivation then even a minute amount of androgens would give significant relief. I have taken doses of 500 mg proviron for extended periods of time and noticed no improvement, in fact I even experienced worsening, my conclusion is that this theory is impossible.


Hey @arkaeik, I hear you - this was the reason I was always confused as to why every time I tried DHT, it wouldn’t work. “Surely SOME increased level of DHT would have an effect, I mean this is why I took the hair pill in the first place - to reduce DHT!” I was convinced it was at the receptor level. I tried local DHT and Oxandrolone - and both really didn’t do anything for my symptoms. Local DHT had a moment of recovery, but then didn’t work at all.

Aside from the point that these drugs generally raise serum DHT levels, and our issues (I would think) are mostly related to brain and penile tissue specific areas (BBB issues may arise and so forth); we are also forgetting the other piece of the puzzle. The study above is meant to largely address what FIN does to our neurosteroid levels and its fundamental impact on our brain functioning and reward systems. DHT is but only one piece of the whole 5-AR ‘cascade’ so-to-speak, and only a piece of what a malfunctioning 5-AR would affect. Even if we had high levels of DHT (which, thankfully I do), if our neurosteroid levels are non-existent or impaired, then no amount of DHT will have an effect on our reward systems. We still won’t be able to get the full erections we’re used to, we won’t have the pleasure centers correctly firing for full libido & stimulation, and our mind-body reward system will be generally incapable of functioning like normally functioning male. I would imagine a malfunctioning 5-AR system would lead to a whole host of issues. Simply introducing increased serum-level DHT would seem to me like putting fuel into a car with no tires.

My goal with the above is to have a collaborative discussion though, I could be very wrong. This is a hypothesis I’m coming to based on years of back-and-forth on this forum, researching, and the testing of multiple protocols. @Sibelio please contribute anywhere where I may be incorrect.

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First, as @orthogs mentioned above, raising systemic DHT will almost certainly not lead to preferential saturaton of important tissues. Research has shown that tissue concentration of DHT in prostate is ten times higher than in serum. That’s because DHT is produced locally in the tissues and the direction of transfer is from tissues to serum.

Second, if 5ar2 is damaged in certain tissues, that leaves 2 other enzymes to produce DHT in other tissues, which may be enough for serum concentrations to appear normal. Further, there is not a good correlation between serum concentration and tissues concentration of DHT, as per the same paper, which is cited in the following post of mine.Tribulus stopped working. What else works? Just because someone has normal serum DHT does not mean they do not have DHT insufficiency in certain tissues.

Third, people with PFS have been found to have higher level of precursor hormones (progesterone, free tesosterone). This is my hormonal profile as well. Higher level of precursor hormones is an attempt of the body to increase the synthesis of 5ar hormones, despite the malfunctioning 5ar enzyme.

Now, when serum DHT is raised through supplementation, this will fool the body that 5a-reductase is functioning properly through negative feedback loops, which in turn will decrease precursor hormones. It is not clear what the total effect on tissues DHT will be but it is clear that tissue concentrations of 5a-DHP and allopregnanolone will fall, as progesterone is reduced. This may lead to worsening symptoms.

I have personally observed this feedback effect. I have very high progesterone, well above range. When I started using DHT, my progesterone fell by 33%. This is described in the following post from the same thread as above: Tribulus stopped working. What else works?

Fourth, local application of DHT to the genital area works well for me. (WARNING: This may be carcenogenic.) It really matters where you apply it, how much you apply, and what the formulation is. In one of the posts above I describe the pattern of application that produces the biggest effect. No doubt such topical application cannot reverse all symptoms of PFS as DHT is lacking not just from the genital area but also from key nerves in the body and in the brain.

Fifth, I am not sure how many of you have joint pain, but I used to have extreme and highly debilitating joint pain. Administering DHT systemically all but eliminates the joint pain, depending on the dosage I use. This is extremely strong evidence that DHT deficiency is causative for joint pain. I hypothesize that soft tissues holding the joint together are DHT dependent and they weaken from lack of DHT, which results in weakened joints. I have additional evidence to support this conjecture (obtained before I even began DHT treatment), as the nature of my joint pain indicates it originates from the soft tissues (spreads along the muscles), and no joint abnormality was found on a MRI.

Sixth, Melcangi’s latest study clearly demonstrated that patients with PFS suffered from methylated 5ar2 gene. This is in addition to previous research finding low levels of 5a-DHP and allopregnanolone in spine fluid, as well as upregulated AR. The latter can easily be explained by low androgen signal due to low tissue DHT.

People have tried to argue that Melcangi’s study proves 5ar2 malfunction is not causative for PFS because only 50% of the sample had that finding. This is an extremely important point that needs to be addressed thoroughly, because failing to understand this point has held our community back for decades and will continue to hold us back going forward, no matter how much research is done on the condition. I may try to address it in greater detail in another post, but here is a short version for now.

Everybody knows and understands that changing the body’s hormonal balance exogenously can lead to a prolonged disruption of hormonal balance upon discontinuing the exogenous intervention, which manifests as hypogonadism. This happens in body builders who take various steroids and then discontinue them, and it is known as HPTA axis shut-down. This also happens in prostate caner patients who take a combination of anti-androgens (including finasteride) and then discontinue them. The latter group takes multiple years to go back to baseline. I may insert the chart from that study later.

Then why can’t we fathom that taking finasteride and then quitting can also lead to prolonged hormonal disregulation that will result in hypogonadism? In fact this disregulation may be very stable as a new equilibrium is established, and may need targeted intervention to change, although is likely to normalize over time by itself. In fact we have evidence that a fraction of PFS sufferers normalize with time. These PFS suffers don’t need to have any changes in gene expression to suffer from hypogonadism.

This is what Melcangi’s study shows as well - a fraction of people with PFS symptomology do not have gene expression problems. In other words, it is very likely that there are two types of PFS. What I would call PFS Type 1 represents hypogonadism secondary to hormonal disregulation. This type is likely to recover over time, especially as their androgen receptors are normalized.

Patients with the second type of PFS, PFS type 2, most likely suffer from malfunctioning 5ar2. This group is unlikely to recover following the same mechanisms as the first group. Put bluntly, these are the people who do not get better over time. They are also likely to have additional symptoms secondary to 5ar insufficiency that the first group may not have. It is important to note that this group may also have hormonal disregulation early on similar to the first group, in addition to having malfunctioning 5ar2, which may partially or seemingly completely resolve over time (but not upon closer inspection of tissue levels of 5ar hormones).

The two types of PFS, type 1 and 2, because they are very different conditions, are likely begotten in different ways. The first type likely happens after finasteride is discontinued and may be related to the degree of AR overexpression. The second type most likely happens suddenly, as a switch being turned off - including from a single pill of finasteride. This mechanism does not require any degree of prior AR upregulation.

Attempts to use one causal mechanism to explain both types of PFS is a mistake. This is manifest when people discount the role of malfunctioning 5ar2 citing evidence from people who do not have this irregularity. Similarly, a theory postulating the existence of a single causative mechanism cannot explain contradictory and apparently mutually exclusive circumstances of getting PFS (i.e. from a single pill vs. after AR upregulation and subsequent AR overwhelm). I talk more about this here: Initial Ideas - Working from First Principles


The theory doesn’t make sense for one very important reason. Normal people who take proviron or other androgenic steroids will experience increased androgenic function in all different tissues. In fact proviron is often used in people with delayed puberty, and it works very well. This is proof that exogenous DHT does in fact reach androgenic tissues, but in people with PFS it must not have an effect due to an unknown mechanism.


Backing up @arkaeik here. Anecdotal experience but I know (non PFS) friends who’ve taken DHT derivatives in the gym and they had pretty clear androgenic responses from it.

@Sibelio Your initial post doesn’t make sense. Why would anyone take DHT derivatives if all they did was raise serum DHT levels in a blood test while not having any effect on the desired tissues?

Also, you’ve stated that local application of DHT to the genital area works for you. I don’t know if you’re aware but Blackfox stated that applying DHT cream to his genital area literally shrank his genitals.


@arkaeik and @borax Thanks for your comments! This is very helpful. I will try to respond later.

If anyone else has any other evidence or theory contradicting what I am arguing, please post.


I have taken Keto-DHT-17 I think it was the name from Propeciahelp and notice effects on brain. Also took Oxandrolone and definetly noticed some pro DHT feelings also. Last time I took 5 pills and drink a lot and I was king of the dance floor and very good eye contact with girls, definetly something going on. I went after my last cycle with Oxandrolone to have some watery semen so I think t affected me somehow.

Last thin to comment is the week that I followed a brocolli + asparagus diet everyday, and last day I didnt took brocolli, I noticed a big surge in male sexual behavour pro DHT, And I thought it was because brocoli is know to block DHT to be in contact with prostate and then suddenly it allowed a lot (maybe more because asaragus Idk).

And how are you today in terms of libido and ED?

It is assumed that finasteride has passed through the blood-brain barrier and damaged our brains. GSK seems to be aware of this.

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Sorry can you explain your post a little more what di you say about brai barrier?

Drugs have to be able to penetrate the blood brain barrier to have effects on the brain, if Finasteride penetrated the blood brain barrier it has free reign on thousands of mechanisms. God knows what damage it produced…

I explained our situation by mailing to the dermatologist who wrote the post. me also asked him if I could personally access the material released at the symposium. I am waiting for a response.

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Thank you man.

Thanks everyone for the critical feedback. I believe the theory I advocate for can account for most of the points raised above. I am not claiming that what I am going to say is the only possible explanation but it is certainly a logical one.

The gist of the criticism above is that normal people without PFS do get an androgen response from systemic DHT, whereas people with PFS do not. The quotes below summarize this criticism.

It is important to know exactly what kind of androgenic effects normal people get from systemic DHT. Are we talking about falling hair, higher libido, larger muscles or deeper voice? It is crucial to specify exactly where the effects are and how strong. More about this later.

Of course we need to exclude from this particular analysis any effect of “other androgenic steroids” that in normal people may work through conversion to DHT in tissues or may require the balancing of DHT they already have present in tissues.

For example, you cannot claim that because Testosterone raises libido in normal people but not in PFS people, therefore PFS people are not sensitive to Testosterone. This is because Testosterone may exert its effect on sexual function largely through its conversion to DHT in key tissues.

Back to the effect of systemic DHT. It is entirely possible and is in fact most likely the case that different tissues in the body require a different concentration of DHT in order to function properly. It is known, for example, that skin at different places in the body has a different concentration of 5a-reductase.

This distribution is not likely to be binary - i.e. either 5a-reductase is present or not, but it is likely that even within tissues with high DHT requirement there is a range of optimal concentrations. There must be a lot of research about this and I encourage anyone to try to verify or disprove the claim above.

It is therefore expected that systemic administration of DHT will be adequate to different degrees for different tissues. One tissue may be getting close to optimal or in fact way above optimal levels of DHT, while another may still be starved.

My only evidence of the systemic effects of DHT administration in people with PFS comes from my own experience. I have observed androgenic effects in a wide range of tissues, which does confirm that systemic DHT indeed reaches tissues and has an effect on them, despite PFS.

What I claim, however, is that the effect is differentiated for different tissues based on their base level requirement for DHT. The tissues responsible for sexual function may require a higher level of DHT, which cannot be supplied through reasonably high systemic administration.

Some of the effects of DHT I have observed are the following:

First, my hair is significantly affected and sheds a lot when I supplement systemic DHT.

Second, my joints react immediately to systemic DHT and stop hurting. This is a profound effect and is the main reason I use DHT.

Third, I also experience stronger body odor when I use systemic DHT.

Forth, I experience a deeper voice, which I admit is quite unexpected and puzzling to me, because I have always assumed that voice masculinisation reaches a peak during puberty and it is not possible to further lower the voice with androgens. I did not observe a significant effect on voice previously with a liquid DHT formulation but I am currently observing it with a liposome formulation, which may indicate a different degree of absorption. I don’t know yet if the effect is permanent or transient but this is an androgenic effect nevertheless.

Fifth, I observe psychological effects of increased aggression and impulsivity and reduced anxiety.

Sixth, I also do observe an effect of systemic DHT administration on sexual function (libido, erection frequency and strength, sensitivity and pleasure) which is dose dependent but it is indeed rather weak for the doses I have used. (I do not use doses that would raise my serum DHT above the normal range). This may easily mean simply that the DHT requirements of the tissues responsible for sexual function are much higher than what’s possible to achieve with systemic administration.

This is confirmed by my experience that sexual function improves significantly more when DHT is applied topically to a broad abdominal and genital area, and the effect is also dose dependent. I get no morning and nocturnal erections when I am at my PFS baseline but I do every night when I apply DHT topically. I can also get spontaneous erections of various strength, which is impossible otherwise.

In no way, however, does this local administration of DHT lead to a complete reversal of PFS, as no doubt numerous unreachable tissues in the body are involved in sexual function, such as the pudendal and vagus nerves, the prostate muscle, and regions in the brain.

The fact that application of topical DHT on the broader genital, perineal and abdomen area (likely reaching the prostate and pudendal nerve to some extent) works better than narrow application to the penis, but worse than systemic application (i.e. application on the hands) indicates the importance of high DHT concentrations in key tissues involved in sexual function.

I cannot explain reports about shrinking penis from local DHT application but I do not find them sufficiently credible. I did read reports about such an effect but one guy claimed to have used the formulation only once and the other only briefly. I find it highly unlikely that any perceived shrinkage as a result of a single or brief DHT application represents in fact tissue loss, as that is simply not physically possible in my opinion.

At the same time, I have also read reports about the opposite with topical DHT administration - penile tissue growth, which I do not necessarily trust either. I have so far not observed any effect one way or another in myself. I believe any effect on the penile tissue is likely to require long-term administration.

As I have said before, such application is likely very risky before proper dosing can be determined and I do not recommend it due to cancer risk. I currently apply the DHT only to the abdomen and not on the penis.

I would like to solicit evidence about the effects of systemic DHT administration in healthy people - not on androgenic functions in general but on sexual function specifically. If systemic DHT in reasonable ranges has only a week effect on sexual function, as I believe is the case, this would completely explain the lack of effectiveness of systemic DHT in PFS people without indicating androgen insensitivity.

Finally, this theory supposes that 5a-reductase type 2 function is absent from key tissues to a greater extent in PFS than during regular fiansteride administration in non-PFS subjects. At least it is my experience that while on finasteride I had reduced but almost normal sexual function, whereas now I have almost complete absence of sexual function.

Any further feedback or criticism would be highly appreciated.


Your theory would explain why many people including a friend of mine report increased libido from proviron. Strange how some poeple respond paradoxically but there are people without pfs who notice no libido increase from mast and proviron too.

Why would my hair thicken back up but hair look prepubescent if there was nothing to the localized dht inhibition?

I don’t understand your comment. I am postulating that systemic DHT would have little effect on libido - PFS or not.

If you are aware of any evidence about the effect of DHT on libido in healthy people, please post. That would be very useful. I am sure there are forums with users who have tried it.

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This theory is parsimonious because it explains all available evidence, in my opinion, in the most simple way possible.

It is also a lot more optimistic theory than a theory arguing that not one gene, 5ar2, but many (androgen-dependent) genes are epigenetically silenced, as that would be much harder to fix presumably.

The theory is easy to test. It requires a single test: DHT concentration in prepuce of people with PFS and controls. An additional confirmatory test would be 5ar2 expression from prepuce.

Almost thirty years since finasteride was unleashed on the public, no such test has ever been done, to my knowledge.

Likewise, this community has waited for Baylor for 7 years and has not mobilized resources to do such a simple and cheap study.