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

General Discussion
#81

Here’s a post on using DHT cream, on a penis enlargement forum (a practice I do not endorse and am skeptical of) back in 2011:
https://phalloplasty.proboards.com/post/2756/thread

Here is a relevant bit:

It is currently being used to treat micropenis cases with some success it appears. It also is used to treat low libido and Gynecomastia (man boobs). It is also currently being studied as a treatment for enlarged prostate. One of the side effects reported in the first prostate study (done in Britain) was improved erection quality.

@Sibelio

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#82

Wow, exciting development Sibelio. Let us know if this sticks.

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#83

Pharmacokinetics of testosterone cream applied to scrotal skin

We conclude that testosterone administration to scrotal skin is well tolerated and produces dose-dependent peak serum testosterone concentration with a much lower dose relative to the non-scrotal transdermal route.

#84

I have read multiple papers about the use of topical DHT creams (but not systemic administration of DHT) for penis enlargement in people with genetic 5ar deficiency who have a micro penis. It does work, although to a limited degree.

To the extent that it does not work well enough, the authors have concluded that it is very hard to get the DHT into the tissues. Their area of application was more narrow than what I use, however.

I try to apply the DHT on the lower abdomen as well as on the penis as there are a lot of blood vessels in that region going down into the penis. Ditto about perineum and all the other areas I talked about.

Note that topical DHT is used in these studies as systemic administration cannot achieve the same high level of tissue concentration.

This is the key argument I have been making about the difference between systemic use of Proviroin, which does not appear to work, and topical use on genital tissues. It is contingent on the fact that these key tissues require DHT concentration 10 times as high as in serum.

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#85

@Sibelio
I have used AndroGel TRT for the past four years. My “Google research” convinced me early on that applying the gel to my balls and perineum would result in higher absorption than application to the shoulders.
I’m pleased that this study backs that up. Thanks. Jim

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#86

@JimWildman Have you posted here about your results with AndroGel?

#87

I believe so. The alternative argument would be that we already have enough (normal levels of) DHT in these tissues but this administration is just supercharging the tissues with even more DHT, which shifts the sexual function curve up all other things being equal. I do not believe this is the case. I may explain why later.

In fact, the dominant theory has argued that adding more DHT would downregulate the system further and a worse outcome will be achieved. Similarly, it has been argued that DHT might boost the system initially but then a lower baseline would be reached following the subsequent downregulation.

I have not observed such effects with my method. The positive effect of DHT has been consistent and has not weakened over time.

It has to be noted that oral DHT administration MAY have worsening effect on PFS symptoms according the following theoretical mechanism.

If we assume that 5ar2 has been selectively silenced and DHT in key tissues responsible for sexual function is low to zero but in other tissues is normal to high (due to higher serum concentration of Testosterone intended to compensate lack of 5ar2), then systemic administration of DHT will suppress Testosterone production. The net effect on libido from higher serum DHT but lower serum T may be negative. We already know that lowering DHT increases Testosterone and the opposite has been shown as well.

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#88

A theory of the pathophysiology of PFS: finasteride, or discontinuing finasteride, permanently disrupts functioning of the SRD5A2 gene. This gene might be responsible for producing the 5-AR enzyme, which in turn metabolizes T to DHT.

Reasoning:

  1. Melcangi et al paper noting methylation of SRD5A2 in CSF of PFS patients
    https://ec.bioscientifica.com/view/journals/ec/8/8/EC-19-0199.xml

  2. Link between the rare disease 5-AR Deficiency and SRD5A2 mutations as noted here:
    https://rarediseases.info.nih.gov/diseases/5680/5-alpha-reductase-deficiency

This condition is caused by mutations in the SRD5A2 gene and is inherited in an autosomal recessive pattern.

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#89

There is a lot more that goes into reasoning than this. I have described it in detail above. True, I need to write a proper summary.

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#90

@anon22245532
“…Have you posted here about your results with AndroGel?..”

Just searched my records.

My first check, pre-Androgel, showed total testosterone at 38 on a scale of 72 to 623. This was the only time the free testosterone was checked, and it was .91 with a scale of 3.67 to 13.9. Both low obviously.

Since then, on AndroGel, my total test has been checked twice yearly:
667, 231, 544,
681-immediately before Proscar
283-Four months post-Proscar
75-without AndroGel last month

Do these numbers help in any way? Jim

#91

This is something which I suppose may well be the case too.

Sibelio, you must be very careful to avoid ‘step changes’ in androgen levels by say, stopping to apply the cream all of a sudden. You’d want to avoid creating a similar condition to what Finasteride would do to DHT levels. It may cause upregulation of receptors and other unknown mechanisms.
But you’re pretty switched on, so I know you’re aware of the risks, as you’ve stated previously.

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#92

Yes, it is a risk. I currently apply the cream only once a day, at night, and I go into very noticeable withdrawal with unpleasant side effects before I apply the next dose. So concentration is fluctuating a lot which is not good.

It is very hard to be constantly dependent on something and manage it well, especially if takes so much time and effort to do properly.

The other thing I have noticed is some prostate pain and difficulty urinating. I don’t know if prostate can get enlarged in 4 days. At any rate, this is a very risky procedure.

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#93

Yes they do, thanks. So it sounds like without AndroGel, your T sinks to the bottom of the acceptable range, or below, and AndroGel boosts it back up?

Still, from patient reports and my own labs, it seems that T levels are not the issue. Rather, the hypothesis is that we cannot properly metabolize T to DHT because of disruption of 5-AR activity, possibly through methylation of the SRD5A2 gene (per Melcangi research).

So even with high T, we would have deficiencies of DHT or other substances in the androgen metabolic pathway.

(Per Traish research, the metabolic pathway is not linear and is complex, so there may be more than one weak link. For example, the disruption of 5-AR could cause further damage downstream in the metabolic pathway, but we don’t know.)

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#94

Great work. There are at least three scenarios for onset. All this is a hypothesis for discussion.

Scenario 1: Take finasteride long-term (months or years)

  1. No immediate PFS symptoms
  2. Optional: develop PFS symptoms later while still taking finasteride
  3. Discontinue fin
  4. Crash (?)
  5. Persistent PFS symptoms

@Sibelio You are suggesting that these scenarios may resolve or improve long-term. The hypothesis is that because finasteride was initially tolerated, this class of patients does not show immediate susceptibility to methylation of SRD5A2 gene.

PFS arises because of dysregulation in the androgen metabolic pathway, but the pathway can recover.

Scenario 2: immediate PFS

  1. Just 1 dose or a few doses
  2. Immediate PFS symptoms
  3. Discontinue drug
  4. Crash (?)
  5. Persistent PFS without resolution

@Sibelio You are suggesting that this scenario may be irreversible (currently) because the SRD5A2 gene has been methylated and no longer functions.

But there is a scenario where Type 1 does not resolve – that’s my scenario. I did not have an immediate adverse reaction to fin around 2007/2008. Mild sexual dysfunction became apparent in 2010. It got much worse suddenly in 2013. Then I stopped fin, crashed, and adverse sexual effects persist to this day with little or no improvement in nerve sensitivity or libido.

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#95

@Sibelio Sorry if I missed it, but, what is the brand of cream you are using, your dose and schedule? Thanks.

#96

I am currently using a cream but that was custom made in a compounding pharmacy. My dose is around 1ml once a day, which is about 1000mg of cream - the size of a 1000mg fish oil pill. This contains 25mg of DHT.

It is not easy to get one’s hands on a DHT formulation. The only commercially available product that I know of is Andractim DHT gel, which is available in Europe. There are ways to get it on the internet but supply is irregular and shipping outside of EU does not work.

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#97

My theory may be wrong or it may have to be made more complex! I am receiving important new data that I currently cannot explain with my theory. The account below is preliminary and incomplete.

When I started the new application method - applying a bigger amount of DHT cream on the perineum and also starting rectal application - I changed one additional thing in my method. I didn’t think this was a significant change but it might turn out to be one.

I switched applying DHT from twice daily to once daily - at night, while keeping total dose the same. I did that for two reasons. First, I get unpleasant mental side effects from high DHT. I wanted to have my DHT concentrations during the day to be lower so I can think better. Second, the new application method is more time consuming and doing it twice a day is difficult.

As I have mentioned before, at present I go into noticeable withdrawal every day hours before my next dose. I am going to describe at a later time what this withdrawal feels like. Importantly, however, I have started to associate rising libido with this symptoms of daily withdrawal. I get the effect consistently every day.

In fact, it seems my libido is strongest at night right before the next dose, which of course is counter-intuitive. Libido is in fact extremely strong - with visual lust as well. I can go into details but let’s just say I have strongly improved sexual function on all fronts.

I am going to do some experiments to test this new hypothesis. I already skipped rectal application last night and did not notice any weaker positive effect today. Today I may apply the cream on a completely different body part and not in the genital region. I have a couple of other tests in mind as well.

I know someone else who says his PFS is in remission when he uses a DHT cream. The curious thing is he uses it only once a day. He does not apply it on genital skin but does systemic transdermal administration. I will investigate this with him further.

I have additional data on hormone levels that I will add later. For now I will say that Progesterone, Estradiol and Prolactin all went down when I started DHT. Testosterone was supposed to go down but didn’t.

I will later describe in detail the nature of this DHT withdrawal, and what I think it is due to, which may point to the etiology of the positive effect on sexual function.

Stay tuned.

@orthogs @anon22245532 @anon5006275 @Famajor @Dubya_B

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#98
  • What DHT analogon/brand do you use? (as far as I know some can be converted into estrogenes others don’t)
  • Applying it to genital skin and rectum is mucosal skin, so I suppose a systemic uptake, please correct me if that is wrong? Is this kind of DHT analogon converted or degredated in the liver? If yes, rectal application bypasses the liver and leads to higher systemic dosage
  • What are your metal DHT side effects (both when taking and withdrawl)?
  • What are the DHT withdrawl symptoms you experience?
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#99

Update: I don’t think it is the withdrawal that’s boosting libido and sexual function. Libido fluctuates throughout the day and across days so it is not easy to time it with the variation of other variables.

More likely this improved positive effect is due to reaching higher DHT concentrations than before, even temporarily. That may be doing something in the brain. Effectively, I am doing spikes of DHT now. Before, I had a more moderate, steady concentration.

It might be worthwhile to review an old post that might be relevant. It argued that the way to treat PFS is through spikes of DHT to reactivate 5ar expression in the pituitary. I am not saying I agree with it completely as there are a few obvious errors in it but I like the general idea.

For one, I have done bigger doses of DHT before and I am not cured. Perhaps a higher concentration needs to be reached regularly for these brain structures to work properly.

I encourage people not to rush into crazy experimentation with high doses of DHT. I will get to the bottom of this, hopefully, at least regarding my conclusion about the effectiveness of the method.

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#100

Quick Update: Andractim DHT gel does not seem to work very well using my method of application, although it still works. The custom made DHT liposome cream I used before works much better. My positive observations above are based on the cream formulation. I will write more about that soon and what I think it means.

Update: Turns out what I wrote in this post may not be true. Gel may be working almost as well as the cream, but something else that’s very important might be going on, which I will try to write about shortly.

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