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)
No immediate PFS symptoms
Optional: develop PFS symptoms later while still taking finasteride
Discontinue fin
Crash (?)
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
Just 1 dose or a few doses
Immediate PFS symptoms
Discontinue drug
Crash (?)
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.
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.
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.
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?
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.
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.
This is a very important update about my experimentation with topical DHT. It adds a completely novel finding with very important ramifications for the development of a theory of PFS.
Summary: Applying DHT to non-genital skin for a day, i.e. withholding DHT from genital skin for 48 hours, led to a “crash” apparent in genital tissues. Whereas previously DHT applied to genital area had a strong positive effect on sexual function, it had no effect on sexual function upon resumption of application after the crash. Presumably, lowering DHT concentrations in genital tissues led to (further) downregulation of 5ar expression in the tissues, which is how I believe PFS happens in the first place as well.
I feared this might happen as I have long postulated that PFS (type 2) happens in conditions of low or rapidly falling DHT levels. Therefore, I was hesitant to skip a day of application but I grew too overconfident after my previous success. @orthogs also warned about this risk in a post above.
To remind you, I was getting a very good effect on sexual function from topical DHT applied on penis and adjacent areas. I had been doing that for many months with excellent results - sexual function increased to 15-20% from my PFS baseline of 2%
Most recently, as I described earlier, I changed my regimen from application twice a day to application once a day with total daily dose remaining the same. This lead to a dramatically better effect, where sexual function increased to perhaps 50-60%.
I speculated earlier about the reason for this improved effect. I think it is due to the fact that with a once a day application I had more cream to apply to a wider area thus reaching more of the key tissues and also more importantly - reach a higher DHT concentration in tissues, which may be more important than maintaining more stable but lower concentrations with twice a day application.
I wanted to test whether the improved effect was due to the systemic effect of spiking DHT concentrations on the brain or on other circulating hormones. For a while I also wondered whether the improved effect might be due to a more extreme DHT withdrawal with a once daily application. This is where I left off previously.
To test this, I applied an equivalent amount of DHT gel (not cream) on non-genital skin (upper abdomen) to test the purely systemic vs. previous local tissue effect. I am very sensitive to the total systemic dose of DHT and I am confident the dose was the same, even though the formulation was different (I changed the formulation in order to conserve the cream which is in short supply). This was the first time in months I had skipped a regular DHT application to the genital area.
This method of application resulted in a much worse (practically non-existent) effect on sexual function. I concluded something I already knew from before - that systemic administration did not have much of an effect on sexual function and it was entirely local application that let to positive results.
After this test, I resumed DHT application to genital area. However, I continued to use the gel. I was rather shocked to discover that the gel had no effect on sexual function, while its systemic effect (on joints) was the same as the cream. I concluded that, while it is absorbed equally well systemically, the gel reaches lower penetration and concentration in tissues, unlike the cream. The cream is a liposome formulation and liposomes are known to deliver higher tissue concentration of active ingredients.
The following two paragraphs describes a side experiment but it is still informative. On the next day I mixed the DHT gel with a non-medical oil-based cream. The gel is alcohol-based and the alcohol evaporates very fast, which makes it hard to apply the formulation to a wide area, nothing to say about putting it on mucose skin. I used the same amount of gel as before (about 2 grams).
During the application, I immediately noticed the absence of the typical rush I feel when I apply DHT. My suspicion was confirmed the next day when my joints started hurting which is strong evidence that my systemic DHT dose was much lower. I also had no effect on sexual function. I concluded that mixing the alcohol based DHT gel with an oil based cram somehow chemically deactivates the DHT.
Then I resumed regular local application using the DHT cream, following the same protocol I had used before that was producing the improved results. To my surprise, I discovered that it had no effect! I used it for a couple of days in a row without any significant improvement. While before I was at 50-60 percent of sexual function now I was at zero.
I had crashed!
I never thought I would utter these words but it happened.
Next, I will describe why I think this happened and more importantly what I think this implies for the etiology of PFS. Stay tuned.
Sorry for asking this very amateurish question but how do you think is it possible that a topical cream used for the genital area can spike libido and arousal (thus in the brain)?
Thank you for your efforts trying to better understand this
It is a good and reasonable question and it has been asked before. I have attempted to give an answer but I can try again.
Libido and arousal are not only in the brain. There is a whole chain of organs and tissues participating in the process and they all play their part. This is not appreciated or understood very well I think.
My experiments have shown me, and that is a result which might be of interest to science in general, that partially restoring the function of sex organs and associated nerves through DHT improves sex response and its perception along the whole chain.
I cannot say if PFS has affected only said organs or also parts of the brain. I assume the latter. Certainly the pudendal nerve can’t be the only nerve affected. So obviously I have not been able to target tissues along the whole chain.
This is reflected in the fact that success was only partial at the peak of my improvement and it was certainly still lacking a big part of the psychological component of arousal and libido. But some of it was back.
I have not measured my DHT recently. The post below describes how my hormones changed soon after I began DHT supplementation 7 months ago.
Before supplementation, my DHT was 175 pg/ml (300-850). After beginning of supplementation and at the peak of DHT concentrations (one hour after application of a fast absorbing liquid formulation), DHT was 605 pg/ml.
I have since reduced the dose to about half of what I used at the beginning but I apply it only once a day so I assume DHT fluctuates between 300 and 550 within a 24 hour period.
When I am at the high end of this range I don’t feel well cognitively. I function much better with lower DHT and I am sure my natural serum level before PFS was always in the low normal range.
Thank you very much for your kind and elaborate answer. I was surprised because my understanding was/is that a stimulus spikes arousal in the brain which would then lead to an erection. This is also my explanation why many of us experience weak erections if there is no constant manual stimulation (and even then a full erection is not always achievable). As far as I can see usually the brain reacts to a stimulus and then activates a physiological process leading to continuous and repeated blood flow to the genital. So as Long as youre aroused blood will be pumped and eventually kept within the genital whereas Masturbation without arousal/excitement in the brain lacks this important process thus reducing or shutting down the erection immediately after stopping manual stimulation. I hope i didn’t get too graphic but that’s my understanding of this matter.
Of course hormonal deficiencies also seem to play a role concerning the sustainability of the erection.
My reasoning made sense at least to me because if you’re distracted or in a not pro sexual atmosphere (thus not being aroused) the erection would also be difficult to achieve and/or easily lost.
Okay this proves my theory kinda wrong haha. It’s pretty bizarre because when I have these very rare windows everything works accordingly whereas otherwise it’s like I described above.
To me it’s also still a mystery how people claiming they feel absolutely no stimulation can get erect with viagra as it is said even in the package that an erection would only occur with viagra if you’re sexually aroused.
Yeah I mean that’s the only thing that works for me is the ability to get those. Otherwise no libido, and everything is super numb. Surprised I can even get erections with how little feeling there is
This is an important paper which demonstrates key points I have made above:
Serum and tissue levels of DHT are independent
Tissue concentrations in prostate and in other DHT producing tissues are much higher than in serum
Direction of DHT diffusion is from tissues to serum
“Yet evidence from clinical studies indicates that intracellular concentrations of androgens (particularly in androgen-sensitive tissues) are essentially independent of circulating levels.”
“[S]tudies in which serum DHT concentrations were markedly elevated by exogenous administration of DHT had almost no effect on prostate DHT concentrations, prostate size, and lower urinary tract symptoms (see “Intraprostatic Control Of DHT in the Presence of Fluctuating Levels of Circulating Androgens” and associated references). The reason for this highlights fundamentally important control mechanisms in androgen target tissues that finely regulate pathways for androgen synthesis and degradation to maintain DHT homeostasis. These intracellular processes do not appear to be affected by circulating DHT concentrations.”
“Although DHT enters many tissues through diffusion from the systemic circulation, DHT in the circulation does not diffuse into the prostate because DHT concentrations in the prostate are markedly higher than the systemic circulation (intraprostatic DHT is on average 6- to 10-fold higher than circulating DHT)”
“Suppression of intracellular DHT levels with 5AR-Is results in reduced levels of DHT in the blood due to reduced leakage of DHT from peripheral target organs”
Dihydrotestosterone: Biochemistry, Physiology, and Clinical Implications of Elevated Blood Levels
Another paper that makes the same point as above: “Circulating concentrations of sex steroid hormones are poor surrogate measures of the intraprostatic hormonal milieu.”
Relationships between circulating and intraprostatic sex steroid hormone concentrations
Abstract
Background
Sex hormones have been implicated in prostate carcinogenesis, yet epidemiological studies have not provided substantiating evidence. We tested the hypothesis that circulating concentrations of sex steroid hormones reflect intraprostatic concentrations using serum and adjacent microscopically-verified benign prostate tissue from prostate cancer cases.
Methods
Incident localized prostate cancer cases scheduled for surgery were invited to participate. Consented participants completed surveys, and provided resected tissues and blood. Histologic assessment of the ends of fresh frozen tissue confirmed adjacent microscopically-verified benign pathology. Sex steroid hormones in sera and tissues were extracted, chromatographically separated, and then quantitated by radioimmunoassays. Linear regression was used to account for variations in intraprostatic hormone concentrations by age, body mass index, race and study site, and subsequently to assess relationships with serum hormone concentrations. Gleason score (from adjacent tumor tissue), race and age were assessed as potential effect modifiers.
Results
Circulating sex steroid hormone concentrations had low-to-moderate correlations with—and explained small proportions of variations in—intraprostatic sex steroid hormone concentrations. Androstane-3α,17β-diol glucuronide (3α-diol G) explained the highest variance of tissue concentrations of 3α-diol G (linear regression r2=0.21), followed by serum testosterone and tissue dihydrotestosterone (r2=0.10), and then serum estrone and tissue estrone (r2=0.09). There was no effect modification by Gleason score, race or age.
Conclusions
Circulating concentrations of sex steroid hormones are poor surrogate measures of the intraprostatic hormonal milieu.
Impact
The high exposure misclassification provided by circulating sex steroid hormone concentrations for intraprostatic levels may partly explain the lack of any consistent association of circulating hormones with prostate cancer risk.
This is not the best place for this post because it is about joint pain but because it adds more evidence for my theory of PFS, the bulk of which is contained on this thread, I am posting it here for now.
I would like to amend the post about joint pain above with some additional evidence. Previously I said that I believe joint pain results from weakening of the joint from lack of DHT. The second part is true - low DHT causes it, as I have confirmed to myself a hundred times, but not due to weakening.
Weakening, I imagined before, happens when there is pressure on the joint through use. For example, walking would weaken the joint. However, I have new evidence that when I take a low dose of DHT, I get joint pain even without moving. I can literary lie in bed all day, as I have done, and I would get hip joint pain if my last DHT dose was too low. Such symptom progression is more likely caused by something like inflammation.
Pain appears very fast when serum DHT drops below a threshold. I take DHT once every 24 hours now and if I delay my dose by a couple of hours or if I have taken a slightly lower dose, I get joint pain. When it first starts, pain is burning in nature and is rather diffuse. Upon administering transdermal DHT, the pain goes away after an hour and a half or so, which is rather astonishing.
In addition, before I began DHT supplementation, I also had elevated Rheumatoid factor IgG – 29.8 U/ml (norm up to 20.0), as described here: Joint pain. I have not measured this recently to compare how it has changed.
Finally, an important paper below explains the mechanism through which DHT protects against joint inflammation. This paper was sent to me by @Lw77.
Dihydrotestosterone inhibits interleukin-1α or tumor necrosis factor α-induced proinflammatory cytokine production via androgen receptor-dependent inhibition of nuclear factor-κB activation in rheumatoid fibroblast-like synovial cell line.
Abstract
Rheumatoid arthritis (RA) is a disease with significant gender differences in its prevalence and clinical features. Interleukin (IL)-1 and tumor necrosis factor (TNF) α produced by synoviocytes are principle inflammatory and destructive mediators of RA. We found that a potent androgen, 5α-dihydrotestosterone (DHT) inhibits IL-1α-induced production and mRNA expression of IL-8, IL-6 and IL-1β from RA patient-derived fibroblast-like synovial cell line MH7A. Promoter analysis of the IL-8 gene revealed that nuclear factor (NF)-κB activation is critical for its transcriptional activation by IL-1α, and DHT inhibited the IL-1α-induced NF-κB activation in a manner dependent on the androgen receptor (AR). DHT also inhibited the effects of TNFα on the cells overexpressed with AR, indicating that sufficient expression level of functional AR was necessary for the inhibitory effect of DHT on TNFα. These results suggest that androgen contributes to the prevention against RA and its gender difference by inhibiting IL-1α or TNFα-induced proinflammatory cytokine production from synovial fibroblast-like cells by inhibiting NF-κB activation in a manner depending on AR.
