Sibelio, have you looked at the theory behind how Zulresso works on treating women with post-partum depression? I think the onset of post-partum depression is triggered by high hormone levels during pregnancy and a similar kind of failure for everything to equilibrate after birth when there is a large step change in hormone levels.
As to back your theory up, i have some psychological (?) obsessions about my erections. So when i start to get an erection, sometimes, i think about my condition and my erection ends in the mid way. I can feel the bloodflow stop. Well, thats kinda very obvious though… i just wanted to say.
How have you been doing lately?
The treatment I was already doing was working incredibly well. Had I not discontinued it abruptly for two days and crashed, against my better judgment, it would have continued to work, as it was working for months on end.
I am yet to write more about what the results of my experiments mean - there are a lot of very important ramifications, which it seems are not realized by most people - and I intend to but I can’t do it right now because I am busy with other stuff.
It seems to me that a permanent solution, if it is possible, needs to achieve an increase in tissue concentrations of androgens (mostly DHT but perhaps T as well) and avoid their sudden withdrawal. Ideally this would happen endogenously - for example through exercise. This is a plausible mechanism for long-term improvement, at least theoretically.
Alternatively, the tissue increase of androgens may be done exogenously - either through DHT or Testosterone - although that route has challenges as I have mentioned. I continue testing this method and I am trying to find out if I can reverse the crash. So far there is no success.
The most immediate and cheapest experiment that can be done to causally demonstrate that (or investigate if) the cell’s androgen signaling regulatory mechanism can be crashed by lowering DHT is in cell culture. That is in addition to the other experiments I have proposed in the posts above.
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Another possible line of treatment may lie in suppressing DNA Methyl Transferase 1, which is responsible for de-novo methylation but also maintaining existing methylation of 5ar2. This may be possible through affecting inflammatory cytokines.
<< We have shown that the SRD5A2 gene contains a promoter with a rich CpG island capable of being methylated.6 Because epigenetic factors can regulate the expression of genes,7 we hypothesized that methylation of SRD5A2 leads to reduced SRD5A2 gene expression and protein production during adulthood in benign prostatic tissues. We show that members of the DNA methyltransferase (DNMT) family regulate methylation of SRD5A2 . The three DNMTs, DNMT1, DNMT3a, and DNMT3b,8,9 can be classified as de novo methyltransferases that are able to both methylate previously unmethylated CpG islands and maintain methylated genomic information by copying pre-existing methylated nucleotide sites into new DNA strands during replication.10,11 Specifically, we show that DNMT1, and not DNMT3a or DNMT3b, regulates methylation of the SRD5A2 gene promoter. This epigenetic modification generally functions to repress gene expression>>
The paper was posted in a different thread, here:
It should be read in conjunction with this other paper as well:
Hello Sibello, I can maybe confirm this. I have never used any hairloss drugs or anything. I have been lurking here for the past 4 hours and was shocked to read that I am suffering from quite a number of symptoms you guys are suffering from.
I abused proviron (and proviron only) in small amounts (2 pills per week for 6 months, total of ~50 pills) starting Jan 2019. I got this terrible rash around July 2019 and quit it cold turkey at that time. From then until now, I have contracted varicose veins in various parts of my body (legs, hemorrhoids, penis and varicocele) which is caused by the rebound effect of estrogen. I am also struggling from a sleeping issues, shriveled penis, blurred vision, minor pelvic pain on right side, loss of morning erections and libido. I am also suffering from depression, anxiety, suicidal ideation although I believe this might be improving (hard to say as I am having intermittent bouts of good days and bad days).
I have got my blood work done which is as follows (taken 2 weeks ago).
S Testosterone 21.2 nmol/L (9.9 - 27.8 )
SHBG 23 nmol/L (17 - 56 )
S Albumin 43 g/L (36 - 47)
Free Test 555 pmol/L (170 - 670)
S Cort 483 nmol/L (133 - 537)
Prolactin 463 mIU/L (90 - 400)
S Oestradiol 130 pmol/L (< 160)
S DHEAS 7.5 umol/L (2.4 - 11.6)
S FSH 5.5 IU/L (1.5 - 9.7)
S LH 4.4 IU/L (1.8 - 9.2)
As you can see my prolactin and estrogen are very high which I believe are contributing to my unstable mood (depression and anxiety) - but now I know there is something deeper at play here.
I also don’t know what my DHT levels are (not that the reading would be accurate and indicative of how I am feeling as you suggest).
Previously, as a person I was very driven, motivated and ambitious (with a very healthy sex drive) but as you can guess, I am now a shadow of that person. I can only hope with time (or any recommendations you might have) I will get back to where I once was.
Just as a side which might be useful for some; cold showers and cold exposure (ice baths) alleviate all my symptoms of depression, anxiety and suicide etc. for a good few hours. Icing my balls also helps too (as the varicocele causes issues too).
My goal right now is to simply wait and reduce my prolactin naturally (with Vitex Chasteberry) and supplement with the standard androgenic vitamins; zinc, vitamin B etc. However, I still have issues with my varicose veins which I am not sure will resolve on their own (all medical evidence points to; no it doesn’t).
I might also add I do have some semblance of sexual desire (libido) but it is at 5% of what it was prior and nowhere near as enjoyable. Getting and maintaining an erection is also difficult (whereas previously automatic, spontaneous and regular).
Hope this helps and keen to hear your thoughts (if it might help me or the others).
Really SHIT situation (Slept at 1am, woke up at 4.30am and 6.40am as I type this).
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Hi @provironabuser,
Welcome to the forum! I am very sorry to hear about your symptoms. You are not the only one who has gotten PFS or something resembling PFS without having taken finasteride. Others have gotten it from extreme low calories diet, or from extreme exercise, or from various supplements and even foods.
I believe PFS is caused when the cells in key tissues lose their ability to regulate androgen signaling through the interplay of 5ar expression and the androgen receptor and are stuck at a state of very low level of androgen signaling. This likely happens when DHT drops suddenly - before the AR can be upregulated enough to maintain a steady androgen signal, which shuts down 5ar expression. As I have written above, 5ar expression is likely positively regulated by the androgen signal.
Sudden drop of DHT may cause PFS either when a 5ar inhibitor is introduced or even without it when exogenously administered DHT is withdrawn. My crash withdrawing from transdermal DHT cream, described earlier, demonstrated the latter case and the way I got PFS originally (after a single pill of finasteride) demonstrates the former case. Your case may be another confirmation.
In your case you took proviron for a while, which probably raised your serum DHT, which would have also downregulated your AR. The tricky part is that higher serum DHT would not affect tissue concentrations significantly, at least tissues with really high DHT concentrations such as the prostate, although it may still affect them sufficiently.
When you discontinued proviron suddenly, the theory goes, the AR being downregulated brought you to a state of androgen signalling lower than your original normal state. This might have been sufficient to crash 5ar expression bringing you to a new equilibrium of low DHT. As I have said before, this process is no doubt a lot more complicated and with many intermediary steps involving other proteins.
I believe it would be very helpful for you to measure your DHT levels, although you may have normal serum DHT and still have low tissue DHT, as I have written before. Your symptoms may alternatively be caused by the high prolactin, although I don’t think your plolactin is high enough to explain your symptoms. You may also want to have a brain MRI to rule out prolactemia secondary to pituitary tumor.
My advise would be to abstain from supplements because you don’t know what effect each supplement might have. For example, zinc may be a 5ar inhibitor and B vitamins may promote DNA methylation. It is best in my opinion to try a natural diet combined with a lot of exercise, particularly resistance training. I am currently in the process of testing this regimen myself and may soon write about some of the observations I have gathered.
Have you in your research seen anything resembling your condition on body-builder forums? No doubt body builders take a lot of androgens that sometimes they get off cold turkey. In same cases that crashes their T production, which is one type of problem, but perhaps in other cases someone may also get something like PFS. I have heard about a state of sexual dysfunction known as deca-dick but I have not researched it. It might be informative to look into that a bit.
P.S. The deca dick reference above was entirely exploratory and not based on any previous knowledge. I know nothing about it and I am not suggesting it is related to PFS. It looks like there are multiple potential mechanism to explain it.
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thanks for this. your theory seems very plausible. So in most simplistic terms we will need to increase AR (5ar) and the androgen signalling.
On the top of my head the only way I can think of this is to go through a period of cell regrowth to heal the body (which will hopefully repair/increase 5ar and the androgen signalling as well anything else that has been damaged).
I am at my wits end here so I am going to continue with cold exposure, cold showers, cryotherapy, intermittent to full day fasts and healthy diet with a lot of probiotics. I hope it helps.
This is so shit but I appreciate your input.
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Hey @provironabuser I’m sorry you’re going through tough times. The admins put a lot of work in developing a scientifically validated survey that is meant to help to stimulate scientific progress and understanding of our problems. It’d be great if you could create a member story and take the survey. You don’t have to do it all at once, you can actually save progress and and complete it within a couple of days. All the best and thank you very much
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In addition to deca dick, Tren dick is a thing too, sometimes persisting for up to seven months after discontinuation. some of the bro scientists have theorized that its possibly due to overstimulation of the CNS because tren is so androgenic
Just searching deca dick on t-nation to see if anyone got over it… found this guy’s response who claimed to be over it, for the most part. Seems he used creatine as a buffer off Proviron.
xColemanx
Proviron is the answer but 100 mg proviron/daily may surprise 5-alpha enzymies.Creatinin helps a lot with raising 5-alpha enzym. 1 service of creatinin + 50 mg proviron /daily is the answer. You must use this 3-4 months.2 months proviron +creatinin, and then creatinin alone.use higher dose of creatinin after you stop proviron. Use some viagra for performance anxiety also. Your mind is important as hormones also.this things worked for me , not %100 but it is ok.im married and have good sex life.
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This is interesting bluejaysfan, thanks for this. Its interesting. I luckily have creatine in my pantry. I will try it regularly for 6 months. See what happens. Check this out;
https://examine.com/nutrition/does-creatine-cause-hairloss/
Am I too simplistic in thinking that we are all suffering from DHT withdrawal - and in theory we need to retraining the conversion of T to DHT?
So, I have been exogenously administering DHT. Therefore, there has been a deregulation of whatever processes that are involved with converting the T to DHT. At this point, it is that enzyme called 5-alpha-reductase. Following from what @Sibelio said below. It makes sense I should do whatever I can to ‘stimulate’ this enzyme, androgen signalling and the receptors.
The way forwards;
Supplementing any and all sources of 5-alpha-reductase (Creatine… TBC)
Blanket Treatment in a hope to promote androgen signalling and stimulation of receptors;
Healthy exercise, Cold Showers, Cryotherapy and Fasting to promote cell growth (TBC)
@Sibelio has been particularly insightful with the following;
< I believe PFS is caused when the cells in key tissues lose their ability to regulate androgen signaling through the interplay of 5ar expression and the androgen receptor and are stuck at a state of very low level of androgen signaling. This likely happens when DHT drops suddenly - before the AR can be upregulated enough to maintain a steady androgen signal, which shuts down 5ar expression. As I have written above, 5ar expression is likely positively regulated by the androgen signal.
Sudden drop of DHT may cause PFS either when a 5ar inhibitor is introduced or even without it when exogenously administered DHT is withdrawn. My crash withdrawing from transdermal DHT cream, described earlier, demonstrated the latter case and the way I got PFS originally (after a single pill of finasteride) demonstrates the former case. Your case may be another confirmation. >
nah you’re probably right, the only issue is answering the question “why don’t we ever come out of withdrawl”. Nobody has a concrete answer to this thus far
Found a few more deca dick possible fixes… here’s the thread. Basically, post #1 and #6.
I think #1 could be dangerous, especially the high dose vitamin A. The guy who posted the #6 option, doesn’t seem to have had it, just thought #1 was overkill. I’ve been looking for a while on that forum and these deca dick cases either dont get resolved often or the guy’s stop posting once the do.
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I’m barely in range on the dht blood test. I wish these deca guy’s had dht bloods just to compare but I didn’t notice any.
So something is up with your conversion to T to DHT since…DHT comes from T (DHT is a metabolite of T). The conversion is not happening or something.
I have no idea what my DHT levels are; but I am going to supplement heavily with creatine and all other supplements to hopefully ignite and restart the 5AR and then DHT. Starting with creatine… then DHT / 5AR boosting foods. For e.g.
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Great. I will take all from this. Not touching any of the drugs though. I made my mistake.
Get some feedback on creatine before you jump in. Maybe the amount you take or brand makes a difference on how safe it is.
OK creatine has been tried by many…some with even worse later results. This is scary.