Because of over expression lowering androgenic activity has helped some.
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Vitamin A supplementation increases levels of retinoic acid compounds, but Vitamin A it is also a 5ari.
All carotenoid are 5ari, for example Astaxanthin.
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Straight up DHT isnât the answer to our cure. Transdermal testosterone heavily transforms into DHT. And DHT derivative steroids exist that donât bring us a cure.
I personally believe there may not be a cure you take once and youâre cured forever, but a treatment that you take daily to replace what is lost in the body.
I have most of the worst physical symptoms of PFS, as well as the worst neurological and sexual symptoms of PSSD. And I only took ADs.
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I also broâŚ
in my point of view that doesnt make sense. what is lost in the body ? something is not working correctly or is silenced. nothing is lost. we dont have a lack of hormones
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Thatâs not entirely true.
ââŚdecreased levels of pregnenolone, progesterone and its metabolite (i.e., dihydroprogesterone), dihydrotestosterone and 17beta-estradiol and increased levels of dehydroepiandrosterone, testosterone and 5alpha-androstane-3alpha,17beta-diol were observed in CSF of PFS patients. Neuroactive steroid levels were also altered in plasma of PFS patients, however these changes did not reflect exactly what occurs in CSF. Finally, finasteride did not only affect, as expected, the levels of 5alpha-reduced metabolites of progesterone and testosterone, but also the further metabolites and precursors suggesting that this drug has broad consequence on neuroactive steroid levels of PFS patients.â - Melcangi 2017
Lowered progesterone, preg, and dihydroprogesterone are found in our CSF. He goes on to say that those further metabolites and precursors (like allopreg) are also effected. Iâm not saying that this is the sole cause of PFS, but simply that it was found that these chemicals are low in concentration in our CSF.
But yes, you may be right that something is silenced or malfunctioning in addition to the low neurosteroids in our bodies. Iâm not disagreeing with you there.
This is amazing information thanks for sharing
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This study reveals valuable information about mental and physical problems in PFS patients. If someone has problems with SRD5A2 then they have trouble creating the steroids that give us energy, confidence, focus, vitality, libido etc etc etc. Here is more on SRD5A2:
Reference: https://ghr.nlm.nih.gov/gene/SRD5A2
âThe SRD5A2 gene provides instructions for making an enzyme called steroid 5-alpha reductase 2. This enzyme is involved in processing androgens, which are hormones that direct male sexual development. Specifically, the enzyme is responsible for a chemical reaction that converts the hormone testosterone to a more potent androgen, dihydrotestosterone (DHT), in male reproductive tissues.â
Although must of us suspected this, it is good to have science to back it up.
If what you said is true, it is very easy and very fast to check SRD5A2 status with all DNA and RNA testing technology that exist today.
What it is even more shameful is that RC Melcangi in Italy had done 2 studies and already published and Baylor study the first part is not even have been published yet
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(emphasis mine)
As far as I understand it, almost half of PFS patients did not have methylated SRD5A2 promoters. If that half also has horrible side effects, the mechanism behind PFS has to start somewhere else and the SRD5A2 might be a downstream effect for some. If 95% had an abnormality versus control and it explained physical symptoms we are onto the juicy stuff :).
If what I am saying is false, correct me. Just how I as a regular sufferer with no scientific background read the above summary.
I agree with you here. Another interesting takeaway from this study is this:
âUnmethylated controls compared to unmethylated SRD5A2
patients showed higher pregnenolone, dihydrotestosterone and dihydroprogesterone,
together with lower testosterone CSF levels.â
Even if you didnât have methylation of the gene and had PFS, you still had lower preg, DHT, and dihydroprogesterone. From my interpretation, methylation isnât the sole cause of lowered CSF concentrations of the chemicals I just mentioned. And in addition, âIn PFS patients, neuroactive steroid CSF levels were not significantly related to the percentage of SRD5A2 gene promoter methylation.â
My TLDR:
- controls are less likely to be methylated in the 5ar2 gene.
- unmethylated controls have more of the neurosteroids mentioned.
- If you do have methylation, the amount of neurosteroids in your CSF is not related to the amount of methylation.
- symptomology (ED, depression, etc.) was not correlated with methylation amount.
- Itâs impossible to tell if the methylation was a result of finasteride, or if we were born that way based on this study
- âIf abnormal SRD5A2 promoter methylation is established prenatally, these subjects
could be predisposed to develop the PFS and alteration of neuroactive steroid levels in thebrain. In this case, treatment by finasteride might precipitate a dormant depressive
phenotype linked to such specific epigenetic pattern, resulting in the clinical picture
described previously.â - There were a low number of subjects in this study, so these results shouldnât be taken as a universal proclamation.
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Boys, please stop being scientists, because you are not! This publication is important, but it doesnât help us. Unfortunately, it has not added important information. There is still a lot of work to do. You have been a scientist for 10 years, but you are not!
@Rb26dett I wouldnât call this information unimportant. Any information is important, and it can tell us about our condition. Read my comment above for my âTLDRâ that I believe highlights the important features of this study. Can you imagine if Melcangi discovered that 100% of the PFS subjects had methylation of the 5ar2 gene? Weâd be freaking out here. I think his study had a good aim (to see if methylated gene sequences were the cause/effect of PFS), but it had shortcomings. I personally applaud Melcangi, although he is very focused on the 5ar2 byproducts and precursors. The more noise is made in PFS research, the better for us. Iâm thankful Melcangi is taking a chance with us at least.
To me, an unimportant finding would be something like, âsome finasteride users experience ED.â
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If mohit âdrag my feetâ khera would finish his lolly gagging comparison of genes study for 6 years now we might actually see which ones are affectedâŚ
Apologies for being a bit off topic but since everyoneâs discussing science, anyone got any idea what would cause the skin to become stretchy/lax and slow to repair?
Even if Khera was to determine which genes have been silenced, at this stage thereâd be little we could do about it anyhow.
Collagen synthesis is dependent on sex hormones although not sure which ones.
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Hopefully it can return to normal or at least near normal if those hormones are restored. I expect some skin damage to persist like the deep stretch marks untill technology gets better, but even if it was firm again Iâd be happy. Look like a pale ghost now lol but it could be worse I guess.