Did you ask Jacobs how prescribing clomid or testosterone fits into his theory of PFS? And IMO, this study is great. We need more researchers looking into fin related stuff. Probably not our root cause here but you never know how these pieces fit into the larger puzzle.
Jacobs suggests reaching out to the study authors and seeing if they have thoughts about how theyâre work connects to our issues. I plan to do that.
I love it. If youâve followed any of my posts over the last few months, most of them are about bashing Jacobs. I mean how ridiculous does that sound? A self proclaimed expert doctor in PFS who charges a hefty consultation fee and he is suggesting that his patient do the legwork to learn more about the condition. Might it make more sense that the doctor who is treating patients reach out to the researchers? Anyways back to the subjectâI emailed a researcher from that study already and still waiting to hear back. Iâve emailed many researchers and it never hurts to try, but Ive had little results. Epigenetics is just too new for even 5AR and androgen researchers to have a theoretical idea of what is going on. They are really dependent on studies, but at least they may have more a theoretical idea than anyone else. Still good to spread the word about our condition.
Why would neurosteroids cause âplaques/fibrosis, body composition changesâ ?
I think fin does damage your cells and it does make sense that this could happen when your at a weak point.
Lowering 5ar fucks up neurosteroids but it also lowers free T among other things which causes payronies and venous leak (plaques/fibrosis). Increase in Estrogen on top of this causes the body changes
If that was the case why did he not get these problems starting from when he commenced the drug?
Lowering is not the same as silencing a gene vincent
Silencing or dramatically decreasing expression of the gene for 5-ar II should have a nearly identical effect as competitive inhibition. Itâs not the enzymes themselves, but their products that matter.
I posted the OP study since many guys here seem to want to increase 5-ar activity, and the study shows a potential avenue to do this if they simply must.
(FYI: There are chemicals in many varieties of mushrooms that have strong anti-TNF-a effects. The drug entaracept/enbrel has an anti-TNF-a effect.)
Also interesting to see a treatment that effects methylation status of a particular gene promoter being used to restore expression of that gene.
-If there is some yet to be revealed gene which is silenced in PFS, perhaps there will be a similar way to restore expression of that gene.
Have to agree with vincent though; if PFS was simply a deficiency of 5-ar activity, why didnât more guys get PFS soon after starting finasteride or dutasteride, and why doesnât everyone who took a 5-ar inhibitor get strong PFS symptoms. Why do some guys with PFS have high DHT if it is a 5-ar problem alone.
Some more information on TNF-a:
Negative Association between Testosterone Concentration and Inflammatory Markers in Young Men: A Nested Cross-Sectional Study
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0061466
Tumor necrosis factor-alpha represses androgen sensitivity in the LNCaP prostate cancer cell line. - PubMed - NCBI
http://www.ncbi.nlm.nih.gov/pubmed/10953159
Acneiform eruption following anti-TNF-alpha treatment: a report of three cases. (could it increase 5-ar I / DHT in skin cells?)
http://europepmc.org/abstract/med/18246701
Good stuff, thanks.
But on the part I bolded below: Isnât the idea that certain neurosteroids that play a potentially critical role in sexual function are products of 5ar? Could it be that this becomes a problem only in guys who exhaust their existing neurosteroids? In other words: I lost my libido after getting dumped â my reaction was close to a nervous breakdown. So I exhausted my neurosteroids, and with no 5ar my body wasnât in position to replenish â and so I lost my libido? Maybe the guys who take 5ar inhibitors and are fine donât undergo episodes that exhaust their neurosteroids, whether through anxiety, emotional crisis, heavy drinking/physical exhaustion etc?
As you can tell, my molecular biology knowledge is pathetic. Iâm just thinking out loud.
Whos genes are silenced?
I know in me T does work to maybe 30 percent of its previous capacity.
I sent my T way below range after quiting long term. Let me tell you. I felt it. My PFS symptoms all got very bad. I can feel t working in my body just not to the same extent as before PFS.
I can see 0 evidence for his
"guys who exhaust their existing neurosteroids? In other words: I lost my libido after getting dumped â my reaction was close to a nervous breakdown. So I exhausted my neurosteroids, and with no 5ar my body wasnât in position to replenish "
Like T your neurosteroids will keep on being pumped out fin should lower them quickly as we know fin acts on 5ar very quickly as it reduced DHT in 2 hours.
Physical or mental stress cause a weakening of the bodies defences. And fin damages some cells in that time and once damaged, stopping will not help as it is no long just an issue of 5ar inhibition.
We all want to think there is one primary disfunction that is hopefully fixable but there could be a lot of working parts to this. All we have are personal connections and theories as to why we get stuck. I crashed on the drug but had no ED or any real hypogonadal issues till I quit fin. Most folks are significantly better on the drug and then they quit and are forever dragged into this mess. For now the epigenetic angle seems most probable and good for these studies for determining epigebetic modulators. May probe invaluable in the end.
I think this is pretty much impossible and so overly complex.
Let us look at a couple of stories
"I only found the bump after it started hurting. If it wasnât for the pain, I would never have noticed it. Itâs not anywhere obvious, so it could have been there for years and years without me knowing. Or it couldâve formed at the same time as PFS. Who knows.
I guess you could say itâs harder than the rest of the tissue.
I havenât written up my story, although I should probably do that. I took fin for about three years with zero side effects. Then the testicular pain kicked in, then libido disappeared and ED started. I stopped taking fin at that point (maybe six to eight weeks after the testicular pain). I started having genital numbness at that point and a complete disconnect between my penis and brainâŚâŚlooking at women I had zero thought or desire of sex, let along physically wanting it.
Right now, 6.5 years off fin, I still have little to no libido, ED, and slight numbness (although this has improved quite a bit). Only other side effect is really dry skin, especially on my hands."
"I noticed problems from day 2 when I had pain in my left testicle. I shouldâve stopped from right there (but the damage mightâve already been done). This continued for a week and I felt it was best to stop taking it. The pain went away but now 6 days after taking SP Iâm suffering from ED, no morning/random erections, having problems sleeping, zero libido, and all the other Fin-like symptoms checked above. Naturally, Iâm freaking out about this. I took my last SP pill on 2/3/08. I can get an erection if I try really hard but itâs difficult to maintain and semen is watery. Thereâs a pain in my groin that gets worse when sitting down and I have problems concentrating/focusing which doesnât help since Iâm in grad school part time. Iâve lost motivation for a lot of things and am in a weird state of depression. Iâm scared to death and even though I never touched Propecia it sounds like Iâm having the same DHT-related symptoms. "
---- I have more like this another fin user had a pain like being kicked in the left ball then he lost libido and crashed.
Any epigenitic change at the cellar level assumes billions of cells have to be changed.
Why would billions of cells all just change over one night or so after being on the drug for years with no side effects? Pretty much impossible. Not evern worth considering.
We know that many guys here go on and off fin without problems till one day something goes bad. Some can take fin for years and years with almost 0 sides until something breaks in their body.
The logistics of having billions of independent cells change in the body at one time is just so overly complex it is not reasonable at all. It would probably be thousands of times more likely to win the lotto.
So how do we explain such pattern? Well it is pretty easy. You can take fin with few side effect till fin directly or indirectly damages some cells which produce hormones. Once these cells are damaged they start hyperexcreeting some kind of hormone or metabolite. From this point onwards your hormonal balance is trashed and there is going to be almost nothing you can do about it because even if you take TRT, cort or whatever those cells will still be hyperproducing hormone x. For some lucky guys here their body can remove or repair these cells and they recover. For the rest of us we will remain in this state until the offending cells are removed.
This way, only 1 cell need to become damaged to cause PFS. And while we have 0 evidence that some kind of systemic genetic changes can occur on fin we have 2 studies showing both FIN and DUT causes cells which autonomously hyperproduce hormones which will remain even after quieting. So I would say something along these lines is at least 1,000,000 times more feasible.
That guy Vincent that felt the mass in his testicleâhe get it removed? That help his condition at all? As for epigenetic changes to the ARâwe know it happens. That was the original purpose of the drug. What it has to do with PFS is still a mystery and whether every fin user has epigenetic alterations that correct after discontinuation or are relatively minor to our level is still a mystery.
No he still has it.
âAs for epigenetic changes to the ARâwe know it happens. That was the original purpose of the drug.â
I thought the purpose of the drug was to bind to and deactivate 5ar?
Can you prove the above statements? I never heard fin was designed to cause epigentic changes nor was I aware that there is any proof that it does cause epigentic changes to the AR?
Maybe I am wrong. I thought fin was supposed to interfere with AR signalling as well. Maybe that has been theorized after the fact.
Why didnât he get the mass removed?
I think you are wrong. I have never seen one piece of evidence showing what you have suggested. We should be careful not to base our opinions on evidence that does not exist.
I am actually speaking to 2 guys with exact same thing. On small spot in their testicle. The doctor said it was a calcification.
Iâve got same thing on one of my testicles. Feels kind of like a piece of rice. Iâve always assumed it was nothing.
I have that too on my left side. When did you get it? I only found mine when I took an anti estrogen. My libido came back for 4 days then a few days after that massive pain in the testicle right from that small spot. Pain lasted 3 days and was really bad. To me this shows that the tissue is active.
Where is your bump? Did you have it before PFS? Only on one side?