Let’s start from basic pharmacological knowledge first. Can anybody find what happens with an irreversible inhibitor in the body? It makes a covalent bond with the enzyme and then what happens? Is it forever? The cells definitely produce new enzymes all the time and the normal function of endogenous hormones returns. The question is, can the accumulating 5ar2-finasteride cause any new kind of problems. Can it even get out of cells? Probably not, so a biopsy is needed and a blood check isn’t enough.
Damn, it´s like basic pharmacodynamics, but I can’t find any info about it…
If drug pooling has occurred (theoretically/practically plausible), the end problem extends beyond that.
Death of two subjects due to imipramine and desipramine metabolite accumulation during chronic therapy: a review of the literature and possible mechanisms.
Swanson JR, Jones GR, Krasselt W, Denmark LN, Ratti F.
Source
Pathology Department, Oregon Health Sciences University, Portland, USA.
Abstract
In two unrelated cases, a 7-year-old boy and a 21-year-old woman died suddenly while receiving chronic imipramine therapy. In the boy, concentrations of imipramine were: Left femoral blood 0.5 mg/L, right femoral blood 1.2 mg/L, aorta blood 1.0 mg/L, liver 68 mg/Kg, and for the active metabolite, desipramine, left femoral blood 6.7 mg/L, right femoral blood 9.9 mg/L, aorta blood 8.7 mg/L, liver 400 mg/Kg. In the woman, the imipramine concentrations were: Femoral blood 0.6 mg/L, liver 37 mg/Kg, and of the active metabolite, desipramine, femoral blood 3.74 mg/L, liver 261 mg/Kg. In both cases, the scene investigation strongly indicated that neither individual had ingested an acute overdose. The very high ratios of desmethyl metabolite to parent drug are consistent with this observation. Impaired metabolism due to a genetically determined “slow metabolizer” phenotype of cytochrome CYP2D6, and/or concurrent therapy with phenothiazines, is suggested as a possible mechanism for the apparent fatal accumulation of these tricyclic antidepressants.
So there’s a variance between levels of the drug depending on where the blood is taken from? Anybody with background have comments if the 6.7-9.9 mg/L variance is significant? The liver concentration of the child is shocking. Something that’s generally assumed (I believe) is that the blood concentrations are relatively even throughout the body, however in this case it’s 33% higher on one side.
CYP3A4 is the enzyme that metabolises Finasteride.
Its actually the induction (increase) of the CYP3A4 enzyme that will inhibit 5a-Reductase and cause hypogonadism and hypocortisolism symptoms see: ncbi.nlm.nih.gov/pubmed/23162091 (something I predicted 2 years ago by the way). This exactly matches the symptoms and hormone/urine/blood tests of a severe case of Post-Finasteride Syndrome like nothing else.
Although there is no reason I can think of for CYP3A4 to work overtime.
But DHT levels return. We can’t be talking of a forever 5ar2 inhibition. It’s not happening.
Well, its all a matter of looking for something similar in the literature. This is clearly worth mentioning in regards to CYP3A4, the urine metabolite (& neurosteroid) results and the symptoms. It might also be worth reading along with this study that shows DHT remains even with increased androgen metabolism: ncbi.nlm.nih.gov/pmc/articles/PMC2488233/.
(then compare this to your ‘stress is causing all our symptoms’ idea viewtopic.php?f=27&t=7388 !)
…
But seriously,
What would you expect to happen if CYP3A4 wasnt working? Wouldnt this be obvious? Why would this cause the symptoms?
(Or if Fin or dihydrofinasteride is ‘stuck’ in 5aR? Why would this happen? Why would this cause symptoms?)
The elephant in the room that we have to deal with first before any other question is how are we going to do this?
I totally agree that this is thing that has and MUST be ruled out through tests/research and we preferably have to prioritize it to top as well. Has Mew, awor or anyone responded to this yet? It’s hard to imagine anyone else with the resources to do this now. I’d gladly participate if possible, sending a serum tube in ice shouldn’t be that difficult innit?
DHT did not return for me. And I’m one of the most severe loss of brain-to-penis connection/sexual dysfunction/E.D. PFS cases out there.
Interesting discussion on the CYP3A4 Enzyme here:
anabolicminds.com/forum/male-ant … zymes.html
Building on the themes of Phase I and II Liver Detox from the above as well as Methylation, MTHFR Genetic Defect discussion by Chris Kresser*:
chriskresser.com/paleo-diet-chal … x-capacity
Another Phase I and II Liver Detox explanation:
vrp.com/detoxification/phase … x-pathways
[Size=4]*disclaimer: yes, he’s plugging his own line of supplements now, after years of putting out free research analysis[/size]
You’ve got before and after DHT test?
Has Melcangi said anything about Finasteride still being inside us ?
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I’ve mentioned this Mark I had a strong believe that finasteride was still blocking receptors and in our system. Hey @Dubya_B remember my theory about finasteride still blocking the receptors would this post not correlate with what I was saying?
Hey, this my first time coming across your post I have also made this hypothesis that this is the reason for PFS. @Dubya_B @awor @Mark2012 @AnhedonicApe
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What’s about all people that take finasteride everyday for years without side effects ?
This is the biggest puzzle maybe it was the liver that couldn’t properly matabolize the drug so it causes it to cross BBB I have no real clue.
I know Finasteride has a half-life, but I was unaware of the fact that Finasteride also inhibited the liver enzyme that breaks-down the drug… That is a major aspect that should be looked into. It could be that the drug stayed in our system for wayyyy too long, causing unknown irreparable harm.
- What ways are there to test if we still have Finasteride in our system
- Anyone have any further insight on whther FIN is actually still in our bodies, I hear about drugs getting left in the system quite a bit
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I’d like to try kidney dialysis,
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This thread is nonsensical.
- Many people who have taken finasteride have no issues
- A small subset of people have issues while on finasteride and they subside when the come for it
- Most PFS sufferers have a ‘crash’ which typically occurs weeks after feeding to take finasteride. This crash brings on the worse symptoms.
- DHT levels usually return to normal.
These factual statements all but rule out Finasteride remaining in PFS sufferers systems.
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This is the central point: induced/overexpressed CYP3A4 creates post-finasteride syndrome: it is as if our body degrades all hormones automatically even after stopping finasteride. Have you been able to understand what this is due to? Is there a way to regulate the activity of the enzyme? I am better off with CYP3A4 inhibitors, on the physical level they cheer me up, but on the mental level they lead me to brain fog and confusion. Sorry if I disturbed you, if you can give me feedback despite the time that has passed, I would be grateful. In my opinion you have hit the real theme. Greetings
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