Thoughts On 5ar And Post Finasteride Syndrome

[TubZy]

This is an extremely interesting study.

DNA methylation of the GC box in the promoter region mediates isolation rearing-induced suppression of srd5a1 transcription in the prefrontal cortex. - PubMed - NCBI







Could hold hope for future therapies, the use of demethylating agents

I ordered DMG after the original post where someone mentioned it. I wonder if it works in that same way.

 

[bloom]

Don't spend too much time on the computer, this study found socialization decreased methylation of SRD5AR1 in the Hippocampus in middle-aged rats.

Environmental enrichment attenuates the age-related decline in the mRNA expression of steroidogenic enzymes and reduces the methylation state of th... - PubMed - NCBI

Aging decreased the transcription of neurosteroidogenic-related genes and increased the promoter methylation state of cytochrome P450 side chain cleavage, 3α-hydroxysteroid dehydrogenase (3α-HSD) and 5α-reductase-1. Exposure of middle-aged rats to environmental enrichment increased mRNA levels of 5α-reductase-1, 3α-HSD and cytochrome P450 17α-hydroxylase/c17,20-lyase and decreased the methylation state of the 5α-reductase-1 gene. Thus, sensory and social stimulation attenuate the age-related decline in the mRNA expression of hippocampal steroidogenic enzymes. Epigenetic mechanisms associated with differential promoter methylation could be involved.

 

[bruschi11]

You increase androgens peripherally puts a negative feedback on the Hypothalamus and Pituitary. Leads to decreased activity of an ALEADY SEVERELY DOWNREGULATED ENZYME IN THE PITUITARY. I'll add that this can explain why men report to get better on a low dose of Fin. Fin doesn't inhibit 5ar1 which is expressed in the brain. Fin reduces blood levels of androgens, increases 5ar1 activity in the pituitary

Would increasing androgens peripherally occur with HCG mono? I know LH, FSH eventually get shut down with HCG mono. Honestly sexually my best time during fin syndrome was with HCG mono and mediherb tribulus. I've used T cypionate and testosterone gel. Both decent for erecctions /libido but horrible for anxiety.

 

[bloom]

Would increasing androgens peripherally occur with HCG mono? I know LH, FSH eventually get shut down with HCG mono. Honestly sexually my best time during fin syndrome was with HCG mono and mediherb tribulus. I've used T cypionate and testosterone gel. Both decent for erecctions /libido but horrible for anxiety.

It's possible it could create a negative feedback on the hypothalamus, from wiki:

Because of its similarity to LH, hCG can also be used clinically to induce ovulation in the ovaries as well as testosterone production in the testes. As the most abundant biological source is women who are presently pregnant, some organizations collect urine from pregnant women to extract hCG for use in fertility treatment.[12][13]

This is the point I'm trying to get at. Increasing androgens peripherally may be beneficial is some respects, but may be extremely detrimental in other aspects with regards to PFS. As I believe there is a downregulation of the 5ar enzyme in the brain, increasing androgens peripherally (i.e in the blood) leads to a negative feedback causing a decrease of 5ar in the brain. The study I posted earlier in this thread showed that mice treated with testosterone caused a decrease of the 5ar enzyme in the pituitary. I believe you are decreasing the activity of the 5ar enzyme in the Brain already severely downregulated. 5ar metabolites, Allopregnanolone, THDOC, 3a-diol are all powerful allosteric modulators of the GABAA receptor. This can explain why you get anxiety from testosterone gel. I believe it explains why I get worse when I increase androgens peripherally.

 

[bruschi11]

I don't think you are off here at all Bloom. This all could be as simple as finding a way to PERMANENTLY upregulate 5ar enzymes back to normal in the brain. Or some sort of a substance to be used long term to significantly upregulate these enzymes in the brain.

I started low dose Prozac today to see how the allo increase would feel. It honestly knocked me out- I've been on the couch today exhausted all day.

Had to try to see what a T cream dose would do- yup yet again anxiety, bad breath (adrenaline response to stress). So although allo is letting gaba function nicely with relaxation. The body is still reacting to testosterone harshly.

I guess research is showing that even filling up all the neurosteroids back to normal levels doesn't do it. There's something that must occur with 5ar activity that is just not understood. If we could find a way to SERIOUSLY upregulate its actions specifically in the brain as you theorize, maybe that is all we need.​

 

[TubZy]

It's possible it could create a negative feedback on the hypothalamus, from wiki:



This is the point I'm trying to get at. Increasing androgens peripherally may be beneficial is some respects, but may be extremely detrimental in other aspects with regards to PFS. As I believe there is a downregulation of the 5ar enzyme in the brain, increasing androgens peripherally (i.e in the blood) leads to a negative feedback causing a decrease of 5ar in the brain. The study I posted earlier in this thread showed that mice treated with testosterone caused a decrease of the 5ar enzyme in the pituitary. I believe you are decreasing the activity of the 5ar enzyme in the Brain already severely downregulated. 5ar metabolites, Allopregnanolone, THDOC, 3a-diol are all powerful allosteric modulators of the GABAA receptor. This can explain why you get anxiety from testosterone gel. I believe it explains why I get worse when I increase androgens peripherally.

Do you know if the 5AR enzyme as a supplement would pass BBB?

 

[bloom]

Do you know if the 5AR enzyme as a supplement would pass BBB?

I don't think there is a 5ar enzyme supplement. If there is I have no idea if it would.

 

[TubZy]

I don't think there is a 5ar enzyme supplement. If there is I have no idea if it would.

Yeah, there actually is, haidut was planning to have a supplier synthesize it a while back although I'm not sure how the stomach acid would handle it, and if it would make it through the BBB.

 

[bloom]

Yeah, there actually is, haidut was planning to have a supplier synthesize it a while back although I'm not sure how the stomach acid would handle it, and if it would make it through the BBB.

That's great, I know there are technologies being investigated to help medication pass the BBB, liposomes, nanoparticles. A 5ar supplement which could pass the BBB could be huge.

 

[JoeKool]

Yeah, there actually is, haidut was planning to have a supplier synthesize it a while back although I'm not sure how the stomach acid would handle it, and if it would make it through the BBB.

holy moly that'd be amazing... there are other forms of delivery ... we know dmso obviously but i don't know how everyone here feels about needles but if that was the only way to get it into the bloodstream, i think there'd be some tolerance

 

[mayweatherking]

I also believe there are different types of PFS, but definitely a nuerological disorder. 4 years after cessation I am mostly dealing with the mental sides such as brain fog, short term memory loss, mild depression and very poor word retrieval. Physically, Ive dealt with sensitivity issues, extreme fatigue, awful back pain and stomach bloating/pain that subsided two years ago after a anti- biotic and steroid shot from my doctor. Sensitivity issues are still there but not as prevalent. Can't explain that but I'm thankful that it went away. To Bruschi's point, and although a Lil different, as I wasn't on trt before fin, I tried to go on trt last September. First week was the best week of my life. I was completely recovered. However, I started hcg shots (mon/wed/fri) a week after my first week of testosterone. I got worse After each hcg shot and by week 4 I was having severe panic attacks and anxiety issues immediately after each hcg shot. As well as slow rate vision and depersonalization. I quit the trt immediately and All issues have subsided except the brain fog/short term memory problems as I stated above. So back to square one. I have been following guys like tubzy, slade and others that have been very helpful in this journey lately. I think there is a lot of helpful things with their protocols to increase the 5ar activity that have helped me since my second crash with the trt. Niacinimide, R andro, peating after a week long water fast were beneficial. I even think my baseline is even better than before the Trt. So hang in there bruschi, stay positive bc it will get better. A lot of very smart people in this forum.

Why did hcg do this, what's your theory?

 

[Gibson2k3]

Not really sure. I believe it affects the thyroid in some way. I know before the trt my body/thyroid was in a hypo state from all the symptoms after my first crash after cessation of fin. Maybe it has something to do with the negative feedback loop that bloom and tubzy are talking about or something malfunctioning in the hormone downstream. On a side note, I took t3 two weeks after my last trt shot and felt completely recovered until the t3 wore off (4hr halflife). This happened 3 more times and then my body didn't react to it at all anymore. Anyways, I just remember on my 4/5th week of injecting the hcg, 30 min after I will feel a pulling sensation in my hamstring and then a full on panic attack. So maybe my thyroid couldn't handle the trt and the Hcg together? Not sure. Just know that what I read from severe hyperthyroid symptoms that anxiety, panic attacks, depersonalization can be part of that issue. I have an appointment with dr mohit khera tom in Houston. Not expecting much but maybe he can shed some light on my reaction. He probably will just echo what a lot of these guys are talking ablout. I guess I'll find out.

 

[bruschi11]

Why did hcg do this, what's your theory?

Yea I have no idea how HCG could be the crasher for someone. If anything it'd be the exogenous testosterone. Kind of shocked to hear this.

 

[bruschi11]

Yeah, there actually is, haidut was planning to have a supplier synthesize it a while back although I'm not sure how the stomach acid would handle it, and if it would make it through the BBB.

Very intriguing. We just need someone all in on this with us to give us a chance. Obviously we can research, try our natural things, but there's some sort of mechanism that needs to be reversed. How awesome would it be if you could just inject an estered 5ar1, 5ar2 enzyme and let the body work from there.

Just like a T-Cypionate but for the 5ar enzyme.

 

[Gibson2k3]

Yea I have no idea how HCG could be the crasher for someone. If anything it'd be the exogenous testosterone. Kind of shocked to hear this.

Yeah. I've thought about if I would get the same reaction without the testosterone. I do think it was the testosterone too though. Maybe the hcg sped up the negative feedback loop? No clue.

 

[bloom]

Yeah. I've thought about if I would get the same reaction without the testosterone. I do think it was the testosterone too though. Maybe the hcg sped up the negative feedback loop? No clue.

From wiki:

LH normally travels from the pituitary via the blood stream to the testes, where it triggers the production and release of testosterone. Without LH, the testes shut down their production of testosterone.[32] In males, HCG helps restore and maintain testosterone production in the testes by mimicking LH and triggering the production and release of testosterone.

Most likely a negative feedback, HCG mimics LH causing the production of testosterone. They've been trying to treat PFS with TRT since day one and it has been a washout, rarely works often makes guys worse. True PFS is not a deficiency of Testosterone, so why treat it as such?

 

[TubZy]

Not really sure. I believe it affects the thyroid in some way. I know before the trt my body/thyroid was in a hypo state from all the symptoms after my first crash after cessation of fin. Maybe it has something to do with the negative feedback loop that bloom and tubzy are talking about or something malfunctioning in the hormone downstream. On a side note, I took t3 two weeks after my last trt shot and felt completely recovered until the t3 wore off (4hr halflife). This happened 3 more times and then my body didn't react to it at all anymore. Anyways, I just remember on my 4/5th week of injecting the hcg, 30 min after I will feel a pulling sensation in my hamstring and then a full on panic attack. So maybe my thyroid couldn't handle the trt and the Hcg together? Not sure. Just know that what I read from severe hyperthyroid symptoms that anxiety, panic attacks, depersonalization can be part of that issue. I have an appointment with dr mohit khera tom in Houston. Not expecting much but maybe he can shed some light on my reaction. He probably will just echo what a lot of these guys are talking ablout. I guess I'll find out.

Same T3 improved my symptoms but even more thyroid surrogates like the aspirin + Caffeine combo works better. I think big doses of pregenolone could work too there is a thread on here saying more than 200mg of preg can cause hyperthyroidism, which is a good thing since it will increase 5AR along with all corresponding androgens and lowering cortisol, but not cause suppression.

That crossed my radar a while ago but I never tried it yet.

 

[heaahde]

Can you check for 5AR levels in youg blood/brain? Or do you look for something else to get an idea how much 5Ar there is from a bloodtest?

 

[freeflow]

Hello guys, i just registered so i can make a reply on this topic. When i take glycine libido appears in 1 hour. Definitely low 5ar in the brain.
These days when i take sorghum or tribulus I feel worse and develop gyno.
My plan is to use mucuna pruriens to increase androgen receptors (my voice drops when i use it and my dopamine comes back), addin glycine to it
and maybe some coconut oil to block dht in the body. When i used coconut oil daily, after some days my morning erections and libido came back somewhat but crashed with ejaculation.
Also the libido from glycine disappeared after ejaculation.

 

[TubZy]

My DMG will be here today, I'll log it when I get it today..