Thoughts On 5ar And Post Finasteride Syndrome

[TubZy]

Hey TubZy,
Are you taking inosine at night to help with sleep?
I am only taking it before aikido to try to curb my noradrenalin. I think it is working. I might be a little less breathless and more resilient on the mat. Not a huge difference though.

Hey..I only used it topically before and I can't say I got any effect from it at all. How much are you using?

@Meatbag has been using it orally before bed and said he notices the relaxing effect from it.

 

[Regina]

Hey..I only used it topically before and I can't say I got any effect from it at all. How much are you using?

@Meatbag has been using it orally before bed and said he notices the relaxing effect from it.

I would guess it is around 750mg of the anabol naturals inosine powder.

caveat: mat energy may (or may not) have improved due to a fractured tooth extraction with concurrent antibiotics lowering endotoxin.
Or it's the inosine.

 

[mayweatherking]

How is your guys digestion? Slow or fast?

 

[BeLiKeWater]

Good work. Yeah Its very clear that the function of 5ar2 enzymes is reduced in the brain and maybe in all areas. Metabolites of 5ar were measured in pfs patients by a Melcangi study and they apeeared to be very very low.. I did contact PFS foundation to measure all 5ar2 reduced metabolites and the subsequents metabolites, for a complete studies of 5ar2 activity after cesation of the drug. They said to me that melcangi studie was enough (he only measured 5dhp and allo in 3 patients) I say bull****! This is the most important study we can do right now. Measure 5AR2 metabolites in all the body, CNS,brain, blood, etc.. in all pfs patients.

Anyways low 5ar2 activity explains most of pfs symptoms, and my blog on solvepfs.com has been proclaiming that. I have been having profound victories over pfs following this route, I did so good that I never felt more manly in my whole life and my brain was incredible fast, etc..

Still I ended with low resources and stopped suplementing, but something click while take niacinamide + L glycine. Also definetly being inmunodepressed really helps libido, unfortunatly gave me some virus infection so I stopped for a while until I control it.

We have to follow this route, you are doing really good job in the thread. Btw 1 month ago I had 2 weeks that I had my libido very high, had to masturbate at least once a day like good old days, unless I got crazy.

Sorghum had made me have 30 days morning erections in the past, my experience with Creatine have been a lot more complex. There is a lot of things that proclaim to activate 5ar activity, so we have a lot of work to do.

Feeling totally exausted, no energy these days... but Im not following any protocol.

 

[TubZy]

I would guess it is around 750mg of the anabol naturals inosine powder.

caveat: mat energy may (or may not) have improved due to a fractured tooth extraction with concurrent antibiotics lowering endotoxin.
Or it's the inosine.

Yeah lol..that seems to be the only brand I could really find too. The highest I went up to was 450mg topically.

Meatbag I think was using 750mg when he noticed the results.

Could be or yeah, the antibiotics could be doing it lol. Try taking it alone before bed and see if you notice anything. Maybe the dose needs to be higher, but at least it does effect GABA (A).

 

[bloom]

I'm starting to realise that PFS in its worst form is a neurological disorder, one reason why it's so hard to treat

 

[bloom]

Focusing on the isoenzymes 5ar1 and 5ar3 which are expressed in the brain may be a way forward

 

[TubZy]

Focusing on the isoenzymes 5ar1 and 5ar3 which are expressed in the brain may be a way forward

Did you try tramadol? Supposely some ppl had luck with it acts like an SSRI and opiate at the same time.

 

[bloom]

Did you try tramadol? Supposely some ppl had luck with it acts like an SSRI and opiate at the same time.

From wikipedia

Mechanism of action[edit]
Tramadol acts as a μ-opioid receptor agonist,[7][37] serotonin reuptake inhibitor and releasing agent,[38][39][40][41] norepinephrine reuptake inhibitor,[37] NMDA receptor antagonist (IC50 = 16.5 μM),[42] 5-HT2Creceptor antagonist (EC50 = 26 nM),[43] (α7)5 nicotinic acetylcholine receptor antagonist,[44] TRPV1 receptor agonist,[45] and M1 and M3 muscarinic acetylcholine receptor antagonist.[46][47] Some of the additional affinity of tramadol have been reported as follows: μ-opioid receptor (Ki = 2.1 µM), κ-opioid receptor (Ki = 42.7 µM), δ-opioid receptor (Ki = 57.6 µM), serotonin transporter (Ki = 0.99 µM),norepinephrine transporter (Ki = 0.79 µM).[48] Relative to tramadol, its active metabolite O-desmethyltramadol has far higher affinity for the μ-opioid receptor (Ki = 3.4 nM (0.0034 µM) for the (+)-isomer).[49]

Its analgesic effects are only partially reversed by naloxone, hence indicating that its opioid action is unlikely the sole factor; tramadol's analgesic effects are also partially reversed by α2 adrenergic receptorantagonists like yohimbine and the 5-HT3 receptor antagonist, ondansetron.[14] Pharmacologically, tramadol is similar to levorphanol and tapentadol in that it not only binds to the mu opioid receptor, but also inhibits the reuptake of serotonin and norepinephrine[3] due to its action on the noradrenergic and serotonergic systems, such as its "atypical" opioid activity.[50]

Tramadol has inhibitory actions on the 5-HT2C receptor. Antagonism of 5-HT2C could be partially responsible for tramadol's reducing effect on depressive and obsessive-compulsive symptoms in patients with pain and co-morbid neurological illnesses.[43] 5-HT2C blockade may also account for its lowering of the seizure threshold, as 5-HT2C knockout mice display significantly increased vulnerability to epileptic seizures, sometimes resulting in spontaneous death. However, the reduction of seizure threshold could be attributed to tramadol's putative inhibition of GABAA receptors at high doses.[42] In addition, tramadol's major active metabolite, O-desmethyltramadol, is a high-affinity ligand of the δ- and κ-opioid receptors, and activity at the former receptor could be involved in tramadol's ability to provoke seizures in some individuals, as δ-opioid receptor agonists are well known to induce seizures.[51]

Mmmh not sure i'd wanna try this 'tramadol's putative inhibition of GABAA receptors'. I've been on Oxycodone, modestly improved my symptoms, nothing compared with benzodiazepines, and nicotinamide. The problem with using things to modulate the GABA A receptor is that you generally develop a tolerance to whatever it is that you're using. There are plenty of things to try to stimulate GABA A: 5a DHP, benzo's, Nicotinamide, Marijuana ect. I'm trying to find other ways to specifically increase 5ar in the brain asides GABA A stimulation, and without increasing it peripherally.
I've noticed with creatine and sorghum flour they provide androgenic effect on my muscles (hardening ect), but cause my mental state to deteriorate and my penis to shrink. My T/DHT blood levels are relatively normal. I think since we have normal levels of T/DHT in our blood your brain thinks 5ar levels are just fine, despite 5ar being low in the Brain. So when you increase these levels in the blood it may have some androgenic effects on your tissues but it has a negatives feedback on the brain, your brain consequently lowers it's expression of 5ar.
Some men with PFS claim to get better on a low dose of Fin. 5ar2 is the only isoenzyme of the 5ar family which is not expressed(at least significantly) in the brain. Fin has (from wiki)

a 100-fold less affinity for 5ar1

. And

By inhibiting 5α-reductase, finasteride prevents conversion of testosterone to dihydrotestosterone (DHT) by the type II and III isoenzymes, resulting in a decrease in serum DHT levels by about 65–70% and in prostate DHT levels by up to 85–90%,[3][25]

I speculate that by inhibiting 5ar2 and 3 and decreasing serum DHT by 70%, your body responds by increasing 5ar's expression, since 5ar1 is not being significantly inhibited and is greatly expressed in the brain, it is brought to levels in the brain to a significant level. It goes something like this.

Increase 5ar products just in blood--->negative feedback leads to decreased 5ar expression in Brain--->decreased 5ar products in Brain/CNS

Inhibit 5ar2 & 3 in blood with Fin--->decrease 5ar products in blood--->Upregulation of 5ar1, consequent upregulation of 5ar1 in Brain---->increase 5ar products in Brain/CNS

Highly speculative, but it explains why certain men get worse by increasing 5ar products in blood, and why some men get better by reducing 5ar products in the blood with Fin.

 

[bloom]

I'll add this explains why I get better on Opiates and GABAA receptor agonists, and get worse in certain aspects on creatine/sorghum. The Blood Brain Barrier is a real issue. I think PFS ultimately will be treated as a neurological disorder.
The Key seems to be to increase 5ar specifically in the Brain, without increasing it peripherally.

 

[sladerunner69]

Probably why androsterone, 5a-DHP, progesterone etc work best.

I too think it is all an issue in the brain. My T is pretty high and DHT is normal. Only issues that remain are poor glycogen stores, lagging thyroid function, poor resistance to stress which could be from burning through glycogen stores. But it seems it all comes down to GABA issues. If GABA was working right and restored I probably wouldn't burn through glycogen stores so quick due to being out of a "stress" state and my thyroid would work better.

How much progesterone are you taking for the beneficial effect? It does seem to oppose dht in higher doses.

I agree that GABA is probably a part of it because too much caffiene seems to really bother me, and caffiene is known to supress GABA release. Perhaps taking plenty of gelatin, theanine, and a bit of taurine and a bit of niacinmide would help resolve this - I will test it.

 

[haidut]

I have found that 11 keto DHT and Andractim, although makes my muscles hard and I feel the confidence and such, seems to LOWER my libido, and gives me a shrinkage effect. Ive been confused about that.

Some aromatizable steroids seem to be necessary for proper libido in human males. Peat has always recommended adding DHEA and/or pregnenolone to DHT when asked about supplementing with it and I think the thread I posted on synergism between androsterone and DHEA adds more evidence to that theory. So, adding even a little Pansterone should help.

 

[TubZy]

From wikipedia


Mmmh not sure i'd wanna try this 'tramadol's putative inhibition of GABAA receptors'. I've been on Oxycodone, modestly improved my symptoms, nothing compared with benzodiazepines, and nicotinamide. The problem with using things to modulate the GABA A receptor is that you generally develop a tolerance to whatever it is that you're using. There are plenty of things to try to stimulate GABA A: 5a DHP, benzo's, Nicotinamide, Marijuana ect. I'm trying to find other ways to specifically increase 5ar in the brain asides GABA A stimulation, and without increasing it peripherally.
I've noticed with creatine and sorghum flour they provide androgenic effect on my muscles (hardening ect), but cause my mental state to deteriorate and my penis to shrink. My T/DHT blood levels are relatively normal. I think since we have normal levels of T/DHT in our blood your brain thinks 5ar levels are just fine, despite 5ar being low in the Brain. So when you increase these levels in the blood it may have some androgenic effects on your tissues but it has a negatives feedback on the brain, your brain consequently lowers it's expression of 5ar.
Some men with PFS claim to get better on a low dose of Fin. 5ar2 is the only isoenzyme of the 5ar family which is not expressed(at least significantly) in the brain. Fin has (from wiki). And
I speculate that by inhibiting 5ar2 and 3 and decreasing serum DHT by 70%, your body responds by increasing 5ar's expression, since 5ar1 is not being significantly inhibited and is greatly expressed in the brain, it is brought to levels in the brain to a significant level. It goes something like this.

Increase 5ar products just in blood--->negative feedback leads to decreased 5ar expression in Brain--->decreased 5ar products in Brain/CNS

Inhibit 5ar2 & 3 in blood with Fin--->decrease 5ar products in blood--->Upregulation of 5ar1, consequent upregulation of 5ar1 in Brain---->increase 5ar products in Brain/CNS

Highly speculative, but it explains why certain men get worse by increasing 5ar products in blood, and why some men get better by reducing 5ar products in the blood with Fin.

Yeah, I don't agree with using tramdol just a few people said it completely reversed their brain fog while using it. I'm assuming from the SSRI properties of raising allopreg. Creatine doesn't do anything for me in regards to DHT, same with sorghum as well.

 

[TubZy]

How much progesterone are you taking for the beneficial effect? It does seem to oppose dht in higher doses.

I agree that GABA is probably a part of it because too much caffiene seems to really bother me, and caffiene is known to supress GABA release. Perhaps taking plenty of gelatin, theanine, and a bit of taurine and a bit of niacinmide would help resolve this - I will test it.

3mg-6mg that is all. Any higher than that I have to add in more DHEA or else get estrogenic type symptoms.

Yeah, I agree caffeine inhibits GABA but I also read it can upregulate GABA receptors too. I think it was this study. This issue is poor glycogen storage with PFS people since caffeine can speed up metabolism and lower blood sugar, PFS people get hit hard from the caffeine causing a bad stress response.

Chronic Caffeine Alters the Density of Adenosine, Adrenergic, Cholinergic, GABA, and Serotonin Receptors and Calcium Channels in Mouse Brain

The density of benzodiazepine sites associated with GABAA-receptors appear increased after chronic caffeine (Wu and Coffin, 1984; Wu and Phillis, 1986).

 

[TubZy]

I also thought about the combo of caffeine + pepcid to help hold onto glycogen stores better, but i havent had time to try it yet

 

[Ron J]

I'll add this explains why I get better on Opiates and GABAA receptor agonists, and get worse in certain aspects on creatine/sorghum. The Blood Brain Barrier is a real issue. I think PFS ultimately will be treated as a neurological disorder.
The Key seems to be to increase 5ar specifically in the Brain, without increasing it peripherally.

Do you have a list of Peaty supplements to raise GABA and 5ar in the brain?

 

[brix]

3mg-6mg that is all. Any higher than that I have to add in more DHEA or else get estrogenic type symptoms.

Yeah, I agree caffeine inhibits GABA but I also read it can upregulate GABA receptors too. I think it was this study. This issue is poor glycogen storage with PFS people since caffeine can speed up metabolism and lower blood sugar, PFS people get hit hard from the caffeine causing a bad stress response.

Chronic Caffeine Alters the Density of Adenosine, Adrenergic, Cholinergic, GABA, and Serotonin Receptors and Calcium Channels in Mouse Brain

The density of benzodiazepine sites associated with GABAA-receptors appear increased after chronic caffeine (Wu and Coffin, 1984; Wu and Phillis, 1986).

why not just take 5a-DHP since it can't convert to estrogen?

 

[bloom]

Yeah, I don't agree with using tramdol just a few people said it completely reversed their brain fog while using it. I'm assuming from the SSRI properties of raising allopreg. Creatine doesn't do anything for me in regards to DHT, same with sorghum as well.[/QU

Yeah, I don't agree with using tramdol just a few people said it completely reversed their brain fog while using it. I'm assuming from the SSRI properties of raising allopreg. Creatine doesn't do anything for me in regards to DHT, same with sorghum as well.

Yeah my focus now is going to be exclusively on 5ar and the Brain. Increasing 5ar and androgens peripherally has been for the most part a washout. In particular 5ar1 and 5ar3, these are the two isoenzymes expressed in the Brain. 5ar1 produces 5a DHP, DHOC, and DHT. All are converted into positive Allosteric modulators of the GABA A receptor. 5ar3 produces DHT, and Dolichol. I'm going to do some more homework.

 

[bloom]

Do you have a list of Peaty supplements to raise GABA and 5ar in the brain?

If you look through the thread there are lots of things: 5a DHP, Nicotinamide, Caffeine ect.

 

[sladerunner69]

3mg-6mg that is all. Any higher than that I have to add in more DHEA or else get estrogenic type symptoms.

Yeah, I agree caffeine inhibits GABA but I also read it can upregulate GABA receptors too. I think it was this study. This issue is poor glycogen storage with PFS people since caffeine can speed up metabolism and lower blood sugar, PFS people get hit hard from the caffeine causing a bad stress response.

Chronic Caffeine Alters the Density of Adenosine, Adrenergic, Cholinergic, GABA, and Serotonin Receptors and Calcium Channels in Mouse Brain

The density of benzodiazepine sites associated with GABAA-receptors appear increased after chronic caffeine (Wu and Coffin, 1984; Wu and Phillis, 1986).

3-6mg that's it? I was under the impression most people were taking 20-100mg per dosage. I have been experimenting with just a few drops (3-5mg)of progestene (which has dmso) but it can tend to make me too relaxed/spaced out and not focused and energized enough to study. I will play around with adding in a little bit of DHEA though.

So how much dhea are you taking now that you have foudn your thyroid functinning better?


Damn taking a look at that study is pretty interesting. The doses they used were gigantic, 100mg per kg. I would be upwards of 5g of caffiene for a human. The results speak for themselves though, a 65% increase in density is quite remarkable. Hard to say if it is a compensation for decreased GABA detection in the serum or if it a positive feedback, (hopefully the latter)