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Thoughts On 5ar And Post Finasteride Syndrome

Discussion in 'Male Issues' started by bloom, Mar 19, 2017.

  1. bloom

    bloom Member

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    It is my belief that PFS is caused by a down regulation of the 5ar enzyme. At first I thought this was not the case as certain supplements (creatine and sorghum flour) which are known to increase 5ar activity worsened my symptoms. This theory has further been dismissed by the observation that Proviron and other steroids generally worsen symptoms in men. I and many others on this forum and elsewhere have observed that GABA enhancing substances (benzodiazepines, alcohol, marijuana) dramatically improve symptoms, libido, brain fog, memory ect. This has been the case for me, so far the one thing which has produced the most profound improvements has been Valium. It is my belief that the most severe cases of PFS are caused by a 5ar downregulation in the Brain/CNS. Normal blood levels of Testosterone and DHT are observed in PFS sufferers. So any attempts to increase 5ar and/or DHT peripherally without directly increasing 5ar in the Brain/CNS causes a negative feedback on the HPG axis

    Haidut found a very interesting study which found that Valium increases expression of the 5ar in the Diencephalon (a section of the forebrain) by more than 2 fold. Caffeine has also been found to increase 5ar in the Diencephalon, and modestly improves my symptoms.


    Sex hormones metabolism in the brain: influence of central acting drugs on 5 alpha-reduction in rat diencephalon. - PubMed - NCBI


    "...Diencephalon 5 alpha-reductase activity showed a highly significant increase (p less than 0.01) after a single administration of carbamazepine, reserpine, diazepam, phenytoin, phenobarbital or disulfiram. A significant increase (p less than 0.05) was also found after a single administration of methylphenidate, caffeine or methamphetamine."


    Opiates also improve my symptoms, others have observed this too. There's a study which shows morphine increases 5ar expression in the CNS of rats.

    In vivo evidence for an increase in 5alpha-reductase activity in the rat central nervous system following morphine exposure

    In vivo evidence for an increase in 5alpha-reductase activity in the rat central nervous system following morphine exposure

    Hossein Amini and Abolhassan Ahmadiani,
    Department of Pharmacology, Neuroscience Research Center, Shaheed Beheshti University of Medical Sciences, P.O. Box 19835-355, Tehran, Iran
    Received 27 April 2005; revised 5 July 2005; accepted 6 July 2005. Available online 6 September 2005.



    Abstract
    In the present study, the effects of acute and chronic morphine exposure on testosterone concentrations in the central nervous system (CNS) and serum were investigated in rats. Acute morphine administration (5 mg/kg, sc) reduced significantly testosterone levels in serum and spinal cord but not in the brain.

    Following chronic morphine administration (orally for 21 days), the brain testosterone was also significantly reduced as well as serum and spinal cord.

    Since, the decrease in testosterone levels following morphine exposure was more obvious in the CNS than serum, we suggested that it cannot be caused by only a direct decline in testosterone levels in periphery, and an increased local metabolism of testosterone in the CNS might be attributed in these effects.

    This hypothesis was supported with the findings that pretreatment with finasteride, a 5alpha-reductase inhibitor (5 mg/kg, sc) blocked testosterone elimination from the CNS following morphine exposure.

    Moreover, the serum concentration of 5alpha-reduced metabolites of testosterone, dihydrotestosterone and 3alpha-diol glucuronide was increased significantly following chronic morphine exposure, but not after co-treatment with finasteride.

    These results suggest that morphine exposure increase the CNS activity of 5alpha-reductase, which is an important metabolizing enzyme for testosterone.

    I have also notice many men claim to have a 'full remission of symptoms' when they are sick with the flu. Marcel from AnabolicApex has found a study where the 5ar enzyme increased following treatment with cyclosporine A (an immunosuppressant drug).


    Greater conversion of testosterone to 5 alpha-dihydrotestosterone, reflecting increased peripheral 5 alpha-reductase activity in nude mice treated ... - PubMed - NCBI


    “Following cyclosporine A (CsA) immunosuppressive therapy in kidney grafts, increased body hair growth (hypertrichosis and/or hirsutism) without significant variation in normal circulating plasma androgen levels (as observed in idiopathic hirsutism) has been reported by several authors. Other authors have described increased hair growth in nude mice treated with CsA.”


    “After 1 h of incubation, 5 alpha-DHT and other 5 alpha-reduced products formed were separated and quantified using a reverse-phase chromatography column fitted to a flow-through radioactivity detector.”


    “5 alpha-DHT formation was found to be increased in the treated groups.”


    It could very well be the case that a suppressed immune system significantly increases 5ar activity in the CNS.


    Marcel's research from AnabolicApex has found that

    Anticonvulsant Potencies of the Enantiomers of the Neurosteroids Androsterone and Etiocholanolone Exceed those of the Natural Forms


    Haidut has also found that DHT and it's metabolites increase 5ar stimulation.



    It could very well be the case that severe androgen depletion particularly in the Brain, as well as severe pro-GABA receptor stimulating metabolite depletion causes a SEVERE downregulation of the 5ar enzyme. Especially in the Brain/CNS.


    It has been observed that blood T and DHT levels are relatively normal in patients with full-blown PFS. It has also been found that 3a-diol-g (intracellular biomarker for 5ar levels) are exceptionally low. Blood levels of T and DHT seem to be a superficial indicator of androgen/5ar status. Since normal levels of T/DHT are often found in the blood of PFS sufferers, merely increasing T/DHT levels in the blood may only serve to induce a negative feedback on the HPG axis. To truly treat PFS one may need to increase 5ar levels in the CNS where the most significant deficiency of 5ar lies.

    If it is the case that there is a severe downregulation of 5ar in the CNS, then this explains why men generally get better on GABA enhancing substances (the above study suggests GABA receptor stimulation increases 5ar expression in the Brain). And why they (we) get worse when we merely increase androgens peripherally.
     
  2. bruschi11

    bruschi11 Member

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    When you speak about GABA- the reason is allllllll allopreg- finasteride decreases allopreg at a median of -350%. A study showed a maximum there of 850%. Blocking 5ar1 definitely leads to problems probably sexually, but the mental, anxiety, depression more so I believe has to do with 5ar2.

    I am currently essentially bedridden. My body is running on nothing but adrenaline. I was someone that probably had very low 5ar activity in the first place. I only went on finasteride because I was on TRT. I believe I REQUIRED TRT due to originally low 5ar activity. For instance, with T in the 750 range (250-100), I had DHT at 26 (15-75). I originally had a low T to DHT ratio if you go by the ranges there.

    This was in 2013 when I was healthy before adrenal fatigue took over my life and dropped T down to the 3-400 range. During this adrenal fatigue, I realized raising T(clomid, d aspartic acid) made me almost back to normal. Incorporating preg/t3 made me close to 100%, but finally opted for Tcream this past summer. Heavy hair loss lead to fin--> me lifeless.

    I theorize that the reason why POST finasteride is so bad is because when 5ar1 returns to baseline, 5ar2 remains low- this causes an even worse issue as DHT causes allopreg and the prog metabolites to drop even more.

    There has to be some sort of experiment where 5ar2 activity is increased substantially. I don't think there is anyway out of this except for those that actually had higher 5ar activity in the first place.
     
  3. TubZy

    TubZy Member

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    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.
     
  4. TubZy

    TubZy Member

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    Actually, big doses of glycine would probably work the best in terms of the research you are putting forward. Seems that is the best way to increase 5AR in the brain. Maybe doses of 16grams multiple times per day to get brain concentrations high enough.

    Glycine Strongly Upregulates 5-alpha Reductase (5-ar) Activity
     
  5. Pet Peeve

    Pet Peeve Member

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    I agree, but I won't take more than 5-10 grams a day. I took 50 grams in one dose once and vomited after a couple of hours. Very unpleasant. Now even small doses of glycine takes me back to how I felt then, though I get the benefits as well. Ugh, just writing this makes me nauseous again.
     
  6. OP
    bloom

    bloom Member

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    Sorry to hear that man. It's not just Allopregnanolone that would be affected. All of the downstream metabolites of 5ar are all allosteric modulators of the GABA receptor (Tetrahydrodeoxycorticosterone, Androstenediol, Androsterone ect). The more I learn about this the more I realise taking a 5ar inhibitor is like taking a sledgehammer to the GABAergic system. As far as I know it is the 5ar1 enzyme which is expressed in the brain. It could be that inhibiting 5ar2, leads inadvertently to 5ar1 downregulation, since all the androgens and products of the 5ar enzyme serve to stimulate the 5ar enzyme resulting in a positive feedback loop (as pointed out by Haidut). It could very well be that GABA receptor stimulation is also part of this 5ar positive feedback loop, I dont know just speculation.
     
  7. OP
    bloom

    bloom Member

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    Yep already on that TubZy, Glycine is great, it does help. However the dosage has to be very specific the study states stimulation of 5ar by glycine at 1uM and 35um. I have found Glycine very hit and miss, very hard to get the appropriate dose. It also states that concentrations of 70uM and 140uM, mainly accelerates 3a hsd activity, I seem to get worse on certain doses of glycine. It's also interesting to note that this is the theoretical cause of post-SSRI sexual dysfunction, increased 3a hsd activity leading to rapid DHT conversion to 3a-androstanediol. Anyway it seems like the real way forward for a lot of us PFS guys is to focus on 5ar and the brain. I'm going to search for things which specifically increase 5ar in the brain. A lot of Psychiatric drugs do it.
     
  8. OP
    bloom

    bloom Member

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    From wikipeida

    [26]Neurosteroids like 3α-androstanediol and allopregnanolone activate the GABAA receptor; because finasteride prevents the formation of neurosteroids, it may contribute to a reduction of GABAA activity (see also neurosteroidogenesis inhibitor). Reduction of GABAA receptor activation by these neurosteroids has been implicated in depression, anxiety, and sexual dysfunction.[27][28][29]


    The last sentence is most interesting. That reduction of GABAA receptor activation by those neurosteroids has been implicated in sexual dysfunction.
     
  9. TubZy

    TubZy Member

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    That is good news though, what kind of benefits did you feel at that dose mentally? At least we know it is really dose dependent lol.
     
  10. TubZy

    TubZy Member

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    Androsterone will take care most of those. Glycine would help too. And in the thread Haidut mentions to pair glycine with pregnenolone to increase its effects further in the brain. So that should take care of most of them. Glycine + androsterone + preg
     
  11. Pet Peeve

    Pet Peeve Member

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    At that dose it felt like my brain was frying. Light changed and the red and yellow tones were more pronounced. In small doses glycine tastes sweet but in higher doses the taste is truly appalling.
     
  12. TubZy

    TubZy Member

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    Interesting I have tried 15 grams at once, I felt a much better response followed by a throbbing headache.

    Caffeine + glycine combo could work well as they both increase 5AR in the brain.

    We can just put an end to this if some can synthesize some 5AR/5ARII powder lol.
     
  13. Pet Peeve

    Pet Peeve Member

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    That would be interesting to try
     
  14. TubZy

    TubZy Member

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    If bcaa/tyrosine combo lowers serotonin in the brain and can increase 5AR, I'm assuming theanine can do the same thing
     
  15. REOSIRENS

    REOSIRENS Member

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    PFS is characterized by frontal cortex damaged... Frontal cortex is reduced in pfs that's why impulsivity anxiety depression and lack of motivation is the main characteristics of pfs people... Frontal cortex is the prime and first body defence against mental stress... What feeds frontal cortex are things(magnesium Retinol potassium testosterone/dhea thiamine Gaba Glycine glucose cholesterol) that enhance 5ar enzymes
     
  16. REOSIRENS

    REOSIRENS Member

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    5ar enhancement works with help of metabolic stimulation that can be conducted with triiodothyronine progesterone sodium/lithium vitamin B12 carbon dioxide
     
  17. TubZy

    TubZy Member

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    That makes sense, poor stress response and a dull headache in the front of the head is what I get. I characterized it as GABA deficiency but prob much more than that you are right. Depletion of GABA would burn through glucose/glycogen stores extremely quick.

    I use most things on your list except thiamine, lithium and retinol. Could you explain why those? Do they upregulate 5AR in the brain? Especially thiamine?

    I didn't see you mention androsterone either.
     
  18. OP
    bloom

    bloom Member

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    A guy from Propeciahelp help had the same thought. He was in communication with an Italian PFS researcher. This is all hearsay but apparently the researcher said the 5ar enzyme is 'screwed up' whatever that means. The poster said what we need is a 5ar enzyme supplement which pass the blood brain barrier. If that's what we need that'd be ideal. It turns out this is a big problem in psychiatry, actually getting medication past the blood brain barrier, there's a lot of research being done on technology which can achieve this liposomes, nanoparticles ect.
     
  19. TubZy

    TubZy Member

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    I think @haidut was looking into this for us but I'm not sure what ever came of it, yeah I agree that would be interesting, I feel like once the enzyme is in the brain it will start to upregulate quicker again. I also think that is why majority of circulating DHT is normal because 5AR in the body is working just not the brain.
     
  20. OP
    bloom

    bloom Member

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    For sure I think the predominate problem is 5ar downregulation in the brain. Like I said any attempts to increase DHT peripherally makes me worse. I read a post from a guy on propecia help who claimed Proviron 'shrunk his ****'. I think there are varying degrees of severity with PFS. The worst being when it is downregulated in the Brain. My biggest improvements so far have come from 'slamming' the GABAA receptor with high doses of Nicotinamide, and valium. Every aspect of my condition improved, mental and physical. Libido, Brainfog, memory, mood. My muscles tightened, I started to sweat again, I started to get spontaneous erections, temperature in my **** increased, my shrinkage reversed. Whereas creatine, and sorghum made me dramatically worse. Shrunk my **** ect. Looking at countless posts from propeciahelp, this is not uncommon. This is a huge clue that the problem resides in the brain.
     
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