Post Finasteride Syndrome, 5ar, And The Brain

Discussion in 'Male Issues' started by bloom, May 17, 2017.

  1. bloom

    bloom Member

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    A lot of you will be familiar with the thread I started 'Thoughts on Post Finasteride Syndrome'. Basically in the thread I try and make the argument that 5ar is downregulated/impaired in some fashion, but where the downregulation/impairment is most significant (meaning where it's lack of functioning is most important in PFS), is in the Brain/CNS.

    GABAA agonists improve a lot of our symptoms: cognition, libido erectile function.

    This study has found that Valium, anti-convulsants, and other drugs which have GABAA agonistic properties, effects on neurotransmission, and brain functioning, significantly increases the activity of 5ar in the Diencephalon of rats:

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

    5ar metabolites, Allopregnanolone, THDOC, and 3a-diol. All have strong GABAA agonistic properties.

    [​IMG]

    Reduction of GABAA receptor agonism has been implicated in sexual dysfunction, from wiki:

    A new study have just come out which strongly suggests impairment of 5ar in the Brain/CNS:

    Neuroactive steroid levels and psychiatric and andrological features in post-finasteride patients. - PubMed - NCBI



    Increase of Testosterone and DHEA in the CSF, along with lower levels of DHT, DHP. And unaffected levels of THP(Allopregnanolone), and an increase in 3a-diol levels, in the CSF, strongly suggests that 5ar is impaired in some capacity in the CNS.

    Again strongly suggestive of impaired 5ar activity. It's also interesting to note that they found DHT is reduced in the CSF, but not in the plasma.

    Men often get worse on treatments to increase Testosterone/DHT. Often get worse on treatments to increase 5ar (i.e Tribulus, Creatine, Sorghum Flour). But report get better on GABAA agonists and other substances which seem to increase 5ar in the Brain/CNS.

    There are several studies I posted on the other thread which strangely suggests there is an inverse relationship between Testosterone levels in the Blood and 5ar levels in the Brain. Moreso and inverse relationship between 5ar1 levels in the Brain and Testosterone levels in the blood. And a positive relationship between T levels in blood and 5ar2 levels in the Brain, the isoenzyme thought to be responsible for 'sexually dimorphic behaviour'


    Regulation of the pituitary 5 alpha-reductase activity by gonadotropin releasing hormone and testosterone in the adult male rat. - PubMed - NCBI

    [Localization of a 5alpha-reductase activity in the nuclear membranes of the anterior hypophysis of normal and castrated adult male rats]. - PubMed - NCBI

    Effects of testosterone on brain mRNA levels of steroid 5alpha-reductase isozymes in early postnatal life of rat. - PubMed - NCBI

    If 5ar is impaired in some capacity in the Brain/CNS as I believe it is. Then these studies can explain why a huge portion of men worsen on TRT, or any treatment to increase androgens peripherally. Some guys report an improvement in libido on TRT but a worsening of anxiety. Other guys such as myself worsen on all fronts with any treatment which increases blood levels of Testosterone and/or DHT. The above studies can explain why this is the case. They strongly suggest somewhat of an inverse relationship with Blood T levels and Brain levels of 5ar. Specifically 5ar1. It can also explain why guys get dramatically better when 5ar activity is seemingly increased in the Brain/CNS, with GABAA agonists, Caffeine ect.

    An appropriate approach to PFS for a lot of us may includes focusing of 5ar and neurosteroids in the Brain/CNS. And for the time being forgetting about increasing 5ar and androgens peripherally since this seems to cause more harm than good. There are several possible treatments being discussed in the 'Thoughts on 5ar and Post Finasteride Syndrome' thread. I'm sure they'll be mentioned again here.
     
  2. OP
    bloom

    bloom Member

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    I think I can explain why high levels of Testosterone were found in the CSF of the guys in the above study. Your brain can synthesise it's own hormones or utilise peripheral hormones. 95% of your Testosterone is made in your testicles, so the CSF levels of T could just be an accumulation of peripherally derived Testosterone being 'banked up' by an impaired 5ar enzyme in the CNS. Here's an image which gives a brief description of Neurons using peripheral Progesterone, to synthesise neurosteroids:

    [​IMG]
     
  3. bruschi11

    bruschi11 Member

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    I am one of those guys that gets increase in libido but increase in anxiety by adding androgens.

    That being said and everything pointed out. I think repairing the CNS is probably our most important goal here.

    Reducing inflammation, allowing gene expression in the CNS to gradually out weigh this imbalance we have.

    Just don't think we can force it with many drugs supplements. History shows this- cleaning, cleaning, cleaning really leads to success.

    I agree with this for sure but I also believe we have some brain damage from our crash. I believe GABA-a is significantly weakened due to the surging androgen response.

    This type of brain damage is for those that really "crashed" several weeks after stopping the pill. If you crashed you know what I'm talking about.

    I do believe there are two types of PFS. "Crashers" and "lasting sides." I do not have a source for this, but somebody with connection to Italian study told me that Melcangi said he believes there are "two types of PFS." I'd imagine these are them to a degree.

    Lasting sides being an easier way out but not easy at all. I think the crashers really suffered brain damage which is scary. Me being one of them unfortunately.

    For the record- the fact we have to be discussing this and be inflicted with this disease is just pure ludicrous. Brain damage man. Just ridiculous.
     
  4. sladerunner69

    sladerunner69 Member

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    I have been taking caffiene pills and it has been pretty good although I feel some atrange pressure in my chest... anyone else experience this?
     
  5. TubZy

    TubZy Member

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    That is the same reason why many of us can't take caffeine anymore like we did prior to fin. Prior to fin I could handle loads of caffeine and stims with zero anxiety, but that was when my neurosteroids were functioning correctly and were modulating the GABA-A receptor preventing a lot of the stress response and anxiety that caffeine can cause due to GABA being an inhibitor on the CNS.

    Same reason why, I can't take much caffeine now WITHOUT niacinamide, a GABA agonist, which is basically filling in the role on the GABA-A receptor that my neurosteroids should normally fill. I also think that is the reason why PFS is so hard to treat because without GABA working properly many things you add that even have a slightly stimulatory effect can make you feel worse because without GABA calming the CNS down you need to be really careful..or else boom you get hit with anxiety.

    Same reason why GABA can have an effect on immunity and stress induced immune suppression with many people ending up with candida, reactivated viral infections, some people had lyme and others were constantly getting sick.
     
  6. sladerunner69

    sladerunner69 Member

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    Yep I could easily call what happened to me brain damage. I can still feel it in my pre frontal cortex and it has been 6 years, although I havent been completely sober and eating well during the entirety of thay time tbh.

    But yeah I think allopreg and those progesterone 5ar reduced hormones play important roles maintaining the brain and other parta of the nervous system. For the crashers I think it can be a long recovery, similar to coming out of paralysis or something. If the change is epigenetic then that can take years to push back into thw correct balance.
     
  7. OP
    bloom

    bloom Member

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    Heterogeneity of rat type I 5 alpha-reductase cDNA: cloning, expression and regulation by pituitary implants and dihydrotestosterone. - PubMed - NCBI

    So this study done in rats, pretty much states that Pituitary hormones increase mRNA levels of 5ar1, and DHT decreases mRNA levels of 5ar1. This can explain why guys with PFS claim to feel better when they take a 5ar inhibitor, you're reducing blood levels of DHT and consequently increasing gene expression of 5ar1.


     
  8. OP
    bloom

    bloom Member

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    Finding a way to simultaneously increase all isoenzymes?
     
  9. OP
    bloom

    bloom Member

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    Yeah I experience something similar, caffeine can increase blood levels of T/DHT, it is very hit and miss for me. It may not be best for us, considering the approach we're now going for.
     
  10. sladerunner69

    sladerunner69 Member

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    I don't believe the chest pressure is related to T/DHT... I think it has something to do with increased blood rpessure which is a common side effect of caffiene. I feel MUCH more energy on the caffeine pills though, and without the stomach cramps and IBS I was getting from coffee. However, I did get a little irritable toward the end of the day which may be from the increased Testosterone as you state. However I think caffiene is still definitely worth that effect because it has been shown to increase 5ar by about 50% in doses from 200-400mg which is phenomenal.
     
  11. TubZy

    TubZy Member

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    It is probably just from anxiety since GABA isn't working properly. I get chest pains from taking things that inhibit GABA sometimes even since fin, it is anxiety related for me.
     
  12. sladerunner69

    sladerunner69 Member

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    Well I didn't get chest pains like that before I started dosing the caffeine pills. Before that I was not focussed on raising GABA, except for drinking my coffee with gelatin and theanine. I think I may just be adjusting to the caffeine dose. You are totally right about one thing though, while taking dhea/androsterone/preg/aspirin/vitamins my anxiety was soaring. I feel muss less anxious now that I am focussing on raising gaba instead of T/DHT, it's remarkable.
     
  13. coppersocks

    coppersocks Member

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    I feel that I'm in the same boat somewhat. I have signs of low GABA; poor sleep health, lack of focus, bouts of anxiety and depression and all of these symptoms are alleviated somewhat in the short term by alcohol consumption and exasperated by smoking cannabis, though I may get better sleep after one night of smoking, anxiety and sleep get much worse after any more than that. If we are to solely concentrate on raising GABA and allopregnenole agonism in the long term, as opposed to T/DHT are the best options simply caffeine, preg, progesterone, 5a-DHP and Glycine?
    Also can lowered allo and GABA account for loss of libido in and of themselves? And if so, is there any point in looking to increase the likes of T and it's offshoots?
     
  14. sladerunner69

    sladerunner69 Member

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    Yeah those seem to be the supplements that I and others have the most success with. Try niacinimide too, and I haven't tried inosine but that looks promising.

    Testosterone/dht doesn't seem to be as important for me anymore. for the first couple of eyars I didn't ahve any DHT and my testosterone was very low, but now that my testosterone is over 500 or 600, and my DHT is almost back to normal, focussing on GABA and the progesterone pathway is giving me much better effects. @bloom theorizes that testosterone actually decreases the 5ar enzyme in the brain, because many people who take testosterone or dhea or supplements with a strong anti-aromatase effect like aspirin, often feel more depressed, irritable, lackluster etc even though physically they feel stronger. As for libido, I thought raising testosterone was the way to go to keep my libido strong but when I took androsterone/dhea it didnt help my libido much at all and actually made sex less mentally stimulating. Remember sex is supposedly like 80% mental so we should be taking thinks that help allievate the side effects in our minds primarily, and 5adhp, niacinimide, caffiene, progesterone, gelatin, seem to be the best at that for most guys.

    Also dieting I believe is the msot fundamental factor in recovery although we no longer talk aout it that much. However i believe the basic peat approach is best. I drink lots of juice and skim milk, eat my liver and oysters, fancy cheeses, mushrooms, potatoes, coffee, pastured eggs, grassfed butter, coca cola, making sure to get plenty of salt and calcium to keep my metabolism strong. I think a strong thyroid and metabolism make optimizes the rate at which we recover.
     
  15. OP
    bloom

    bloom Member

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    Glad to hear this man
     
  16. OP
    bloom

    bloom Member

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    Well I have a theory for the PFS crash. The above studies demonstrates that castration increases 5ar expression in the brain. Another study mentioned above demonstrates that Testosterone administered to male/female rats increases 5ar2 expression in the brain but DECREASES, 5ar1 expression. So you bring down T/DHT levels in the blood with a 5ar inhibitor: 5ar1 is upregulated in the Brain, 5ar2 is downregulated. When you go off the 5ar inhibitor levels of T/DHT FLOOD the Brain causing a downregulation of 5ar1, and consequently the infamous PFS crash. Very simplistic and not a complete theory. But it can explain the type of PFS you have. T brings back libido, but induces anxiety. In this case I would think 5ar2 is operational since the T is bringing back your libido, but reducing 5ar1 activity since it's also causing you anxiety. Just my two cents. The trick seems to be to increase expression of all isoenzymes. Lets not forget 5ar3, this is very important.
     
  17. OP
    bloom

    bloom Member

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    I'll add i've experimented with a 5ar inhibitor curcumin a few times. When i take it i experience DRAMATIC improvements in mood, brain fog, anxiety, memory.But not so much libido. It's a bit similar to taking a morphine based drug. This is why i think PFS is so hard to treat. Because of this seeming inverse relationship between T/DHT and 5ar1 expression in the Brain. Restoration of 5ar1 expression before anything else may be a good idea. How to acheive this? No idea, i've been researching into epigenetics, but frankly im an amateur. Vitamin c can act as a demethylating agent, and 5ar2 expression is regulated by dmnt1, a methyltransferase enzyme which seems to have the capacity to silence 5ar2 expression.
     
  18. bdawg

    bdawg Member

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    @bloom, have you had an increase in social anxiety symptoms post finasteride? my theory is that what you guys are experiencing is similar to what social anxiety sufferers have from birth ie low GABA neurotransmission
     
  19. OP
    bloom

    bloom Member

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    Yeah sure, anxiety is super common with PFS
     
  20. TubZy

    TubZy Member

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