Thoughts On 5ar And Post Finasteride Syndrome

[bruschi11]

Thanks @JoeKool will do when and if I trial it.

Currently stabilizing on the 2.5mg fluoxetine and adding in the PEA. Will be interesting. Will be an interesting as I've never seen a PEA user for PFS on any of these sites.

EDIT: ^^^ I just can't believe how badly my writing has become since PFS. These things are happening all the time now where I re-read my work and say "WHAT!?"... All I can say is wouldn't it be nice if one little thing like PEA could change EVERYTHING.

 

[bruschi11]

https://www.researchgate.net/public...lamide_vs_NSAID_in_the_treatment_of_TMJD_pain

Conclusions: Our preliminary data suggest that PEA is an effective tool for treatment of TMJD, in patients with synovitis and osteoarthritis pain. It is a non-gastrolesive effective analgesic with a longer half-life than NSAID (12 versus 4 hours).

Publication insights: Palmitoylethanolamide vs NSAID in the treatment of TMJD pain. Available from: https://www.researchgate.net/public...lamide_vs_NSAID_in_the_treatment_of_TMJD_pain [accessed Apr 7, 2017].

Was looking for a half life for PEA. Very good thing we get the 12 hours here. Good stuff (hopefully).

 

[ContinuousHeal]

Guys, given my experience with years of good use and no side effects, combined with what I could only describe as nerve damage, in my years of researching PFS, this post still seems to be extremely important, and connected to the discussion in this thread, though different. Would love to get your takes.

http://www.hairlosshelp.com/forums/messageview.cfm?catid=10&threadid=85335

 

[TubZy]

https://www.researchgate.net/public...lamide_vs_NSAID_in_the_treatment_of_TMJD_pain



Was looking for a half life for PEA. Very good thing we get the 12 hours here. Good stuff (hopefully).

How much PEA are you planning to usE?

 

[bruschi11]

Amazon.com: Palmitoylethanolamide (PEA) 400mg Capsules 180 Count: Health & Personal Care

I loaded up this morning to get it in the system. I took 1600mg overall. Not sure what exactly I'm going to do.

I'm not the best guide for this because again I'm stabilizing on 2.5mg fluoxetine. And that 2.5mg sounds low but definitely feels pretty strong to me. I will say by this time of the day I usually am experiencing anxiety. I am not yet. I feel as calm as I've felt since starting the fluoxetine. We will see.

 

[bruschi11]

Again, I am using fluox at 2.5. But its been 8 full days of using this now. Dose has varied between 2.5mg and 10mg. Today just 2.5mg where I am going to try to remain.

That said, the "5a-dhp feeling" I would get that I initially got from fluox (but it subsided after a few days) has come back pretty strongly today. I am hoping, thinking, it must be the PEA. This feeling must be the increasing allopreg levels.

 

[TubZy]

Again, I am using fluox at 2.5. But its been 8 full days of using this now. Dose has varied between 2.5mg and 10mg. Today just 2.5mg where I am going to try to remain.

That said, the "5a-dhp feeling" I would get that I initially got from fluox (but it subsided after a few days) has come back pretty strongly today. I am hoping, thinking, it must be the PEA. This feeling must be the increasing allopreg levels.

You should try skipping the fluox for one day and just use PEA and see if you get the same feeling

 

[bruschi11]

You should try skipping the fluox for one day and just use PEA and see if you get the same feeling

I would but I just really haven't felt this sense of relaxation in a long time. I can tell you for sure- the PEA did something today regarding allo. Fluox on its own wouldn't have done this. Zero libido right now or any other good effects. Just a major relaxation, 5a-dhp feeling. And you know more than anyone that anxiety has been my biggest concern.

 

[heaahde]

Does accutane affect the same thing as finasteride?

 

[TubZy]

No they didnt use anything to inhibit 5ar in the study. The takeaway from this study is that administration of testosterone was able to decrease the expression of 5ar in the pituitary. Whats also interesting to note is that the study states that castrated rats have INCREASED expression of 5ar in the Pituitary, and that administration of Testosterone was able reverse the increased expression of 5ar in the castrated rats. Peripheral testosterone levels seems to be involved in regulating the expression of 5ar in the Pituitary.

I think anything that stimulates cAMP will stimulate 5AR, hence why caffeine and forskolin show enhanced 5AR activity. If you know anything else that stimulates cAMP could be worth looking into.

 

[bruschi11]

One Theory To Explain Them All? The Vagus Nerve Infection Hypothesis for Chronic Fatigue Syndrome - Simmaron Research

Could this be part of our problems? I'm not saying the whole thing- but those of use very sensitive to stress. Incapable of taking it. It seems that those that fix the gut and truly clean the body having success would be fixing the gut to brain connection.

Maybe the majority of us had a minor issue here beforehand and the depletion of neurosteroids. gaba disruption just topped it off.

Edit: found this on solvepfs thrown on there by "im23" about a year ago. Don't want to be taking anyone's findings. But I am very much onto the CNS aspect right now.

While raising 5ar in the CNS is part of our goal, I wonder if calming the CNS (vagus nerve surgery even?) would possibly in itself allow 5ar to peak its head.

 

[bruschi11]

http://www.medscape.com/viewarticle/804311 ---> For treatment resistant depression. Significant improvements here and this is for people that were depressed for 2-20 years without any success before.

https://www.ncbi.nlm.nih.gov/pubmed/12948617 --> Below- if this is all a GABA-A mediated disease we have here. If any procedure can bring this back to normality, I think its worth it.

Abstract
Vagus nerve stimulation (VNS) is an important option for the treatment of drug-resistant epilepsy. Through delivery of a battery-supplied intermittent current, VNS protects against seizure development in a manner that correlates experimentally with electrophysiological modifications. However, the mechanism by which VNS inhibits seizures in humans remains unclear. The impairment of gamma-aminobutyric acid (GABA)-mediated neuronal inhibition associated with epilepsy has suggested that GABA(A) receptors might contribute to the therapeutic efficacy of VNS. We have now applied single photon emission computed tomography (SPECT) with the benzodiazepine receptor inverse agonist [123I]iomazenil to examine cortical GABA(A) receptor density (GRD) before and 1 year after implantation of a VNS device in 10 subjects with drug-resistant partial epilepsy. VNS therapeutic responses resulted significantly correlated with the normalization of GRD. Moreover, a comparable control group, scheduled for a possible VNS implant, failed to show significant GRD variations after 1 year of a stable anti-epileptic treatment. These results suggest that VNS may modulate the cortical excitability of brain areas associated with epileptogenesis and that GABA(A) receptor plasticity contributes to this effect.

 

[bruschi11]

https://selfhacked.com/2015/07/30/2...agus-nerve-and-all-you-need-to-know-about-it/

Going through this list on selfhacked, I'd say the majority of these have been in practice for the many guys that have beat pfs. Furthermore, healing the gut's impact on the vagus nerve is profound.

 

[freeflow]

Sexual behavior reduces hypothalamic androgen receptor immunoreactivity. - PubMed - NCBI
This was posted on solvepfs, sexual behaviour and its connection with AR in the brain
This explains why i crashed my 95% recovery with 1 fap.

 

[bruschi11]

http://cancerres.aacrjournals.org/conte ... 1052.short

Variable expression of 5-alpha reductase 2 in the aging adult prostate is regulated by DNA methylation

BACKGROUND:

5-alpha reductase type 2 (SRD5A2), an enzyme that is critical for prostatic development and growth, is utilized as an inhibitory target by finasteride for patients with bladder outlet obstrution secondary to BPH. However, we have found that many aging benign prostate tissues do not express the enzyme. Since the SRD5A2 promoter contains a CpG island, we hypothesized that somatic methylation of the promoter would be regulated by DNA methyltransferases leading to suppression of SRD5A2.

METHODS:

Benign prostatic tissues from wild-type mice at 3, 6 and 12 months of age were used. In addition, 96 prostate samples from human male patients who were treated by TURP for bladder outlet obstruction secondary to BPH were used. Methylation of SRD5A2 promoter was assessed using Methylated CpG Island Recovery Assay (MIRA). DNMT1 siRNA and 5-AZA-C were used to determine the methylation status of SRD5A2 in benign prostatic cell line, BPH-1. To determine the effect of CpG methylation, SRD5A2 promoter-luciferase constructs were methylated in vitro using M.SssI methylase. Statistical analyses were performed with JMP Pro version 11 (SAS Institute Inc., Cary, NC).

RESULTS:

We analyzed 96 human BPH samples from transurethral resection of prostate (TURP) surgeries and found that absence of SRD5A2 was closely associated with hypermethylation of the SRD5A2 promoter region. We found that methylation of SRD5A2 was regulated by DNA methytransferase 1 (DNMT1) and the cytokines, TNF-alpha, NF-κB and IL-6, regulated DNMT1protein expression and thereby indirectly affected SRD5A2 promoter methylation and gene expression. Suppression of cytokines inhibited activity of DNMT1, while over-expression of p65 or treatment with TNF-alpha or IL-6 up-regulated DNMT1. In addition, we found that methylation of the SRD5A2 promoter and concomitant decrease in protein expression were closely associated with patient's increasing age (P<0.05). Finally, in murine prostate tissues, cytokine levels, DNMT1 and global methylation were all increased in older mice. Induction of inflammation with lipopolysaccharide (LPS) stimulated the TNFR1/NF-κB/IL-6/DNMT1 pathway, leading to hypermethylation of the SRD5A2 promoter and silencing of SRD5A2, while treatment with both LPS and TNF-alpha inhibitor reversed this pathway and reactivated SRD5A2.

CONCLUSIONS:

Expression of SRD5A2 is not static and ubiquitous in benign adult prostate tissues.

We show that SRD5A2 expression is lacking in many benign human adult prostate tissues. Methylation of SRD5A2 promoter region, which is regulated by DNMT1, accounts for absence of SRD5A2 expression in many adult human prostate tissues. Methylation and expression of SRD5A2 may be used as a gene signature to tailor therapies for more effective treatment of prostatic diseases.

First off, inhibiting the inflammatory cytokine TNF-Alpha will reactivate SRD5a2. Lets start there.

 

[bruschi11]

Vagus nerve stimulation inhibits cytokine production and attenuates disease severity in rheumatoid arthritis

A lot to this article, but one major quote I'll provide. But I'd say read the full thing.

To determine whether vagus nerve stimulation inhibits TNF production in humans, we studied seven epilepsy patients [five male, two female; mean age 35 y (range 25–43 y)] who were implanted with a vagus nerve-stimulating device using a coiled cuff electrode (Cyberonics) on the left cervical vagus nerve. These patients had no history of inflammatory or autoimmune disorders. Peripheral blood was collected before, during, and after vagus nerve stimulator implantation surgery. Endotoxin was added to the whole blood to stimulate the production of TNF by monocytes for 4 h (13, 23). The application of current-controlled electrical pulses (single 30-s stimulation at 1.0-mA output current, 20-Hz pulse frequency, 500-μs pulse duration) significantly inhibited whole-blood TNF production compared with baseline levels before electrical stimulation (Fig. 1A). The inhibition of TNF release following vagus nerve stimulation during general anesthesia cannot be attributed to a placebo effect, because the subjects were unconscious and were not aware of the nerve stimulation. Whole-blood production of interleukin (IL)-6 and IL-1β was also inhibited significantly by vagus nerve stimulation (Fig. 1 B and C). To our knowledge, this is the first report that the delivery of electric current applied directly on the cervical vagus nerve to stimulate the inflammatory reflex inhibits the endotoxin-induced release of TNF, IL-1β, and IL-6 in humans.

So electrically stimulating the Vagus Nerve significantly inhibits TNF release.

 

[bruschi11]

https://selfhacked.com/2015/07/30/2...agus-nerve-and-all-you-need-to-know-about-it/

I'll just post the list of the 28 ways to stimulate the Vagus Nerve- do the majority of these not look like PFS success story techniques? Please tell me if so because I think these strongly correlate with success.

32 Ways to Stimulate The Vagus Nerve

• 1) Cold
• 2) Singing or Chanting
• 3) Yoga
• 4) Meditation
• 5) Positive Social Relationships
• 6) Breath Deeply and Slowly
• 7) Laughter
• 8) Prayer
• 9) PEMF
• 10) Breathing Exercises
• 11) Probiotics
• 12) Exercise
• 13) Massages
• 14) Fasting
• 15) Sleep or Lay on Your Right Side
• 16) Tai Chi
• 17) Gargling
• 18) Seafood (EPA and DHA)
• 19) Oxytocin
• 20) Zinc
• 21) Tongue Depressors
• 22) Acupuncture
• 23) 5-HTP (Serotonin)
• 24) Chew Gum (CCK)
• 25) Eat Fiber (GLP-1)
• 26) Coffee Enemas
• 27) Coughing or Tensing the Stomach Muscles
• 28) Thyroid Hormones/T3 Are Normal
• 29) Sun (MSH)
• 30) Carbohydrates (insulin)
• 31) Orexin
• 32) Ghrelin

Also another link on self hacked for inhibiting TNF-Alpha

https://selfhacked.com/2014/09/01/supplements-lifestyle-factors-influence-tnf-interleukin-6-il-6/

 

[bruschi11]

I theorize like @bloom that PFS is a central nervous system condition where inflammatory cytokines like TNF-Alpha cannot be contained due to weak Vagus Nerve function. Due to elevated inflammatory cytokines invading this whole CNS, 5ar remains silenced until one can correct Vagus Nerve function.

There's a lot more to this reasoning, but it appears the Parasympathetic Nervous system is just extremely violated- its almost like its under severe malfunction.

I believe some of us may even need Vagus Nerve Stimulation surgery in order to have a chance of beating this.

Hacking The Nervous System | The Huffington Post

 

[LukeL]

Amazon.com: Palmitoylethanolamide (PEA) 400mg Capsules 180 Count: Health & Personal Care

I loaded up this morning to get it in the system. I took 1600mg overall. Not sure what exactly I'm going to do.

I'm not the best guide for this because again I'm stabilizing on 2.5mg fluoxetine. And that 2.5mg sounds low but definitely feels pretty strong to me. I will say by this time of the day I usually am experiencing anxiety. I am not yet. I feel as calm as I've felt since starting the fluoxetine. We will see.

I'd be cautious about taking fluoxetine - there are several studies showing its negative effects on leydig cell function (also on androgen production) in the testes. Here's one and I've definitely seen another one online but don't have time to find and post

• 
  
• 
  Journal article : Crescent Journal of Medical and Biological Sciences 2014 Vol.1 No.2 pp.37-41 ref.19
  
  Abstract : Objective: Fluoxetine is widely used in the treatment of neurological disorders. Hence, considering the adverse effects of this drug on the endocrine axes of the body is very important. Fluoxetine has been shown to cause significant changes in testicular tissue structure and sex hormones in rats. It seems that antioxidant compounds such as vitamin E can reduce free radicals and inhibit these changes. Therefore, the aim of this study is to investigate the therapeutic effects of vitamin E on testicular tissue damage caused by fluoxetine use. Materials and Methods: In the present study, 40 Wistar rats (weight=250±10 gr) were randomly divided into 4 groups; control group that received normal saline (with intraperitoneal (IP) method), fluoxetine group (n=10) that received 10 mg/kg of fluoxetine (IP), vitamin E group (n=10) that received 100 mg/kg of vitamin E (IP), and the treatment group that received both vitamin E (100 mg/kg) and fluoxetine (10 mg/kg) for 28 days. On the 28th day of the study testis tissue was removed and sent to the pathology lab and blood samples were taken for analyzing of testosterone and total antioxidant capacity. Results: The highest testosterone levels are related to the control group and the lowest levels are related to the fluoxetine receiving group. Significant differences were observed between sperm density in the seminiferous tubes, spermatogonia cells, and primary spermatocyte, and leydig and sertoli cells in the experimental groups compared to the control group after a 28-day period. Conclusion: Fluoxetine can damage the leydig cells and decrease activity of testis and production of testosterone, but vitamin E can repair the leydig cells and reduce damages caused by fluoxetine.
  ISSN : 2148-9696
  
  URL : http://www.cjmb.org/.../21
  
  Record Number : 20153123936
  
  Publisher : Celal Bayar University
  
  Location of publication : Manisa
  
  Country of publication : Turkey
  
  Language of text : English
  
  Language of summary : English
  
  

• http://scholar.google.com/scholar_l...s&volume=1&issue=2&pages=37-41&issn=2148-9696

 

[bruschi11]

I'd be cautious about taking fluoxetine - there are several studies showing its negative effects on leydig cell function (also on androgen production) in the testes. Here's one and I've definitely seen another one online but don't have time to find and post

• 
  
• 
  Journal article : Crescent Journal of Medical and Biological Sciences 2014 Vol.1 No.2 pp.37-41 ref.19
  
  Abstract : Objective: Fluoxetine is widely used in the treatment of neurological disorders. Hence, considering the adverse effects of this drug on the endocrine axes of the body is very important. Fluoxetine has been shown to cause significant changes in testicular tissue structure and sex hormones in rats. It seems that antioxidant compounds such as vitamin E can reduce free radicals and inhibit these changes. Therefore, the aim of this study is to investigate the therapeutic effects of vitamin E on testicular tissue damage caused by fluoxetine use. Materials and Methods: In the present study, 40 Wistar rats (weight=250±10 gr) were randomly divided into 4 groups; control group that received normal saline (with intraperitoneal (IP) method), fluoxetine group (n=10) that received 10 mg/kg of fluoxetine (IP), vitamin E group (n=10) that received 100 mg/kg of vitamin E (IP), and the treatment group that received both vitamin E (100 mg/kg) and fluoxetine (10 mg/kg) for 28 days. On the 28th day of the study testis tissue was removed and sent to the pathology lab and blood samples were taken for analyzing of testosterone and total antioxidant capacity. Results: The highest testosterone levels are related to the control group and the lowest levels are related to the fluoxetine receiving group. Significant differences were observed between sperm density in the seminiferous tubes, spermatogonia cells, and primary spermatocyte, and leydig and sertoli cells in the experimental groups compared to the control group after a 28-day period. Conclusion: Fluoxetine can damage the leydig cells and decrease activity of testis and production of testosterone, but vitamin E can repair the leydig cells and reduce damages caused by fluoxetine.
  ISSN : 2148-9696
  
  URL : http://www.cjmb.org/.../21
  
  Record Number : 20153123936
  
  Publisher : Celal Bayar University
  
  Location of publication : Manisa
  
  Country of publication : Turkey
  
  Language of text : English
  
  Language of summary : English
  

I've always been against SSRIs, but based on my current belief on how to beat PFS and the current situation where my brain is 100% in requirement for some sort of low dose mental drug to maintain a horrible HPA axis dysfunction issue, I am ok with using at these ultra low doses. Currently using 3.3mg. Also fluoxetine has proven to significantly decrease inflammatory cytokine TNF-Alpha which I believe ultimately may be the cause of PFS.

Adding more to this- like most with PFS, I have been one to immediately grab for the benzos during anxiety. We need to kick this. Benzo withdrawal is horrible for the vagus nerve and a major reason for vagus nerve malfunction. Everytime we take a benzo we go through withdrawal that next day. Addicted or not, we have to kick these benzos.