What I believe PFS is

General Discussion
#42

I will consult my theory with a truly professional in the matter ( No more urologist, endocrinologist, general medicine, nor even neurologist) I believe this is need to be consulting with an specialist on Neurobiology.

I will strongly recommend to everybody stop experimenting with any type of drugs and even supplements, until we consult this matter.

It this theory is true, It going to be a shameful for the international medical community that WE with OUR EFFORT (I say this because I believe that WE ALL participated ) where who find the cause of the issue, even we don’t have all the details of what sub-type of GABAA receptor or receptors are affected, but at least we are in the right track.

I know that this finding if true this is only 1/2 of the issue ( for those that do not are producing DHT at all, the problem probably is related with the AR, and the Baylor or the other study in Italy can come with the answer for it).

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#43

Yes. It has been rumored that Melcagni and his cohorts don’t put credence in the Di Loreto study. I don’t know if their criticism is valid and based on flawed methodology of the study or if it is simply a matter of them refusing to acknowledge a study that they believe isn’t supportive of altered neurosteroidogenic enzyme expression as the root cause. I’m certainly not a scientist professionally, but have an educational background in biotechnology, and don’t see any problem with how the Di Loreto study was conducted or understand how these two hypotheses aren’t compatible enough to converge at the point where loss of AR signalling can explain both overexpressed AR and the findings of Melcagni’s team.

What is concerning, and you know this first hand, is that some scientists deny the physical aspects of PFS because they are not supportive of their beliefs.

I’ll leave it at that.

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#44

I will repeat again here something that a geneticist a Baylor told me,He said that it is impossible that finasteride can cause an a Genetic or Epigenetic Change, and this guy is an specialist in the matter, he is not an urologist, or endocrinologist, his specialty is genetic at the Baylor University.

Now I am not totally clear, but I believe that AR can up-regulated and down-regulated, I believe that they are changing up and down as the litigant concentration change.

But anyway, I still believe that at least some of the PSF suffer do not have any problem with AR, also
the range are normal and are producing DHT.

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Altered methylation pattern of the SRD5A2 gene in cerebrospinal fluid of post-finasteride patients: a pilot study
#45

I still say after its all said and done whatever the reason is the end result is that Testosterone is not used correctly by the body anymore…All these symptoms correlate back to this…Brain, body, all…

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#46

Sex differences in GABAA receptor binding in rat brain measured by an improved in vitro binding assay

The distribution of GABAA receptor sites was studied in female and male rat brain by an improved in vitro binding assay using 3H-muscimol and carefully washed membrane fractions. The binding studies revealed a single class of binding sites exhibiting the properties of GABAAreceptors. The specific binding of 3H-muscimol was measured in four brain areas: the preoptic brain area, mediobasal hypothalamus, corticomedial amygdala and cerebral cortex. The equilibrium dissociation constants ( K D) ranged from 11.2 to 23.3 nM in diestrous females and from 13.1 to 50.4 nM in males, the maximal number of binding sites ( B max) from 3290 to 10240 fmol/mg protein in females and from 5495 to 17449 fmol/mg protein in males. In the preoptic area and mediobasal hypothalamus both, K D and B max, were significantly higher in males than in females. The sex differences in the binding of muscimol observed in vitro indicated sexually dimorphic GABAergic neurotransmission that is probably related to the control of gonadotropin secretion and/or sexual behavior.

As you can see the GABA receptors seem control no only anxiety, depression, the good feeling, but also sexual behavior.

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#47

@imscaredman high grade Bulgarian tribulus with protodioscin is supposed to increase androgen receptors. If you haven’t read through it already, you should check out @Apr1989’s two theads (one from this year, one from 4 years ago) on this. A bunch of users (including me) currently trying out trib cycles. Sorry if you know all this already.

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#48

Precisely, when I meet Dr Khera I told him about this guy that recovered with Tribulus and he said that he can’t confirm it, but it is possible, due Tribulus work the libido side.

Supplementation of T. terrestris is regularly incapable of increasing levels of androgenic/estrogenic hormones in blood or urine samples, however, synergic actions over NO synthesis, GABAergic signaling inhibition (through DHEA), dopaminergic signaling and potential for bioconversion to androgens (1875mg doses), indicate a possible application in the treatment of erectile dysfunctions and HSDDA. Protodioscin (PTN), a common saponin from T. terrestris, may stimulate nitric oxide (NO) and other mediators tomodulate central dopaminergic activity and libido. PTN may also be converted to DHEA, which is capable of inhibiting GABA signaling, therefore promoting improvements in sexual function . B. The relationship between PTN and testosterone (TST), of stimulation or direct conversion, is still unknown, however, in vivo models indicates that T.terrestris may influence concentrations of TST and C. dihydrotestosterone (DHT). PubChem compound database
codes: CID=441891 (PTN); CID=6013 (TST) and CID=10635 (DHT). Adapt
https://www.researchgate.net/publication/320909030_Tribulus_terrestris_L_zygophyllaceae_safety_and_effectiveness_of_steroidal_metabolites

#49

I have a question for anybody that want to discus.

While on finasteride DHT levels are reduced to almos zero or very low,
allopregnanolone for example is made from DHT, It mean while in the drug allopregnanolone is going to be also very low probably undetected.
Many of us took the drug for many years and they where able to functioning sexually while in the drug with very low allopregnanolone and without proper levels of the rest of the active neuro-steroid that are derivative of DHT.
Now people still thinking that our sexual problem low libido is low level allopregnanolone.

Do this make sense?

#50

Alloregnanolone is not made from DHT, it’s made from DHP.
You are probably thinking of androstanediol, which is formed by further reduction of DHT by 3a-HSD enzymes.

To answer your question, it doesn’t make sense, but low allopregnanolone is exactly what has been found in PFS patients.

About the sexual symptoms, it’s almost as if something that detects testosterone and DHT, 2 important male sexual hormones that still serve a function in regulating sexuality in women, and sends some sort of signal as a response to detecting those homones, isn’t functioning correcly.

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#51

its strange, but when i was ON fin i had even higher libido. on fin men tend to have higher T, higher e2 because its sth left that didnt convert to dht. i also felt like having 0 cortisol on fin, superflat stomach,sleeping 11h soundly, always chilled mindset.no ambitions,yet no worries.
in few words: my version of PFS feels like going from no cortisol to skyhigh cortisol (high levels conirmed)

#52

I was taking clonzapaem off and on for 2 years before I took FIN… wondering if there is a connection. Oddly i don’t take it anymore though when I really think about our situation that makes me anxious so i try not to. I read somewhere that there might be a connectoin between those that had prior anxiety issues and pfs?

#53

Hey dude - I would keep hope. When I crashed for the first few months I literally felt like I was tripping on lsd or something. Total sensory disconnect with mind and body. One of the halmark things I noticed is that I couldn’t feel my muscles and they wouldn’t get sore - I was lifting like crazy to beat pfs. Benching 235 and I weigh 155. Stil couldn’t feel soreness. I even remember I would flex my biceps super hard (in the past this would cause pain cuz I squeezed too hard) and after the crash I felt nothing. Well… that’s all normal now. I workout and I get sore as shit and I can feel my body pretty well. So I think that will improve.

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#54

Did these scientists explain you why they believe that Di Loreto’s study is not reliable or why they believe that it is impossible for finasteride to cause an epigenetic change?

#55

If it is not epigenetic, which it has not been proven to be so and from the looks it may never be proven?? Only one other thing it could be…Autoimmune. Certainly because of testosterone nut functioning correctly but why? It appears that the body is just unable to readapt back to it for some reason…

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#56

No, man. You misunderstood. Melcangi and Santi consider both an epigenetic change and a reduction of neurosteroids, but that does not concern the AR receptor. This they said.

#57

I insist that the problem lies in penile tissue changes. The lack of libido comes in part because the body gets frustrated when blood is not flowing normally, nerves are not transmitting information as in the past, etc (whereas in the past, there were nice sensations instead).
We need to push for more detailed studies of penile tissues (not just corpora cavernosa, but also tunica albuginea). Eco-doppler can test some of those changes, but not all.
If many in the group have venous leak even after injection, it’s because the tissues have changed, it’s obvious.
Epigenetics, neurological changes, etc., can be a possibility, but I cannot understand why there is no serious research about penile tissue changes as the core of PFS.

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#58

PFS sufferers have been shown to have very low levels of neurosteroids in their brain. This will certainly have a strong effect on mood, libido, etc. Why fixate exclusively on the penis?

#59

It’s a problem of cause-effect.
Low levels of neurosteroids can be also found in depression and in post-traumatic stress disorders (PTSD).
How will you avoid depresion or PTSD if you see that your penis is unable to have a normal erection, you cannot masturbate as in the past, etc.?
I still don’t understand why the histological side (changes in the penile tissue) is still underestimated as the cause of the problem.

#60

Because it isn’t an issue for some PFS guys who still suffer from a host of other effects like brain fog. Therefore it can’t possibly be the root cause of the condition.

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#61

I also had brain fog for a couple of years (I was not even able to tell what I had for dinner the day before…). I am much better now. But the physical problem remains.
In any case, nobody knows exactly what is happening on the physical level either, and no matter how much I insist to urologist and even to people in this forum, nobody seems to care about this issue, and I think they are overlooking something important here.