haidut

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After a decade of denying that a thing such as PFS exists, mainstream medicine seems to be wisening up to the fact that this poison does a lot more than lower the "bad" DHT. Up until very recently, it was common to simply measure blood steroid levels and then declare that they had rebounded upon stopping finasteride. However, this new study measured steroid levels in both the blood and CFS and found that finasteride induces broad dysregulation in steroid synthesis affecting levels of pregnenolone, progesterone, 5a-DHP, allopregnanolone, DHEA, DHT and T. With such broad effects on steroids it is not a surprise that finasteride induced major depression in 50% of the patients taking it and moderate depression in the rest. Perhaps the most troubling finding is that finasteride caused physiological damage to the nervous system by inducing atrophy in the pudental nerve, a nerve which is crucial for proper sensation in the genitals.
Pudendal nerve - Wikipedia
This nerve damage is probably what causes the persistent erectile dysfunction (ED) in males taking the drug since the study did not find a correlation between the depression and erectile dysfunction in the patients under study. In the past, the persistent ED in people with PFS was blamed on their depression, which the official story said was pre-existing.
The nerve damage is not at all surprising given the reductions in levels of progesterone and 5a-DHP that finasteride caused. I posted a few studies on 5a-DHP being crucial for protecting from and possibly reversing peripheral neuropathy in various conditions like diabetes and neurological diseases like MS. Whether administration of progesterone and/or 5a-DHP can reverse the nerve damage caused by finasteride remains to be seen. But at least one thing is clear - PFS is a real and persistent condition given the widespread damage finasteride causes across both structural (pudental nerve) and functional aspects (steroids) of the nervous system, which can take years to reverse.
Finally, I am stunned that a chemical with such broad psychological and physiological toxic effects is not only approved for use but actively pushed on older men both for helping hair growth and "protecting" their prostate. If this study gets more press coverage we may see a class-action lawsuit against the maker of finasteride and a blackbox warning from FDA, but I doubt the drug will ever be banned.

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

"...Eight out of sixteen subjects (50%) sufferred from a DSM-IV major depressive disorder (MDD) as diagnossed by MINI. BDI and BAI of subjects with MDD, as compared with those without the disorder are shown in Table 2 showing significant higher levels for those with MDD. All patients (100%) showed some degree of ED, with a mean score at erectile fucntion domain of 10.31 (+/-9.48) (Table 3). In particular, we found 10 men with severe ED (62.50%) and six with mild-moderate forms (37.50%). Although a clear cut off for normal values was not proposed in the literature for other IIEF-15 domains, our patients showed a low score also for orgasmic function, sexual desire and overall satisfaction domains, compared to general population [48] (Table 3)."

"...As reported in Table 4, the levels of some neuroactive steroids analysed in CSF of PFS patients were significantly different versus those in healthy controls. In particular, the levels of PREG, as well as of its further metabolites, PROG and DHP, were significantly decreased in CSF of PFS patients. On the contrary, the levels of DHEA and T were significantly increased. The levels of metabolites of T, such as DHT, 3a-diol, and 17b-estradiol (17b-E) were also affected in CSF of PFS patients. In particular, we reported a decrease in the levels of DHT and 17b-E, associated with an increase in the 3a-diol levels. Assessment of the levels of neuroactive steroids in plasma of PFS patients showed similarities and dissimilarities in comparison to what observed in CSF. Thus, the pattetn in plasma did not exactly reflect what observed in CSF. In particular, at variance to what observed in CSF, the plasma levels of PREG were significantly increased. In addition, the levels of PROG and T metabolites, such as DHT, 3a-diol, and 17b-E, were unaffected in plasma of PFS patients. Furthermore, the levels of THP that were unaffected in CSF, showed a significant decreased in plasma. In agreement to what observed in CSF, the plasma levels of DHEA and T showed a significant increase and those of DHP a significant decrease."

"...We also reported abnormal somatosensory evoked potential of the pudental nerve in PFS patients with severe ED, the first objective evidence of a neuropathy involving peripheral neurogenic control of erection. We have presented the first objective evidence in PFS patients of peripheral neuropathy of the pudental nerve, which is critical for normal neurogenic control of erection. PN_SEP abnormalities were found in 25% of PFS patients, in spite of normal neurological examination and no prior history of neurological disease. Moreover, no evidence of metabolic, toxic (e.g. alcohol abuse), or inherited disease known to be associated with peripheral nervous system damage which might be correlated with PN_SEPs alterations was detected."

"...It is important to highlight that as mentioned above, a signfiicant decrease in the levels of PROG was observed in the CSF of PFS patients. This may suggest a possible association between this neuroactive steroids and MDD symptomatology. Indeed, a role of PROG in depressive symptomatology associated to different pathologies has already been proposed [53]. Larger studies are warranted to further evaluate the role of CSF PROG levels in PFS patients with MDD."

"...Another importan finding here reported is that the effect of finasteride on neuroactive steroid levels do not only affect the levels of 5a-reduced metabolites of PROG and T (i.e., DHP and DHT respectively) and further metabolites (i.e. THP), but also PROG and T themselves, as well as their precursor (i.e. PREG, and DHEA). Thus, finasteride treatment has broad consequences on neuroactive steroid levels."
 
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Interesting finding Haidut. Did not know about the pudendal nerve/ed connection.

Some questions:
- What are your thoughts on Pregabalin(lyrica) for nerve issues? ... safe compound? could be carcinogenic?

- Any other types of medications/peptides worth trying for ed/nerve issues(if hormones are in range)?

Thanks!
 

aguilaroja

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....this new study measured steroid levels in both the blood and CFS and found that finasteride induces broad dysregulation in steroid synthesis affecting levels of pregnenolone, progesterone, 5a-DHP, allopregnanolone, DHEA, DHT and T.
...finasteride caused physiological damage to the nervous system by inducing atrophy in the pudental nerve,...
Neuroactive steroid levels and psychiatric and andrological features in post-finasteride patients. - PubMed - NCBI

I referenced this study in a different thread
Finasteride Lowers CSF Neuro-steroids/pregnen Differently From Blood
to make this point:

Since Finasteride changes hormone levels differently in brain fluid (CSF), doctors & providers may not see changes on the blood tests done commonly at office visits.

To measure CSF levels, a lumbar puncture (spinal tap) is done. Few doctors, and probably no endocrinologists, do that at an office visit.

So a patient WITHOUT major blood level changes may have significant brain fluid changes. This is a missed diagnosis, not a “psychological issue”.

Hormone depleted CSF can affect not only the brain and spinal cord, but influence the peripheral nerves directly. See, for instance,

Cerebrospinal fluid outflow along lumbar nerves and possible relevance for pain research: case report and review
 

TubZy

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I don't think the nerve is totally ****88, but think it is very sensitive. Sensitivity wise caffeine and niacinamide has restored sensitivity for me (other things have as well but not as strong at caff/niacinamide), but I'm not sure if it acting directly on the nerve or not bc both of those substances do many other beneficial things.
However, I will caution that using too much progesterone can cause decrease sensitivity and numbness from what I noticed while adding in some DHEA can help restore sensitivity.
 

aguilaroja

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Interesting finding Haidut...
- What are your thoughts on Pregabalin(lyrica) for nerve issues? ... safe compound? could be carcinogenic?
- Any other types of medications/peptides worth trying for ed/nerve issues(if hormones are in range)?...

I beg pardon, in advance, for floating thoughts about questions posed for @haidut.

Lyrica (pregabalin) in in the anticonvulsant (epilepsy/seizure-reudcing) class of medications. Doctors have been using anticonvulsant pharmaceuticals for many decades to try and treat chronic pain. Lyrica remains under patent until at least 2018. Lyrica/pregabalin does have a useful aspect that it increases GABA. It is less desirable for other biochemical and practical issues. See for instance:
Pregabalin - Wikipedia

Dr. Peat’s thoughts about metabolism and seizures may be also to the use regarding lyrica & anticonvulsants for nerve issues:
http://raypeat.com/articles/articles/epilepsy-progesterone.shtml
Eclampsia in the Real Organism: A Paradigm of General Distress Applicable in Infants, Adults, Etc.

The Melcangi article provides evidence that hormones “in range” for blood (or saliva, or urine) may not fully reflect changes in CSF.
“Neuroactive steroid levels were also altered in plasma of PFS patients, however these changes did not reflect exactly what occurs in CSF”.
 
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Thanks for the reply aguilaroja. A lot of this stuff about enzymes/aminos/neurotransmitters etc is over my head. But from what I did read on some of those links you posted:

From epilepsy-progesterone "The most popular anticonvulsant drugs are both neurotoxic and teratogenic, that is, they damage the patient's brain, and greatly increase the incidence of birth defects."..."Excitotoxicity, in its simplest sense, is the harmful cellular effect (death or injury) caused by an excitatory transmitter such as glutamate or aspartate acting on a cell whose energetic reserves aren't adequate to sustain the level of activity provoked by the transmitter.

pregabalin wiki: "It increases extracellular GABA concentrations in the brain by producing a dose-dependent increase in L-Glutamic acid decarboxylase (GAD), the enzyme responsible for making GABA"

gaba wiki: GABA is converted back to glutamate by a metabolic pathway called the GABA shunt.

From Pfizer "The exact mechanism of action of LYRICA (pregabalin) has not been elucidated. These findings are based on preclinical animal models. The clinical significance in humans is unknown."...
https://www.pfizerpro.com/product/lyrica/fibromyalgia/mechanism-of-action
https://www.pfizerpro.com/product/lyrica/fibromyalgia/mechanism-of-action
 

haidut

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I referenced this study in a different thread
Finasteride Lowers CSF Neuro-steroids/pregnen Differently From Blood
to make this point:

Since Finasteride changes hormone levels differently in brain fluid (CSF), doctors & providers may not see changes on the blood tests done commonly at office visits.

To measure CSF levels, a lumbar puncture (spinal tap) is done. Few doctors, and probably no endocrinologists, do that at an office visit.

So a patient WITHOUT major blood level changes may have significant brain fluid changes. This is a missed diagnosis, not a “psychological issue”.

Hormone depleted CSF can affect not only the brain and spinal cord, but influence the peripheral nerves directly. See, for instance,

Cerebrospinal fluid outflow along lumbar nerves and possible relevance for pain research: case report and review

Thanks for making this point here as well. I think the reductions in progesterone and 5a-DHP are what's possibly behind the nerve damage. Peripheral nervous system health depends primarily on thyroid, myelination and inflammation and deficiencies in progesterone and its metabolites would certainly affect all 3 of these factors. So, hopefully restoring pudental nerve conductivity is as simple as a few weeks/months of thyroid/progesterone therapy.
 

haidut

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tallglass13

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In the conclusions, I see 5a-androstandione, I thought this is a metabolite upstream of 5a androstanediol...am I mistaken?
 

tallglass13

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Either way, finasteride is blocking a few other 5a hormones aside from DHT, so I was thinking that the balding hormone is one of those instead of DHT.. what do you think, Id like to know your thoughts @haidut. thank you in advance.
 

JoeKool

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Thanks for making this point here as well. I think the reductions in progesterone and 5a-DHP are what's possibly behind the nerve damage. Peripheral nervous system health depends primarily on thyroid, myelination and inflammation and deficiencies in progesterone and its metabolites would certainly affect all 3 of these factors. So, hopefully restoring pudental nerve conductivity is as simple as a few weeks/months of thyroid/progesterone therapy.

Hello @haidut

I'm using ~25mcg T3 and 4-5drops 5aDHP.

Are you suggesting regular progesterone and/or anything other than T3? Dosage recommended too please? In regards to healing said nerve.
 

REOSIRENS

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I have always mentioned that pfs guys have to approach their side effects in relation to post traumatic stress disorder and traumatic brain injury systemic damage...studies are starting to clarify that there is no different between the brains of PFS people and TBI ones
 

haidut

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Hello @haidut

I'm using ~25mcg T3 and 4-5drops 5aDHP.

Are you suggesting regular progesterone and/or anything other than T3? Dosage recommended too please? In regards to healing said nerve.

I think this is a good protocol. You may want to try to add 30mg - 50mg pregnenolone daily as pregnenolone also has trophic effects on nerves. Nobody knows the exact formula/dose for recovering from nerve damage but the doses mentioned match animal study protocols for peripheral neuropathy, which this nerve damage is an example of.
 

JoeKool

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Big thank you @haidut

I should've mentioned I'm using 100mg preg in the morning plus ~10mg preg from pansterone on the genitals, split into two dosages...

But thank you, I'm patiently seeing results... making a minor adjustment such as adding Andro within the next 14 days... maybe a progestene too...

This forum is the real deal... real ppl offering real help... undoing the biggest mistake of my life... taking fin :(
 
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I think this is a good protocol. You may want to try to add 30mg - 50mg pregnenolone daily as pregnenolone also has trophic effects on nerves. Nobody knows the exact formula/dose for recovering from nerve damage but the doses mentioned match animal study protocols for peripheral neuropathy, which this nerve damage is an example of.

This is all very useful information. Possible damage to the pudental nerve sounds very concerning.

What also caught my eye is that it sounds like issues with this nerve could cause constipation issues as well which is another common symptom of PFS.

I will be following your advise and adding cycles of preg and prog for the next several months. The 30mg-50mg of preg sounds like a good start. How much preg exactly is in one drop of StressNon? I started taking 5 drops of StressNon on the inner arm four days ago. I'm not completely following the dosage instructions though. The StressNon bottle says 12 drops and than mentions 20mg of preg but is not saying if each drop contains 20mg or if all 12 drops would be 20mg.
 
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Some people are somehow unaffected or even feel better on it. But yeah, I dont undersstand how such an awesome intelligent and successful machine of a man could be taking fin either.

dam I feel like a skum bag saying this but maybe that's exactly what we need joining this fight. That's not even mentioning his endless resources
 
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