(Study) Neurosteroid Levels in PFS patients

Science Other Studies
#1

The study from Italy…
onlinelibrary.wiley.com/doi/10.1 … 9/abstract

Neuroactive Steroid Levels are Modified in Cerebrospinal Fluid and Plasma of Post-Finasteride Patients Showing Persistent Sexual Side Effects and Anxious/Depressive Symptomatology

Abstract
Introduction

Observations performed in a subset of subjects treated with finasteride (an inhibitor of the enzyme 5α-reductase) for male pattern hair loss seem to indicate that sexual dysfunction as well as anxious/depressive symptomatology may occur at the end of the treatment and continue after discontinuation.
Aim

A possible hypothesis to explain depression symptoms after finasteride treatment might be impairment in the levels of neuroactive steroids. Therefore, neuroactive steroid levels were evaluated in paired plasma and cerebrospinal fluid samples obtained from male patients who received finasteride for the treatment of androgenic alopecia and who, after drug discontinuation, still show long-term sexual side effects as well as anxious/depressive symptomatology.
Methods

The levels of neuroactive steroids were evaluated by liquid chromatography–tandem mass spectrometry in three postfinasteride patients and compared to those of five healthy controls.
Main Outcome Measures

Neuroactive steroid levels in plasma and cerebrospinal fluid of postfinasteride patients and healthy controls.
Results

At the examination, the three postfinasteride patients reported muscular stiffness, cramps, tremors, and chronic fatigue in the absence of clinical evidence of any muscular disorder or strength reduction. Severity and frequency of the anxious/depressive symptoms were quite variable; overall, all the subjects had a fairly complex and constant neuropsychiatric pattern. Assessment of neuroactive steroid levels in patients showed some interindividual differences. However, the most important finding was the comparison of their neuroactive steroid levels with those of healthy controls. Indeed, decreased levels of tetrahydroprogesterone, isopregnanolone and dihydrotestosterone and increased levels of testosterone and 17β-estradiol were reported in cerebrospinal fluid of postfinasteride patients. Moreover, decreased levels of dihydroprogesterone and increased levels of 5α-androstane-3α,17β-diol and 17β-estradiol were observed in plasma.

Conclusion

The present observations confirm that an impairment of neuroactive steroid levels, associated with depression symptoms, is still present in androgenic alopecia patients treated with finasteride despite the discontinuation of the treatment. Melcangi RC, Caruso D, Abbiati F, Giatti S, Calabrese D, Piazza F, and Cavaletti G. Neuroactive steroid levels are modified in cerebrospinal fluid and plasma of postfinasteride patients showing persistent sexual side effects and anxious/depressive symptomatology. J Sex Med ;:–.

How does AR expression affect 5-ar activity?
#2

Holy f-ing shit. I am 99.9% sure this is the cause of our problems. I’m feeling fogged to shit right now, so I can’t do any research, but I will try to look up some of these pathways later today! This is totally it. Smoking gun.

#3

I wonder if this change in CSF is also the cause of this god damned pressure in my head. I would bet the house on it.

#4

It was published 4 days ago, strange i thought it is from 4 months ago.

#5

CSF increased:

testosterone
17β-estradiol

CSF decreased:

tetrahydroprogesterone
isopregnanolone
dihydrotestosterone

Plasma decreased:

dihydroprogesterone
5α-androstane-3α
17β-diol
17β-estradiol

Does this mean certain enzymes are just not working or is it the whole down regulation of androgenic response. Increased testosterone I guess could be from not being converted to DHT, but increased estrogen? Maybe thats why people have brief recoveries on aromatase inhibitors. But the brain possibly readjusted to maintain PFS conditions.

I wonder what would happen if someone took progesterone and an aromatase inhibitor. Sounds risky though.

#6

This needs to be made into a ‘sticky’ thread

This news is massive on the whole research front and explains why I’m currently in a mental home and whilst others take they’re lives.

This study also supports that the anxiety and depression symptoms are a long term persistent or permanent effect as it alters the brain.

This has been a fantastic discovery but has also added to my worried state of mind that I have left.

#7

They seem to link this to just depressive symptoms but I am sure the sex hormones are somehow affected. So what the hell does all this mean?

Btw- increased estradiol (esrogen) levels in the CNS, a I predicted! Can I get some props around here? Anyone? Anyone?

#8

They say the clinical study at harvard is the “stepping stone” for future research, but isn’t this very revealing? This study shows the imbalances present and from them doctors can infer which enzymes don’t work or what the hell is going on in the brain.

#9

Extemely revealing, no if they link this to androgen receptor and poor gene expression we may have something.

#10

So even months/years after stopping finasteride, it seems testosterone is preferentially being converted to Estrogen vs DHT.

They should try giving mice with PFS progesterone + aromatase inhibitor. I wonder if this will force an up regulation of the androgen steroid synthesis pathway.

#11

Fina, it’s as we have said all along, fucked up brain receptors

All NEUROLOGICAL !!!

#12

Isn’t this a typo? Isn’t 5α-androstane-3α,17β-diol (aka 3-aDiolG) usually lower than normal?

So increased Test & Estrogen and lower DHT & 5-alpha-reduced metabolites are what is found when using Finasteride. Do they mention what may be causing this continual impairment?

Since they don’t compare like-for-like in the CSF and serum, does that mean the ‘impairment’ of these hormones is different/worse in the nervous system?

Do they mention if this may also be happening in the peripheral nervous system?

Do they mention that most studies say 5-alpha-reductase-type 2 isn’t thought to be in the CNS?

#13

Who wants to immortalize this study by putting it in the Finasteride Wikipedia page?

en.wikipedia.org/wiki/Finasteride

#14

Second Amendment- you have access to change things on wiki? That’s amazing . Screw Merck!! Bring on more studies!!!

#15

Shit, just realized the page was under semi-protection and my account can’t edit protected pages. It’s bound to get put in there sooner or later – hopefully sooner.

#16

Damn I pray the news outlets run with this story. Would potentially help other scientists, doctors, and researchers some material to theorize. I think I will run it by dr. Jacobs

#17

Two questions:

  1. Is this ultimately good news? Or does it show that its likely that PFS is incurable, or is it just too early to tell?

  2. Is this the result of the research that started in September 2011, where 63 men submitted saliva samples, etc.? I know that was taking place in Europe, and two years seems about right for results to be published…

Anyways - we are getting answers which can never be bad. But we do need to get this information into more doctor’s hands…

#18

Well, I don’t think it’s bad news. Myself and others have been having sustained improvements over the months which is a good sign and suggests its probably treatable at the very least, but to eary to tell. Others have reported reversal of symptoms which also bodes well for all of us. If we had no improvements, zero change from crash we would all be pretty hopeless right now, which is how I felt in year one of this aweful syndrome, but there is no doubt improvements are happening just incredibly slowly.

#19

With Mothers cells. Several have been cured.

#20

What mother cells?