PFS caused by Neurosteroid pathway interruption?

General Discussion
#22

So I’m currently 36. I got PFS from Saw-P at age 26. At that time I got all the sexual sides only. Not that sexual sides only don’t suck because they do. At age 29 I took saw-P again and developed digestive and insomnia issues on top of sexual sides.

Then recently as in this past summer after taking my recovery attempts to the next level I had one of the most advanced saliva hormone tests done currently available in a normal clinical setting. This is how I discovered that I’m low in a not so well know neurosteriod called pregnenolone sulfate. I’ll edit this post and include a chart later so that you can see where and how in the hormonal pathway pregnenolone sulfate is being made. Most of the hormonal pathway charts you find on line will not include it.

Then i started googling the heck out of pregnenolone sulfate leading me to discover that it’s a neurosteriod that negatively modulates the GABA receptors. The exact opposite as Allopregnanolone, 3a-diol and benzodiazepines which act as positive allosteric modulators of the GABA receptors.

Now if I’m low in the bodies main negative allosteric modulators of the GABA receptors it’s my theory that this is a possibly mechanism/scenario in which the result is that the GABA receptors may stay in a constant state of insensitivity/down regulation in order to avoid “excessive positively modulation”. Because maybe it’s the case that the GABA receptors need a proper balance of negative and positive modulation in order to stay “balanced” because after all that’s the point of a “modulator”.

So if there is no negative allosteric modulator present because there is no or not enough pregnenolone sulfate then maybe the “next best thing”is that the GABA receptors become less sensitive to the effect of the neurotransmitter GABA. And if this happens maybe the bodies main excitatory neurotransmitter glutamate adjusts to match the misregulated main inhibitory neurotransmitter GABA

Keep in mind that low pregnenolone sulfate has not been replicated in anyone else yet. Also keep in mind that the exact imbalance that could results due to having low pregnenolone sulfate could be different then my proposed mechanism. I’m simply going with the most logical outcome of outcomes that could in theory result from the lack of negative allosteric modulation of the GABA receptors.

I think the lab may send a test to the UK. I will find out and let you know.

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#23

Ok I follow your theory - makes sense and thanks for explaining. Certainly in line with my original line of thought.

Please do let me know about test availability in the UK, I am very interesting at exploring a deeper level of testing vs what you can infer from simple bloodwork. It would be great to collect results from a wide number of PFS sufferers.

On a side note, I am glad you have mentioned that you crashed from SP. My hair loss continues to steadily progress and this is a good reminder to stay away from anything that inhibits 5AR at all costs!

Thanks again and keep in touch

1 Like
#24

An interesting finding indeed. Please keep us posted as you continue to delve into this.

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#25

We can just try low dose Fluoxetine for it.

#26

Scott,

You can order a test from the U.K. but you would need to pay for the shipping cost to have your completed test kit sent back to ZRT lab in the US.

You can order the test for $370 USD plus shipping . It’s discussed in detail in this thread:

#27

Thanks a lot for this.

I have just paid for a full blood hormone test here in the UK to be done. I will await the results (I have never actually had my blood hormones done before), assess my levels and then potentially look to get this done too.

On another note - as my hair loss has continued in the past years since I have been recovering from PFS, I have looked at other ways to address the hair loss problem at an androgen level and came across RU58841 (topical Anti Androgen). There is little literature on the substance as it is a ‘research chemical’.

However - I did a lot of reading into it’s mechanism of action and as I surmised that my issues were due to the upstream nerosteroid cascade we have been discussing in this thread, disrupted due to low 5AR levels and not due to a lack of androgens themselves, I decided to try it at a very very low dose. Stupid I know, although a calculated risk in my trivial pursuit of hairloss.

Used it for 2 days at 0.05% and it definitely created small episodes of PFS like cognitive symptoms. Now I am not a pharmacologist, however to my knowledge there should be no known interaction of RU58841 and the neurosteroids discussed here.

RU is a nonsteroidal anti-androgen. Meaning it binds to the AR without transcribing any effects and also has a very short half life (1 hour, whilst it’s metabolites have a half life of up to 20 hours).

I am saying this for 2 reasons:

1 - It is evidence to suggest that a disruption to androgen activity is at play here alongside potential neurosteroid issues. Albeit this is not in line with my original hypothesis.

2 - Topically applied solutions can still act systemically. I am sure we all knew this already, but even a very very low dose of this stuff clearly did have systemic implications in me.

Sharing as this may be a useful anecdote for the community and a reminder that we should avoid all anti androgens regardless of mechanism of action.

#28

Hi @Trazohell @5-alpha-victim @scott7777

I noticed you haven’t completed the patient survey yet. When you have some time, could you please complete it using the instructions in this video I created: https://www.loom.com/share/c298a179a0e64cba8ef9e69ae0122ac4

I cannot understate how important this resource has been when liasing with researchers and clinicians, and your participation would be much appreciated.

Thank you for your help.

Best,
Mitch

#29

@Sugarhouse

I completed the survey

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#30

The studies specifically stated it worked on females and not on males. So it does something different in both male and female brains. I wish I was wrong but it’s what the study says. I’ve been trying it for a couple of months with zero progress and realize why .