Summary of what PFS is

[LondonUK]

Hi all, sorry to be a pain but can someone do a high level summary of the key scientific mechanisms in play with PFS?
My doctor wants to help me but needs succinct information before possible referrals to specialist Departments

I’ve read the literature, reports, theories but I just can’t get my head round it at a high level. Not sure if that’s due to my mental symptoms or general IQ…

If anyone could spend a short amount of time replying that would be great.

@borax did something in 2018 but I assume it’s now outdated with all the PFS Network / Foundation studies since

[dome1234]

Hey Mate

I believe the best paper out there was written by Axolotl. Most concepts are quite complex, but here is a very brief summary of what PFS is according to his view and the current state of research:

Post-Finasteride Syndrome (PFS) is a severe condition that arises after the use of 5-alpha reductase inhibitors, such as Finasteride, which are commonly prescribed for androgenetic alopecia (hair loss) and benign prostatic hyperplasia (BPH). PFS is characterized by a range of persistent physical, sexual, and neurological symptoms that can continue long after the medication is discontinued.

Key Points:

Symptoms:

Physical: Muscle atrophy, fatigue, dry and thinning skin, decreased beard growth, changes in body temperature, gynecomastia (breast tissue growth in men), and changes in fat distribution.
Sexual: Erectile dysfunction, loss of libido, decreased ejaculate volume, genital anesthesia, and penile atrophy or deformation.
Neurological/Cognitive: Depression, anxiety, cognitive impairment (brain fog), memory issues, insomnia, and sensory disturbances.

Mechanism:

PFS is considered an epigenetic disorder resulting from androgen deprivation. This leads to overexpression of androgen receptors (AR), which can cause polyglutamine toxicity—a situation where protein abnormalities due to excessive repeats of glutamine can result in cell dysfunction and death.
Persistent AR overexpression is found in the tissue of PFS patients, contributing to the broad range of symptoms observed.

Clinical Implications:

PFS is often misdiagnosed as psychosomatic, leading to inappropriate treatments. Proper diagnosis and understanding are crucial for managing this condition effectively.
There is no known cure or consistently effective treatment, making management of symptoms the primary approach.

Research and Understanding:

The condition is not well understood, and research is ongoing to uncover the molecular mechanisms underlying PFS. Current hypotheses suggest that specific epigenetic changes induced by androgen deprivation play a critical role.
The condition affects younger men more frequently and severely, particularly those using the drug for hair loss.

Conclusion:

PFS is a complex, multifaceted condition requiring further research to develop effective treatments. Understanding the epigenetic changes and AR regulation is crucial for advancing the knowledge and management of this debilitating syndrome

Here ist the full paper: Post-Finasteride Syndrome as an Epigenetic Post-Androgen Deprivation Syndrome

[aki]

Definitely this report is the best. Extraordinarily high level, but we can see the outline of PFS. I have great admiration for this work.

By the way, I have a question.

It shows that overexpressed AR cannot work normaly and it causes every symptoms. – I understand.

Finasteride deprives us of androgens. It is quite natural that deprivation of androgens can bring AR (epigenetically) overexpressed. – Absolutely.

So, after cessation of fin, harmful severe symptoms should happen. It is inevitable.-- It’s OK.

My question is why AR-overexpression can not return to normal with time.

Just because it is epigenetic? or a special epigenetic modification as a kind of aging irreversible process?

is there any hypothesis about it? or no idea?

If anyone knows, please teach me.

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I have one more question.

According to the researches, AR-overexpression itself is destructive disaster for our life system. And it is probably inevitable for everyone that finasteride brings AR overexpressed. Because it deprives us of androgen.

So, why is it that only few people fall into PFS?

If AR-overexpression itself is the cause of PFS, no one can avoid it. Don’t you think so? Or, for most people finasteride does not increase their AR?

If anyone knows, please tell me why.

if it is that when androgen came back after the cessation of fin, under the condition of AR-overexpression something(X) which causes PFS happens only in few unlucky prople, I can understand it. In this case, AR-overexpression is not the cause but one condition. And the true cause(X) should prevent AR from returning to normal. (But this assumption may be not true.)

Or, AR-overexpression caused by finasteride immediately returns to normal after cessation of the drug in the case of most people, but doesn’t so in few people because of their predisposition. Is this the reason?

[LondonUK]

Thanks both, and to the report writers

I think my incorrect answer based on what I’ve read is that genes are changed (abnormal) so AR can’t go back to normal unless the genes are changed to normal again (this fixes PFS) or you take supplements to down-regulate AR which doesn’t cure but can alleviate symptoms.

But then some people on here say their AR is not over expressed without answering how/why so it confuses me.
The AR over-expression when the ‘crash’ happens makes sense i think but also I think there’s some credibility with some sort of auto immune activation but how this connects i have no idea

I should be seeing Dr Bouloux soon so I will press him on his take and revert

[aki]

But then some people on here say their AR is not over expressed without answering how/why so it confuses me.

The idea that AR is not overexpressed is nonsence, at least in PFS patients.

[M_C]

@LondonUK - you can print out this PDF with key research papers and highlights.

And here are some good tips about how you should speak to your healthcare practitioner about PFS.