The Post-finasteride Syndrome: Clinical Manifestation of Drug-Induced Epigenetics Due to Endocrine Disruption


#1

Purpose of Review

Post-finasteride syndrome (PFS) is a disorder characterized by a set of clinical symptoms experienced during use or after drug discontinuation. This cluster of symptoms encompasses overall sexual dysfunction (SD), erectile dysfunction (ED), loss of libido, depression, suicidal ideation, anxiety, panic attacks, insomnia, and cognitive dysfunction. To date, there is lack of comprehensive understanding of the biochemical and pathophysiological mechanisms responsible for the adverse effects of finasteride. More importantly, there is lack of knowledge and effective clinical tools for treatments of this condition, resulting in outright dismissal of complaints by individuals afflicted with this syndrome. Psychological symptoms and cognitive dysfunction of PFS are far more serious and difficult to treat than sexual dysfunction symptoms and may lead young men to contemplate, attempt, or even commit suicide. Therefore, an urgent need exists to fill the knowledge gap in physiology, pathophysiology, and clinical management of patients with PFS.

Recent Findings

Finasteride treatment impairs biosynthesis and function of neurosteroids, which are critical regulators of central (CNS) as well as peripheral nervous system functions and modulate a host of neurotransmitter receptors, such as gamma amino butyric acid receptors. Thus, finasteride-induced neuroendocrine disruption of biosynthesis of critical signaling molecules results in pathophysiological states, which contribute to inhibition of biochemical pathways responsible for a host of physiological functions, ranging from sexual activity, mood, and cognition. In addition, finasteride-induced epigenetic changes in gene expression, including upregulation of androgen receptors (AR), increased histone acetylation, and methylation results in undesirable biological outcomes such as impairment of dopaminergic signaling and modulation of other neurotransmitter receptors, may be the underlying mechanism causing persistent or permanent adverse effects, manifested in anxiety, depression, and suicidal ideation.

Summary

The medical community has an obligation not to turn a blind eye on this rare yet debilitating condition in young men. Patients with this condition should not be stereotyped or stigmatized by untrained and unprepared clinicians, due to lack of awareness and knowledge pertaining to this new and rare syndrome. Greater awareness and education is needed among the medical and scientific communities in order to develop better approaches for managing men with PFS. It is paramount that steps are taken to develop better understanding of the underlying mechanisms contributing to the onset and progression of PFS and to promote educational and training programs to increase awareness and improve management of this condition.


Pete1989's story
#2

Great…More understanding is what we need…All Dr’s that are capable or prescribe this garbage should be required to read and talked to their patients about this and make sure they are aware of the very serious health risks of this drug…


#3

I didn’t even need to see a doctor to get this in the UK, I literally ordered it online from the nation’s biggest pharmacy, Boots, a household name spanning generations. I bought it, essentially, as an over the counter medication. As few multiple choice online questions and a few days later the packet’s landing on my doormat. A total of 1mg of the drug has wrecked my brain and body.


#4

They don’t mention the physical sides which I wished they would more…It is sounding more and more like epigentic silencing someway of some genes causing androgen metabolsim to basically stop in certain areas or tissues of the body…


#5

The medical community has an obligation not to turn a blind eye on this rare yet debilitating condition in young men. Patients with this condition should not be stereotyped or stigmatized by untrained and unprepared clinicians, due to lack of awareness and knowledge pertaining to this new and rare syndrome

Word up! Some of us expect an apology from the medical community in the future. Holding my breath for this.


#6

They owe us a bit more than that frankly.

It if looks like a duck and quacks like a duck :wink:

However, I’ve read this paper in its entirety now. It does take physical symptoms into account in mentioning patient’s perspectives. It is largely great imo and an unusually good review. Apart from a few inaccuracies it’s really good. Lots in here and very much takes this seriously. Skipping the science, I’ve put some excerpts below that show it’s very much on our side:

Use of finasteride, a 5α-RI, in men with BPH or AGA is associated with adverse sexual side effects including decreased or loss of libido, orgasmic, and ejaculatory disorders, ED, and testicular atrophy (Fig. 1b). Other complaints include dry skin or thinning of skin, weight gain, insomnia, panic attacks, brain fog, elevated glucose, and lipids. Other prevalent symptoms include psychological/neurologic conditions of self-harm (suicide), slow cognition, psychological pathologies, emotional anhedonia, and insomnia. Patients seeking medical help for loss of libido and ED were among the first to recognize the adverse effects of finasteride prescribed to prevent male pattern hair loss (MPHL) due to AGA. Loss of libido and increased incidence of ED are serious issues of selfesteem, quality of life, and well-being and are signs of something terribly amiss with physiological process.

VigiBase database of the Uppsala Monitoring Centre and the World Health Organization’s Programme for International Drug Monitoring [135] report 212 adverse event cases of suicidal ideation, 31 cases of suicide attempt, and 46 cases of completed suicides among former and current finasteride users. These men were desperate to seek help for a condition that they never imagined to be precipitated by a drug taken for a non-pathological condition, such as MPHL (AGA). Patients report fatigue, social isolation, cognitive dysfunction (brain fog), and insomnia. There are a number of reports on patients who attempted suicide and others who committed suicide.

Many patients are frustrated by the perception in the medical community that such condition does not exist and they are labeled to suffer from psychological disorder, rather than an organic disorder, attributed to a biochemical imbalance due to enzyme inhibition of a key biochemical pathway in steroid and neurosteroid biosynthesis and metabolism. The lack of clinical knowledge pertaining to this syndrome and the absence of awareness in the clinical community regarding this syndrome produced a narrative that this condition does not exist, and patients seeking help for this condition are suffering from psychological or psychiatric disorders. This had translated into loss of credibility and confidence by patients in their doctors and huge loss of faith in the medical community at large.

…What is more distressing to patients is that many clinicians dismiss that this drug has any real adverse effects and the stories concerning sexual dysfunction and/or suicide are either made up or exaggerated. Few, however, fully appreciate the magnitude of this syndrome and are frustrated by the fact that little attention is paid to improve care for such afflicted patients.

It is imperative that the medical and scientific communities do not dismiss this syndrome and stereotype patients afflicted with serious and debilitating disorder. The scientific and medical communities need to develop better understanding of the pathophysiology of this syndrome in order to develop new and better tools for patient treatment and management. Increased physicians as well as patients’ awareness of PFS is another dimension that needs to be emphasized and acted upon by the medical profession. The time to act is now.

Also interesting to note is its mention of the persistent problems induced by amongst others the relin class of anti-androgens, and also SSRIs, which of course @awor and I strongly suspect a link between.

It’s really nice to see this support from Dr Traish in putting out such an impassioned publication. The time to act is definitely now.


#7

it is not surprising that finasteride through a mechanism of endocrine disruption elicits slow, yet irreversible pathophysiological changes that lead to the constellation of symptoms known as PFS.

Fuck…


#8

Has anyone purchased the complete pdf? I read the whole thing last night on my phone but now you have to pay 40 bucks for it I should have downloaded it then…I am gonna purchase it later today and send it to my Dr Gordon.


#9

After sending it to Gordon he relayed to me that all PFS patients he has, have had one or more traumatic brain injuries before using finasteride and he believes there is a preexisting neuro inflammation that could act as a natural selector for users to become symptomatic on finasteride…


#10

From the excerpts this reads like a good summary of our problem and the obstacles we face with the medical community. It will hopefully spread more awareness among the medical community. Traish has been writing about PFS for years and must have been one of the first professionals to publish serious papers about this problem. We can only thank him for his help to put our problem on the map.


#11

And yet, doctors continue to claim PFS does not exist.


#12

This is M.plan. No question. Imagine pfs ppl would print flyers with the most important info.in it and widespread overall? (a guy told me this concept). I just wonder.
Did you see how he smiles at the end? Mofo. Psychological related - haha. And he has not even one study on that. Even M.had to change the labels due to new evidence of certain pfs symptoms.


#13

We should make a thread of shame consisting of quotes/papers/videos, etc from all doctors we can find who deny the existence of PFS.


#14

Most symptoms appeared suddenly. For many the remiss just as suddenly. I’m not a medical scientist (despite having a hard science background), but I remain unconvinced that the pathology comes about slowly, and remain equally unconvinced that it’s irreversible.

I have experienced a multitude of recoveries where functionality has been FULLY restored. Many others claim similar experiences, with some reporting a complete reversal of symptoms permanently.

My feeling is that PFS is definitely due to an endocrine disruption, where they system is stuck in a state of metastability, with hysteresis, preventing normal functioning. When it’s ‘pushed’ far enough one way or the other it can return to a new metastable state. But if it isn’t, it reverts back to it’s symptomatic state. Think of it like a ball on a track with several valleys. It needs to be pushed over a peak before it settles into a new valley, but the push needs to be severe enough to take it over the hill.


#15

Mine manifested very slowly over the course of months after stopping but I had side effects on the drug or else why stop? Like an underlying change to the body has happened and then your body reacts and trasforms slowly around it in the coming months…

Also I did not think I had a TBI before taking finsteride but Gordon said it takes very little to cause this…Then I remember breaking my arm as a kid, getting hit in the head one time with a rock and having sticthes…He sees a lot of War veterans he said any physical trauma like that will cause it even shockwave will disrupt nuero steroids he says and all pfs patients he’s seen had a previous TBI…He thinks its part of the reason for developing the condition…


#16

Where is his evidence? I’m not saying it’s baseless but I would very much like to see evidence for his theory. What I think he appears to be applying the following deductive reasoning:
TBI sufferers have shown to have disrupted neurosteroid levels.
PFS sufferers have shown to have disrupted neurosteroid levels.
Thus PFS is merely an exacerbation of underlying TBI.

Is there any evidence of causality?


#17

It is epigenetic. We have tweens (pvdl and his brother) who stopped at the same time and developped the identical symptoms at the same time.


#18

That would actually strongly support that there is a genetic predisposition to this. @pvdl, any chance you can upload 23andMe raw data for yourself and your brother? Your data would be a huge support for the Genome project @Ghost, @axolotl and I are working on here:


#19

This is what he sent me orthogs…

Thanks for the article… read similar issues in past and will read this one.

Bottom line, same as in TBI. The epigenetic benefits of all the neurosteroids are protective and regenerative.

Stop the neurosteroids and you lose these supportive factors.

Anything that alters the normal homeostatic balance of neurosteroids leads to the symptomatic complex in PFS.

I have been tracking the PFS patients on a historical note; they all have had one or more Traumatic Brain Injuries.

The pre-existing neuroinflammation might be a compounding condition that acts as a natural selection for those that will become symptomatic when using Finasteride.

Just a thought and awareness that I am tracking.

Best

Mark


#20

i actually hit my head pretty badly 3 years ago and now I think of it, i became kinda depressed ever since.

Got pfs after 5 pills with every side possible