WARNING. These common meds might give you permanent sex. dysfunction

[Tragedy]

Hi.
I'm writing a post that I really wish someone had written many years ago so that I could have read it. It would save me from ruining (a big part of) my life.

I am going to talk about 3 (not so) rare sexual syndromes that are PERMANENT. They are either very related to each other, or the same thing with different names. Before doing so, it is necessary for me to explain in detail my background, otherwise you can't judge how legit it is what I am about to say. Please bear with me.

It seems relevant for me to write this post because ED and sexual issues are a common topic on this forum. Also this week is my 5 years anniversary of having this syndrome. No cake though.

I will divide this post into:
-My background
-The 3 syndromes and most of the substances causing it
-What to know about these syndromes
-My symptoms
-What to do if you think have it
-What to do if you don't have it. aka How not to get it
-EDIT: More science details for the nerds.
==========================
==========================


MY BACKGROUND
I was doing a BD in Psychology.
In 2018 I got this syndrome (Type #1. More on that later).
I did a traineeship in a psychiatric hospital and got my degree with a thesis on this syndrome.
I got then a MD (not official yet) in psychology & neuroscience with a thesis on these syndromes (plural). I enrolled in such master because I thought it would help me studying this syndrome better.
I did a short traineeship on EEG (recording electrical brain signal with a hat).
I did a traineeship in a neurobiology lab where I was doing data analysis on mice behavior and analysing brain samples. More specifically I was studying apathy-like behaviors in mice with neurodegenerative disorders.

In this 5 years of being ill, being one of the "leaders" of the Italian group of patients with this syndromes, I have personally visited labs, talked with doctors and researcher, held presentations about this syndromes in front of psychiatrists and doctors... and made friendship with other presidents of European and international patient's associations. Some of the researcher studying this syndrome have it themselves. A dear friend of mine, who also has it, launched a crowdfunding campaign and we got 50k that we are using for the most up-to-date research on these syndrome worldwide. The doctors studying it are the same doctors with whom I wrote my MD thesis. In this years I have read some thousand scientific articles about this topics and neuroscience in general. Just for my master thesis I read 250 of them.

I am probably in the top 100 people worldwide who know most about these syndromes. It is not bragging, just the sad reality. I would give away literally everything that I own, including my underwear, not to know anything about it and not to have this syndrome, without thinking a second. But here we are.

DISCLAIMER: I am not a medical doctor, nor I would like to be one, therefore I cannot tell you what substance to take or not to take. I am a researcher in neuroscience, take this as a neuroscience lecture.

==================

THE 3 MEDS THAT CAUSE THIS SYNDROME

#1 - Serotoninergic Drugs. NAME: Post SSRI Sexual Dysfunction (PSSD)

This common belief that low serotonin = depression is blue pill psychiatric bullshit. In 50 years of research, the evidence for it to be the case is close to zero. I am not saying that antidepressants cannot work. For certain people they do work, but the reason why they work is currently unknown. The most recent hypotheses say that they might work due to their activity on neurosteroid hormones. Anyway...

Antidepressants sold nowadays are mostly serotoninergic, meaning that they rise the serotonin in the brain, at leas short term. Despite the name of this type1 syndrome, it is not caused just by SSRI antidepressants but by any serotoninergic drugs, e.g. SSRI, SNRI, SARI, tricyclic antidepressants, supplements like 5HTP... and also a continuous use of serotoninergic recreational drugs like MDMA and LSD might cause it too.

Antipsychotic drugs, that are not usually primarily serotoninergic, might cause it too. Though if you have psychosis you have a bigger problem to think about. The reason I am mentioning them is that doctors, against every single international guideline out there, often propose them as a quick fix for other problems, e.g. for sleeping. I myself have been proposed antipsychotics (olanzapine) for sleeping and I refused.

----

#2 - Hairloss Drugs that mess with your DHT and hormones. NAME: Post Finasteride Syndrome (PFS)

If you come from the GLL world, you have probably heard some of these terms. As a matter of fact, the first time I heard about Finasteride was a decade ago from Chris' article on hairloss. It was waaaay before me getting into this field.

Moreplatesmoredates has also a video on PFS but I haven't watched it yet, so I can't comment on that.

Long story short, in genetically predisposed people, the hormone DHT makes hair die. Testosterone turns into DHT thanks to an enzyme called 5 alpha reductase (5-aR).
Hairloss drugs blocks this enzyme so that testosterone doesn't turn anymore into DHT.

The drugs that cause that are: Finasteride, Dutasteride, some supplements like Saw Palmetto, and less commonly but also possibly minoxidil. The last one is a different category of drugs but nonetheless I knew people who got it from minoxidil.


----

#3 - Skin Drugs that treat acne like isotretinoin. NAME: Post Accutane Syndrome (PAS), aka Post Retinoid Sexual Dysfunction (PRSD)

Retinoids are a class of drugs that treat acne and prevent scarring. These drugs, according to guidelines, should be used only in severe cases, especially when taken by mouth and not topically by cream.

Their real and precise mechanism of action is still unknown but they have effects on both your hormones and your brain. Your neurons have receptors for these substances and they are influenced by them.

One of the most famous one is Isotretinoin.

=======================

WHAT TO KNOW ABOUT THESE SYNDROMES

The most important thing you should know is that they can be permanent.

There is no way to predict who is gonna get it and who not. As a matter of fact, my sister has taken serotoninergic drugs many times without any negative effect, and my best friend has taken finasteride and saw palmetto several times without any negative effect. Nonetheless I got the syndrome from serotoninergic drugs and another dear friend of mine got the syndrome from finasteride. He is now the president of an European recognized association of patients with post-finasteride syndrome.

These 3 syndromes are clearly related because they are too strange and similar to one another not to be related. Yet none knows what is the cause and what would be the cure. Whoever finds one, gets 200.000$ of prize the next day. Patients are collecting money both for studying the issue and to motivate researchers to study it.

Symptoms can be related to sexuality, emotions (lack of emotions, apathy, inability to feel love or joy or fear,...), cognition (brain fog, difficulty in concentrating...), physical (dry eyes, dry skin, nerve pain, genital pain...).

They can appear after months of substance use, after a single day of use, they can appear the second or third time you use the drug after a break, they can appear after you have already dismissed the drug for some week... it's wild.

Doctors worldwide don't know about the existence of these syndromes. When I started this journey 5ys ago, the number of doctors who knew about it was close to zero. Now there are probably 100 doctors worldwide who have heard about it but don't expect them to know much anyway. Most of these doctors probably heard about it from either me or one of my friends from the associations (USA, Canada, UK, Germany, Italy and Australia for sure.

There is no cure but there are several cases of people who healed either with time or taking some substance that somehow re balanced their system. The same substance can have great effect, no effect or very negative effect on someone, so it is a lottery, often a dangerous one.

This syndrome can happen both for males and females. Many cannot stand it and take their lives. Few people who I have met in these years are not here anymore.

===================

MY SYMPTOMS

I had already used antidepressants in the past with no side effects. I was also a very sexual guy. Super high libido and I had never had any sexual issue in my life. Sex was the only perfect thing I had. It was amazing.

They prescribed me these antidepressants for sleep. Looking back, this prescription was against any guideline and had no scientific justification. I wasn't even depressed.

After few days of taking this pills, my libido got cancelled completely. My penis became less than one inch small and white as a piece of paper, no blood flow. My testicles got smaller. I started having pain in my testicles and issues with my pelvic muscles. Severe ED. My orgasm got completely cancelled: ejaculation (those few times I could manage to reach it) became exactly like peeing. No sensation at all. No pleasurable sensation at all. I also got genital anesthesia, meaning that if you blindfolded me and burn my penis with a lighter I wouldn't even notice. Completely anesthetized to touch.

I got scared and I quit these pills cold turkey. For the first few months I couldn't think, it is difficult to explain it by words but my brain was a white screen, wouldn't produce any thought even if I tried, I would just stare at the wall the entire day and be convinced I was doomed to be retarded for life.

Every single doctor I consulted (general, psychiatrist, endocrinologist, urologist..) laughed at me and said I was just having anxiety and my side effect was not possible. This was the hardest part, I don't really know how I managed not to take my life, that's amazing to me still nowadays.

Obviously my 5y GF with whom I was living, left me some month later.

For the first entire year I had micro-penis, completely numbed and i couldn't feel any emotion, nor sexual, or positive. I also didn't have any negative emotion anymore, no sadnes or fear. I used to be quite an anxious guy but overnight I became "brave" because I didn't have any fear of death.

After one year I got some episodes of flu with high fever and all my symptom disappeared for 24h. Then I got them back but less severe. So I went from 0 functionality to 100, then back to 20 and slowly improving from there over years. Now, exactly 5 years later, I am having 40-60% functionality depending on the period. ED disappeared and I can feel some touch again and sometimes even a feeble orgasm. Though now I tend to have premature ejaculation and pelvic contractions and pain. I have had sex a lot of times, even very nice or crazy sex, totally worth having. nonetheless it is not the same.

===========================

WHAT TO DO IF YOU THINK YOU HAVE THIS SYNDROME

-If you took one of the substances I mentioned:

You should read this scientific study "Diagnostic criteria for enduring sexual dysfunction after treatment with antidepressants, finasteride and isotretinoin" by Healy et al. 2022.

I know some of the doctors who published it. These are the only diagnostic criteria out there. Check the boxes and try to self assess the situation. You should also print it and show it to doctors you will visit in the future, because it is a good proof you are not crazy. Nonetheless expect a lot of denial, especially in the beginning when you are a bit naive. Here you need to be prepared and strong.

Join one of the forums (even better if you join several) about these syndromes and talk to people. Beware that the environment is toxic because most of these people are suicidal or in great pain. The most famous ones are pssd forum , and propeciahelp forum.

If you live in a big western countries, chances are that there might be some official association about this syndrome. Reach out to them.

Please don't take your live. I have been there and I was also very close, but many years later my life is better and I am glad I didn't. Also scientific research and AI are going fast, we might find a cure sooner than later.

Watch out, because any substance, supplement or med might make your symptoms worse. In my case, an antibiotic knocked me out for several months. Before taking anything, make some research to see what effect this substance had on other patients.

Don't freak out. Easy to say, harder to do.


-If you took a substance I didn't mention

It is a bit trickier. It is possible that you got the same mysterious syndrome due to some med or supplement like Aswakanda or Ipericum (St. John's worth) or whatever. The previous advices still apply to you. Try to research to see if someone else on the forums got the same issue.


=======================

IF YOU DON'T HAVE THE SYNDROME, aka HOW NOT TO GET IT

If you don't have this syndrome, congrats. You won the life lottery (at least this one). If you still have ED, chances are it is fixable with some change. Some of the knowledge of these forums might still be useful to you. They talk a lot about science, lab tests, supplements and so on.

Sadly there is no way to predict who is going to get this syndrome and who is not. In my experience, I have reason to believe that if you have already used these substances it the past, you might be more likely to get it. Maybe there is some sensitization mechanism, I don't know.

If you take these substances by pills, as opposed to skin cream, the chances are way higher. It is still possible though to get it from skin absorption, but less likely.

Ask yourself why you are taking these substances, if there is any alternative thing to try.

For example I am having hairloss and for now I'm doing dermaroll, skin stretching and massages to reduce DHT (very important!), injections of peptides in my scalp and other alternative things.

If you really have to take the mentioned substances, start them at very low dose and increment over time. Same thing applies when you stop them. Especially if you know you are a person who is very sensitive to substances in general (alcohol, recreational drugs...).

I would also advice not to do repetitive start and stop of substances. These changes are not good and you might increment the chances of getting it.

Consider alternative meds that are unlikely to give you these syndromes. You can research them in the forums or ask for advice. Wikipedia is not a good source. According to wikipedia I shouldn't be here writing this long post.

In general take responsibility of your health. Prevent illnesses, fix your diet and sleep, take sun, vit D, vit C, study these things. I also used to be a person who would take a med for any headache or minor issue, now if I have a headache I heal through breathing and head strong massages. It works. In the last 5 years I have very rarely taken any med.

Take the harder road but the right one.



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-EDIT# More science details for the nerds can be found here: viewtopic.php?p=64251#p64251




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[pancakemouse]

Incredibly informative post. What's the best source of data around likelihood of contracting these syndromes per unit of time/usage, so we can assess risk?

[Juicy3lf]

A most excellent post and I send my condolences to you on your condition.

There is a lot here that we can use to grow and heal ourselves, and be inspired to do so further.

I, myself, have had some form of ED for about eight years, which was also completely denied by doctors. Even after seeing urologists, I was told this is entirely psychological. They didn't care about my symptoms, and didn't care to give any thought to my case.

I didn't take any drugs at the time but was practicing jelqing the night before. I was struggling with the truth that my ex-gf from two years before (I didn't know it was possible to get laid) had cheated on me constantly during our relationship, and categorically refused to admit anything. Women leaving me without certainty is the most pain they have given me but I'm better at reading them and I'm more at peace with it. This caused me to have, along with my high libido, a tendency to get horny and use masturbation a lot to cope. During a particular session I noticed it was bigger than usual until suddenly I felt an extremely sharp pain in one side. I can't remember if it deflated immediately and I tend to think not. It continued for several hours and did change location to the same side on the base. I went to the hospital but they pretty much concluded I was an idiot and sent me away with no comment. Over the course of weeks I could not urinate or get an erection without the same pain, but I was still stuck in emotional-horny mode. I'm literally just trying to ejaculate so that will go away but I can't do it without causing myself more pain. I've been stuck in a similar cycle since then.

Over the months and years I was unable to wear ANY underwear without causing pain, I had repeated tingling sensations, burning sensations and any sexual activity lead to aching feelings. The appearance also changed to more blue, more thrombotic veins, spider veins, red tracking marks and more redness. I'm not rough with it and not hammering it fifty times a day either. Have tried periods of abstunence for two weeks to see if it makes any difference and there was a slight difference due to reset horniness.

At least they did set me up with the two types of genital ultrasound tests. Those were both 'normal' - a term which I take offense to. The radiologist didn't make any notes or records other than that word. However, I'm more or less satisfied that the vascular issue can be ruled out.

It appears to me based on the lack of vascular, arterial damage or plaque that the issue has nothing to do with damaged or ruptured blood vessels, but much note likely to be related to nerves. This explains the painful sensations I had and the different locations where they can be felt.

I've not been able to get a 100% erection at all in the last eight years. Even if my cock is getting the best blowjob from a cute girl it still won't be at 100%. Medication makes some difference but also doesn't work sometimes. My aroused state is somewhere between 50-70%.

I have a protocol to follow. I just need the fortitude to get through it, and let the past go.

[Lord Rey]

Thanks for this post. I'm sorry you had to go through this. If I had to deal with such extreme symptoms, I think I would seriously consider ending my life.

Fortunately for me, I'm far from having such extreme problems. That said, I'm suffering from more and more memory failures, brain fog, and my libido is getting lower than usual, to the point of me thinking that I want to get laid more for the validation than for the sex itself currently.

I just stopped antidepressants a week ago. I took Asertin for a few months. I experimented with kratom too, but I don't think it's good for me even if I like the short term effect of it. I'm at the lowest point in my life currently, broke, depressed, back living with my parents, and no girl to have sex with. I just feel that I failed.

I hope to somewhat turn things around in the coming months, but I think I need some kind of therapy. I always felt like something was wrong with my brain. I have stupid OCDs and my mood often swings between hopelessness and anger.

Anyways, I hope you'll heal completely sooner than later man!

[MILFandCookies]

That sucks man - looks like you've been through an intense journey.

Def important to research drugs before you take them.

I'm currently taking finasteride, thankfully with 0 side effects, although it's clear there's ED and hypogonadal symptoms with some people.

I will say, permanent PFS hasn't been confirmed with data except with a few anecdotal cases. That said, side effects are certainly a thing for some poeple. And they last a long time too.

Finasteride permanently blocks 5-aR - meaning when a molecule of finasteride disables a molecule of 5-aR, that molecule of 5-aR is out of commission permanently.

And your supply of 5-aR cycles every few months. This means that if you have side effects with finasteride, they will last for months after you stop the medication, since you have to wait until your body cycles out the 5-aR in your system which is currently bonded to finasteride molecules and not functioning.

I'm not saying nobody has permanent disability from finasteride, but the evidence so far is inconclusive - that said, it does have the potential to put you out of sexual commission for months on end.

It's def. important to research any med you take. Respect for you continuing your journey despite setbacks, and I hope you get back in action 100% soon.

[Tragedy]

Thanks everyone for your love, it means a lot to me <3

I'll try to reply to all of you.

What's the best source of data around likelihood of contracting these syndromes per unit of time/usage, so we can assess risk?

Sadly estimating the precise risk is impossible at the moment for several reasons.

-There has been a massive cover up by the pharmaceutical companies, for obvious reasons, despite them being aware of these syndromes since the 90's. I have personally witnessed 2 studies being cancelled in a shady manner. The last one in 2021: we had organised one specifically with the purpose to get data. Through a big gov institution we were to assess the number of PSSD cases in patients taking antidepressants, random sampling different regions in the whole Italy.The thing was official and listed on the institution website but at the end they just ghosted us after a while with no explanation.

-Devising a study would have some difficulty, specifically in selecting the control group, i.e. people to whom to compare. Take for example my case. If they had asked me some year ago, I would have replied that I took antidepressants for 6 months as a teenager without any side effect. They would put me in the "immune" group and take my DNA for a big comparative analysis. Few years later I would use antidepressants again and get the syndrome, screwing their result. Since these side effect can happen any moment, it's difficult to do studies on the probability to get it. Not impossible but not immediate.

The only data available at the moment states that "PSSD may not be dose dependent" (Ben-Sheetrit, 2015).
Some studies on finasteride have hypothesized 2% of permanent effect in people taking it but the number seems to be higher.

Forums regarding the syndromes have thousands of registered users but we are talking about young nerdy guys who know English and who have stronger symptoms and who manages to figure it out on their own that they have a syndrome despite doctors' denial. That's a sample of a sample of a sample. It would be like trying to figure it out how many people have ED worldwide by how many people have it on this forum. Not really feasible.


If you want my personal educated guess based on all I have read in these years and me talking to both researchers and patients: If you take one of the substances I mentioned, you might have a double digit chance of getting some permanent side effect. I couldn't say if that number is 10 or what. For sure is higher for people who do the risky things I mentioned above (sudden changes, start&stop, etc). But that's my estimate.


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It appears to me based on the lack of vascular, arterial damage or plaque that the issue has nothing to do with damaged or ruptured blood vessels, but much note likely to be related to nerves.

Sad to hear that man. I was also thinking about nerves while reading your story. I know jelquing and pumps since 2010 and reading stuff in this years I got the impression that pumps, if used properly, are way less risky than jelquing. I never tried to do it myself because for the first part of my 20s I was in a stable relationship and then I got this syndrome right away.

Your story is anyway very relatable, I also have tingling and burning sensation and pain, but mostly in mostly on my balls and anus. I am also having difficulty to reach 100% erection, especially in the gland.

Are you familiar with concepts like Pudendal Nevralgia, Small fibers neuropathy, Low laser therapy, Extracorporeal ShockWave Therapy?

For me pelvic floor therapy helped a bit.

I just stopped antidepressants a week ago. I took Asertin for a few months. I experimented with kratom too, but I don't think it's good for me even if I like the short term effect of it. I'm at the lowest point in my life currently, broke, depressed, back living with my parents, and no girl to have sex with. I just feel that I failed.

I feel you bro. I'm struggling a lot with brain fog and memory. I also relate about being broke, at my parents and depressed. We will manage to get through this. Can you tell me more about how was your cognition and health before and during antidepressant and what's the reason you started?

When you stop it, it's quite tough for some month. That's the hardest part but it gets better


----

I'm currently taking finasteride, thankfully with 0 side effects, although it's clear there's ED and hypogonadal symptoms with some people.

I am happy to hear that for you it is going well how long have you been taking it?

Regarding the science, don't take it wrong but I have to disagree. Studying this stuff and talking with researchers and patients has been my (unpayed) job for my last 5 years. I have spent a couple of grands to travel to organize things and to donate to finance more research.

If you search on PubMed right now, you will find 58 articles mentioning the term "Post finasteride syndrome" and way more if you just search for finasteride persistent effects.

This being said I don't want to scare you. I have seen some denial in Fin users community, which is "funny" because among all the syndromes it is the one where data are more solid and the one it is becoming known between average doctors. The fact that even Moreplatesmoredates and Huberman, the famous neuroscientist from Rogan podcast, addressed the topic it is no coincidence. The reasons why there is some resistance in some Fin users despite so much data and studies on its reality and mechanisms (not on the numbers) is unclear to me, and I am guessing it is some copying mechanism which I totally get it. Having to choose between hair and the risk (big or small) of being castrated is a situation nobody should experience. I am loosing hair myself and I would love it to be able to take finasteride and to forget about it.

I don't want you not to use, I just want you to have informed consent and aware choice, which is what I couldn't have. Some people might find the risk worth, some other not. That's totally personal and respectable. Also keep an eye on your functionality levels and don't make sudden changes.

Regarding the actual science behind it, it is sadly more complicated than that. I do have a MD in neuroscience and I did have several courses in pharmacology and neuroendocrinology, yet when I talk to the first line researchers from the lab, I struggle a lot to keep the pace. Very difficult to analyse such things without having a strong background in biochemistry applied to neuroendocrinology processes.

The reason why post finasteride syndrome (and the others) happens is unknown but there are many hypotheses. I could spend a week trying to summarize them with no avail.

The level of DHT itself and what 5aR is doing is of no importance after one gets the syndrome.
The most important mechanisms that seems to have a role are:

-level of allopregnanolone in the liquor (a hormone that regulates neurons and that is also very present in the fluid where the brain swims in).
-DNA methylation of some genes (it's like cancelling some word from a book of recipes)
-Upregulation/downregulation of androgen receptor and estrogen receptor.

These mechanisms are tissue-dependent, which means that one might have for example estrogen receptors downregulated in the penis tissue or androgens upregulated in some specific areas of the brain.

One of the latest branch of hypotheses that I am following is that a sudden drop of DHT might result in a consequent sudden increment in testosterone, which applies some transcriptional change on the estrogen receptors. Testosterone is related to sex seeking behavior while estrogen is related to libido, physical arousal and even penis nerve electrical transmission, something that would explain why I cannot feel touch down there.

Anyway, one day I will get the balls to open a YT neuroscience channel on these topics, which I have been fantasizing for years. Meanwhile stay all safe!

[MILFandCookies]

I'm pretty well researched and understand much more than the average person but you seem to be mugh more knowledgeable than me.

It's definitely very important to be informed before you take medication. I've seen the shitty side of the pharmaceutical cartels and been fucked over massively, so I support you raising awareness here. As for PFS, the data I see is conflicting, and I don't have enough to proclaim whether or not it exists for sure, just enough to be skeptical of either side without more data. You seem to know more about it than me, so fair enough on your claims. It's best to be skeptical in any case, it can only help to be more cautious.

To answer your question, I've taken it for 3.5 months so far. 1mg orally every day.

[Tragedy]

I get you I am also super skeptical. To be honest, if someone had told me that his penis got 10x smaller overnight, I would't have believed it before experiencing it myself. I recall that at the time I was questioning if it was some episode of psychosis xD

Anyway, if you feel any interest in the topic, PFSnetwork and propeciahelp are great sources, as long as you put as a priority you being happy and not stressed about it.

I see that it's not that long, nonetheless good that you are doing fine in these months. Also, luckily not everyone is genetically sensitive to side effects. Anyway, keep an eye from time to time, just to be sure not to experience any subtle drop in performance or sensations.

[Juicy3lf]

@Tragedy

Your story is starting to make me think I was poisoned. I do have a tendency to get fucked over by cunts.

I did one session on jelqing, probably way too hard but I had no idea what I was doing. I know I'm not the only one to arrive here. During normal exercise I usually go way harder than the average person, maybe that's what I did here. I was well above average but I believed it was too small. Women only say it's too small because it gives them power over a man. They cannot be trusted.

I also have had two girls come down roughly on top of me, causing pain. This is the main reason you don't stick your dick in crazy. They can be vindictive. But again, I might be paranoid.

I haven't heard of any of those conditions you mentioned. I too came to the conclusion that pumps were much safer. The glans in particular is most soft on mine, whilst the body can be quite hard still.

I didn't do much research over the last eight years because I've been dealing with survival problems and possibly an abusive situation. It was too much.

What's your therapeutic protocol rn?

I have heard of laser therapy and shockwave. I've heard shockwave can be controversial so havent done it, and its new.

I have acquired a medical IR device as part of my plan which I think is the same as lasers.

[pancakemouse]

Sadly estimating the precise risk is impossible at the moment for several reasons.

-There has been a massive cover up by the pharmaceutical companies, for obvious reasons, despite them being aware of these syndromes since the 90's. I have personally witnessed 2 studies being cancelled in a shady manner. The last one in 2021: we had organised one specifically with the purpose to get data. Through a big gov institution we were to assess the number of PSSD cases in patients taking antidepressants, random sampling different regions in the whole Italy.The thing was official and listed on the institution website but at the end they just ghosted us after a while with no explanation.

-Devising a study would have some difficulty, specifically in selecting the control group, i.e. people to whom to compare. Take for example my case. If they had asked me some year ago, I would have replied that I took antidepressants for 6 months as a teenager without any side effect. They would put me in the "immune" group and take my DNA for a big comparative analysis. Few years later I would use antidepressants again and get the syndrome, screwing their result. Since these side effect can happen any moment, it's difficult to do studies on the probability to get it. Not impossible but not immediate.

The only data available at the moment states that "PSSD may not be dose dependent" (Ben-Sheetrit, 2015).
Some studies on finasteride have hypothesized 2% of permanent effect in people taking it but the number seems to be higher.

Forums regarding the syndromes have thousands of registered users but we are talking about young nerdy guys who know English and who have stronger symptoms and who manages to figure it out on their own that they have a syndrome despite doctors' denial. That's a sample of a sample of a sample. It would be like trying to figure it out how many people have ED worldwide by how many people have it on this forum. Not really feasible.


If you want my personal educated guess based on all I have read in these years and me talking to both researchers and patients: If you take one of the substances I mentioned, you might have a double digit chance of getting some permanent side effect. I couldn't say if that number is 10 or what. For sure is higher for people who do the risky things I mentioned above (sudden changes, start&stop, etc). But that's my estimate.

What about tretinoin? I've been applying it for 4 years pretty much nonstop.

My guess is that tretinoin is far safer than the above two substances, especially since I haven't heard of a single issue with it until your post, but I had heard of the two others.

[Tragedy]

I didn't do much research over the last eight years because I've been dealing with survival problems and possibly an abusive situation. It was too much.

What's your therapeutic protocol rn?

I have heard of laser therapy and shockwave. I've heard shockwave can be controversial so havent done it, and its new.

Understandable, I am also taking time until I have good money. I just did some session of pelvic floor therapy and some exercises one needs to do at home.

About shockwave, a dear friend of mine did it on his penis (he had some issue, long story) and found it to be beneficial. I don't know much more about it.


----------

My guess is that tretinoin is far safer than the above two substances, especially since I haven't heard of a single issue with it until your post, but I had heard of the two others.

I get you. Based on the substance itself, I wouldn't have any reason to think it is less dangerous compared to the others:

-Retionoids have effects on 5aR, on Androgen receptors, on Estrogen receptors, they modulate neuronal activity, they modulate immune system activity and are implied in autoimmune diseases.

-They have a strong teratogenic effect: you can't give them to pregnant women, otherwise the baby either dies or comes out with strong physical defects.

Also my feeling is that the effect of retinoids might be more physical compared to other syndromes. I went to check my BD thesis to see if I had any data about this (sometimes it is difficult to remember on what exact study I read what) and I found just a survey they had done in 2019. The sample is too small to draw strong conclusions, 51 people affected by PSSD, 133 by PFS, and 28 by PRSD. It shows the severity of symptoms for each substance and for each domain (sexual, physical/neurological, mental/emotional)



I do agree though that PRSD seems less widespread compared to the other syndromes. It can be the case that as you pointed out retionids are less likely to cause the syndrome, or it might be due to:

-The fact that retinoids are in general less used compared to other substances.
Global market share of antidepressants is 20 billion USD, Finasteride 360 million USD, Retinol 1.5 billion USD. THOUGH, for retinol, most of its use is very low dose and on cream form.

-Retinol, compared to others, is the only one to be used mostly on cream form. While skin absorption has effect on general blood level, the rate of absorbtion is definitely lower and more gentle. Less chances of getting high spikes and sudden changes. Therefore less risky.

-Demographics: let's be objective, it's young nerdy men in their 20s and 30s who mostly create and use forums to discuss geeky things, including illnesses. So the only representatives are young men who used retinoids in pill, as opposed to the general use.

-For awareness, there is the need of someone putting in place websites, forums, informations... The reason I found out I was having this syndrome is because someone before me took the effort to create such websites in italian, the whatsapp groups of patients etc. For retinoids I have seen less of these infrastructures in place, and their main forum, that used to be quite active, for whatever reason has been down for at least one year. More awareness = more data.

Anyway, the point of this thread is awareness and information, not dissuading people from using these things. If it tretinoin cream is working great for you, I am more than happy!

[Lord Rey]

I feel you bro. I'm struggling a lot with brain fog and memory. I also relate about being broke, at my parents and depressed. We will manage to get through this. Can you tell me more about how was your cognition and health before and during antidepressant and what's the reason you started?

Yeah, so I always had mental issues for as far as I can remember. It was mostly OCDs and anxiety. I basically was (still am somewhat) obsessed with hygiene, especially with keeping my hands clean. So I'm used to washing my hands very often (and used to do that long before COVID, so long before it was cool ). I'm obsessed with keeping my valuable stuff clean too, thus I really hate dust and I waste a ton of time cleaning my stuff even if it was clean already… For this reason I hate when people touch my stuff without my permission, because after that my stupid brain will force me to clean again because my stuff was touched by the dirty hands of someone else…

As I grew up, my OCDs were less and less an issue, but my anxiety went up on the other hand. With the rise of anxiety, and because I was a fucking loser getting bullied in high school, I ended up having my first depression and suicidal thoughts at 16. I was hospitalized for a few months and got antidepressants for the first time in my life. I can't tell what was the impact of those pills, I don't even remember their name, but I felt that it wasn't doing much. I still felt like shit… What I clearly remember is that in this hospital I kissed my first girl haha.

I went on different pills on and off during my 20s, but except one kind that I used to sleep (again, I don't remember the name), I never felt any major difference with or without antidepressants.

Fast forward to a few months ago, I started to feel depressed again, so I tried to take Asertin on the recommendation of my ex (who is a doctor). I started with a very small dose of 25 mg (half a pill). Then I don't know if these pills are to blame or not, but a month later I reported in my log having a major breakdown during a sex party that I co-organized, see here: viewtopic.php?p=57871&sid=ed74275d6af0a ... 02e#p57871

Since this event, my mental health has become a lot worse. I went back into depression and I'm far from being out of it. I noticed my brain had more and more memory failures, which is me forgetting a lot of stuff and having black-outs even after drinking moderately. I have a constant brain fog and a short attention span too… I basically have trouble focusing on anything. My procrastination (which was already a big problem of mine) went through the roof. On top of that, my mood went to shit, swinging between despair and rage.

During this summer, I tried to increase my dose of Asertin first, but seeing no positive results, I then tried to stop it… oh boy, I felt even worse. Now, I finally stopped after gradually lowering the dose, but my depression and all my mental issues are still there. I'm at the lowest point in my life currently, because even when I was hospitalized, I didn't suffer from feeling that shitty and wondering if my brain is permanently damaged or not. Besides, at 16 I had all the opportunities in front of me… If only I knew how to grab them…

Speaking of missed opportunities, that's another big problem of mine: I'm always haunted by my past and feel like I failed my life. I can't forgive myself for being such a loser who missed A TON of opportunities to succeed with money/career/business and girls.

Anyways, I have to sleep now so I'll end this post there. Thanks for reading me!

[Tragedy]

Speaking of missed opportunities, that's another big problem of mine: I'm always haunted by my past and feel like I failed my life. I can't forgive myself for being such a loser who missed A TON of opportunities to succeed with money/career/business and girls.

Your whole story is too relatable for me. Many years ago, my psychotherapist told me something I will never forget: "you will have such great life that you will not even have time to remember the past and have regrets".

I also have/had OCD, mine was based on repetition and perfectionism. Psychotherapy worked a lot, I did Short Strategic Therapy, based on Watzlawick, Nardone, Bateson and the Palo Alto school (I'm adding these details because abroad might be known with different names).

I had to do many tasks like repeat things a specific number of times and other missions more related to social anxiety, like faking feeling bad in a mall and ask for help.

Anyway, psychotherapy works but it is tricky to find the right person, one needs a bounch of different tries. Numbers game is everything in life.

Regarding the sex situation, I read it and yes, I agree with all other guys, antidepressants might have had a big role. They really fuck your brain chemistry and my very personal yet scientific opinion is that they should be used only where everything possible failed multiple times and/or where the person is rotting in bed.
I don't say it out of ideology, I really studied such things in deep details in my career.

Your brain fog is very expected after stopping the drug. In my case I was completely mentally retarded for at least 6 months, then it started to heal. Now my brain fog is mostly unrelated (sleep).

You should just hold tight and let time heal you. If later doesn't get better, hit me up, I have a big sample of patients with those syndromes and many of them had good improvement in their persistent brain fog, by using supplements and what not.

In the meantime, vitamin C, D and magnesium/potassium are the foundation of any well-being.

[Tragedy]

This is very interesting although I would be curious through what mechanism exactly sexual dysfunction is caused here and why it is permanent?

I'd also be curious how effective stuff that I do myself to help with sexual dysfunction and ED apply to such cases.

What are you exactly doing?

Regarding the actual mechanism, despite its mysterious nature, there is some insight. First of all, these three classes of substances act in very different ways.

-Finasteride & Co. act exactly as explained by @MILFandCookies.
-Antidepressants act on serotonin, and
-Retinoids inhibit the activity of sebaceous glands through different mechanisms. This reduction occurs by decreasing the expression of certain receptors, which are involved in immune response.

Therefore, on one side, these substances are entirely different; on the other, the syndromes they cause are too similar not to be the same.

For example, numbness in the genitals is a super rare symptom in other conditions and is usually related to nerve damage. Another strange commonality among many is that these syndromes can appear AFTER discontinuing the substance, even if you were fine while taking it. Usually, starting the substance again doesn't help much. This is also a rare occurrence in other syndromes.

So, based on the premise that it's statistically unlikely for them not to be related, we started to explore what links them all and found many connections. Just to give a couple of examples:

Recently, my colleagues, with the funding from our crowdfunding, discovered that the enzyme Phenylethanolamine N-methyltransferase (PNMT), responsible for adrenaline synthesis (which is also important for erectile function), is partially inhibited by both finasteride and antidepressants. For the first time, we proved worldwide that this selective serotonin reuptake inhibitor (SSRI) is not selective and acts on something different than serotonin.

The enzyme 5-αR, which is inhibited by finasteride, is also necessary for the synthesis of Allopregnanolone in the brain (a steroid important for neurons). Indeed, Allopregnanolone is reduced in the plasma of patients who have dismissed finasteride. It is interesting that we also found it to be lower in patients who stopped antidepressants.

Retinoids, on the other hand, increased the expression of 5α-R in the liver and demonstrated the ability to affect serotonin transporter SERT (same effect as antidepressants). Retinoids also reduces the level of DHT (same as finasteride).

So, it is clear that they are all closely related. The difficult part is finding the exact important element(s). It is like finding a needle in a haystack.

Why though does this ED persist permanently? That's also an interesting point. It doesn't seem to be due to some toxic effect or complete disruption of a process because there are people who heal and have partial or momentary recoveries.

Myself, after the first year of complete chemical castration, I woke up one morning completely healed for 24 hours, which is not compatible with the destruction of whatever.

This characteristic leads us to think that there might be some switch that doesn't manage to turn back on after discontinuing the substance. Probably, we are dealing with some negative feedback mechanism where the body's receptors are stuck in a loop that is difficult to break free from.

As for the remedies to try, sadly, I have to be extremely cautious with any substance I ingest because with this condition of imbalance, everything has the power to set me back to 0%. Many dear friends of mine lose all improvements after taking some supplement or medication and I experienced the same thing myself in 2019, where an unrelated antibiotic kicked me back from 40% to 0 for several month in a row. That got me again close to suicide.

Currently, I am back to 40-60% of functionality, and I can have a sex life, although not as good as before. I have become very paranoid about trying things. I will start experimenting in the near future since I have reached the 5-year mark with no satisfactory improvements, but I will be extremely cautious.

[Tragedy]

Even more confusing and puzzling is that this effect is not consistent across the board. Some people have no issues, others might but they heal, but in rare cases it is permanent. So strange. If I'm understanding properly?

Yes, you got it totally right.

And yes, I do agree that this occurrence is very weird, that's why it would be extremely unlikely for these 3 syndromes not to be the same thing. 1 I would get it, but 3!?

Also the biochemical discoveries of the links among the substances reinforced this assumption.

I would move your focus toward something else though: the strangest part is not the fact that it lasts. Many illicit drugs users irremediable ruin their body despite stopping the substance. Also different legit medications cause lasting side effect, they are called iatrogenic syndromes.

Take for example fluorochinolones antibiotics ruining cartilage joints or NSAID meds such as ibuprofen causing damages to the ear cells with detrimental effects on hearing...

This is a pretty common thing.

The weard shit is the fact that it can happen even after a single pill or the fact that it can happen after you have already stopped the substance for some day.

This last event is rare but not unique though, for example there is another well known syndrome called Tardive Dyscinesia that has similar features.

Even more weard in these sexual syndromes though is the fact that one can momentarily recover for some hour or day and then get it back.

Normally one cannot recover from a body damage in half an hour or wake up completely healed. This shit normally only happens in the Gospels!

Therefore is reasonable to think that we are dealing with hormonal/neurotransmitter unbalance that can be momentarily balanced back in a quick way and that it cannot manage to get back to proper levels on its own. This would also explain the variability among subjects, because the level of unbalance can be different from every individual.

Just to be clear, some of the things that I mentioned since the beginning of this thread are well established facts, while others are logical conclusions based on what we currently know about human body.


Regarding biohacking I can't wait to read your protocols. I am also planning to make it a business in the future.