Post Finasteride Syndrome - Neurological Phenotype - completely lost and looking for help
Introduction:
Hi there, I’m new to the subreddit here, and looking for help from anyone who has found themselves in a similar situation. Despite my extensive suffering over the last 5 years, I have spent very little time perusing the forums and exploring various protocols / therapeutic efforts - predominantly as I believed my phenotype was pathologically “different” to many of those inflicted with this torturous condition - I also believed that I had found a long-term solution, and I felt at the time that most hormonal / supplemental therapies would not be beneficial for me. I have recently tried to familiarise myself with the fantastic work of Dr. Will Powers, and his efforts have provided me with some hope that there may be a breakthrough imminently. Therefore, apologies in advance if I am unfamiliar with some of the recent updates or theories on the pathophysiology of this condition.
This will be a lengthy post as I have never formally posted on any PFS forum to date, so I will attempt to be as detailed as possible, as this may help someone else avoid the potential pitfalls I have encountered. When sifting through this subreddit and other forums, I have previously found difficulty in ascertaining how various medications and treatments have helped patients, and therefore I am giving a thorough step-by-step account of my experience, in the hope that this may benefit patients / research in the future.
I appreciate that most of what I say is conjecture; and will be difficult to comprehend without the lived experience of this nightmare. I will refrain from extensively referencing the limited literature that is available, given the widespread uncertainty regarding the pathophysiology of this condition. I believe there are countless mechanisms at play which may account for the wide array of symptoms experienced by PFS patients.
Reminder: Remember that this is an incredibly complex illness with immense variation between phenotypes. This is just my experience.
TL;DR.
I am a 28 year old doctor (previously well) with a 4-5 year history of very severe cognitive / neuropsychiatric sequelae of PFS, likely secondary to severe dysregulation / downregulation of GABA-A receptors, possibly as a consequence of impaired neurosteroid signalling (allopregnanolone + ?other neurosteroid modulators of GABA-A receptors). Previously have experienced a major deterioration in symptoms (in the long-term) after a trial of Zopiclone (GABA-A agonist) and to a lesser extent, alcohol (GABA-A activity); and partial recovery with strict long-term ketogenic diet and avoiding further GABA-A activation.
I recently have had a further stepwise deterioration in symptoms despite continuing with the same protocol I have used for the last 4 years, and I cannot identify what has changed. Therefore, I am looking for anyone who has had any improvements with any therapeutic efforts exploring this potential pathological mechanism - which may be unique to me and a minority of the cohort here.
Finasteride - 2019-2021. Stopped and restarted.
As a 21 year old medical student, I first started noticing hair loss in 2019. This was on the background of a significant family history (on both sides). I started taking 1.25mg oral finasteride daily and applied topical minoxidil 5% twice daily. This was extremely effective at slowing my hair loss. At the time, I failed to recognise any potential side effects - but with the benefit of hindsight, can reflect and identify a significant personality change whilst on the drug at the time. I started to experience significant anxiety, became irritable and confrontational with friends / family and, ultimately after 13-14 months on the drug - developed severe insomnia that was refractory to any medical treatment / psychotherapy. This was also associated with an inability to reach a “euphoric state” from alcohol (which would have happened previously) despite drinking increasing quantities of alcohol (entirely irrelevant at the time but is now relevant when linking this with the potential pathophysiology). I did not experience any sexual side effects during this period - other than potential loss of libido secondary to my heightened sympathetic state.
After exploring other potential causes, I stopped taking finasteride at this point in 2020, and felt 100% again immediately - my sleep recovered to baseline, my anxiety significantly improved over the next week and I was left perplexed at how this all instantaneously resolved on cessation of finasteride (Insomnia was not a recognised adverse effect of finasteride at the time). This should be the end of my story.
Alas, after an acceleration of hair loss in the following months, I decided to experiment again with 1.25mg oral finasteride and within a day, started experiencing profound insomnia. I had not heard of PFS at this point, and decided to continue taking 0.625mg every 2nd day - subtherapeutic for hair loss, but I was able to tolerate this without significant side effects. After a few weeks of this, I stopped taking finasteride in May 2021 due to a recurrence and progression of insomnia - I have not taken another dose of any 5-ARI since then, but have never recovered. Unfortunately, my symptoms have worsened considerably since.
2021-2022:
Initially - my only symptom of PFS was insomnia. I experienced a very similar sleeping pattern in the months after cessation - to when I was on the drug. Early morning wakening was a hallmark (often pathognomonic of depression - ) and it felt like my quality of REM / Deep Sleep was significantly impaired. My sleep “architecture” as such appeared to be permanently damaged. This got progressively worse over a period of 8-9 months before I sought help. This coincided with my first clinical placements as a medical student and I tended to agree with the hypothesis that this insomnia was likely caused by stress and environmental factors as opposed to an iatrogenic cause. As the months progressed, my sleep pattern continuously deteriorated to the point where I would sleep 1-2 hours a night for weeks on end. I became increasingly anxious over these months, and would ruminate over everything. Interestingly, my sleep would drastically improve after drinking alcohol, and I would be considerably happier and more relaxed in the 1-2 days after drinking, before the poor sleeping cycle restarted.
I trialled a variety of treatments for insomnia during this period and have summarised their effects below. These may be of some benefit to those suffering from PFS related insomnia. These are categorised in no particular order.
CBT for Insomnia - No discernible benefit despite learning good sleep hygiene practices.
Body scanning / meditation / breathwork: Relaxing effects but no improvement to sleep.
Magnesium glycinate - mild improvement but not substantial enough to improve sleep by itself.
Mirtazapine - some improvements to sleep, I personally experienced side effects such as dry mouth, increased appetite and possible ?akathisia-like symptoms - these all resolved on cessation of medication. It reportedly has effects on sleep architecture so some people may find benefit.
Phenergan: I have actually used this in the long term for insomnia. Intermittently I have experienced drowsiness / hangover effect, but otherwise well tolerated and have experienced improvements to sleep with this.
Melatonin: Minimal effect.
Amitriptyline: Very brief trial - did not experience benefit with this.
Zopiclone / Zolpidem: see below. Very bad idea in the long term.
TRT (Testogel): This was a short trial (3-4 weeks) after my initial consultation with an endocrinologist. It did nothing for my symptoms - but likely was too short a trial to draw a meaningful conclusion. This trial has not been repeated as I believe it doesn’t address the core pathology at play. I possibly noticed increased libido during this time, but was worried about the long term sequelae and self-ceased this. This was a year or so prior to the development of sexual symptoms (see below).
GABAergic supplements: Taurine, Valerian Root, GABA, Lemon Balm - I believe these to be potentially safe options for sleep / anxiety in phenotypes similar to myself. These each demonstrate varying activity in GABAergic transmission and may / may not contribute to downregulation / tolerance at the receptor site. (Please refer to the first link in the discussion section). I did not trial these supplements during this phase but have since experienced significant short term benefit from these in recent years.
Glycine: Have derived short term benefits from this at various timepoints - improves sleep and takes the “edge” off the all-consuming anxiety associated with this condition.
2022: Major stepwise deterioration likely secondary to Zopiclone (likely further rapid downregulation of the previously dysfunctional GABA-A receptor).
Prior to this time, alcohol was the most effective agent in “improving symptoms” in the short term. I started to take Zopiclone (GABA-A agonist) nightly for sleep - in total for roughly 3 months straight. Immediately this substantially improved sleep, I noticed a significant improvement in anxiety and was feeling back to 100%. I tried to stop this after a two week period but immediately was unable to sleep again - similar to the previous 8-9 months, so I continued to take it every night - without realising the possible deleterious consequences I was about to incur.
Within a few weeks of persistent once daily Zopiclone use, I developed a plethora of new symptoms seemingly on a weekly basis, some of which I did not believe were possible. This included constant panic attacks and sympathetic overdrive, severe cognitive dysfunction, significant memory loss, dissociation and depressive symptoms, neuropathic pain and parasthesia to name but a few. I had not experienced any of these symptoms prior to Zopiclone use. These occurred in a very distinct, discrete, stepwise fashion - given the presentation and precipitating factors - likely consistent with GABA-A receptors actively downregulating over a period of 3 months or so. This was the very definition of a nightmare - and thankfully - this “downregulation” stabilized on cessation of the Zopiclone - once I was able to identify what had taken place. After cessation, I did not experience any further deterioration in symptoms - but have been left in a state of significant cognitive dysfunction, experiencing brain fog, word-finding difficulties and profound memory loss since 2022 (see schematic below). I want to clarify that these symptoms are nothing like the minor cognitive dysfunction and memory issues one might experience after a period without restorative sleep.
It was during this time that I began to research PFS as the likely cause and begin to explore therapeutic options. I attended a Psychiatrist and Endocrinologist during this time - who had previously seen 2-3 cases of PFS - and confirmed the underlying diagnosis. I began to explore GABAergic supplements (as recommended by patients with similar symptoms)- and saw considerable benefits with a variety of these in terms of controlling symptoms in the short term. However, I don’t believe these had any effect in relation to the long-term upregulation / downregulation of the GABA-A receptor, and the potential use of these may be a barrier to long-term recovery from this specific pathology.
Ketogenic diet and partial recovery 2022-2025:
Immediately after this rapid deterioration of symptoms, I started the ketogenic diet. I was entirely skeptical of any elimination diet, but after multiple recommendations, and given the severity of my symptoms, I was open to trying anything. Within 7-10 days, I noticed a substantial alleviation of symptoms and can categorically say that it has been the most important intervention in my journey to date. I noticed significant improvement in the first 3 months and returned to a slightly more “functional” state - progressing upwards through some of the similar “stages” of symptoms (see associated schematic) to the point at which I have largely remained for the last 3-4 years. I don’t particularly want to expand on the sheer hell that this condition has wreaked on my life, but I believe that the diet has had positive long-term effects, and I feel that it should be one of the first line treatments for anyone with a similar presentation / phenotype. I acknowledge that other elimination diets / fasting may be equally efficacious.
I have continued to see improvements after the initial 3 month period, but had to self-cease the diet on multiple occasions secondary to significant fatigue, lethargy and pre-syncopal symptoms (inadequate energy production). Initially, this was down to a poor understanding of the diet and the need for adequate fat consumption - however, despite attending a specific ketogenic dietician and correcting my calorie consumption - I still suffer from significant lethargy after the 6 month mark during every attempt of the diet - which has limited my long-term recovery. Supplemental daily electrolytes, a multivitamin and BHB salts have aided the process but not solved the energy issue. I have never attempted to avoid any particular 5-ARI food.
The rate of long-term improvement slowed down considerably after the first 3 months, and was relatively slow (but consistent) between 2023 and early 2026. The most significant improvement was noted after a 15 month stint in long term ketosis, and this provided me with enough evidence to suggest that this was the long term “cure” for my condition. At that current trajectory, I estimated it was going to take a few more years to “recover” to my premorbid baseline. This is likely in the context of significant GABA receptor downregulation and I wouldn’t expect everyone to experience a similar trajectory or length of recovery pursuing this approach.
I have largely avoided alcohol in the last few years (while this has conferred some immense short term benefits and temporarily improved all symptoms during my sporadic use (including brief improvements to cognition and memory, although I have never felt “drunk”) - I believe this likely has similar effects to Zopiclone (GABA-A downregulation) in the long term and should be avoided. Anecdotally, I noticed similar benefits while consuming non-alcoholic beers (bizarre considering the negligible alcohol content in these drinks but ?possibly possesses some GABA-A activity). I feel that even the sporadic use of alcohol likely slowed my recovery during this 4 year period.
On a simplistic scale, I believe that the ketogenic diet addresses a GABA/Glutamate imbalance, and enhances the ability / makes it possible for the receptors to upregulate in the long term. I experience similar benefits in long-term ketosis as I would in the short term when taking a GABA-A agonist such as taurine. This is obviously entirely subjective - but is an experience shared by some who appear to have a similar phenotype to myself. I am not convinced that the ketogenic - associated BDNF and gut microbiome benefits had anything to do with the improvements I had seen.
I appreciate this may be unique to me. This is the spectrum of symptoms I have experienced; each stage is discrete and may encompass a spectrum of symptoms from a “stage” either side. My hypothesis is that the specific symptoms I experience at a certain point in time are directly correlated to the likely percentage / degree of downregulation at the GABA receptor site.
I have been “stuck” in stages 4-6 for the last 3-4 years. Each stage consists of a number of steps with associated minor changes to symptoms. This schematic is how I can personally identify when a potential treatment is improving / disimproving my clinical situation. This is a long term assessment but often can identify minor changes on a monthly basis. I believe that the vast majority of those in the neurological “arm” of PFS are stuck somewhere between stages 1-3 - the treatment for all of us should theoretically be the same - it may just take longer for me to recover to Stage 0 (full recovery) given the likely degree of downregulation.
My recent deterioration has caused a rightward shift to re-enter Stage 6 (see below). I cannot identify what has precipitated this, and hence my concern.
2026: Further deterioration - unknown cause.
During my most recent stint on the diet in late 2025 / early 2026, I noticed limited benefits in the long run, which was alarming. (I usually would notice significant improvements at the 1, 5 and 9 month mark, which I did not experience on this occasion). I transitioned back to a normal diet as a break (ketogenic diet is labour and time intensive) and noticed a rapid deterioration in symptoms within a few weeks. This was a stepwise deterioration which followed the pattern of the schematic I have provided and was very similar to the previous Zopiclone - induced deterioration seen in 2022. However, I have not identified any obvious trigger for this, which is concerning. Thankfully, transitioning back into ketosis has stabilised this deterioration for the moment, but I have not yet returned to my baseline (stage 4-5 of the last 4 years - (nor do I expect to in the short term given the trajectory of my condition).
I believe that there has been further GABA-A receptor downregulation in recent weeks/months, but cannot identify what may have caused this. I have done previous stints off the ketogenic diet and have not experienced similar deteriorations so I am confident this is not the sole trigger. This period has rapidly negated most of the benefits I have witnessed in the last 4 years and would suggest there are alternate mechanisms at play now.
The only other “variables” that I can identify within this timeframe was taking Cialis (tadalafil) on a few occasions. For those wondering, this slightly improved erectile quality, but I cannot fathom a potential link between these. I also suffered from recurrent viral infections during this period, which would cause significant fatigue for a week and likely has caused disruption to my gut microbiome (noting the Melcangi studies). These viral infections have had no impact on my neurological symptoms otherwise. I have not noticed any benefit with probiotic use at any point, despite using multiple strains at various timepoints
I want to clarify that this “stepwise deterioration” that I speak of is dissimilar to my understanding of the “crash” experienced by so many. The deterioration occurs usually over a period of 2-3 days, with a subsequent deterioration after 7-10 days and appears to be a pretty structured deterioration following a pattern such as the schematic provided. These stepwise deteriorations feel like a switch has flipped. I have experienced one “crash” as such which I have detailed below.
Sexual symptoms post one dose of Silexan (Lavender oil). 2023. Recovery.
Whilst on the drug, or in the initial 2 or so years with the condition, I never experienced any of the common sexual symptoms reported by many patients. I failed to recognise the various phenotypes of the condition and due to a lack of sexual symptoms, I didn’t actually believe that I had PFS for a considerable period of time. In my attempts to find a long-term sleeping aid, I took one dose of Silexan, without recognising its potential anti-androgenic effects.
The next day, I woke up with severe testicular pain and in the following days - noticed profound persistent erectile dysfunction and loss of libido, among other symptoms. While this would be catastrophic to most here, the neurological sequelae have been so all-consuming that this felt like a minor roadblock and has not influenced my aforementioned neurological trajectory in any way. I did not experience an exacerbation of “brain fog” or further cognitive decline during this period, nor did this contribute in a negative sense to any anxious / depressive symptoms in the long term. I have never experienced any of the skin wasting, atrophy, penile or muscle changes seen by many.
Thankfully, I have seen a 80-90% recovery in this area over the last 3 years, and am now functional in this regard again. This has categorically not responded to the ketogenic diet or any other supplements which have improved the neurological symptoms. I have not explored any therapeutic efforts targeting any androgenic pathways and do not plan to do so, in fear of inducing any further symptoms in this area. I believe that time was likely the most important factor in this recovery. Given the timeline and contrasting precipitating factors, I feel that, in my unique case, the mechanism at play here is entirely discrete from the aforementioned GABAergic dysfunction. I also feel that I would have likely never suffered from any sexual symptoms had I avoided the obvious precipitant in this instance.
Anecdotally, for anyone who intends to adhere to a long-term ketogenic diet, I personally have noted a decline in erectile quality as the months progress in ketosis (likely secondary to inadequate energy production). This immediately reverts to baseline on cessation of the diet.
I am not an Endocrinologist, and have a limited understanding of the likely pathophysiology of the PFS-induced sexual symptoms, and will refrain from commenting on this. Dr. Powers appears to have made substantial progress in this area in recent times, and I would advise consulting his research and organising appropriate investigations with a specialist prior to experimenting with hormonal therapies.
Research and Therapeutic efforts
I wanted to include an extensive analysis on the activity of allopregnanolone and various derivatives on the GABA-A receptor, but I cannot claim to fully grasp the intricacies of these neurosteroids and their direct effects. I could spend hours delving into the vast array of scientific papers I have consumed, as I know many of you have, but my recent deterioration in symptoms has shaken my confidence in my previously “reliable” theory.
On a simplistic level, and as reported in literature, I believe the 5αR1 and 5αR2 inhibition has (at some point and maybe irreversibly) led to the reduced synthesis of allopregnanolone and likely widespread dysregulation at the GABA-A receptor. This has led to possible hypersensitivity / tolerance issues at the specific receptor subunit sites.
https://forum.propeciahelp.com/t/my-recovery-and-neuro-biological-disorder/43602
I recently came across this recovery post, and while the recovery has seemingly not been replicable to date, I independently have concluded that I likely have a similar underlying pathology. I do not fully comprehend the technicalities of GABA receptor subunits and their expressions within the CNS, but I feel that this is a route to pursue. He cites some important papers that I would encourage people to read in their own time. He poses a hypothesis in that his allopregnanolone production was not necessarily impaired, but its activity on the receptor site was altered.
A first step for me would be actually identifying a low serum allopregnanolone level vs. progesterone / pregnenolone levels - which would reflect an issue with neurosteroid conversion vs. a potential issue at the receptor site. I am unsure if a urinary allopregnanolone level can be reliably tested / would even be beneficial?
In an attempt to replicate the above, I have also trialled Bacopa in an attempt to upregulate GABA-A receptors - with no discernable benefit. I do not believe it either slowed / sped up my partial recovery on the ketogenic diet. I believe this patient’s extensive fasting likely mimics a ketogenic state - which is doing the vast majority of the work in this instance. I agree with his hypothesis that in theory this should work, and would encourage others to try, but I personally have not derived benefit from this. I would be hopeful that a substance that can effectively upregulate GABA-A receptors should theoretically lead to an improvement in my symptoms in the long-term.
I have previously never seen a Neurologist - I had seen significant improvements with diet alone and wasn’t willing to pursue further consultations and investigations for a merely academic purpose (Lumbar puncture has some risks associated). This stance has obviously changed now so I intend to visit a private neurologist in an attempt to organise similar investigations to the above patient (Lumbar puncture with CSF analysis of allopregnanolone levels / GABA-A receptor subtypes) - which should glean some important information.
If anybody has any recommendations for further investigations or neurologists who have experience dealing with the above, I would be forever grateful. I am happy to travel overseas if necessary as I feel that these niche investigations may be difficult to organise for myself without a clear indication. Despite being a doctor myself, I have had some lousy interactions with fellow work colleagues and friends and can only imagine the grief endured by many in consulting the medical profession.
I will also organise appropriate investigations (DUTCH complete. etc) as recommended here. I live outside the USA, but have recently joined the waiting list for Dr. Powers. I acknowledge his excellent and progressive work in recent times, but I have yet to draw a conclusion on how his hypothesis fully links in with my lived experience.
Laboratory results:
An initial hormonal panel was done in 2022 when I first saw an Endocrinologist. I do not have the results to hand. Mildly raised serum cortisol. Every other result in the panel was within the normal range. Serum testosterone was in the low to normal range - hence the trial of TRT.
Routine bloods have (on multiple occasions) been normal. There hasn’t been an indication to explore this further previously until now.
Discussion:
I appreciate that there is a hesitancy in the community to recommend treatments to others (for good reason). Given my trajectory, I feel that my symptoms will continue to deteriorate in the upcoming weeks - months, and I need the scales to tip in the other direction. Therefore I am looking for advice - if anyone in this “neurological” cohort has had positive experiences with the below? I would appreciate a reference to previous posts / scientific literature if deemed appropriate.
Lithium Orotate - Not pharmaceutical lithium carbonate. This is first on my list of potential treatments. I have recently seen the attached testimony who appears to have had considerable benefit with this in a similar scenario to myself, quoting a potential mechanism for his improvements. I am unsure if the framework and infrastructure included are essential, but it is something I will explore.
https://www.reddit.com/r/DrWillPowers/comments/1tf4rq4/functional_pfs_recovery_5_years_neurological/
Etifoxine - theoretically has modulating abilities at the GABA-A receptor. I am wary of any medication with activity at the GABA-A site given my previous experiences and the unpredictable nature of the response.
Bacopa monnieri - Properties as denoted above, I may try this again over an extended period.
Zuranolone / Ganaxalone: allosteric modulators of GABA-A receptors. Their theoretical utility would depend on the serum allopregnanolone / steroid precursor results. I know that their use has been discussed in forums for decades.
Progesterone / Pregnenolone: I gather that Dr. Powers has some experience prescribing these. Theoretically, this may lead to increased downstream allopregnanolone production, and therefore downstream activity on the GABA-A receptors.
Faecal Microbiotal Transplant: Entirely clutching at straws here. As a potential reset to the gut microbiome.
Various antidepressants / antipsychotics: I won’t cite individual agents but numerous agents reportedly increase serum allopregnanolone levels. Low dose fluoxetine for example, is said to increase serum allopregnanolone concentrations. I have always been against trialling the above classes given the potential side effects and unpredictability of these medications in inducing possible sexual dysfunction.
https://www.adxs.org/en/page/534/allopregnanolone#fn_48
Some interesting studies are included in the references here. I have read countless studies of various medications increasing / mimicking allopregnanolone - it is obviously a minefield to deduce if any would be beneficial in this instance.
Reflection:
The last few years of my life have been an unprecedented disaster, a nightmare which I have never woken up from. I acknowledge that, over time, the symptoms have become easier to deal with, but they have never reduced in severity. A “saving grace” (silver linings and all that) is the profound memory loss I have experienced, and the impaired ability to learn and consolidate new information. I wake up each day with a very hazy memory of the previous day, week and year, and therefore do not dwell on the five year misery I continue to endure. My memory pre 2022 is largely preserved in comparison, and drawing on this cognitive reserve has enabled me to somehow graduate with my best friends and work full-time as a junior doctor for the last 3 years, which has brought me immense joy and pride. This has been a major protective factor for me, despite the massive challenges this condition brings on a daily basis.
The reality is, that despite being an optimist - I am not convinced I’ll have a positive long-term outcome given my recent trajectory. I have taken a step back from work to pursue researching my own condition, and therefore looking for help from the community. Unfortunately, my recent deterioration renders it more difficult to fully comprehend the latest research and therapeutic efforts and draw concise conclusions from these. I had always planned to engage in research in this field, once my symptoms had recovered sufficiently; however, I have never been in a position where I felt able to effectively do so.
I want to acknowledge the great work done by the PFS community at large, and personally thank anyone who has advocated for use of the ketogenic diet previously. Some patients demonstrate incredible bravery when trialling new treatments without comprehending the potential deleterious sequelae of these efforts. These anecdotes have been incredibly useful for me over the years in deciphering which avenues to pursue.
I could write so much more in this section, a few paragraphs cannot encapsulate the roller coaster of symptoms and emotions I have survived through. Every day has been a struggle, and I encourage everyone to keep fighting the hopelessness, exhaustion and uncertainty associated with this. With the increasing prevalence of the condition, coupled with recent discoveries, I do believe that the pendulum is beginning to swing in our favour.
If anyone is experiencing similar issues, please reach out to me via DM. I cannot provide medical advice over text / over the phone, but am more than happy to answer any questions to the best of my ability.