r/DrWillPowers • u/TraditionTime8124 • 9h ago
From the PSSD community on Reddit: GOV.UK recognizes PSSD
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r/DrWillPowers • u/Drwillpowers • Sep 14 '26
Post by Dr. Powers Why "X treatment crashed me bro" is counterintuitive to the reality of these conditions, and that which makes you feel a little bad may be in reality, what you need to recover. I think I have figured out the true nature of the low libido/anhedonia/substance resistance in PFS/PSSD and how to fix it.
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This will not be a brief post, but I need to express this out loud so people understand my reasoning here, as I've been quiet as of late, but mostly because i've been making tremendous progress, but I wanted to be sure it was real and not just a statistical anomaly.
Currently, my largest target is unraveling the "anhedonia" aspects of PFS/PSSD. As of this point, I have enough castration trial patients that I can state that I have not had a single patient who had androgenic signal loss issues that underwent castration that after castration ended had no improvement in that domain if not complete recovery.
Every single castration due to androgenic signal loss PFS patient thus far has had signs of increased androgenic signaling on no supplemental medication (aka their own hormone production) sometimes even during, but always after castration ends. This includes acne, muscle mass increase, sleep quality, erection quality, hair loss, etc etc. Pretty much any and all signs of "this person has more androgenic signaling happening" has resulted from all treated cases (I can't speak for Sommer, but I think this is also true for hers).
However, most of the cases which ALSO have anhedonia, low libido, and other oddities like "blunted effects to substances like alcohol/weed/benzos" (a hallmark trait) have had either minimal improvement or no improvement from the castration trial.
This says to me, "there is another problem yet to solve" and my current theory on this is that the problem is caused by an EXCESS of neurosteroid production which was initially caused by an SSRI, or the "crash" of Finasteride reducing them and the body overcorrecting to this. These neurosteroids are positive allosteric modulators of GABA-A. Imagine that in excess, these guys are propping open a channel that downstream has inhibitory effects on multiple neural networks. If you ALWAYS have 3mg of Xanax in your system every day of your life, your brain will rewire itself to cope with that, and if you suddenly stop taking that xanax out of nowhere, you can literally die from having a seizure.
Request for help: I am still trying to find a combination of locations where I can send a patient to get a lumbar puncture done, and then the CSF collected can be sent for mass spectrometry in order to get the specific concentrations of various neurosteroid molecules calculated such that I can compare them to known control values. This will allow me to figure out WHICH specific ones are being overproduced. My main assumption right now are that the top 2 candidates are Androsterone (and its metabolic derivatives) and THDOC. I'd like to prove this with a lab rather than "I think this is high, so this drug inhibits it, and thus should produce X symptoms, so I give it to patient #1, and oh look, cool, they are getting X symptoms, insane X symptoms from taking an NSAID, which otherwise would never ever happen unless I was right". (This is a shitty way of proving I'm right).
Regardless, I have been using various agents on patients that are known to inhibit the production of these neurosteroids, or, help in the clearance of their downstream metabolites in order to lower the levels of these in the brain. Thus, removing a major agonist of the Gaba-A system overall.
As a comparative example, you can give a stimulant to a hyperactive kid with ADHD, and they are calmed by it. Why? Because stimulating various inhibitory circuits in the brain can "Up the downing" and thus have an overall calming effect. One of my favorite hat tricks as a doctor is finding a patient whom is basically failing at life due to crippling anxiety, and whom has already failed controlling it with a multitude of different drugs, including SSRIs, benzos, beta blockers, antihistamines and buspirone to no avail. I have also ruled out a deficit of pregnenolone/17OHP/cortisolic issues. I then inform this patient, okay, I'm now going to give you an amphetamine to treat your anxiety and they look at me like I'm a lunatic. But, I tell them how many times before this has worked, and they trust me, and so they take it. I get a message 24-48 hours later with "oh my god I can actually drive a car again and not be terrified" or "I feel calm and not anxious for the first time in 15 years". Its astounding how giving a stimulant can calm these patients, but this is how it works. It stimulates inhibitors (and also improves executive dysfunction) which has a massive impact on improving their anxiety and overall wellness. This is not my go to treatment for anxiety, but more "this always seems to work when everything else fails despite seeming paradoxical at first".
THIS IS THE IMPORTANT PART OF THIS POST
There exists an enzyme, 3α-hydroxysteroid oxidoreductase and its job is to be the primary oxidoreductase (sometimes also called called 3α-hydroxysteroid dehydrogenase or 3α-HSD) which acts as the primary enzymatic bridge between active androgens and their downstream metabolites, 3α-androstanediol and 3α-androstanediol glucuronide (3α-ADG)
This is the reaction. Look familiar? Yeah. See those UGTs? That was the big break in my research on PFS over a year ago now when I was like "uh...why are more than half of my PFS patients having zero androgens in their urine on dutch testing?". That was the first peel on the outside of the onion, and once coupled with me deep diving into their genomes, the mystery started to unravel.
When you dick with DHT metabolism, you can get other enzymes to be up or downregulated in response to the change that was artificially induced from some SSRI or Finasteride. You can even get the syndrome from something stupid like the antibiotic doxycycline (Because it alters your gut flora, and in doing so, alters the amount of beta glucuronidase present in the gut semi-permanently, and in a susceptible patient with glucuronidation/excretion issues, you get a pile up).
Yeah, so if you upregulate your 3A-HSD, you start producing a shitload of cerebral THDOC.
THDOC is a positive allosteric modulator of GABA-A, and excessive GABA-A signaling is how you produce a phenotype of anhedonia, low libido, etc etc. The standard PFS/PSSD bullshit.
Lately, i've had a crazy amount of luck utilizing Calcium D-Glucarate (1 Gram every 8 hours) simultaneously with Indomethacin (yep, the NSAID), as I'm increasing clearance while simultaneously inhibiting the synthesis of THDOC with the indomethacin.
When this starts happening to the patient, you know what happens?
"NO WAY DR P, THAT INDOMETHACIN CRASHED ME BRO, I FELT LIKE SHIT! ALL MY MUSCLES CRAMPED UP, I FELT LIKE I HAD THE FLU, I WAS ANXIOUS AS FUCK AND HAD PALPITATIONS AND PANIC ATTACKS, IM NOT TAKING THAT SHIT AGAIN".
And if this was pre Dr. Powers theory 2025, everyone would agree "Indomethacin crashed me bro" and it would be placed on the discard pile of drugs that could treat PFS/PSSD.
But, its not "crashing" the patient. What is happening is I have just chemically deleted their self produced biological xanax. In the same way that we make "endorphins" as endogenous opiate molecules, THDOC is like your own built in xanax prescription. When you're on a massive absurd, bonkers amount of xanax every single day of your life, anhedonia and low libido kinda makes sense. If I suddenly make you stop it, you can quite literally have a seizure and die.
Some of these patients have even been through benzo or alcohol withdrawal in their past, as they just coincidentally had a history of use/abuse of those substances, and described the experience as nearly identical to what that felt like.
But the wildest part of all is while feeling super anxious and like shit, "BUT I WILL SAY, I AM HAVING INSANE LIBIDO WINDOWS AND AT TIMES EVEN FEELING MANIC LIKE MY ANHEDONIA IS BACKWARDS!".
After sometimes many years of being like this, me removing the brake on those downstream neural networks is like taking a 15 year old out for a driving lesson and letting them understand how the gas and brake pedal work. They sort of stomp on the gas and brake for a while as they learn to drive and realize that you can make more small and subtle adjustments. So "extremes" of signaling happen when in that state, as the movements in any direction are exaggerated without the presence of that normally very high dysfunctional level of positive allosteric modulation of Gaba-A signaling.
So what I'm doing, is simply lowering the dose of the treatments. Then sending them back into the game with a pat on the butt and saying "get in there champ, give em hell! stay tough!" knowing full well that what I am asking them to do is going to suck. This process is not going to be fun. They are going to be repeatedly sacked by anxiety/muscle cramps/feeling of impending doom/etc for the remainder of this many months long football game over and over and over again as they are basically addicted to their own biologically produced xanax and i'm forcing them to go into withdrawal and contend simultaneously with living in a world that's quite literally on the precipice of major societal upheaval from a multitude of causes.
But, seeing the patient know full well that this is going to suck, but having the bravery to trust me and go back out there and restart the drug that "crashed" them at a lower dose and endure these "side effects" deliberately so that they can actually rewire their dysfunctional networks and get back to their Pre-Drug-Catastrophe brain state?
Thus, it is time to tell you the truth. I regret to inform you that it does not seem PFS and PSSD will be instantly curable in patients with non-androgenic problems, aka psychological symptoms (anhedonia/low libido/etc) as simply as castrating them and uncastrating them. For androgenic signal loss only issues? I think it is a functional cure for most if not all of that subtype of patient. We have enough success cases now that I can say that confidently (there are even people and doctors commenting on my threads from around the world now who did this with their local physician and are reporting improvements/recovery for that specific problem). I can't fake that. (Not that I am even trying to sell anything here anyway).
But for those with a neurosteroid excess problem (traditional anhedonia/low libido/etc), I am attempting to prove my current theory with CSF analysis if I can find somewhere to do it, but my model predicted that these neurosteroids are produced in EXCESS (contrary to the historical dogma of "low allopreg/neurosteroids" and that any removal of them would be met with a "CRASH" of severe anxiety/palpitations/etc, but also increased libido and improvements in anhedonia. That appears to be exactly what's happening.
In addition, I regret to inform you that spending months to years in this dysfunctional state has resulted in pathological rewiring of downstream neural networks due to this pathological GABA-A state, and that there will be no "one pill solution" to fixing this in the same way there is no one pill solution to quitting a severe heroin/meth/benzo/etc addiction. The true cure is going to be the slow, gradual reduction in neurosteroid production (done under doctor supervision as crashing yourself too hard could literally be fatal in the same way that cold turkey-ing benzos/alcohol can be fatal). Doing this slow, gradual reduction in specific (based on lab result custom tailored and targeted) neurosteroid production until I've got someone back to their original baseline, and then tapering off the medications. We are going to have to rewire the dysfunctional downstream networks. The good news is, medicine has a shitload of experience in doing this slow gradual rewiring, and we call it "addiction medicine" and it's a literal specialty board certification and there are a ton of doctors vastly more talented at it than I am. Once I work out the best way to test/prove the specific glitched neurosteroid, and know what is the perfect agent to target that specific one, this shouldn't be that hard to do with some random doctor and not accidentally kill yourself in the process from a seizure.
Don't like autistic hyperverbosity? Alright, then just read this summary of the state of my research as of Sept 14 2026:
TLDR: PFS and PSSD anhedonic/low libido states are likely caused by (need CSF mass spectrometry to prove it but i'm nearly certain) pathological increases in the synthesis of specific neurosteroid molecules which act as positive allosteric modulators of GABA-A, resulting in over time, downstream network remodeling. This is the reason why most of you had a very high libido, but also problems with anger/irritability/anxiety/etc before developing the disorder. You had a system that was living on the razors edge. Taking the drug+ a combination of genetic glitches (which I have detailed in other posts) results in a pathological buildup of certain metabolites, which crowd various synthesis and degradation pathways for androgens and neurosteroids. This results in the up or downregulation of different enzymes (depending on your inborn glitch) which produces wild derangements of neurosteroid production in the EXCESS direction, which over time, pathologically rewires your brain. Substances like alcohol/benzos/weed stop doing much to you as you're already so wildly overmodulated in terms of GABA-A that its like pissing into an ocean in terms of their effect. To fix this, we will need to slowly bring down the level of the pathological molecules utilizing various targeted therapies (including temporary castration / cdg / indomethacin, and other molecules I am less confident in) until your level of GABA-A signaling "feels" insufficient to you, causing muscle cramping, anxiety, and palpitations (and other low gaba-a signs) if done too quickly. This is not a "crash" this is what is going to be necessary to reverse the dysfunctional network remodeling that the excess neurosteroids did in the first place. A culture of chasing windows and avoiding crashes has quite literally indoctrinated thousands of people into staying away from the very things that actually might have helped them.
This is my new model of PFS/PSSD/Post Drug syndromes that specifically revolve primarily around low libido/anhedonia, and what I will be doing with my patients likely for the remainder of the year, as my results with it in just the first few weeks have been utterly astounding. I don't want to copy any quotes out of the private emails sent to me by my patients, but if any of you want to comment here with your experiences and back up that I'm not full of shit, I would welcome that. Its kind of like my 17-hydroxyprogesterone post. It sounds like the rantings of some quack until you get to the comments and see how many people talking about how its life changing for them. Being an iconoclast sucks (I'm not looking forward to the fallout of trying to convince "the experts and researchers" that the problem isn't low neurosteroids but rather an absurd excess of them). I am really really tired of being "that quack" and so I greatly appreciate when my actual patients (or those using my methods) come onto a thread and give their real, unfiltered experience with these treatments (both the good and bad) as that's what people really need to see. I don't have millions of dollars or a university research team having published years of my research study results (yet) and so for now, those anecdotes are the best I have to offer.
As always, I hope this helps suffering people.
- Dr Powers
r/DrWillPowers • u/Drwillpowers • Jul 25 '26
Post by Dr. Powers New Here? See this Post to get started for anything from PFS/PSSD/PAS etc to Gender Dysphoria treatment or anything else Dr. Powers works with. This is now the official starting point for anyone new to the subreddit!
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This is a bit of a placeholder post for now, but I wanted to make use of the hard work of various patients/supporters in providing an organized "getting started" for someone who arrives here and is like "Why is everyone talking about X on this subreddit about a Detroit Family Physician with giant cats?"
So if you're new here, and looking for information, aside from simply going through all posts with the same flair as this post, here's some getting started info!
This is not an exhaustive page containing all possible important information on this subreddit, but its a good starting point. If someone would like me to add something to this page or think it belongs on this post. Comment it below and I will update it.
Looking to get a whole genome sequence done?
I have a 20% off coupon code through sequencing.com and they do good work for getting me the data I need to do my job!
PFS/PSSD/PAS/Post drug syndromes:
The most important link here: Dr. Will Powers Interview [PFS / PAS / PSSD Summit 2026] Dr. Powers mechanism and treatment plan that he is currently trialing for PSSD/PFS
Current mechanistic explanation of the Anhedonia/Low Libido/Immune to substances phenotype:
https://www.reddit.com/r/DrWillPowers/comments/1wgdfut/why_x_treatment_crashed_me_bro_is/
List of all treatments I've ever tried since 2019 to treat PFS/PSSD and other post drug syndromes: https://www.reddit.com/r/DrWillPowers/comments/1fyc1mg/list_of_treatments_for_post_finasteride_syndrome/
Dr. Powers Neurosteroid phenotype theory: https://www.reddit.com/r/DrWillPowers/s/H2ILwaHtwz
Dr. Powers PSSD/PFS gene list:Current list of all genes I use when searching for possible genetic causes of someone developing Post Finasteride Syndrome (PFS) or Post SSRI Sexual Dysfunction (PSSD) : r/DrWillPowers
Dr. Powers most recent PFS trial update: https://www.reddit.com/r/DrWillPowers/s/ogxakgUPFz
The tests that Dr. Powers sees strange results in for PDS patients: You know, PSSD and PFS may actually be the same thing. Anyone got any data for me? : r/DrWillPowers
Wondering if you could be at risk of the development of these syndromes? These are the lab tests most commonly anomalous in these patients:
How to read your WGS from sequencing and make a comprehensive report for Dr. Powers to read: https://www.reddit.com/r/DrWillPowers/s/3YDGZuvB0j
Also, the creator of that post has developed a number of programs that make analysis of your own genome much easier. He's very active in the community, and wants to help people. You can message him at /u/Excellent-Push2833
Gender Dysphoria Related Posts and Medical conditions commonly linked to gender dysphoria:
A possible root cause for the syndrome of PTSD / POTS / hEDS and Hypermobility / MCAS / Hashimotos / IBS / Chronic Fatigue Syndrome / Myalgic Encephalomyelitis ( ME/CFS) , Other Trans/queer population related super common health problems and how to cure them:
Post on genes related to the development of gender dysphoria:
The hidden pitfall of monotherapy, and why MTFs like caffeine:
How to properly draw labs:
Random other posts of note :
Top upvoted posts of all time, posted by Dr. Powers:
Dr Powers's publications.
Dr. Powers' novel crofelemer idea getting its patent 6 years later:
Dr. Powers' Giant Guinness World Record therapy cat because why not:
https://www.reddit.com/r/cats/comments/xwjd12/my_cat_fenrir_just_broke_a_guinness_world_record/
Medical conditions associated with gender dysphoria (2025)
Doctors and researchers have observed that many people with gender dysphoria share a cluster of medical conditions tied to atypical estrogen signaling (high or low) at birth. This observation suggests a biological intersex condition for a subgroup of individuals, distinguishing their experience from the framing of gender dysphoria as a purely psychiatric phenomenon.
For a full overview please see the wiki: Medical conditions associated with gender dysphoria.
2025 Update:
Based on published research and clinical observations, a specific biological hypothesis has emerged: that the common intersection of medical conditions for a subgroup of individuals with gender dysphoria is tied to the production, metabolism, or activation of the estrogen receptor.
While other genetic factors can influence estrogen signaling, the CYP1B1 and CYP1A1/CYP1A2 genes, which are responsible for breaking down estrogen, have become key players and are often the first genes looked at. These genes, once thought to only play a minor role in a rapid metabolic process, can significantly alter hormone balance especially when their variants are paired with other mutations, particularly those that result in reduced COMT activity. While the individual components of these pathways are well-studied, their combined effect represents a novel and crucial insight. You can find more details on the Estrogen Metabolism wiki page.
Better Care
This simple awareness of these interconnected conditions has already helped people improve their own health and lead to better transition outcomes. It has provided a starting point for previously unsolvable mysterious edge cases and empowered individuals to take charge of their health.
Improved Clinical Management
- Non-Classic Congenital Adrenal Hyperplasia (NCAH): Some women with NCAH often show elevated adrenal androgens such as DHT and 11-oxygenated androgens. This NCAH can interfere with feminization, cause anxiety, dizziness on standing ("POTS-like" symptoms), and other issues. Getting proper diagnosing and then targeted adrenal support can reduce comorbid symptoms such as excess androgen.
- Challenges with Feminization: Some women struggle to feminize despite high estrogen levels. Addressing any metabolism issues (COMT support, methylation, low magnesium, etc.) can sometimes help with this issue as well as other health problems associated with low estrogen signaling such as constipation.
- Challenges with Masculinization: Some transgender men fail to masculinize as expected because they rapidly convert testosterone into estrogen or have high levels of high-affinity estrogens. Recognizing that this is a possibility can lead to getting lab work and supportive treatments like aromatase inhibitors or COMT cofactor support to increase inactivation of high-affinity estrogen when that is the issue.
- Addressing Rare Conditions: With the understanding of what typically goes on, when encountering outlier cases, clinicians (Dr. Powers and others) knows where to look and is much more likely to be able to identify genetic issues such as reduced STS enzyme or Estrogen Insensitivity Syndrome (EIS), and possibly work around them, something that would have been impossible a decade ago.
Diagnostic Clarity and Preventing Regret
- Inverted Sex Hormone Signaling: Individuals with the genetic profile for inverted sex hormone signaling are given autonomy to first resolve their underlying endocrine issues before undergoing HRT. In some of these cases, medical or social transition may no longer feel necessary or desired. This outcome upholds patient autonomy by ensuring they have all the information needed to pursue the most suitable path for them.
- Avoiding Misdiagnosis: For individuals who don’t match the expected phenotypes or hormonal signaling patterns, further investigation can sometimes lead to alternative, more appropriate diagnoses. This process ensures individuals receive the most effective care for their specific needs, supporting them in making the most informed decisions about their well-being and helping to prevent potentially regretful outcomes.
Autonomy, Identity, and Sexuality Support
- AMAB people who have Congenital Copulatory Role Discordance (CCRD) and low estrogen signaling who don’t wish to transition, may still need a minimal level of estrogen for overall health and well-being as they age.
- For those wanting to try every other option first, understanding their individual biology allows for supportive interventions that rarely, but occasionally, are enough to reduce dysphoria.
- For individuals considering HRT, this framework allows folks here to share what happened to them so others with similar phenotypes can know what might be common patterns, especially around sexuality post-transition. While historically it was nearly unknown what would happen, this helps those be better informed about possible outcomes if they go on HRT, such as becoming bisexual, or switching from gynephilic to androphilic, or vice versa. To be clear, this still needs a formal study, and is only a noted anecdotal pattern.
Managing Comorbid Conditions
- Many experience comorbid conditions such as ADHD symptoms, poor sleep, hypermobility-related pain, IBS, or inflammatory bowel disease-like flares. Watching for, identifying, and addressing any underlying endocrine imbalances through known methods can sometimes lead to a subtle or dramatic improvement in these conditions.
A Note on Vitamin D deficiency
And if you are reading this, please do get your Vitamin D level checked! Due to both genetic factors and lifestyle (e.g., lack of sun exposure), Vitamin D deficiency is a common and easily correctable condition.
A Call for Further Research
This hypothesis is based on a combination of existing published research, clinical observations, and reported data from individuals. While these insights have provided a valuable framework it does not yet represent a complete picture. The hypothesis has reached a maturity stage where future research can be more targeted to areas with the highest probability of success. Further formal studies are needed to validate and expand upon these findings, including larger sample sizes of existing work, formal replication, and the publishing of edge cases as case studies.
Thanks to everyone who has helped
The progress made in all these rare conditions is a collective achievement. When we started we had a list of common conditions, many of whose connection was initially a mystery. The progress we have made so far would not have been possible without the contributions of so many, from researching medical conditions, reading papers, investigating personal DNA, to reviewing and refining the wiki. Thank you to everyone who continues to contribute their time, data, questions, and insight. We welcome continued feedback to keep improving.
For a comprehensive overview, please see the full wiki: Medical conditions associated with gender dysphoria.
Second time for visibility:
This is not an exhaustive page containing all possible important information on this subreddit, but its a good starting point. If someone would like me to add something to this page or think it belongs on this post. Comment it below and I will update it. Another good page to check out to find relevant posts is to simply sort all posts by my username, u/DrWillPowers which are assigned a special "Post by Dr. Powers" flair.
All are welcome here! Thanks for coming, and be excellent to each other!
- Dr Powers
r/DrWillPowers • u/Middle-Surround8444 • 8h ago
MTF HRT Medical Question / Discussion 3a-ADG and DHT labs not available
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What the title says! I'm pretty sure my country doesn't have 3a-ADG labs. The only DHT labs I could find measured free DHT and cost twice as much as rent! I'm still looking, of course, hoping that I find them in some obscure panel, but I also think that's likely not going to happen.
So, I was wondering if I should just trial dutasteride, and if tolerated, continue it?
The reason I bring it up is because some of my androgenic symptoms like mild acne, oily skin, body odor, dandruff didn't get better on 5 mg EEn weekly despite T being suppressed (34 ng/dL). I'm not on progesterone or any anti-androgens.
Also, maybe it's a silly question but can trans women get PFS/PSSD from duta? I know nothing about these conditions so I'd love for people to inform me. I don't really mind sexual dysfunction and/or loss of libido but I'd really hate for my mood to tank.
r/DrWillPowers • u/Dragonvarine • 3h ago
Post SSRI Sexual Dysfunction Syndrome (PSSD) Low neurosteroid type?
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What the exact test needed to know if I'm excess or deficit?
I have emotional blunting, anhedonia, DPDR, and a weird drugged feeling, possible substance blockage.
But I'm also very overly anxious, very severe health anxiety. Paranoid that my heart might die on me for no reason.
M. Mushrooms managed to feel good on the comedown (but trip was very bad) so unsure if substance blockage.
r/DrWillPowers • u/Minepolz320 • 34m ago
Post SSRI Sexual Dysfunction Syndrome (PSSD) Heart rate variability?
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r/DrWillPowers • u/Rich_Paint_200 • 1h ago
Repost : Scientists found that the creatine supplement millions take for muscle gains is quietly raising brain energy levels and slowing early Alzheimer's cognitive decline by 30%
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r/DrWillPowers • u/Competitive-Ad-3179 • 18h ago
Post Finasteride Syndrome Spine Juice
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Hi all,
As many have mentioned, most valuable next step seems like getting CSF testing available for us
I would like to help here, but from the calling around I’ve done thus far, I’ve mostly gotten “That’s not a thing, why are you talking to me”
Under what conditions could this legally exist? Do we need to establish this as a lab that can be ordered in general, and potentially fund raise to establish that and get a sufficient number of controls to establish a range? Have a study for it?
I know others have been working on this, and id like to know how I can best help, it seems that cold calling without understanding more here is not the move
r/DrWillPowers • u/Surroundphil • 19h ago
Prednisolone temporarily made me feel like my entire body was finally functioning normally, not just hypomania. What could explain this?
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Hi Dr. Will Powers community,
I have a question about an unusual experience I had while taking prednisolone, and I am wondering whether anyone has encountered something similar or has ideas about the underlying mechanisms.
I have had Crohn’s disease since my teens and have also struggled with chronic depression, severe anhedonia, fatigue, brain fog, and a general feeling of not functioning properly for many years.
At one point, I was prescribed prednisolone at 50 mg per day for my Crohn’s disease. What happened during that period was striking and difficult to describe. (Although I have to say I took prednisone multiple times and did not have such experience.)
It was not simply that I felt happier or more energetic. It felt as though my entire body had suddenly started functioning the way it was supposed to.
My depression symptoms improved dramatically. I felt much more alive, my mental fog lifted, and my energy and general sense of well-being improved. It was as if a fundamental problem that had affected both my mind and body had temporarily disappeared.
I realize that corticosteroids can cause euphoria, hypomania, or even mania. I have considered that possibility, but my subjective experience seemed broader than just an elevated mood. It felt more like a restoration of normal functioning than an artificially elevated state.
I have tried several antidepressants and other treatments over the years, but none has reproduced that experience. Some treatments have affected individual symptoms, but nothing has come close to the overall change I experienced on prednisolone.
This leaves me wondering what might explain the difference.
Could it have been related to:
Suppression of systemic or neuroinflammation?
Effects of glucocorticoids on brain circuits involved in motivation, reward, and energy regulation?
An effect on the HPA axis or another hormonal pathway?
An interaction between my Crohn’s disease, immune signaling, and depressive symptoms?
Or was it more likely a corticosteroid-induced mood state that subjectively felt like a return to normal?
I understand that the fact that prednisolone helped does not prove that inflammation or a hormonal abnormality was the underlying cause. I am trying to understand why its effects felt so fundamentally different from those of antidepressants.
Has anyone encountered a similar response to glucocorticoids, particularly someone with chronic depression, anhedonia, and an inflammatory disease? Are there any plausible mechanisms or relevant research papers worth looking into?
I am not looking to use prednisolone as a psychiatric treatment, given its risks. I would like to understand what this response might tell me about my underlying condition.
Sorry if this is posted in the wrong sub, please suggest me another then.
r/DrWillPowers • u/Couple-Economy • 18h ago
Post SSRI Sexual Dysfunction Syndrome (PSSD) xanax while on pssd
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quick one from myself
i have pssd. so according to excess metabolite theory my brain is flooded with my own ' internal xanax/gaba modulators ' hence my sympthoms.
so in this model of PSSD ( excess metabolite ), should xanax work on me when i take it in a form of a pill or not ?
intuitively, it shouldnt, because i am flooded with my own positive allosteric modulator of GABA-A
but it works even in v small dose
so why is my intuition wrong here ? different receptors, different places in brain , something else ?
kind reagrds
r/DrWillPowers • u/J40897 • 19h ago
Post Finasteride Syndrome Excess Neurostoids Theory Question (PFS) for Dr. Will Powers
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Alright, so i understand that some of might be suffering from excess neurostoids. But is there anything that you would suggest naturally that may help us drain, like vitamins or lifestyle factors? Or avoiding certain things? Any vitamins that may help Glucuronidation. Just natural methods while you're still figuring out the logistics and stuff.
For myself I can't feel euphoria from alcohol/vitamins, but sometimes I can a little bit, but also don't feel urgency if I lose things unless it's something extremely important. Last night I probably only got 2-4hours of sleep, but don't feel tired like pre fin. Libido doesn't really seem to be an issue either, also feel sedated if i take magnesium glycinate too. But I'm just curious to know if there's suggestions for natural protocol while we wait to see more progress in the future
r/DrWillPowers • u/amr5502 • 1d ago
Post Finasteride Syndrome Man acquires PFS from anti fungal steroid cream prescribed for rash
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I found a really interesting post on Propecia help recently that really puts into perspective how wide spread this disorder actually could be and it’s only the lack of knowledge thats keeping this from reaching mainstream
to quote the thread:
I have no history of using finasteride/propecia/accutane. However I was given an antifungal topical steroid cream for a rash on my inner thighs/buttocks and inner arms.
My symptoms include 0 libido. No morning/spontaneous erections, erection only through stimulation, goes down fast. Genitals are numb, and I also LEAK URINE!!!
u/DrWillPowers I immediately mentioned this in the discord and we agreed we would absolutely love your take on this one sadly the post was from 2018 but the odds are good he would match recent Dutch results
it proves beyond a doubt genetic predisposition but it also suggests the triggers for this go beyond anything hormonal.
r/DrWillPowers • u/Minepolz320 • 1d ago
Post SSRI Sexual Dysfunction Syndrome (PSSD) Little proposal for PSSD and etc community
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r/DrWillPowers • u/Numerous-Artist-4373 • 17h ago
Post Finasteride Syndrome Window😍
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Guys I guess I’m having a window now at night I don’t have the dpdr and my minde is so clear, I still have a little tinnitus. Do I need to do anything?
Thanks
r/DrWillPowers • u/Complex_Coffee_9685 • 1d ago
Post Finasteride Syndrome Going insans
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Im almost 100% certain CdG made me worse and im on the brink of checking out. It gave me massive anxiety and panic attacks that have lingered a month after stopping. Gave me better penile sensitivity that has of this week disappeared and is now back to full numbness. I haven't been able to sleep well since and I constantly feel hot. I wish I would've never tried that shit legit turned my stable pfs into a nightmare. Do NOT take it!
r/DrWillPowers • u/Extension_Shift1520 • 1d ago
Post Finasteride Syndrome Why is Dr. P saying relugolix works for everybody who tried it when the results have generally been neutral to bad?
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With the exception of like one or two guys, nobody improved. What's going on?
r/DrWillPowers • u/idkwhattoput10188 • 1d ago
Do any of you experience alleviation of biochemical dysphoria to such a profound level
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I’m mtf, and for me the difference between running on testosterone vs estrogen, is night and day, and I just find it so hard to believe people who don’t experience internal/mental changes with HRT.
Not to say their experiences are not real, just that I find it hard to imagine not experiencing the changes that I experience with HRT. But we’re all so individual so I guess it makes sense.
r/DrWillPowers • u/Excellent-Push2833 • 1d ago
Post SSRI Sexual Dysfunction Syndrome (PSSD) Dr powers I think you may have meant SRD5A1 def due to too much androsterone. NSFW
gallery
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We think the massive PAM pool is downregging SRD5A1. I have never ever nor have i ever needed to shave my armpits
Crashed for the first time when i was 13-14 somewhere around there
r/DrWillPowers • u/stokanch • 1d ago
Post SSRI Sexual Dysfunction Syndrome (PSSD) I need help
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Hello everyone, I want to share my story and ask for your advice regarding CDG. I'm 22 years old, a man from Belarus. This text will be translated by AI, so I apologize in advance for any errors.
First, I want to describe who I was before this illness, and then what triggered it and what my symptoms are. From early childhood, I had OCD — it wasn't severe, and I didn't even understand what it was, until it worsened at age 16. My father also has OCD; as long as I can remember, I noticed various rituals in him but didn't understand what it was back then. But I didn't treat my OCD after it worsened — at the time I was sure everything was fine. I won't go into details, but I managed to control it within a year without medications or medical intervention. Like many of you, I also had a high libido. I was an extremely anxious person, but despite all that, I had a wonderful life — I felt physically and psychologically relatively healthy, I exercised, had a good position at a good workplace, everything was going very well for me, until the moment I started taking isotretinoin (Accutane) for moderate acne.
After that, I developed severe insomnia, and in general I felt very bad physically and mentally. At that time, my OCD somehow disappeared, even though I felt terrible — I had anxiety and slept only three hours. I also developed premature ejaculation, although I had never had anything like that before. But it was as if I didn't even have the ability to fixate on anything. I tried to continue the course until the third month of taking it, since everyone said these were made-up claims and that an acne medication couldn't cause such side effects. In the end, I stopped the medication on the third month on my own, because I understood that I wasn't the cause of this state — the medication was.
After that, I waited a month, but the insomnia still didn't go away, so I went to a psychotherapist for the first time. He prescribed me sertraline 50 mg, and after three weeks of gradually starting the medication, I began sleeping normally. My sleep was also accompanied by constant vivid dreams. Overall, I started feeling normal — the premature ejaculation turned into the opposite, where I couldn't finish for a long time. I hadn't known about this wonderful property of SSRIs before. The anxiety also went away, and for the first three or four months I simply enjoyed the calm.
Then, in the 5th month, I realized that something seemed to be missing in life, that something important had disappeared. And then I understood — my emotions were gone. I realized I was doing everything mechanically and felt like a robot. Also, during the medication, my OCD didn't return (I pay attention to this because maybe the nature of this illness can show what exactly is wrong with me right now). And so, after 6 months of taking it, I finally stopped the medication, thinking that everything was over and that I just needed to wait a little and I would return to my baseline. But that never happened.
For the first month and a half, I had brain zaps and an unclear state of well-being that constantly changed. At the four-month mark after stopping, I realized that my emotions were taking too long to return, for some reason. Also, during the medication, I lost my orgasm — finishing became purely mechanical. I thought it would pass after stopping, but everything remained the same. I also developed a strong brain fog, memory problems — I feel like I have dementia. The number of my thoughts has greatly decreased, as if — I can still think, but my brain seems to be atrophied and thoughts just leak out of my head and can't stay there for long. My premature ejaculation also returned to roughly the same degree it was after Accutane.
My sleep feels very unclear — I still have vivid dreams every night, the boundaries of sleep are completely absent, as if. I understand that I slept only because I remember a dream, but mostly I feel as if I didn't sleep at all. It's quite hard to put into words. I also noticed a number of other minor symptoms: I have poor perception of cold and heat, and temperature changes as well. My body's sweating is greatly reduced, although before I could sweat heavily. Alcohol and other things like energy drinks don't affect me. At most, I was able to feel the effect of alcohol at 5% once (I remember during SSRI use I also drank heavily once, but I was about 40% as drunk as I used to get before the medication).
Also, when I say I don't feel emotions, I mean I don't feel either positive or negative emotions. I can't experience joy or sadness at all. I also realized that I don't feel any stress or worry — just complete emptiness.
It's already been 7 months since I stopped the medication, but the doctors I've seen don't understand at all what's happening to me and only offer me new SSRIs, which I definitely don't want to take. I had tests done, but there's nothing severely abnormal there. I had low vitamin D, but it was low even before I started taking Accutane. I corrected it to optimal values, but it gave no result. I also have low vitamin B9, but taking methylfolate doesn't change my condition at all.
I also recently reviewed my tests and remembered that my progesterone was 1.4 nmol/L, while the lab's norm is up to 0.474. I don't understand objectively whether this is high, because different labs have different norms, and I don't quite understand how to objectively determine whether it's high. I thought this analysis mattered only when I read this subreddit and heard about Dr. Powers' theory. For some reason, I believe very strongly in this theory — it seems to explain all the symptoms I feel, and also explains why people suffering from PSSD aren't helped by dopaminergic drugs or serotonin regulators, which many have tried and also didn't succeed with.
I would like to ask those who understand how CDG works to explain it in simpler language, so I understand what I'm dealing with. Many people write that it lowers dopamine and the amount of sex hormones and so on, but what I've read and tried to find out says that it only helps excrete processed metabolites, and I don't quite understand how it works because of that. Also, if you have any other advice about what can be done, I would be very glad to hear it.
In addition, I want to say a HUGE THANK YOU to Dr. Powers. Quite recently I was in very strong despair and thought that I would hardly be able to change my condition in my lifetime. But after I learned that such a doctor exists and saw what he does for all of us, hope settled in me that I had been missing so much. I truly admire you — people like you, doctor, I think there are very, very few. You give all of us that very hope that is so lacking because of all this. For some reason, I'm sure you will find the problem of our ailment. I am immensely grateful to you for your work.
r/DrWillPowers • u/Longjumping_Neat5090 • 1d ago
MTF HRT Medical Question / Discussion Alternative to suppository progesterone? Any advice is appreciated, having issues with medicating because of ADHD.
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Hi, Im Itzel. I'm 27 and I've been transitioning mtf since 2023. I started at a low mono dose of oral estradiol for a few years, and switched to injections in late 2025. Then, about two months ago I also got on 100mg bio identical prog.
I started prog specifically with the suppository method in mind. However, the longest stretch I've been able to consistently take it as a suppository was for about two weeks. I have ADHD and sensory issues, and I have a job with a pretty chaotic schedule. I dont have a consistent bedtime or nightly routine. I have external hemorrhoids and sensitivity around my anus, so even using lubricant the whole process is pretty uncomfortable (and lubricant just adds to sensory issues). So, I've been missing a lot of days and when I do remember I usually take it orally.
Is there anyway to get a dose as effective as suppository through another method? The days/weeks I've been able to take it suppository, I think I really notice a difference. One thing I noticed for sure was a relief to my sensitive gut issues, and emotional stability. I do still feel like I've been seeing effects overall, but I just want to;make sure I'm taking it as effectively and consistently as I can. Thank you all!
r/DrWillPowers • u/46XX_ • 1d ago
MTF HRT Medical Question / Discussion COMT method with endogenous estrogen?
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Hi!
Does anyone know how to adapt the current methods to fix slow COMT while having endogenous estrogen?
Because all methods involve stopping hrt for some time, and my DR won't prescribe me blockers again :/
So im not rly sure how I can test it rn
r/DrWillPowers • u/the_practicerLALA • 1d ago
Post SSRI Sexual Dysfunction Syndrome (PSSD) If you are taking iron supplements please let me know what you are taking please
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I started liposomal iron powder and today I feel tingling sensations Ive had these rarely before too....Im 21 months PSSD wondering is it safe for me to take Iron who is taking it
r/DrWillPowers • u/JuckJuckJuck • 1d ago
Post Finasteride Syndrome Dutch Test Results
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Hey friends, would love your help interpreting these results. I am a 45 y/o male, 2 years with PFS; I used oral finasteride and topical minoxidil with very mild side effects for years, which would cease if I stopped taking the drugs. 2018-2022ish. I began to observe worsening of symptoms in '22, which was when I stopped finasteride but continued minoxidil. I found a combo pill of dutasteride and minoxidil in fall '24. Took the plunge, immediate consequences. Haven't been the same since.
I've enjoyed every symptom that's been discussed; mercifully, not all at once. They seem to ebb and flow. At the moment, there seems to be a panic/anxiety just below the surface, that frequently rips me out of sleep. I have worsening glans numbness and anorgasmia. I've not had many windows, maybe 2 or 3. I'm a bit older than some of the cases I see here, for all of you in your 20s with this - you all have my deepest sympathy. What a rotten thing to go through. Physically, at 42/43, I was still a competitive athlete and cyclist. Now, lifting and exercise has become a necessary burden; I can't describe how bad I feel if I miss a day, which is extremely difficult with kids and a demanding job.
Ok. Happy to answer any questions, so grateful for this sub and for Dr. Powers and his practice. It's real and meaningful hope for any kind of resolution on something other doctors will tell you doesn't exist.
r/DrWillPowers • u/Adventurous_Lie2188 • 2d ago
My CDG experiment and potential crash
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I've been dealing with PSSD since stopping Vortioxetine on april 2025. Since then, I have zero libido, ED, and a bit of anhedonia. I've always been able to manage relationships since I was able to get erections with cialis and stimulation (more mechanical since I have no desire).
Since I'm a UGT2B17 delete, I wanted to give a try to CDG. So I did CDG for about 10 days, starting with 500mg daily, and got up to 1000 mg daily. I stopped CDG last week because I got sick, some kind of a flu (first time in 18 months). Since stopping CDG, I'm not able to get any erections, even with cialis and I'm kind of depressed / anxious. I don't know if this is due to the virus I got or a crash from CDG... I'm starting to panic because I just started a new relationship which is wonderful but I cannot have sex anymore...
Is a crash from CDG permanent or temporary? Will I be able to get back to my baseline? Any solutions to get back to my baseline?
r/DrWillPowers • u/AmazingName100 • 2d ago
Generic prescription medication doses are not always accurate when compared to brand name doses?
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Something that might be worth considering, especially with the current medication shortages.
According to this:
https://youtube.com/shorts/rIx3qePMaK4?is=n4scR2y1Qq8a8Zbm
If you took a brand name prescription consistently your dose would have remained the same. If you were swapped to a generic medication the dose can vary up or down by up to 25%. The video refers to ADHD stimulants but is this true for all prescription/generic medication?
Might it be possible some people with PFS/PSSD were getting fluctuating doses, rather than maintaining a dose that's consistent? If so, could this have been hard for our bodies to adapt to (long term patients) or given people a higher dose than expected as a starting dose? (one pill cases)?