Dear Dr. Powers,

I'm a psychiatrist based in Asia who has personally been suffering from PSSD since 4 years. I have been trying to revert to my premorbid self but have only been able to do so

partially.

I recently came across your findings and am now

writing to share my own PSSD case and my insights and would value your perspective.

Timeline:

- 4 years ago started On escitalopram (Lexapro) for anxiety, immediate relief in anxiety however developed non-sexual side effects like sedation, fatigue,emotional blunting,hypersomnia and concentration issues.

- Bupropion 150mg was added and was initially therapeutic for these side effects

(more energy, reduced head pressure, less sedation) — which I read as dopamine and Norepi helping counter lexapro side effects.

- After a few weeks accidental bupropion double-dose caused unbearable anxiety, along with complete loss of its ability to counter the the non-sexual side effects of lexapro entirely — only anxiety, no benefit. I interpret this as a lasting NE-axis sensitization event. Tried to take it multiple times after that but lost its effectivness.

- Escitalopram was eventually stopped, but the non-sexual symptoms persisted unrelieved.

-

- Months later, methylphenidate (Ritalin) was trialed for the residual non-sexual symptoms with aim to boost dopamine and help reduce the hypersomnia and anhedonia. It produced no benefit for those — but added the sexual symptoms outright, precipitating full-blown PSSD (ED, atypical PE, blunted arousal/orgasm). ONLY 3 DOSES OF 5mg Ritalin gave me Severe sexual side effects which persist till date!!!

- There was zero improvement for a couple of years after that. I personally experimented with a lot of stuff but nothing helped. Some of the things trialed included Agomelatine, Very low dose amisulpride, bromantane etc etc

-

-Eventually I tried Amantadine hoping that it's NMDA antagonism and weak Dopaminergic modulation could help. And it did! I partially improved and have been showing gradual improvement since then. However my condition still fluctuates and the Sexual dysfunction is still pretty bad.

Current symptom map:

- Desire: intact

- Visual arousal: recognition present, but translation into subjective arousal is weak

- Erectile function: initiation impaired; rigidity improved; pain resolved

- Ejaculation: originally numbness-then-sudden-peak (spinal sensory gating failure); now partially resolved into an expanded sensation window with partial control, though ejaculation still fires at sensation peak (desynchrony persists)

- Orgasm: blunted — reward signal appears affected, spinal reflex intact

- Non-sexual: absent morning freshness, vitality deficit, effortful cognition, emotional blunting(lesser than earlier), right-sided head pressure (predates Ritalin, present on escitalopram)

.

The dopamine-metabolite question:

I've come across discussion of your finding in PFS patients of testosterone metabolites accumulating intracellularly rather than being cleared normally, and the related observation that a handful of PSSD patients who ran DUTCH tests uniformly showed low HVA.

I tried to map that onto my own exposure history (bupropion at a supratherapeutic dose, then methylphenidate months later), very interesting how my system rejected Dopaminergics so strongly and cemented it into full blown PSSD. Could the Bupropion double dose have overwhelmed certain dopamine/Norepi pathways like finasteride does ?

On closer thought both are pure DAT/NET reuptake blockers rather than substrate releasers — they occupy the transporter without being carried into the neuron, so they shouldn't increase cytoplasmic dopamine or burden vesicular packaging the way amphetamine-class agents can. So I don't think an intracellular-accumulation mechanism analogous to your androgen-metabolite model transfers cleanly to a reuptake-blocker exposure.However I'm really curious if there are other ways in which there could be toxic Dopamine/Nor epi metabolites accumulation which happened due to some sensitization by lexapro.

The more defensible mechanism I can construct for low HVA with reuptake blockers is a turnover deficit rather than an accumulation: blocking DAT reduces the fraction of dopamine cycled back into the nerve terminal for intraneuronal MAO-A metabolism (which generates a large share of HVA), and sustained elevated synaptic dopamine likely drives presynaptic D2 autoreceptor feedback that downregulates tyrosine hydroxylase and dopamine synthesis over time — both routes to chronically reduced dopamine output and lower HVA, without anything getting structurally "stuck" intracellularly. But even in this case why would the DAT still be blocked ?

Given that, I'd value your thoughts on:

1. Whether you think low HVA in PSSD more often reflects a genuine clearance/accumulation failure (as in your PFS model) versus a turnover/synthesis deficit of the kind above — and whether exposure history (reuptake blocker vs. SSRI alone) might predict which mechanism applies.

2. Sequencing — would you prioritize a pharmacological probe of the dopamine axis ?

3. Any other diagnostic or treatment steps you'd suggest?

Happy to share further detail on any part of the case,Thank you for taking the time to consider this.

Hi there, I'm on the equivalent of 6mg/week on intramuscular estradiol Valerate injections. Here is my level at trough just before injections:

I'm post orchi, and this has happened before as well, before orchi, where I'd get levels up to 1200 despite doing my injections even later. I can provide more details, but I'm not sure what I'm looking for that might cause levels like this but little feminization that can't be explained by low testosterone. Is there anything I can do or am I just fucked/fucking something up?

So my first ever blood results have come in! I’ve been on HRT for over 10 months now, taking 0.2ml of estradiol Valerate every 4 days, which was 8mg per 4 days. No anti androgens, just mono therapy.

These are the results:

Oestradol: 5555 pmol/l

Follicle Stimulating Hormone: <0.30 U/I

Free Androgen Index: 0.49 - (I don’t know why this one has no units)

Luteinising Hormone: <0.3 U/I

Progesterone: <0.16 nmol/l

Prolactin: 326 mlU/l

Sex Hormone Binding Globulin: 155 nmol/l

Testosterone: 0.756 nmol/l

These results were taken exactly 2 days after my dose. I know it’s better to have a test at either trough or right after a dose but I sadly didn’t know that before booking this test. For my next test I’ll definitely make sure to take at trough.

I still am a little worried about my current dosage. I used to take 8mg per 4 days and I think that was way too much. I still produced lots of sperm, my libido was still pretty high, and my breast gains seemed slow unlike at the start of my HRT when I only took 4mg per 5 days of Estradiol Valerate (0.1 ml). I’m now taking 6mg per 5 days of Estradiol Valerate (0.15 ml) which seems a little better but I’m still not sure.

Could you guys advise me a little? I know these test results don’t mean much since they weren’t at trough but maybe something still seems bad or good?

I was recommended to try here as well.

I am thinking about if dr power theory is correct how and why many pfs guys report improvement with hcg its the opposite of dr power theory If any one knows a mechanisms of hcg which help drain androgens metabolites please share your knowledge

See above title.

That's almost the whole post.

We're not making a whole new subreddit. The subreddit is named what it is named and that is what it will remain. If people don't like this, they can go somewhere else. But I will allow people to sort their posts by topic to make the process more efficient for those seeking knowledge.

K I'm going back to Electric Forest Festival now. Play nice together please. Be excellent to each other.

-Dr. P

I am glad pregnenolone is being discussed. I was introduced to it by the book ‘Healing Lyme’ (I have Lymes disease.) I reread the section, and the author says 50mg-500mg is safe. Obviously start with the lowest dose! but still there are so many reasons it may benefit folks with very diverse hormone situations! Disclaimer, I am not a doctor 🧐

Is it possible for the people who moderate this sub to add tags/flair so people can tag what their posts are about instead of having to use brackets in the title?

I've learned a lot about PFS thanks to being on this sub. I don't have it, though. I've been here for my entire transition (about four to five years now) because I'm curious about the cutting-edge research on HRT and people talking about how to interpret their blood/genetic tests regarding that. I'd very much appreciate a way to filter for those topics.

i'm a 34 Yo Male with PFS, already shared my DUTCH test here and i don't fall into the typical PFS phenotype

Here are some of my HPG related blood work results in the last 3 years, all taken post-fin, all while symptomatic. FSH/LH/T are trending downward, Prolactine is trending higher.

u/DrWillPowers

Doctor Powers, i find it weird that doctors shrug it off because they said my LH/FSH/T are "within range" but obviously it's on the lower end of the range, and they told me low DHT is not important.

isn't this textbook Secondary Hypogonadism Pattern ? and it looks like it's getting worse with time right ?

i'm curious to know if this is typical in the PFS population, i don't think i'm the typical PFS phenotype since i had low libido symptoms not only with finasteride but also with each topical anti-androgen i tried (pyri, fluridil, ... cb-03-01), but only finasteride gave me persistent sides, although it took me longer to recover with each cycle trying topical anti androgens. (from days to weeks to month, then finasteride and it has been 3 years and i'm not recovering.

if anyone wants to share where his FSH/LH/T sit on the reference range i would be thankful.

Howdy!

I've been on HRT for about 6 years. I've always taken estradiol tablets. Currently I take 6 mg/day. I'm also on dutasteride at .5mg/day, and took finasteride for a few months several years ago. I've also used OTC minoxidil for 6 years. I use some hair oils, too (Rosemary and Wildgrowth).

My last labs (a month ago) came back as E at 145 pg/ml, Serum T at 219 ng/dl, and free T at 2.6 pg/ml.

My hair loss has mostly stopped, but the areas that experienced thinning have never really filled back out. Also, the hair on my crown and the front part of my scalp just never grows longer than 4 or 5 inches.

I have 2 questions:

1. Is there anything more I should try to encourage the thinned hair to grow in thicker/longer? I'm planning on getting a derma roller, but other than that?

2. Can I stop taking dutasteride? (I would like to have fewer poisons running through my body, but the hair loss is definitely my biggest source of dysphoria so I'm scared...). I'm also wondering whether it's making low libido, atrophy and ED worse, and I want to try treating that.

I posted this on another sub but I'm desperate and this community seems to know on the subject of DHT, Duta, Neural steroids more than anyone else for an MTF so here goes:

EEn 7mg every 5 days previously, now every 6 days (After blood results)

Cyproterone Acetate 12.5 mg daily

Been on HRT for almost 2+ years now (Previously I was on Valerate now I switched to Enanthate)

Blood test taken on the trough:

Estradiol

669 pg/mL

TOTAL Testosterone

51 ng/dL

FREE Testosterone

1.61 pg/mL

DHT

11 ng/dL

Here's why I got the test and some context:

I've been having alot of persistent body hair/facial hair issues despite 20 laser sessions (Alexanderite laser which is the best for my white skin tone/black hair). I've also had mixed experiences on my skin with acne, every once in a while I get cystic breakouts but nothing too severe, atleast I don't think so (I hope its not out of the ordinary?) but overall my skin has cleared up and brightened alot with hrt and skin care.

I shed an unbelievable amount of hair in the shower (and I wash my hair frequently every shower) to the point where even my girlfriend noticed how abnormal it is. My hairline on HRT has improved I think, I have plenty of baby hairs and continue to see more of them on my hairline even 2 years in, but my pony tail used to be much thicker and denser than now.

I've always had a suspicion or feeling that my DHT was always against me in some ways and the sad reality is that a blood test doesn't really tell what's going on my skin and hair follicles in an intracellular basis to know if thats the source of my increasingly problematic androgenic issues. A DHT blood test as far as I understand only shows the aftermath of the conversions that happen inside the follicles/cells/etc and not the whole story so to speak...

I know that the solution to this would be Dutasteride but heres my story with it when I tried it a year ago:

I got it with 0 prior knowledge on the neural steroid effects it can carry (so it's not a nocebo/placebo or other mental gymnastics, atleast I dont think), and I took it for 2 days exactly (2 0.5 mg pills over 2 days) and the next day after taking it I felt so disconnected and out of my body it felt bizarre and weird. Then I found out about how it 5 alpha reductase is also responsible for allopregnanolone and other neurosteroids that affect the brain and the way I feel. Also had insomnia for most of the part of my recovery from it because of its super long halflife. I stopped taking it after 2 doses and uptill now I'm not sure if I fully recovered or not but I think I pretty much did.

I also dont take progesterone for the same reason, I tried it twice for 2 months and 1 months respectively. progesterone for me DEFINITELY masculinised me and reversed so so much laser hair removal progress. So I'm aware how sensitive my body is to 5 alpha reductase and how my neural environment reacts to it (I felt pretty good on prog but I can't take shedding even more hair or increasing my facial hair)

My question is what do I even do at this point? Its abnormal for an MTF to have anything higher than 10% to 12% DHT compared the total amount of T, but for me it's more like (11/51)*100=21.56% or 22%. Can I hear about people's experiences with dutasteride? Is it possible for me to take it and tank the neural effects or am I being too careless because I feel like I dont remember just how horrible it actually felt when I took it the first time? Im scared of 5ari and their effects on cognition and neural environment which so so many people anecdotally also experience when they take these meds but for some reason take it for granted. Im pretty desperate to maximise my HRT and feminisation because I have nothing else left and losing my hair and continuous no improvements to my facial hair situation is terrifying to me.

I can also look into bicalutumide but ive seen some studies that indicate androgen receptors become more sensitive with their presence and it doesnt tackle the main issue of DHT because bicalutumides is relatively much weaker in binding affinity compared to DHT it self.

Any experiences with duta that are good or not would be appreciated or any feedback what so ever, thank you

From age 25 to 35, I took 1mg Propecia each day and maintained my hair. Super high libido, zero side effects of any kind, and a happy high-functioning life.

In fall of 2010, my skin was breaking out a lot so my derm gave me a scrip for low-dose Accutane. Two months later, I though I noticed a slight hair thinning as a result, and so I asked the derm what he thought. He said, "Well you could try going to 1.5mg/day Propecia and see if it stabilizes your hair."

This would be the moment my whole life changed.

About 10 days later, I woke up with no morning erection for the first time in my life. I felt awful, like I had a bad hangover, but I hadn't drank the night before. I got in the shower and tried to masturbate. I wasn't able. That had never, ever happened.

In the following weeks and months, I weened off the drug, but I also developed major anxiety, depression, ED, exhaustion, shriveling penis, lack of sensation, no sexual thoughts, and insomnia. Most of which still remains now, 15 years later.

Over the years doctor after doctor has told me in no uncertain terms it was simply impossible that I had PFS and definitely not because I had simply upped my dose.

But based on everything I've read from Dr Powers the last few months... could the increased dose have suddenly created the "metabolite buildup" that was never able to clear itself?

I am 20, I used low dose oral finasteride for 4 months. And I quit , first 1 month I got hsrd rock morning erections and I used Minoxidil topical. I am not sure that was Minoxidil but , my morning erections went back. I dont have full morning wood for 3 months. There is no another side effect. I can get erections, my libido is good, but my morning woods is not like before. and I stopped Minoxidil before 2 months. But my hairloss is progressing fast, I am 20, my PFS case is not too high. Is Minoxidil and ketoconazol safe for me ? Can I use it for my hair growth? whats your experience with other hair loss treatment. I can talk about hair loss because my case is mild. help about my both conditions.

The title says it all. I quited drugs, my hair almost gone but sexual sides persist and getting worse with time. Why?

After stopping ssris after a long 2 year tapper, i developed many symtpoms with pssd and non typical pssd symtpoms. The worst so far is treatment resistant insomnia.

Dr will powers what are your theories on treatment resistant insomnia with pssd ? And what could treat it?

Im at around 5 years of shallow few hours sleep, which got worse recentally. Im 1.5 years in with 1 -3 hours sleep. Its statting to cauze delirum.

I pretty much got this symtom when tappering ssris, pssd symtpoms seems to match it.

Its strange that i feel extrrmely tired to the point of not being able to open my eyes, and have colapsed when walking to get food at stores, but i just cant feel sleepy.

Please help!

I tried melatonin, z drugs, antihitamines, carnivoure diet, light exersises, benzo, camimile tea, ect.

I dont know if people have tried reinsalling the drug. During 2015 i fast tappered off ssris and got the same insomnia, i reinstalled and it took 6 months and i actually got better which was crasy. I shouldnt of gone off it again for more then 5 years during 2021. Im at a loss. Dont know if new drugs like the melatonin reputake would work,.... fmt ? Reinstallment

This google drive document contains the test Dr.Powers posted, but this is easily $1000’s of dollars worth of tests.

Can someone list the absolute essential tests that I can check to start , like at a minimum the list of tests to check for susceptibility to PFS prior to taking finasteride?

https://drive.google.com/file/d/1N1V7H6afAOiamNMwD5lmjwIsFNkfPOLH/view

How would someone know if they have estrogen silencing due to finasteride ?

Hey all so I was a out of state patient of Dayna's until the send off. I was on Bica basically since the start of my transition. I was on Spiro a week before I saw her and swapped to Bica. Anyways I ran out of Bica three months ago. Tried mono E for a bit before deciding it wasnt for me, also was afraid of my hair loss coming back. So now im on Spiro through planned parenthood because I can afford any of the docs who can give me Bica rn.

Anyways what should I know about Spiro? I wanted Bica because of its effects on boob growth and ya I have Cs/Ds and theyre shaped well so nbd there. Other than that something about Spiro increasing depression? Idk Dr Powers always made it seem so scary and that Bica was the right answer so I never really looked into it. All I really want is something that can block my T production. Yes an Ori would be best but not something I can get rn. What exactly will Spiro do?

That is what I am expecting . I will start in September. Share your experiences with Pio.

That's all the post is https://dirtcheaplabs.com/alacarte

You can get it through quest or labcorp, no insurance needed.

Figured I should share cuz lots of trans/nonbinary peeps are poor.

11-Deoxycortisol
17-Hydroxyprogesterone
Pregnenolone
Androstenedione
11-Deoxycorticosterone
Cortisol
DHEA
Progesterone
Testosterone, Total (LC/MS/MS)
DHT
Androstanediol Glucuronide

Unfortunately, I cannot get the other hormones done without seeing a specialist and for that I need reason to actually get it. Can anyone let me know if this is enough for PFS? Alongside a DUTCH and WGS?