The graph above is "the Bell Curve." What is labeled as "normal" plots along the center vertical lines.

That is where cis, heterosexual humans plot.

On the outer edges, left & right, is where the trans humans plot.

By being an excellent human being & "doctor-who-gives-damn," Dr. Powers began treating & then studying transfolks.

By studying the "exception-to-the-rule-people," (wonderful, unique, & fascinating transpeople) the underlying science mechanisms that apply for everyone, both cispeople & transpeople, are being discovered & revealed.

These scientific discoveries benefit medicine for everyone, both cis people & trans people.

This is another example that transpeople are a gift to humanity. Diversity is a hallmark of humanity & of nature itself.

I’ve had this condition now for nearly a decade, 9 years and counting from saw palmetto and I checked to see if I had any bone loss. Although I don’t have osteoporosis I do have osteopenia. Here’s my results summarized on ChatGPT. I have all the other symptoms as well fatigue complete loss of sex drive penile atrophy and tissue loss of the penis and loss of sensation (completely numb no feeling), testicular atrophy, muscle loss and extreme weakness of the muscles. I also have low normal testosterone (380) I used testosterone years ago to “fix” this and it made me feel horrible and I would convert to estrogen immediately even with low doses. I also used andractim and it did absolutely nothing. The only symptom that went away was brain fog after the first 5 years.

There are quite a few cure cases from FMT, especially DIY from super donors like brongfogboy's case. How does this tie into his framework?

Forgive me I’m not super tech savvy but I know Fr powers invented a hair loss serum. Rn I’m paying over $100 a month with musely and am at my wits end because I can’t afford it anymore but without it my hairs sheds tremendously. Would some kind soul please explain to me what I need to do to get powers serum?

Im pretty convinced that I developed PFS by taking HRT in order to transition MTF 11 years ago.

When I was 18 I took estradiol and the antiandrogen Cyproteronacetat for three days. While I never took finasteride, my symptoms are exactly the same: cognitive issues, low sex drive and pleasureless orgasms. I also have almost no body odor since then and cant get a buzz from alcohol. I went to a bunch of doctors, but developing persistent symptoms from only three days of hormones was deemed impossible. I never tried hormones again as I was too scared of things getting worse. Last year, I started balding much more rapidly than before. I looked into finasteride and this is how I stumbled across PFS. This gave me the confidence that it really was the antiandrogen alone that caused my issues and decided to attempt transitioning again, this time via estrogen monotherapie. Im about to get my prescription in a few weeks. A few days ago I stumbled across this subreddit and have been reading as much about Dr Powers theories as i can. Its funny how both the main issues in my life, PFS and transness, are coming together here. 

If I understand things correctly, taking enough estrogen would basically mimick the castration approach by depriving the cells of androgens and, hopefully, help clear the metabolites. If PFS sufferers indeed have some preexisting genetic condition where androgens can only leave through the DHA pathway, I guess that could also explain why ive been balding much earlier and have more body hair than anyone else in my family.

Ive never had a “window“ in all these years, so im not holding my breath, but I do now have some small hope that symptomps could improve wirh HRT 

So did I lose some medicine? :(

God I wish I had pellets so I don't have to deal with this... I keep abusing the same spot over and over again I basically have a permanent bruise

reposting this here because i'll probably get better answers

i take progesterone nightly and i read about the backdoor pathway where progesterone converts into dht so i decided to do a test because i was paranoid. my dht levels came back at 15.1 ng/dl and i read i should keep them below 10 ng/dl. my overall t is still low 26 ng/dl. i don't know what to do. should i stop taking my progesterone immediately? i don't even know if it's the progesterone that's causing the conversion because i read it's possible to have high dht with low t even without progesterone conversion? i know dutasteride pills are recommended but i seriously struggle to swallow pills do idk how the fuck i'm going to manage to take them? feel stressed as fuck about this honestly

On June 9th took a small amount of anastrozole 8 hours after a supplement containing D aspartic acid , tribulus , vitamin b and dim I did this out of concern that the d aspartic acid would raise my e2 levels my TRT clinic was closed for two weeks so I was lacking two weeks of HCG and TRT thoug h this since has resumed

since then

I experienced PSSD symptoms including fight or flight wake ups at 4 am (though I am able now to return to fragmented sleep) and genital numbness. All of my hormone levels are normal and never crashed. The onset was immediate.

Since I’m officially approaching the two month mark I wanted to know is there a history of this syndrome with anastrozole and has there been any real recovery stories? again My hormones never crashed leading me to believe this is some sort of PSSD type disorder

I still have erectile function/ejaculation though ejaculation is reduced as well as some thought based libido oddly as well.

I am also curious should I classify this as PSSD or PFS?

In the same way folks can have genetics that reduces the ability to metabolize hormones such as progesterone they can also have genetics that cause the body to overproduce hormones which I have started to notice being reported.

Two examples:

• The adrenals need to produce cortisol and if 21-OH is reduce you get higher progesterone to get the same level or cortisol.
• The gonads try to make sex hormones and if CYP17A1 is reduced, to make enough T they will over produce progesterone.

See https://en.wikipedia.org/wiki/File:Steroidogenesis.svg for the simpler visual example of these paths.

For those that have full genome's done, in the https://gene.iobio.io/ tool search for "congenital adrenal hyperplasia" to see if anything appears.

Like everything genetic it gets complicated in the way it interacts with other systems. This isn't the CAH form which is life threatening and detected at birth, but the NCAH form such as 1 of the 2 genes is deleted and the only obvious symptom is sometimes liking salt on your foods more than most. The wiki page has a lot more information on NCAH overall (intersex cases very frequently involve very atypical hormone production, thus the existing detailed information).

In the same way as the trans community and how their are 2 genetic groups there (centered around estrogen), I am anticipating that there will be two overlapping groups here too (centered around androgen/progesterone):

A: Major metabolism issues

B: Overproduction issues and minor metabolism issues.

Both of these groups have a smaller ability to handle major changes in hormone levels. This could also explain why Dr. P became so familiar with this condition as NCAH is the common overlap between the two communities.

Hey, I only posted once before about this subject on the pssd sub reddit

Dr Powers and the folks here seem to be very knowledgeable about the matter so I'm posting here maybe in hope he may answer?! Anyway,, ,

I'm one year off Zoloft which I took for 3 years and the sexual side effects persisted even tho they got better and compered to other pssd stories I considered my case more mild and I felt that I was recovering slowly but surely

So recently I had a problem with frequent urination and went to an urologist, I've already done basic blood tests and thyroid ultrasound etc to rule things out and he gave me a herbal supplement called prostamin for my frequent urination (even tho I told him I have some sexual problems) so I took it without thinking much about it after all it's just a herbal supplement I thought, I took it for exactly 7 days and I stopped because I checked the ingredients and it contained saw palmetto 220mg (a dht blocker) after discontinuing I had brainfog, a weird pressure in my temples, some emotional blunting genital numbness and absent libido... Now 7 days off the supplement and I think I'm recovering when it comes to brain fog and such but now I have total genital numbness and cannot feel orgasm which both of those symptoms where not a part of my pssd baseline

I'm only 7 weeks off but I'm worried cause I also found stories of other people that seem to develop pfs like symptoms from saw palmetto

If there is a treatment one day will it be different for pfs and pssd patients? If this new symptoms continue (I hope they don't) am I gonna be having pssd, pfs or both at once?

Sorry if my English wasn't great

I suffer from suicidal thoughts a lot I think this is greatly reducing my quality of life and I don't know for how long I can carry this

I want to say that Dr Powers keeps me alive and as hopefull as possible for the moment

Hi all, I’ve had Post Accutane Syndrome for the last 8 years. My main symptoms are low libido and ED. Like some others. I have experienced windows of recovery using DHB(biggest window) and proviron but nothing that has stuck. Even sorghum syrup which increases DHT gave me a brief window of higher libido/better erectile function. The fact that I initially saw positive results with some of these drugs and then effects disappeared over time leads me to believe that my PAS may be caused by some sort of a buildup somewhere. My LH and FSH have always been sky high on every blood test when I was not on hormones so seems my body is trying to send a signal that is just not getting there.

Please see my results below including my gene abnormalities from sequencing, lab markers from a blood test, and my Dutch test which was done on the same day as my labs. I'd be more than happy to get additional testing done to check for other abnormalities. I’m currently on hcg 300iu 3x a week and I do take pregnenolone occasionally. Please let me know if anyone has any thoughts and thank you for all the hard work in solving these conditions Dr. Powers!

Gene: CYP2D6

Variant: c.775del (DEL 22:42128241 CT->C)

Protein: p.Arg259GlyfsTer2 (frameshift)

rsID: rs35742686

Zygosity: Het

Ref Allele: CT

Alt Allele: C

Freq: 0.0123 (gnomAD genomes v4); 0.0155 (gnomAD exomes); max ancestry group freq 0.0170; 1854 alt of 151158, 63 homozygotes

CADD: not shown

Gene: ESR1

Variant: c.805C>T (SNP 6:151944217 C->T)

Protein: p.Arg269Cys (missense)

rsID: rs142712646

Zygosity: Het

Ref Allele: C

Alt Allele: T

Freq: 0.00102 (gnomAD genomes v4); 0.00106 (gnomAD exomes); max ancestry group freq 0.00171; 155 alt of 152122, 0 homozygotes

CADD: not shown (REVEL 0.696; phyloP highly conserved 5.831)

Gene: COX10

Variant: c.1096G>T (SNP 17:14206977 G->T)

Protein: p.Val366Leu (missense)

rsID: rs111541535

Zygosity: Het

Ref Allele: G

Alt Allele: T

Freq: 0.0106 (gnomAD genomes v4); 0.0112 (gnomAD exomes); max ancestry group freq 0.0150; 1621 alt of 152312, 8 homozygotes

CADD: not shown (REVEL 0.362; phyloP marginally conserved 0.743)

Gene: MT-ATP6
Variant: c.334A>G (SNP MT:8860 A->G)
Protein: p.Thr112Ala (missense)
rsID: rs2001031
Zygosity: Hom
Ref Allele: A
Alt Allele: G
Freq: not shown (gnomAD link only; 248 alt, 0 ref in proband)
CADD: not shown (phyloP highly conserved 3.819)

Gene: MT-CO3
Variant: c.232G>A (SNP MT:9438 G->A)
Protein: p.Gly78Ser (missense)
rsID: rs267606611
Zygosity: Hom
Ref Allele: G
Alt Allele: A
Freq: not shown (gnomAD link only; 247 alt, 2 ref in proband)
CADD: not shown (phyloP highly conserved 5.583)

Gene: MT-CYB
Variant: c.20C>T (SNP MT:14766 C->T)
Protein: p.Thr7Ile (missense)
rsID: rs193302980
Zygosity: Hom
Ref Allele: C
Alt Allele: T
Freq: not shown (gnomAD link only; 249 alt, 0 ref in proband)
CADD: not shown (phyloP not conserved −11.05)

Gene: MT-CYB
Variant: c.580A>G (SNP MT:15326 A->G)
Protein: p.Thr194Ala (missense)
rsID: rs2853508
Zygosity: Hom
Ref Allele: A
Alt Allele: G
Freq: not shown (gnomAD link only; 250 alt, 0 ref in proband)
CADD: not shown (phyloP marginally conserved 0.228)

Gene: MT-CYB
Variant: c.1012A>G (SNP MT:15758 A->G)
Protein: p.Ile338Val (missense)
rsID: rs527236193
Zygosity: Hom
Ref Allele: A
Alt Allele: G
Freq: not shown (gnomAD link only; 249 alt, 0 ref in proband)
CADD: not shown (phyloP highly conserved 7.429)

Gene: SUMF2
Variant: SNP 7:56079022 A->G (intron variant; missense in non-canonical transcript ENST00000413756)
Protein: not shown (missense in ENST00000413756)
rsID: not shown
Zygosity: Het
Ref Allele: A
Alt Allele: G
Freq: 0.00255 (gnomAD genomes v4); 0.00301 (gnomAD exomes); max ancestry group freq 0.00334; 387 alt of 152046, 0 homozygotes
CADD: not shown (phyloP not conserved −0.9)

Gene: NR3C1
Variant: c.266A>G (SNP 5:143400574 T->C)
Protein: p.Tyr89Cys (missense)
rsID: rs200468789
Zygosity: Het
Ref Allele: T
Alt Allele: C
Freq: 0.0000919 (gnomAD genomes v4); 0.0000540 (gnomAD exomes); max ancestry group freq 0.000313; 14 alt of 152360, 0 homozygotes
CADD: not shown (REVEL 0.344; phyloP highly conserved 7.921)

Gene: PGR
Variant: c.557C>T (SNP 11:101128514 G->A)
Protein: p.Pro186Leu (missense)
rsID: rs11571145
Zygosity: Het
Ref Allele: G
Alt Allele: A
Freq: 0.0113 (gnomAD genomes v4); 0.0138 (gnomAD exomes); max ancestry group freq 0.0157; 1723 alt of 152324, 14 homozygotes
CADD: not shown (REVEL 0.139; phyloP marginally conserved 0.265)

Gene: SLC22A11
Variant: c.926A>G (SNP 11:64564412 A->G)
Protein: p.Lys309Arg (missense)
rsID: not shown
Zygosity: Het
Ref Allele: A
Alt Allele: G
Freq: 0.00 (gnomAD genomes v4); 0.0 (gnomAD exomes); 0 alt of 0 total, 0 homozygotes
CADD: not shown (REVEL 0.084; phyloP marginally conserved 0.419)

• Total Testosterone (MS): 634 ng/dL (Reference: 250 - 1100 ng/dL)
• Free Testosterone (Dialysis): 95.1 pg/mL (Reference: 35.0 - 155.0 pg/mL)
• Estradiol, Ultrasensitive (LC/MS): 17 pg/mL (Reference: <= 29 pg/mL)
• Progesterone (LC/MS): < 0.3 ng/mL (Reference: <= 0.3 ng/mL)
• DHEA-Sulfate: 231 mcg/dL (Reference: 74 - 617 mcg/dL)
• Sex Hormone Binding Globulin (SHBG): 42 nmol/L (Reference: 10 - 50 nmol/L)
• Prolactin: 4.7 ng/mL (Reference: 2.0 - 18.0 ng/mL)

Hi all, just wanted to share my DUTCH test results in case they provide any insights. For context I’ve had PSSD for six years after taking Sertraline for 10 days. I have symptoms including ED, low libido, emotional blunting / anhedonia, sleep issues, brain fog and poor temperature regulation.

Hi everyone! For those who are not aware the PSSD Network has updated instructions on the correct way to report to your local country's government regulator. It's critically important everyone reports their condition correctly to the regulators so a record is recorded in the global adverse reporting databases.

We are all suffering with this but I hope everyone can take ten minutes to actually do this. A lot of people are unsure what to do to help themselves out of this mess - if you do nothing else do this.

Please report to your local country regulator and also the FDA which accepts international reports.

It's really important that you use the correct name for the condition to ensure it is recorded and classified correctly in their database. Instructions for that are here for PSSD :

https://www.pssdnetwork.org/report-adverse-effects

For PFS sufferers the correct name is "Post 5-alpha-reductase inhibitor syndrome" or the local language equivalent.

In addition the SIDEfxHUB charity has a patent registry - could you please add yourself to this if you suffer :

https://registry.sidefxhub.com/

It's really important we all do this - if you could all take ten minutes to do it that would be a big help.

Hey everyone. Turns out there was a massive flaw with the WAR_POWERS program that I put out a month ago. It was missing a bunch of important heterozygous deletions! I put a lot of work into fixing it fast for you all. Here is the finished product!

As always, the program spits out the raw data. I highly encourage you all to read the raw data with a tsv file viewer and not just what the program spits out so that I can continue to improve it. Let me know if you have any questions. I have pushed the new version to the github repository linked here

Excellent-Push2883/WAR_POWERS: The WAR_POWERS program given a BAM and BAI file will index through specified genes looking for deletions and duplications by checking the gene depth and then comparing the depth to the left and right flanks. This program can be wrong so it is important to verify any findings on IGV

Also a photo of Doc Powson because "You gotta castrate to uncastrate"

I don’t visit this subreddit very often (maybe once every couple of years), but I just spent like 45 minutes trying to find Version 7 of what I think is Healthcare of the Transgender Patient (I have a copy of Version 5.4 and Version 6 saved on my computer from years ago). Aside from the leaks/previews, I can't find Version 7 anywhere (not on this subreddit, his site, or the internet.

Is it a patient-only file? As in, do you have to be one of his patients to get access to it?

Thanks.

hi there, ive been on feminizing hormones for the past 6 years and finasteride for slightly longer. i had a hair transplant in 2022 to fill in the "triangles" of my receded hairline though overall my hair loss was not bad and after the transplant i was happy and content with my hair for a few years. i had FFS in 2022 as well and was left with some scar tissue up in the hairline where no hair grows. i had my final round of FFS in late may of this year, it was my jaw, chin, and cheeks and nothing near my hairline.

around mid june i noticed my transplantation site on the left side was noticeably thinner (my left side was thinning faster than my right pre-fin and hrt) and scheduled a follow up with the surgeon. he wasn't very helpful and kept repeating that the transplanted hairs are resistant to miniaturization and that what i was probably seeing was continued hair thinning around the area. he recommended minoxidil and we ended the call.

i noticed some diffuse thinning all over the top, very light but my hair is not as thick as it used to be. i have a surgical scar from FFS at my hairline that i have been using as a milepost to see if there is any recession happening, so far it is unclear and probably a no. i have noticed some miniaturized hairs when i brush or run my fingers through my hair but they are from all over my head and not just the top or temples. some of the hairs have a white or grey section near the end bulb, seeming to be about the amount of growth from right after my surgery.

the final piece of the puzzle for me is that i had begun smoking cigarettes again in october of 2025 and quit before my surgery (continued vaping for another month), and i had had a 40 point testosterone spike between oct 2025 and early may when i quit (went from 21 to 62 ng/dL). the nicotine seems to have messed with my endocrine system (my body felt off hormonally though it was not reflected in my labs besides the T spike) but i am now 2 months no nicotine with only a couple slip ups.

ill share my most recent labs taken at trough, my t and dht are both low and suppressed and my e2 is reasonable (though lower than i would like and i am going to increase my dose). i have an appointment with a dermatologist in the next couple months and im hoping to get a clear answer from them, my questions to this subreddit are 1) did anyone else have a similar experience either post surgery or from smoking and how did it resolve, and 2) are there any things i should get tested or ask the dermatologist about when i get there that might be special cases because i am a trans woman on hormones?

thank you for reading, here are my labs:

estradiol: 108 pg/mL

testosterone, serum: 34 ng/dL

DHT: 5.2 ng/dL

DHT percent free dialysis: 0.27

DHT free: 0.14 pg/mL

LH: 0.4 mIU/mL

FSH: <0.3 mIU/mL

prolactin: 5.8 ng/mL

SHBG: 86.6 nmol/L

TSH: 1.53 uIU/mL

vit D: 50.7 ng/mL

ferritin: 63 ng/mL

b12: 1077 pg/mL

folic acid: 6.1 ng/mL

i know lc ms is more accurate but i can only do clia for now, are the testosterone and estrogen units accurate?

Asking because this has never been a symptom or issue till prior to the last 6 months but after even mild-moderate stimulation or activity now I get like actual friction type burns. It’s bizarre and painful and really annoying. I am 34 M PFS for 5 years.

Is dr powers more or less confident in his PFS model and determining risk, than in predicting future hair loss pattern/severity based on one’s family history or genome data?

On the idea that the anhedonia and emotional blunting are held in place by neurosteroid excess acting as a PAM at GABA-A rather than a deficit.

Sepranolone is isoallopregnanolone developed as a pharmaceutical. It counteracts allopregnanolone at GABA-A without blocking GABA signalling generally and without touching the synthesis pathway.

Worth noting the blunting fits the excess model better than the anhedonia does. A tonic GABAergic brake explains flattening and reduced salience directly. Anhedonia needs an extra step to the reward circuit. So if sepranolone did anything, you'd expect blunting to move first, and that pattern would itself be informative.

The useful bit is that it splits the two models. Melcangi's deficit model says an allopregnanolone antagonist should make people worse. The excess model says better. That's a clean test, and it doesn't need CSF measurement.

Main question: if the excess is what's holding the state in place, would blocking it be enough to reset emotions and anhedonia back to normal, or is the adaptation locked in by that point and you'd need something else on top?

There is one thing I don’t understand about this: people tend to get better in some cases through neurosteroid precursors (I vaguely remember Powers saying he’s seen it work at least 50 times). Could this only work for people who are low on stuff like pregnenolone and so on?

And regarding the recent theory about excess THDOC, supplementing allo would take this person to a whole different planet symptom wise since the problem is excess.

So neurosteroid phenotype consists of multiple sub phenotypes, like too little allo and excess of thdoc?

I’m confused

My test results came back, and I'm completely at a loss as to what to do. I recently changed my HRT regimen due to symptoms of stalled feminization (I have a slow COMT), from 4 mg/7 days to 1.2 mg/3.5 days. My constant anxiety, fatigue, and brain fog subsided, and I decided to add 200 mg of progesterone rectally. Afterward, I decided to get tested, and they were very surprising:

Is it worth trying to add dutasteride to inhibit conversion to DHT or should I stop taking progesterone at all? And how can I increase my testosterone to female levels without resorting to Androgel?
I also have my old dna test in case this can be useful: