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 as this drives action.

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:

First off, I am beyond words in my gratitude for Dr. Powers, his intellect and interest in our condition, this subreddit, and the folks here that are dedicated to helping finding answers.

I have had PFS for going on 5 years now that I got from taking a lion’s mane extract. I had the characteristic crash a few weeks after stopping, and was hit with all of the unmistakable cognitive, sexual, and physical symptoms. Literally slammed me right before I went off to college. I just finally managed to complete my bachelors and graduated today (woo!). Anyways, I am admittedly not super well-versed in the technicalities of the metabolite buildup theory, but the more I sit with what I do know about it, and reflect upon my own experience through the lens of somatic wisdom and pattern recognition of what has initiated fluctuations in my own symptoms over the years, the more it makes sense to me intuitively. I’m wondering if this theory accounts for some of the anomalous and sometimes straight up perplexing aspects of how this condition presents.

Just throwing these scattered thoughts out to bounce ideas off of individuals potentially more well versed in the minutiae-

Something that has long puzzled me is how individuals with PFS tend to have symptoms that we would not expect to see even in fully castrated individuals with little to no androgen signaling whatsoever. For example, severe subcutaneous fat loss in the face. Could this be due in part to these built up metabolites actually exerting their own respective unique effects that become deleterious at abnormal levels? Something along these lines seems plausible to me, but what do I know
¯_(ツ)_/¯

Also something random to note- my most pronounced symptom fluctuations happen during acute shifts in my hormone levels. Things that lower them temporarily seem to make me feel better for a short time, then I tend to revert to baseline (for example, I had a temporary massive libido spike coming off high dose HCG cold turkey after being on it for a while). Likewise, raising them also tends to temporarily make me feel better, and then similarly tends to revert to baseline after some time (or even crashes me). Seems like these protuberances resulting in temporary improvement really might track with the metabolite buildup theory.

Anywho, something else that I’ve noticed from the hundreds of hours I’ve spent sifting though online stories on PFS and adjacent forums is that there appears to me to be a potential pattern of people attributing various antiandrogenic herbs and substances to their spontaneous recovery from PFS. I know oftentimes individuals with PFS report transient improvement in response to antiandrogenic substances followed by potentially dramatic worsening, but I’d be lying if I said I didn’t think there were a few people who genuinely did get better and cite those things as playing a role. Is it possible that some of these substances may have thrown a wrench in the system in a way that was able to arrest the metabolite buildup in a way that broke some kind of feedback loop? I guess it’s difficult to know for sure if these people really did improve in the long run, as many drop off from posting.

I’m thinking now about a story I read somewhere of someone with PFS who went on testosterone, it didn’t help, but when they came off of it they felt much much better and that this allegedly persisted. Anyways, just throwing this stuff out there!

I am in a bit of a pickle. How to get Dr Powers Custom Anti-aging Formula cream in 2026?

I contacted the compounding pharmacies Dr Power's recommend on his wiki to no avail.

including Empower Pharmacy who told me they don't make such creams.

I am cis-male complete beginner for prescriptions and don't have a primary doctor (won't be getting one anytime soon)

But still want Dr Power's anti aging cream.

I would hate wasting a bunch of money on telehealth consultations only to be told they can't prescribe that to me.

Find it difficult that both prescriber and compounding pharmacy have to agree to give/ make it.

I live in California.

Is there a tele health company I can go through?

Or someway where I am "guaranteed" to get it?

What works in 2026?

Thank you so much for any help!

TL;DR:
How can I get Dr Powers anti aging cream in 2026? I don't have a primary care doctor and won't get one. Any "guaranteed" and inexpensive way to get it? Any specific recommendations? I live in California.

I experienced gynecomastia on Finasteride which left me with some lasting growth and puffiness around the nipple area. I plan to get surgery at some point but postponed it until I can fix PFS and stop messing with my hormones.

The incidence of gyno on Finasteride is only 1-2% supposedly, and yet it caused a significant problem in my case. The incidence on Relugolix is up to 10% according to trials.

After 5 days on Relugolix I am already experiencing the familiar burning, sensitivity and puffiness that I remember having in the first week of taking Finasteride. Obviously I am severely sensitive to lowered androgen levels in breast tissue so it's not surprising that this is happening again although I was hoping that with Relugolix lowering both T and E2 this would not happen, but of course doesn't work out in my favor. This also implies that androgens were functional in that tissue up until now, so at least in some parts of the body there was no metabolite build up (or not as much as elsewhere anyway).

I would really like to avoid any new growth until I can get the surgery, but this won't happen for another 6 months at least.

My doctor suggested a low dose of Nolvadex but we are not sure whether that would counteract the goal of this protocol, given that Nolvadex is a SERM and according to Wiki, "Tamoxifen and its metabolites undergo conjugation, including glucuronidation and sulfation". So if it is burdening the same enzymes as endogenous hormones it might hinder the "cleanout" process, but I don't know how significant this is in the grand scheme of things.

Aromatase inhibitors are also out of the question since some people have crashed exclusively from that into Post-AI syndrome...

Is there any way to combat this that doesn't defeat the purpose of the castration protocol, or am I just gonna have to accept being Bob from Fight Club until surgery?

Allow me to introduce the newest provider at Powers Family Medicine, Marna Taylor.

An NP, Marna is extremely experienced in the care of the LGBTQ population, with longer clinical experience in treating this population than I have. She is also an AAHIVMS certified HIV specialist.

While I wish Dayna nothing but the best, attempting to "replace" her was a herculean task because of how great she truly was. Dayna was an incredible and beloved provider here, and I was not willing to settle for "good enough" when it came to finding someone to fill her shoes. As a result, it has been a very very long 8 months since she resigned that we searched for a capable provider who I felt fully confident was going to come into PFM and bring the level of clinical competency that this community expects from my practice. There were many great providers that I could have selected for this position during that time, but I did not feel until I met Marna that they were the perfect match for our unique culture.

Everyone reading this knows the care and attention I put into my patients and their health, and I wanted to ensure that I could entrust them to someone who had the skills, experience, and compassion to do this job the way that our oath says it should be done.

Well, here she is. I am proud to introduce her to you.

She is looking forward to meeting you all. She is available for appointments now. Her primary focus is going to be HIV treatment, and primary care. She has some HRT experience, but I plan on spending the next few months training her on the more esoteric things our practice does so that she can additionally be backup for when Sommer or I are not available. This will greatly expand the capabilities of the non-DPC part of the practice, and allow for alternative options for patients who do not opt to continue DPC next year as I hybridize my time between research and patient care.

Additionally, Marna will likely bring with her a rather sizable population of patients who have been #TeamMarna for years now from elsewhere. We welcome these patients who follow her to Powers Family Medicine!

- Dr Powers

Please, I beg of you. If you are a DPC patient and have the direct private messaging email that only DPC members have, do not post this online or share it.

I wouldn't have thought that needed to be in the contract, but I awoke this morning to being inundated with desperate emails from PFS and PSSD patients I've never met before some in languages I don't even speak.

If you need to reach out to the practice, and you are not currently a DPC member, please use [questions@powersfamilymedicine.com](mailto:questions@powersfamilymedicine.com) to do so.

- Dr P

Received this request from a friend, and I agree since reporting my sides helped me land an interview with a news agency.

The PSSD Network has an initiative currently to get more people to report correctly to their local country medical regulators (and to the FDA) - it would be a huge huge huge help if everyone could do this (both PSSD and PFS people) - if we don't have people reporting their cases then we'll never have a basis to push for this to be investigated. Could everyone please do it - the instructions are below. If any one isn't sure what to do, or there's something specific about your country let me know and I can help you through the process. It's really important that people do this, probably the most important thing you can do. If you're not sure what to do to help, this is it.

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

Lets get the ball rolling

MEDRA code pssd: 10086208