I was reading some studies done in the past 10 years that basically say homosexuality is linked to less sexually dimorphic ( or partially reversed ) patterns of white matter tracts and gender dysphoria is linked to body self processing networks / thicker midline cortex structers, ifof differences, some smaller level of defeminisation ( ftm) or demasculinisation (mtf) when controlling for sexual orientation.

Wondering how does this gel with estradiol or estrogen being a factor in brain masculinisation ? Where does one even look for it. There are barely any opportunities to study the cortical homonculus even in cis folks.

Seems like the visible neural signature for being trans is quite similar to both trans men and women.

I was also reading some studies basically saying that synesthesia is extremely common in trans people even controlling for autistic traits, wonder if we are just literally experiencing our bodies differently than other people

https://www.frontiersin.org/journals/child-and-adolescent-psychiatry/articles/10.3389/frcha.2024.1356802/full

TL;DR; Help me understand how to combine the various metaphors for how PFS works to better understand potential risks/rewards from quitting finasteride.

After about 18 months taking compounded finasteride/minoxadil for hair loss, I've just learned about PFS. I started estrogen monotherapy a few months after starting on the hair loss pills, and so even before learning about PFS my Dr and I were already discussing dropping the finasteride (since it's likely not doing all that much for me), but now having learned about PFS I get the impression that quitting finasteride can actually increase the risk/severity of negative side effects/symptoms.

Given that, I'm trying to understand the risk dynamics that might arise from quitting finasteride vs staying on it.

Since Dr Powers seems like one of the few experts who's actually making progress here, I've tried to read up on his theory of PFS to see if I could figure out what the right way to think about this is. Here's what I've gathered so far:

• I've seen the DVD-R / DVD-RW metaphor about how finasteride can cause some aspects of the body to adjust to the presence of finasteride creating a dependency, and then fail to re-adjust back when the finasteride is removed. This explains why some people only get symptoms after quitting and would suggest that quitting without symptoms would be risky.
• I've seen other explanations with metaphors about different kinds of damage in an RPG (e.g. fire spells, ice spells, blunt trauma, etc.), and characters with greater or lesser susceptibility to fire. That seems to frames PFS as a sort of accumulation of effect, which explains why some people get PFS after a single dose, others get it after a couple years and still others are fine. If I understand it correctly, that suggests that however many HPs one person takes from each "fire spell", they're less likely to run out of HP if they stop getting hit by fire spells (i.e. quitting should lower risk).
• I've seen still other comments from the PFS community at large, claiming that once you quit finasteride, restarting it drastically increases the risk of severe finasteride side effects (which I don't know how to fit into the model at all)

Unfortunately, I don't nearly understand the biology or epigenetics nearly enough to stitch these different ideas together into a single cohesive way to think about the risk for people who are already on finasteride.

Obviously, I need to talk to my doctor about this, but since most doctors know almost nothing about PFS, I'd love to go into that discussion with a bedrock understanding so I can have a more intelligent discussion with them, and advocate for myself effectively.

Can someone help me stitch these different metaphors together, to help understand the risk calculus that would go into a decision about quitting finasteride?

Hey guys,

Ive been going through posts regarding breast growth and see you are all so freaking informative its insane so im posting for your input! :)

Im 26 yr old born female. I have pretty regular cycles. Ive been a life long vegetarian who did not focus on getting appropriate fats and proteins.

My breasts are like an A cup and my butt/hips/thighs hold majoroty of my weight (very pear shaped). I would love your guys input as to how to change this and grow my breasts!! Id love to go as big as i can get them.

If it helps my labs are below

Day 10 or 11 of my cycle

Estradiol- 511 pmol/L

Free tesosterone- 5pmol/L

SHBG- 148nmol/L

FSH- 4 IU/L

LH- 7 IU/L

17-OH progesterone- 0.8nmol/L

Androstenedione- 4.8 nmol/L

DHEA sulphate- 4.4 umol/L

Testosterone- 0.9 nmol/L

FAI- 0.6

TSH- 1.75 mIU/L

Haemoglobin- 130 g/L

Platelets- 278 10^9/L

C reactive protein- x<1 mg/L

Iron- 28 umol/L

Ferritin- 40 ug/L

Bilirubin- 16 umol/L

Alk phos- 81 U/L

Gamma GT- 8 U/L

ALT- 15 U/L

AST- 20 U/L

Albumin- 42 g/L

Protein- 68 g/L

Globulin gap- 26 g/L

Glucose(random)-5.2nmol/L

Vit D- 82 nmol/L

Height- 162cm

Weight- 55kgs

Bust-78cm

Waist-66.5cm

Hips-96.5cm

Thank you!

Anyone here with PCOS that have been prescribed bicalutamide? What are your experiences?

I have non-insulin resistant PCOS (have elevated testosterone and DHEA-S along with polycystic ovaries on ultrasound). I deal with hirsutism, hair loss, and acne, which are all things I'd be taking the bicalutamide for. I couldn't really handle spironolactone side effects. Just adding this info in case it helps.

I’ve been on hrt for 4.5 years yet haven’t seen the results that you’d expect. Check my account if you want to see for yourself. Genetics and lack of a chaloric surplus aren’t the issue.

December 2021-May 2022: 2 mg estradiol sublingually daily and 25 mg of bica every two days

May 2022-June 2023: 6 mg EV subcutaneously every week, 25 mg of bica and 100 mg of P3 orally every day

May 2023 test results: Estradiol 577 pg/mL, testosterone 7 ng/dL

June 2023-August 2025: 4 mg EV subcutaneously every week, 25 mg of bica every day

July 2023 test results: Estradiol 386 pg/mL, testosterone 25 ng/dL, free estrodiol 1.2%, SHBG 94.7 nmol/L

Feb 2024 test results: Estradiol 251 pg/mL, testosterone 27 ng/dL

August 2025 test results: Estradiol 276 pg/mL, testosterone 19 ng/dL

August 2025-November 2025: 6 mg EV subcutaneously every week, 100 mg of P3 orally daily

November 2025 test results: Estradiol 567 pg/mL, testosterone 32 ng/dL

November 2025-February 2026: 4 mg EV subcutaneously every week, 25 mg of bica and 100 mg of P3 every day

February 2026-present: 4 mg of estrodiol sublingually every morning and 2 mg of estrodiol every night, 25 mg of bica and 100 mg of P3 orally daily

March 2026 test results: Estradiol 237 pg/mL, testosterone 33 ng/dL, free estrodiol 1.1%, SHBG 122 nmol/L

This week I started take methylated vitamin b supplements to see if they would make a difference. Nothing so far.

That is all.

I'm not really sure how else to describe it, but in my 4.5 years of transitioning my E2 has always been on the low end kinda no matter what I take

I first started on oral pills 4mg then to 6mg them to 8mg, by 8mg i would still hover at like 70-80 pmgl (250-300 pmol)

I then transitioned to sublingual pills, and started at 8mg which got me to a bit better of a position being like 95-120pgml (350-450pmol) my dr did let me go to 10mg also which provided around the same levels, however my last result on 10mg did hit 180pgml (660 pmol) which is the highest I've been.

My dr did try gels also, im not sure on the concentration of it, it was only for a little while, and my levels sucked, from memory I think it was like 55pgml (200pmol)

So that brings to me now in the last 4 months, I've started injections (EEn) at 6mg once a week, i do .16ml of a 40ml vial (6mg), and just got my results at 120pgml (443pmol)

I suppose I don't really care for chasing a higher number anymore like I used to, I'm more just confused at how i'm always on the lower end compared to alot of the girls I see here or anywhere else on the same dosages.

I've feminized fine the whole time, so idk 🤷‍♀️

My testosterone has been fully suppressed the whole time as well, I got put on Cypro and very quickly went to 0.1-0.3nmol with like no free T at all as well.

I've quit blockers a year ago and am still completely suppressed.

My partner is doing estradiol injection monotherapy, took her first shot yesterday (wooooo!!!)
We're concerned with the proposed dosing pattern, however.

"Inject 0.25 ML (1.25 MG) Subcutaneously every two weeks. May increase gradually to 0.5 ML (2.5 MG) over first 3 months."

I'm a trans guy and have been doing shots for almost a decade. In that time, I've heard that the every-two-weeks schedule is like 20 years out of date and it needs to be every week. A cursory search of the metabolism of E. Cypionate seems to support this idea. We're very concerned about negative or nonexistent effects from starting too slow and essentially not having hormones half the time, since EC has an elimination time of a week.

We share a doctor, who happens to be the main gender clinic in our area, so they're supposed to be really knowledgeable about these things, so I'm honestly really surprised to see this on the scrip. They've been truly amazing with everything else so it's shocking to see such an older idea.

Is this really a normal starting dose pattern?

Additionally, we're wondering what the increase pattern should look like. We're currently thinking (.25, .3, .35, .4, .45, .5, .5, .5) for the 8 shots in those 3 months.

We will be discussing all of this with our doctor next Wednesday as well, so it's not that we're looking for medical advice - I just wanted to put the question to the hive mind so to speak, as we've been following this sub for a long time and actually used it to kind of form the rough draft of what her transition is going to look like.

Thanks for any info yall can help us with!!

I need to reverse the bit of shrinkage I have, but this would add androgens to the system.

What do you think

Specifically, stimulation of the somatosensory cortex and the motor cortex of the legs and hands reduces the general symptoms of PFS/PSSD, including tremors, weakness, and analgesia over the body, as well as taste, smell, and sound perception. It even partially helps with libido and sexual function, to the surprise of my neurologist and me,

as short update at 7 session seems this even somehow affected emotion blunting and anhedonia it also improved quite significantly, for now i continue sessions

i want to mention classical rTMS protocol for depression/ocd did absolutely nothing for me, i did 20 session into DLPFC, nothing changes at all nor better nor worse

update seems like even my personality drug response and emotions slowly coming back online

Can people who develop post-finasteride syndrome after taking a finasteride or dutasteride pill recover naturally?

From what I've read, trans girls lose tend to lose most penal function, but some of them can remain tops. I would like to simulate this effect by only partially transitioning by taking lower doses of estrogen.

My body dysphoria is that I identify with long hair, low body hair, feminine curves (i don't even mind breasts) but I would also like to keep a functional penis.

The dysphoria is so strong that I'm willing to spend my life researching and develop biological modeling so that this transgender endocrine phenotype could be reliably prescribed.

Hi all,

I wanted to share the story of my functional PFS recovery. This is a case study and a contribution to the ongoing efforts to understand this illness. I think Dr. Powers' thesis ties into my case.

Dr. Powers: if you read this and want to review my labs, I would be happy to provide them or discuss my experience over a call. Anything I can do to help.

Everyone else: Please remember that this is an incredibly complex illness with immense variation. What worked for me may not work for you. Exercise extreme caution, and TEST before assuming anything.

It's been a hellish journey with a lot of ups and downs. I am one of the people who had rapid onset neurological destruction from finasteride. I do not have the more typical PFS that results from years of finasteride, and I didn't primarily have the sexual dysfunction. My PFS was almost entirely neurological.

It's taken me some time to figure out what may have happened to me, and I wanted to make sure that I was in a place of functional recovery before posting. One important note: I started taking mirtazipine about 3 months in. Despite my recovery, I do not recommend starting this drug, as it is very destabilizing to get off of and I think its contributions to my recovery were minimal.

It is only through the grace of God that I'm alive. There were stretches of this past 5 years where a sip of coffee would crash me into a months long spiral where I would wish for death. If you are there, do not give up. I am now dating a woman who I plan to marry, and most days I don't think about PFS at all. I drink coffee without issue.

I'll try to answer as many questions as I can. If you are someone whose case is very similar to mine, I can make myself available for a call to help with specifics.

I am a private person but I cannot keep silent about my functional recovery given that it could potentially save lives. Below is a summary of my case and theories -- I have a longer memo that Claude prepared for me that I can email to those who want it that goes into more detail. For some reason I cant post it here. I'm not a big reddit person so I will check back every few days to answer questions.

summary:

Neurological-Predominant PFS: A Case Study and Integrated Mechanistic Framework

TL;DR

Severe PFS from 10 days of finasteride (November 2021). No primary sexual dysfunction. Predominantly neurological — panic, dread, depression, food/chemical trigger sensitivity, autonomic dysfunction. Dramatic response to nutritional-dose lithium orotate (2.5mg). Identified mechanistic framework integrating Melcangi's neurosteroid work, Powers' Phase II thesis, and a novel piece about molybdenum-sulfation bottlenecks that may explain why some patients develop severe PFS while others tolerate finasteride. Sharing in case it helps others with similar phenotype.

Clinical Profile

• Male, early 30s, 10 days finasteride 1mg in November 2021
• Acute onset: brain zaps, inability to stand, severe panic. Never resolved.
• 4+ years of neurological PFS
• No erectile dysfunction, no anorgasmia, no loss of libido — distinguishes this case from typical PFS presentation. That being said, I didn't exactly have a high libido during the worst of it, given the level of suffering.
• Severe trigger sensitivity: fructose, antibiotics, pungent oils, NAC, B1, betaine HCl
• Each trigger produces a specific phenomenology: simultaneous overwhelming panic + dread + depression. This is the fingerprint of acute GABA-A receptor antagonism, not anxiety disorder.

Key Lab Findings (Selected)

HTMA (Trace Elements Inc): Comprehensive trace mineral depletion

• Lithium: 0.001 mg% (ref 0.003-0.020) — floor
• Molybdenum: 0.003 — floor
• Manganese: 0.004 — floor
• Cobalt: 0.001 — floor (B12 deficiency)
• Iron: 0.5 — biounavailable
• Magnesium: 2.1 — low

DUTCH (Jan 2022):

• Androsterone: 4034.6 (ref 500-3000) — ELEVATED
• Total DHEA production: 6249 (ref 3000-5500) — ELEVATED
• Classic Phase II sulfation accumulation pattern

MycoTOX: OTA 30.44 (ref <7.5), Citrinin 57.30 (ref <25) — significant burden

OAT: Arabinose 37 (fungal overgrowth), DHPPA 0.03 (beneficial bacteria absent)

Genetics (23andMe):

• COMT V158M Met/Met (slowest, ~25-30% normal activity)
• MTHFR C677T + A1298C compound heterozygous
• SRD5A2 V89L heterozygous (~30% reduced baseline 5-AR activity BEFORE finasteride)
• Multiple SULT2A1 heterozygous variants (reduced sulfation capacity)
• HLA-DQ2.5 heterozygous (celiac susceptibility, family history positive)
• HLA-DRB1*1501 (mold biotoxin susceptibility)
• SOD2 AG (mitochondrial antioxidant impairment)

The Integrated Mechanistic Framework

Three Layers Operating Simultaneously

Layer 1 — The Amplifier (CNS-wide): Lithium depletion → unchecked GSK-3β → NF-κB neuroinflammation → suppressed BDNF → destabilized circadian clock → amplification of every alarm signal into psychiatric catastrophe.

Layer 2 — The Sensor (Gut/enteric NS): Inflamed epithelium + sensitized enteric nerves + primed mast cells + fungal overgrowth → vagal alarm signals to brainstem from any chemical perturbation. Every food/supplement trigger routes through this same pathway. Acid activates ASIC receptors. Pungent oils activate TRPV1. Fructose activates osmotic + TRPV1 + fungal feeding. Antibiotics dump endotoxins. Same nerve, different inputs.

Layer 3 — The Infrastructure (Mineral cofactors): Comprehensive depletion means no compensation possible. Even when body tries to reroute metabolism around finasteride blockade, alternative pathways are bottlenecked by missing cofactors.

The Lithium-SRD5A1 Hypothesis

• Finasteride silences SRD5A2 (acutely + chronically via methylation - Melcangi 2019)
• Normally SRD5A1 can compensate by producing allopregnanolone
• SRD5A1 compensation requires intact infrastructure: TSPO function, mitochondrial steroidogenesis, BDNF, GSK-3β inhibition
• In lithium-depleted individuals, SRD5A1 cannot compensate because the cellular infrastructure isn't functional
• Result: total neurosteroid collapse. Both 5-AR isoenzymes non-functional.
• Lithium repletion → restored SRD5A1 → allopregnanolone production resumes → GABA-A receptor function recovers

My response confirmed this: Day 3 of lithium orotate 2.5mg felt like I was on a benzo (couldn't even lift weights at the gym). Allopregnanolone hitting upregulated GABA-A receptors that had been deprived for years. Within 2 weeks: autonomic function returning (sweating, hunger, temperature regulation), panic-free morning waking, dramatic improvement in trigger tolerance.

The Molybdenum-Sulfation Bottleneck (Novel Integration)

This explains why some people develop severe PFS while others tolerate finasteride.

• Molybdenum is cofactor for sulfite oxidase which produces sulfate
• Sulfate is the substrate for PAPS (phosphoadenosine phosphosulfate)
• PAPS is required by every SULT enzyme — including SULT2A1 which sulfates androgens AND neurosteroids
• Even if SULT2A1 is genetically perfect, it can't function without PAPS substrate
• Critical depletion of molybdenum → critical depletion of PAPS → sulfation crashes systemically

This means Phase II metabolic pileup (Powers' framework) has two layers:

1. Genetic enzyme reduction (heterozygous SULT variants)
2. Cofactor substrate depletion (molybdenum-driven)

Combination is multiplicative. SULT at 60% capacity + PAPS substrate at 15% availability = ~9% effective sulfation output.

The neurosteroid implication: SULT2A1 also sulfates the excitatory neurosteroids that antagonize GABA-A receptors (isoallopregnanolone, 3β-androstanediol). When sulfation collapses, these accumulate. Net effect at GABA-A: not just too little inhibitory modulator (allopregnanolone depleted), but too much antagonist (excitatory neurosteroids accumulating). The receptor is pushed toward excitation from both sides simultaneously.

This is the mechanism behind the panic-dread-depression triad. It's GABA-A receptor antagonism across every limbic and prefrontal region simultaneously, not anxiety disorder.

Why Fructose Is the Most Extreme Trigger

Three mechanisms simultaneously:

1. Gut pathway: osmotic stretch + TRPV1 + fungal feeding + zonulin + mast cell degranulation → vagal alarm
2. Sulfation pathway: fructokinase depletes hepatic ATP (20-50%) and traps phosphate → PAPS production crashes acutely → excitatory neurosteroids accumulate
3. Amplification: unchecked GSK-3β converts the above into psychiatric catastrophe

Three simultaneous mechanisms, same target (GABA-A receptors), minutes timeframe. Explains the disproportionate severity.

What Helped Me

First sustained improvement (2024) — addressing infrastructure:

• Na/K Up (foundational minerals, B vitamins)
• Creatine monohydrate 5g/day (ATP buffering protects PAPS synthesis; also reduces SAMe demand freeing methyl groups for slow COMT)
• Beta-glucan 1,3/1,6 from S. cerevisiae, every other day (trained immunity reverses mycotoxin-induced immunosuppression; directly binds OTA in gut; Dectin-1-mediated neuroprotective signaling)

Dramatic response (2026) — addressing the neurosteroid mechanism:

• Lithium orotate 2.5mg elemental nightly (Seeking Health)
• Within days: GABA-A buffering restored, autonomic function returning, trigger tolerance improving
• 5-day recovery from histamine crisis that would have been months of destabilization pre-lithium

Current stack:

• Lithium orotate, BPC-157, beta-glucan, charcoal, Na/K Up, creatine, vitamin C (low dose), L-glutamine, molybdenum glycinate (Carlson, just started), mirtazapine, red-blocking glasses, strict elimination diet

The Relationship to Dr. Powers' Work

Dr. Will Powers has been developing a Phase II metabolic accumulation framework for PFS, validated by Dr. David Healy at RxISK (May 2026). His diagnostic insight is real and important. His work focuses on sexual dysfunction outcomes.

My case extends his framework in two ways:

1. Neurological-predominant phenotype — same Phase II impairment pattern but presenting as panic/dread/depression rather than sexual dysfunction. Patients with this phenotype are underrepresented in current PFS research.
2. Cofactor-driven dimension — the metabolic pileup may not be purely genetic. Molybdenum status determines whether genetic SULT variants are subclinical or catastrophic. This could explain the 99%/1% split in finasteride response — most people with SULT variants have adequate cofactors and don't develop PFS.

Dr. Powers' framework and the lithium-SRD5A1 mechanism aren't competing — they describe different aspects of the same disease. Some patients may need androgen receptor restoration (Powers' focus). Some may need neurosteroid production restoration (lithium-SRD5A1). Some need both.

If You Have Neurological-Predominant PFS

This may apply to you specifically if:

• You took a 5-AR inhibitor (finasteride, dutasteride, doxycycline, metronidazole, saw palmetto, etc.)
• You have severe panic/anxiety/depression/cognitive impairment
• You have characteristic trigger sensitivities (especially fructose, alcohol, antibiotics, sulfur compounds)
• Sexual function is preserved or only mildly affected
• You've been told it's "just anxiety" or "medically unexplained"

Tests worth discussing with your practitioner:

• 23andMe + Promethease (or similar) for Phase II variants
• HTMA with TEI methodology (lithium, molybdenum, manganese specifically)
• DUTCH for steroid metabolite pattern
• MycoTOX for OTA/Citrinin if any mold exposure history
• OAT for fungal overgrowth markers
• Standard bloodwork: kidney panel, thyroid (full), B12, MMA, ferritin

What I would caution against:

• Sporanox/itraconazole (is itself a 5-AR inhibitor — would replicate the original injury)
• High-dose NAC or sulfur supplementation before repleting molybdenum
• Adding many interventions simultaneously (variables can't be interpreted)
• Pharmaceutical lithium without psychiatric indication (nutritional doses are completely different)
• Aggressive antifungal protocols before immune system is supported

This is not medical advice. Every intervention needs to be evaluated by a qualified practitioner with full access to your medical history. I'm sharing the mechanistic framework because it integrates pieces nobody else has put together, not because I'm prescribing a protocol.

Closing

I'm not fully cured yet. I'm about a year into functional recovery with a framework that finally makes sense after years of suffering. The mechanism is real. The mineral testing is informative. The lithium response is dramatic when the mechanism applies. The molybdenum piece may be the missing link explaining why some get PFS and others don't.

If you have the neurological-predominant phenotype and this resonates, get the testing. Do not just jump onto this protocol without first confirming you have similar lab markers. Find a practitioner willing to engage with the mechanism. Start with infrastructure (minerals, beta-glucan, creatine) before challenging the system. Be patient — recovery is months to years, not weeks.

You are not alone. Your symptoms are biochemically explicable. The path forward is real.

Happy to answer questions in the comments. I'll share more detail on any specific mechanism, intervention, or lab finding for anyone working through their own case.

Hello Dr Powers,

I am still awaiting my Sequening results and DUTCH results back, been suffering since winter 2020.

You said that Lupron works on the body by cutting down LH and FSH back down to zero, removing the androgenic signalling then naturally coming back online - similar to turning off the WiFi router then turning it back on again.

If some people have crazy high Androstanediol Glucuronide but then have** **next to zero urinary androgens and others have the flip reverse, how can Lupron work for super low Androstanediol Glucuronide?

I can understand if there is too many people at the house party and you cut the flow of people into the house party people will slowly but surely leave. However, if there's no one at the house party to begin with then surely that will make the house party (androgen build up) even worse?

Apologies for the house party reference but I can't think of a more appropriate way to describe the ins and outs of androgen build up in a cell.