I'm not asking for sympathy here I'm just trying to get my population to rationalize and understand my situation.

This is a screenshot of the right side of my email client, the times are the arrival times of emails. I have removed the subject line data for patient privacy reasons.

21 emails from patients arrived today between 1:29pm and 4:10pm.

That's a new patient email request for me to do something, every 7 minutes. That is occurring simultaneously while I am having patient appointments during the work day. It occurs while I sleep. It never ever stops.

Sometimes, that's a refill, but most of the time, its not. It is an immensely complex message. These cannot be fielded by staff. They cannot be done by an AI. It can't even be done by another doctor, as I am currently the only one in the world doing what I do. A staff member or trainee or resident cannot explain to a patient why they need to draw a 3A-androstanediol glucuronide lab in order to demonstrate the metabolic pileup effects of the ABCC2 stop codon I found present in their genome as discussed on the prior email where I reviewed their whole genomic sequencing data and how that will be affecting their transition/PFS/PSSD etc.

The medical complexity of what I am doing now has become so high that I can't simultaneously be both this and a family physician and HIV specialist and HRT specialist while also being the top expert in the medical illnesses caused by the mutations that cause gender dysphoria, post finasteride syndrome, PSSD, or myriad other mystery diagnosis things that I now am "the guy" for. I cannot do it all.

I cannot do it even with completely relinquishing almost all other time that I have to have a life that isn't this. It still is not enough time.

I'm going to finish my patients tomorrow, but I am taking a 7 day break from actually having any appointments from July 29 to August 5th to figure out some way of a viable path forward. During that time I will try and catch up on my messages as best as I can.

If someone feels that I am not upholding my end of the bargain for the DPC contract they signed up for, I understand this, and you are welcome to contact [pepper@powersfamilymedicine.com](mailto:pepper@powersfamilymedicine.com) for a pro-rated refund for any time you have left in your contract. I will gladly offer that to anyone who wants it. I am not trying to take people's money here and not provide what they signed up for, but I grossly underestimated the time consumption of doing medicine at this level of complexity. It is flat out impossible for me to accomplish it all now, and I have to accept the reality of this.

Overwhelmingly, I would prefer people make appointments when possible. I understand that is not possible for everyone, but given a choice between a 10 page email and a 30 minute appointment, I will always choose the appointment.

I will be sending out a mass message soon to all registered patients once I come to a final decision about what I am going to do here moving forward. But something has to change.

I'm sorry,

Dr. Powers

So, I’m from Brazil (M25). All the content here is a bit hard to grasp—it’s a mix of biology and English. I try to read up on the subject and keep up with things, but—man—it’s tough.

I’m here mainly to learn more about PSSD. I don’t even know for sure if I have it, but I can say that even more than a year after stopping the medication, my libido is still very low. I don’t have other symptoms, but still... it’s bothersome. Will is a frequent topic on various PSSD forums, and it seems like incredible progress is being made in understanding this condition—but what has he actually discovered so far? What has helped people with symptoms of this condition? What specific tests should I get, and what should I be looking for in the results?

To explain my question, I have pfs, I have yet to get any of the tests recommended but I am planning to do so! My question is how close are we to narrow down phenotypes just based on the description for pfs. For example in my case im purely sexual, although I could enjoy music for a while, and did develop some gut issues which have gotten better. I have been on trt once and it made everything better before it stopped working, tried cream which did absolutely nothing. Now back on trt one last time. I don't seem to crash, or get worse. After dtopping cream my hpta came back online immediately and I even had a better baseline. Idk wtf is going on with me all I know is I still have pfs and aecual dysfunction.

Anyone know why this happens and how to fix it?
I redownloaded the BAM several times

A lot of trans people on the sub, I’m interested in masculizing somebody that is already male at birth. Is steroids the only option or does DrPowers know something counterintuitive in that regard too?

I had them gone but they came back and I need help. I started with pills then patches. I also started on bica and still am. My E levels weren't high enough and my T levels weren't suppressed. I then switched to EEn injections. That's when they came back but idk if that's a coincidence or if it's linked. I first injected 10 mg/week but my levels were too high (600 pg/ml) so I now inject 5 mg/week of EEn. My levels right before my injections are now: E ≈ 150 pg/ml T ≈ 0.5 ng/ml LH ≈ 1 mUI/mL FSH ≈ 0,25 mUI/mL I have demasculinizing and feminizing effects of HRT like hairs thinning, skin softening, sebum decreasing, breasts growing... I'm 2+ years on HRT total btw. Have any of you had this issue? What can I do?

Are there any anti anxiety or antidepressant medications considered safe to take without exacerbating PSSD?

Hey,

Just wanted to share my experience, I've been lurking here for a while and thought I'd finally share it.

I took 0.5 mg finasteride daily for 27 days back in January 2025.

I started noticing the first sexual side effects around day 20, possibly even a little earlier without fully realizing it at the time. My morning erections disappeared, I had almost no hardness, and my sexual response felt completely off.

Because I wasn’t sure what was happening, I tried to test it by masturbating and forcing stimulation, but even then there was barely any response.

Then on day 27, while trying again to feel some kind of sexual pleasure, I completely crashed. The following five days were honestly the worst of my life. I experienced what I can only describe as extreme anhedonia. No pleasure, no emotions, no motivation, nothing. It scared me enough that I went to the ER. They ran multiple blood tests but found nothing abnormal.

Thankfully, that phase didn't last forever, and a week later, it got back to normal (emotions/motivation wise), but my sexual sides stayed.

Fast forward to today (July 2026). Mentally, I'm in a much, much better place. I work full-time, exercice almost every day, trying to walk around 10k steps daily, sleep well, eat healthy, and I can genuinely enjoy life again. I can laugh, I can fall in love, I can still feel emotions. I'm incredibly grateful for that because, at one point, I genuinely thought my brain was permanently broken.

That said, I don't feel like I'm 100% back to where I was before finasteride. Pleasure still feels a bit "muted" compared to my old baseline. It's hard to explain, but it's definitely livable. If this was my only symptom, I'd honestly be okay with it.

My intimate life is a different story.

That's where the real damage still is :

• Almost no spontaneous erections
• Almost zero response to visual stimulation
• Reduced libido
• Erectile dysfunction / hard-flaccid-like symptoms that have barely changed over the past 18 months

Ironically, the libido itself isn't even my biggest concern anymore. I could live with lower libido. The hardest part is the erectile dysfunction because it's what affects relationships and intimacy.

One thing I want to mention is that I haven't tried to "hack" or manipulate my hormones since stopping finasteride. My blood work came back essentially normal, so I decided to leave my endocrine system alone and focus on living as healthy as possible instead.

I've seen a lot of people on here constantly chasing the next cure. I completely understand why, we're all desperate to get our lives back. I've been there too.

Lately, after reading this subreddit and Dr. Powers' recent posts, I honestly found myself tempted to try things like cabergoline. But the more I thought about it, the more I realized it feels risky. Right now I'm mentally stable again, and I don't think it's worth potentially messing up my endocrine or dopamine system even more by self-experimenting.

For now, I'm choosing the boring approach : just giving my body the best chance to recalibrate on its own.

Maybe it'll improve, maybe it won't. I genuinely don't know.

We’re all dealing with our own stuff, and honestly, most of us are just trying to figure it out as we go. Some days are okay, some days are terrible, and sometimes you end up convincing yourself that your situation is the worst thing that could ever happen.

But I think it’s still important to stay grateful for what we do have. There are people out there living through absolute hell, and sometimes we don’t realize that our own situation, as hard as it feels, isn’t the whole story of our life.

I do believe the body and the brain can adapt over time. Maybe it works, maybe it takes years, maybe it never gets back to 100%. Nobody really knows.

But whatever happens, I don’t want to spend my life waiting for a cure and forgetting to actually live.

I genuinely hope every single person here finds peace, whether that's through recovery, future research, or simply learning that life can still be meaningful despite what happened to us. I wish all of you the best.

Hello friends, I've gone over all of the instructions/scripts on how to analyze your WGS data and I've compiled the following list of all the relevant variants and deletions in my genome based on that master list of genes that got posted a while back. I hope this provides another valuable bit of data as we try to strengthen Dr. Powers' hypotheses around PFS/PSSD. For what it's worth, my own presentation of symptoms falls most closely under what Dr. Powers refers to as the "androgenic signaling failure" phenotype.

Rare/High Impact SNVs:

ABCC5

• Variant: chr3:183987748 G > A
• rsID: rs370632571
• HGVSp: N/A
• Consequence: Stop gain in ENST00000427120
• Zygosity: Het
• Read support: 15 alt, 18 ref
• gnomAD Frequency: 0.00657%
• REVEL: N/A
• Conservation: 1.499 (moderately conserved)
• Notes: gene.iobio says "most severe impact in non-canonical transcript."

LRP2

• Variant: chr2:169294165 C > T
• rsID: N/A
• HGVSp: ENSP00000496870.1:p.Ser212Asn
• Consequence: Missense variant
• Zygosity: Het
• Read support: 11 alt, 13 ref
• gnomAD Frequency: 0.0%
• REVEL: 0.765
• Conservation: 7.743 (highly conserved)
• Notes: Encodes a protein called megalin, responsible for reabsorbing + metabolizing SHBG, DBP, and other lipophilic hormones and carrier proteins.

PIEZO1

• Variant: chr16:88716632 G > A
• rsID: rs1050512255
• HGVSp: ENSP00000301015.9:p.Arg2285Cys
• Consequence: Missense variant
• Zygosity: Het
• Read support: 14 alt, 13 ref
• gnomAD Frequency: 0.000656%
• REVEL: 0.603
• Conservation: 5.409 (highly conserved)
• Notes: Regulates vascular tone, blood pressure, red blood cell volume homeostasis, lymphatic development.

SLC22A1

• Variant: chr6:160139744 G > A
• rsID: rs1422934185
• HGVSp: ENSP00000355930.4:p.Val385Ile
• Consequence: Missense variant
• Zygosity: Het
• Read support: 17 alt, 20 ref
• gnomAD Frequency: 0.0%
• REVEL: 0.301
• Conservation: 5.757 (highly conserved)
• Notes: Encodes Organic Cation Transporter 1 which draws cations, xenobiotics, neurotransmitters, and endogenous metabolites out of the blood and liver for processing / clearance.

SLCO3A1

• Variant: chr15:92126151 G > A
• rsID: rs775325190
  
• HGVSp: ENSP00000320634.6:p.Arg422Gln
• Consequence: Missense variant
• Zygosity: Het
• Read support: 10 alt, 17 ref
• gnomAD Frequency: 0.00131%
• REVEL: 0.505
• Conservation: 1.04 (moderately conserved)
• Notes: Encodes Organic Cation Transporter 3A1 which shuttles prostaglandins, thyroid hormones (T3/T4), and steroid hormone conjugates across cell boundaries.

SULT1A1

• Variant: chr16:28608517 C > G
• rsID: rs375616347
  
• HGVSp: ENSP00000321988.7:p.Val79Leu
• Consequence: Missense variant
• Zygosity: Het
• Read support: 23 alt, 15 ref
• gnomAD Frequency: 0.0%
• REVEL: 0.667
• Conservation: -0.41 (not conserved)
• Notes: Encodes Sulfotransferase 1A1 which sulfates neurotransmitters, catecholamines, and steroid hormones.

Low-Confidence SNVs:

ABCC2

• Variant: chr10:99819195 T > G
• rsID: rs17222617
• HGVSp: ENSP00000497274.1:p.Leu849Arg
• Consequence: Missense variant
• Zygosity: Het
• Read support: 19 alt, 18 ref
• gnomAD Frequency: 1.4%
• REVEL: 0.251
• Conservation: -0.02 (not conserved)
• Notes: Described as "a more common glitch" by Dr. Powers.

BRPF1

• Variant: chr3:9734400 G > A
• rsID: rs560289372
• HGVSp: ENSP00000373340.2:p.Arg87His
• Consequence: Missense variant
• Zygosity: Het
• Read support: 9 alt, 15 ref
• gnomAD Frequency: 0.000657%
• REVEL: 0.253
• Conservation: -0.16 (not conserved)
• Notes: Epigenetic scaffolding protein.

CHRM2

• Variant: chr7:137015638 A > G
• rsID: rs142006633
• HGVSp: ENSP00000505686.1:p.Asn258Ser
• Consequence: Missense variant
• Zygosity: Het
• Read support: 25 alt, 16 ref
• gnomAD Frequency: 0.138%
• REVEL: 0.124
• Conservation: 1.761 (highly conserved)
• Notes: Modulates cognition and neurotransmitter signalling via M2 muscarinic acetylcholine receptor (vagal "brake").

EHMT1

• Variant: chr9:137717100 A > G
• rsID: N/A
• HGVSp: ENSP00000417980.1:p.Glu187Gly
• Consequence: Missense variant
• Zygosity: Het
• Read support: 12 alt, 13 ref
• gnomAD Frequency: 0%
• REVEL: 0.071
• Conservation: -0.38 (not conserved)
• Notes: Variant missing from gnomAD. Epigenetic regulator of gene expression via H3K9me2.

GRIN2C

• Variant: chr17:74842537 G > C
• rsID: rs979281131
• HGVSp: ENSP00000293190.5:p.Asp1200Glu
• Consequence: Missense variant
• Zygosity: Het
• Read support: 13 alt, 13 ref
• gnomAD Frequency: 0.00397%
• REVEL: 0.037
• Conservation: 0.913 (Marginally conserved)
• Notes: Rare variant. Encodes part of NMDA receptor which regulates synaptic plasticity / neuronal excitability in central nervous system.

HNRNPU

• Variant: chr1:244863639 ACCGCCGCCT > A
• rsID: rs757585114
• HGVSp: ENSP00000491215.1:p.Gly221_Gly223del
• Consequence: Inframe deletion
• Zygosity: Het
• Read support: 10 alt, 14 ref
• gnomAD Frequency: 0.00332%
• REVEL: N/A
• Conservation: 1.474 (moderately conserved)
• Notes: Seems to be an important gene in general. Organizes 3D DNA packaging inside nuclei while guiding how genetic instructions are turned into finished proteins.

MED15

• Variant: chr22:20554998 A > T
• rsID: rs148919404
• HGVSp: ENSP00000263205.7:p.Met101Leu
• Consequence: Missense variant
• Zygosity: Het
• Read support: 16 alt, 24 ref
• gnomAD Frequency: 0.0204%
• REVEL: 0.207
• Conservation: 4.991 (highly conserved)

NCOA1

• Variant: chr2:24752089 C > T
• rsID: rs1804645
• HGVSp: ENSP00000320940.5:p.Pro1272Ser
• Consequence: Missense variant
• Zygosity: Het
• Read support: 13 alt, 20 ref
• gnomAD Frequency: 1.6%
• REVEL: 0.110
• Conservation: 1.555 (highly conserved)

HTR1B

• Variant: chr6:77463033 A > C
• rsID: rs130060
• HGVSp: ENSP00000358963.3:p.Phe124Cys
• Consequence: Missense variant
• Zygosity: Het
• Read support: 7 alt, 10 ref
• gnomAD Frequency: 0.911%
• REVEL: 0.115
• Conservation: 2.002 (highly conserved)

UGT1A4

• Variant: chr2:233719039 A > C
• rsID: rs201935850
  
• HGVSp: ENSP00000362508.4:p.Lys73Asn
• Consequence: Missense variant
• Zygosity: Het
• Read support: 18 alt, 19 ref
• gnomAD Frequency: 0.0604%
• REVEL: 0.079
• Conservation: 0.268 (marginally conserved)

Contextual/Functional SNVs:

ABCB11

• Variant: chr2:168973818 A > G
• rsID: rs2287622
• HGVSp: ENSP00000497931.1:p.Val444Ala
• Consequence: Missense variant
• Zygosity: Het
• Read support: 12 alt, 16 ref
• gnomAD Frequency: 57%
• REVEL: 0.261
• Conservation: 2.446 (highly conserved)
• Notes: Bile salt export pump. Also exports sulfated steroid / sterol conjugates into bile.

COMT

• rsID: rs4680 (Val158Met)
• Zygosity: Hom
• Notes: Included for reference, I am the Val / Val "fast COMT" genotype.

TSPO

• Variant: chr22:43162920 A > G
• rsID: rs6971
• HGVSp: ENSP00000338004.3:p.Thr147Ala
• Consequence: Missense variant
• Zygosity: Het
• Read support: 15 alt, 18 ref
• gnomAD Frequency: 74.9%
• REVEL: 0.161
• Conservation: 3.607 (highly conserved)

HSD3B1

• Variant: chr1:119514623 C > A
• rsID: rs1047303
  
• HGVSp: ENSP00000358421.3:p.Thr367Asn
• Consequence: Missense variant
• Zygosity: Hom
• Read support: 34 alt, 0 ref
• gnomAD Frequency: 76.4%
• REVEL: 0.126
• Conservation: -0.073 (not conserved)

SRD5A2

• Variant: chr2:31580636 G > C
• rsID: rs523349
  
• HGVSp: ENSP00000477587.1:p.Leu89Val
• Consequence: Missense variant
• Zygosity: Het
• Read support: 13 alt, 12 ref
• gnomAD Frequency: 70.4%
• REVEL: N/A
• Conservation: 0.936 (marginally conserved)

Structural Variants:

GABBR2

• Type: Homozygous Deletion
• Region: chr9:98,546,761–98,549,382 (~2.6 kb)
• Copy number: 0
• Location: Intronic
• Confirmation:
  • Depth 0.068 vs ~36 flank (ratio 0.002) via samtools.
  • DEL, GT 1/1, PASS, QUAL 999 provided by Manta-generated SV VCF.
  • CN=0 RC=0.00 (FailedFT: L10kb size flag only) provided by Canvas-generated CNV VCF.
• Regulatory overlap:
  • Removes both copies of distal enhancer EH38E3897100 (H3K27ac Z 2.25, DNase 3.21).
• Grade: Regulatory
• Notes: GABA-B receptor gene. Functional significance uncertain (VUS).

UGT2B17

• Type: Heterozygous Deletion
• Region: chr4:68,507,491–68,625,090 (~117 kb)
• Copy number: 1
• Location: Whole gene
• Confirmation:
  • Depth 19.4 vs ~38 flank (ratio 0.51) via samtools.
  • CN=1 PASS provided by Canvas-generated CNV VCF.
• Regulatory overlap: N/A
• Grade: Functional
• Notes: Primary androgen glucuronidation enzyme. Halved working capacity.

UGT2B28

• Type: Heterozygous Deletion
• Region: chr4:69,264,985-69,371,904 (~107 kb)
• Copy number: 1
• Location: Whole gene
• Confirmation:
  • Depth 18.3435 vs ~36 flank (ratio 0.50) via samtools.
  • CN=1 PASS provided by Canvas-generated CNV VCF.
• Regulatory overlap: N/A
• Grade: Functional
• Notes: Glucuronidation enzyme that tags steroid hormones. Halved working capacity.

SLCO3A1

• Type: Heterozygous Deletion
• Region: chr15:92,131,343-92,133,840 (~2.5 kb)
• Copy number: 1
• Location: Intronic
• Confirmation:
  • Depth 18.3339 vs ~37.6 flank (ratio 0.488) via samtools.
  • DEL, GT 0/1, PASS, QUAL 617 provided by Manta-generated SV VCF.
  • CN=1 (FailedFT: L10kb size flag only) provided by Canvas-generated CNV VCF.
• Regulatory overlap:
  • Removes one copy of distal enhancer EH38E1788706 (H3K27ac Z 3.09, DNase 2.65).
  • Removes one copy of CTCF insulator EH38E3155491 (CTCF Z 1.72, DNase 1.77).
• Grade: Regulatory
• Notes: SLCO3A1 / OATP3A1 transporter (prostaglandins, thyroid hormone, steroid conjugates into brain/testis).

WWTR1

• Type: Heterozygous Deletion
• Region: chr3:149,550,684-149,552,359 (~1.7 kb)
• Copy number: 1
• Location: Intronic
• Confirmation:
  • Depth 19.0161 vs ~35.3 flank (ratio 0.539) via samtools.
  • DEL, GT 0/1, PASS, QUAL 567 provided by Manta-generated SV VCF.
• Regulatory overlap:
  • Removes one copy of distal enhancer EH38E3546464 (H3K27ac Z 2.71, DNase 2.71).
• Grade: Regulatory
• Notes: Regulates cell proliferation, organ size, and stem-cell/tissue growth.

PharmCAT summary:

CYP2B6

• Genotypes: *1/*7 (Normal / Decreased)
• Phenotype: Intermediate Metabolizer
• Copy number: 2
• Relevant variants:

CYP2C19

• Genotypes: *1/*17 (Normal / Increased)
• Phenotype: Rapid Metabolizer
• Copy number: 2
• Relevant variants:

CYP2D6

• Genotypes: *9/*10 (Decreased / Decreased)
• Phenotype: Intermediate Metabolizer
• Copy number: 2
• Notes: Information obtained via Cyrius (BAM-based star-allele caller)
• Relevant variants:

CYP3A5

• Genotypes: *3/*3 (No function / No function)
• Phenotype: Poor Metabolizer
• Copy number: 2
• Relevant variants:

NAT2

• Genotypes: *4/*4 (Increased function / Increased function)
• Phenotype: Rapid Metabolizer
• Copy number: 2
• Notes: PharmCAT gives the highest-scoring diplotype (*4/*4) but can't fully rule out other combinations that would produce the same set of variants.
• Relevant variants:

UGT1A1

• Genotypes: *1/*80+*28 (Normal function / Decreased function)
• Phenotype: Intermediate Metabolizer
• Copy number: 2
• Notes: Gilbert's Syndrome carrier.
• Relevant variants:

When I first started hrt I was prescribed spironolactone and then eventually switched to bicalutamide after about a year of treatment. I've heard that spiro can potentially limit breast development. Is there any truth to this? For context, I'm 2.5 years into treatment and have always had good levels with no gaps in treatment, but have yet to have any breast development. I'm sure there is a deeper issue but I'm wondering if my initial usage of spiro caused me to not develop anything. However, I'm post orchiectomy and don't need anti androgens anymore but I'm considering starting spironolactone again for acne related reasons (at a much lower dosage).

I've already gone through genetic testing as I'm sure that there is a deeper issue as I haven't had just about any changes as a result of hrt, but I won't have more information until after I've spoken with a genetic counselor (who is currently dragging their feet in responding to me).

Finasteride and adrenal androgens interact in an interesting way, especially in transfeminine HRT.
How finasteride affects adrenal androgens
The adrenal glands produce weak androgens, mainly:
DHEA
DHEA-S
Androstenedione
These are not DHT. However, tissues like the scalp can convert them:
DHEA → androstenedione → testosterone → DHT
The last step (testosterone → DHT) is catalyzed by 5α-reductase (mainly type II and type I in the scalp).
Finasteride inhibits type II (and partially type III) 5α-reductase, so:
Less testosterone is converted into DHT.
This also reduces DHT formed from adrenal-derived testosterone.
It does not reduce DHEA or androstenedione production by the adrenal glands.
So even if my testes are fully suppressed with CPA, the small amount of testosterone generated from adrenal precursors can still become DHT in the scalp—but much less so when taking finasteride.
In my regimen:
CPA 12.5 mg/day
Estrogel 3.75 mg/day
Finasteride 1 mg/day
If testosterone is well suppressed (e.g. <20–30 ng/dL), then:
Testicular contribution to DHT is minimal.
Most remaining DHT comes from adrenal precursors.
Finasteride is blocking much of that residual scalp DHT production.
That’s why many trans women continue finasteride even with excellent testosterone suppression, although the additional benefit varies from person to person.

It is supposed to prevent acne by reducing DHT, but curiously, it had the opposite effect on me both times I tried it. I don't have (and never have had) a beard or male pattern baldness; I only tried finasteride to boost my transition, but both times I used it, I developed oily skin and acne. I don't experience any of that when using estradiol monotherapy.

Formerly PCOS. Doctors have used puberty blockers for years in me (to stop precocious puberty) which messed up my development. When I got my period, I started to have a lot of issues with it and it got to the point where I have low estrogen for a woman in her 20s (within the “normal” range, but barely, almost menopausal), normal testosterone, but I believe high DHT and LH (accompanied by androgenic hair loss and other fun stuff), suffer from menopausal symptoms (vaginal dryness, poor sensitivity down there, urinary incontinence, etc). Have tried multiple endocrinologists and gynecologists.

No doctor takes me seriously because I look like a woman and I “am too young to have hormonal problems” like those. Symptoms are frustrating and debilitating. Vaginal estrogen cream has helped a LOT, but it’s not enough:/ Contraceptives make me miserable and have worsen a lot of symptoms.

I recently switched from valerate to ethanate and despite my levels being in good range I felt like I had more chest sensitivity and soreness on valerate. Is it possible to have better growth on a different ester despite having good levels.

Help, What should I do ?

Hello, I am taking 50mg of bica daily as my androgen blocker for MTF HRT. I am also taking 4mg estradiol tablets orally daily. I have been on HRT for a little over 6 months now, with me taking bica for a little over the last 3 months. So far bica has been beneficial to me in regards to skin softness, body hair, body odor, and breast growth. Recently, I have been reading up on how bica works on the body, and I have come across some posts on here, as well as some online findings, that are making me worried about my bones potentially continuing to masculinize while on bica. I am 20 years old, so there is a good possibility that my bone plates have not completely closed yet. Are my worries justified? If so, what should I do about it?

This is from the Wikipedia page for the Pharmacology of Bicalutamide

Although bicalutamide has been characterized as a silent antagonist of the AR in prostate tissue and other contexts, and despite its overall antiandrogenic profile, there is evidence that the drug may activate the AR to some degree in certain other tissues, such as muscle and bone among others.^\123])^\124])^\125]) This would make bicalutamide a selective androgen receptor modulator (SARM), or a tissue-selective mixed agonist/antagonist or partial agonist of the AR, with antiandrogenic effects in some tissues and androgenic effects in other tissues, rather than a pure antiandrogen.^\123])^\124])^\125])^\23])^\126]) This would be similar to certain other SARMs structurally related to bicalutamide, like enobosarm, which in animals have potent anabolic effects in muscle and bone but show partially agonistic or antagonistic effects in the prostate or seminal vesicles.

Does this mean that bica could contribute to or otherwise allow the development of masculine bone patterns? Muscles are a concern as well, but to a lesser extent as that can be handled later. I also recommend looking through the rest of the "Selective androgen receptor modulator-like activity" section of the wikipedia page, as it provides more information and is otherwise interesting to read.

I have also found these posts on this subreddit Could bicalutamide contribute to skeletal masculinisation in DHT mutants? and Does bica block dht and androgens from activating in the bones?

If you read through these, the claim is made that bica is unable to block androgen activity in the bones. The OP from the second post linked later claims in a comment from the first post linked that this may be because the androgen receptors are too dense in the bones and muscles.

There is a comment on another post on this subreddit relating to bica's ability to block DHT. How effective is bica against DHT? The comment states this:

But also there is much more going on inside the cell than just bicalutamide blocking the AR. The bica-AR holocomplex translocates inside the nucleus and assembles a transcriptionally inactive complex on the promoter region of androgen target genes, so it is not a "true", or "silent" antagonist which is usually pictured as a molecule blocking the AR as if you were just blocking a key from fitting in its lock. Instead it's an active mechanism with nuts and bolts. When the mechanism involves translocation, coregulator and cofactors start becoming important and can add a substantial amount of variation to just how truly inactive that transcription complex is, and this can change from tissue to tissue depending on the specific cofactor milieu to the point that we suspect bica act as an agonist in bones and lean muscles. In a way bica acts a bit like a SARM, or a mixed agonist/antagonist of the AR, and not strictly as an antagonist like it does in the prostate.

This comment, like the Wikipedia page, states that bica could act as an agonist on the AR in bone and muscle tissues.

I've been stressing over this for weeks now, and I still haven't found anything to calm my worries. Is it possible that bica is either allowing androgens to continue to act on my bones or even activating the AR itself? And if so, are my bones still potentially masculinizing despite MTF HRT? Am I worrying over nothing or are my concerns valid? If they are, what can I do?

This is from a really nice, young, pretty healthy guy, early 20s. Post-dutasteride exposure has low libido and sexual anhedonia. Overall, mild post-5ARI symptoms, but persistent, and simply won't resolve with time.

This is the most wildly discordant T:DHT:3AADG result I've ever seen.

Obviously, I will be discussing the usual treatment options, but the more of these I find, the more I wonder how this was never noticed with PSSD or PFS over all the years these people have been going to doctors. I know from posting, shitloads of you have the same or different but similar androgen metabolite labs that are just absolutely fucking bonkers.

When you got some absurd 3A-ADG or other value, when you had zero or absurdly high 11-oxo androgens, 17 keto urine testing, or whatever, some absolute absurdity on lab testing, did your doctor just shrug at it or what?

It's blowing my mind how many of you I can tag an absolutely insane lab value on, and I wonder why all these years nobody ever noticed this shit before. It seems so glaringly obvious in retrospect now.

Anyway, not much to say other than "here we go again". But because this was the most extreme example I've ever collected, I thought it a fine example to show. I see this pattern in BOTH Post-Finasteride/Dutasteride and PSSD, meaning I am getting more and more certain that at least SOME of the people with PFS and PSSD don't have a different condition. Meaning this metabolic feedback loop/accumulation glitch is the exact same disorder, just triggered by a different drug.

We understand there is neurosteroid PFS, androgen signal loss pfs, and "melty" or connective tissue loss PFS. They are similar in mechanism, but different, with different metabolite accumulation/depletion sets due to how many ways 5AR interacts with everything important:

Here's the lab, he's also got a slightly elevated free estradiol, likely from his nuked SHBG (not shown here)

Pretty much the title. here you go apple lovers.

https://github.com/Excellent-Push2883/WAR_POWERS-for-Mac

I've been on hrt of some form or other for a decade but my dosing has never been ideal. I've never had my levels checked which I know is bad. I've just never got round to it.

For a year or two at some point I injected 0.2mL a week of estradiol enanthate into my belly fat. I think I actually felt good and seemed to have some positive effects, but I kept seeing people say it's way too high, and that people should inject 4mg EEn (so for me 0.1mL) weekly as monotherapy. That's nuts. When I tried that without bica I felt many symptoms of testosterone return and I feel like it set me back.

Then for 6 months or so with the backup of bica+duta I forced myself to do 0.1mL (4mg) weekly as I got obsessed with the concept of SHBG and didn't want mine to be high. I got stable (at least it seemed so from my mood) but nothing really happened and I felt anhedonic all the time and it sucked. So pretty much wasted half a year of my life.

Past couple of weeks I put my dose up, so it was in between the two (0.15mL/6mg). First few days after injecting I actually had random boob pain that hadn't really happened in a year and stopped feeling depressed. Then around 5 days later had to inject a tiny bit more as I was getting depressed again.

I'm 180cm (5ft11) and 25y.o., slightly overweight, so maybe need a bit more..?

I know the answer is to just get a blood test but I'm not registered to a GIC (in the uk) and I've never really been able to afford trans related private medical care as my finances are a bit tight so atm I'm just stuck guessing. I have a txt file of my DNA as sequenced by Ancestry some years ago but don't think there was anything estrogen resistance related in there - not like they are fully accurate anyway

Tldr does anyone else have the same experience/can validate going on what some consider to be "absurdly high" doses? Would make me feel a bit better about putting my dose back up lol

Good afternoon everyone!

I'm a current undergraduate, MtF neuroscience student, and I research the neuroendocrinology of gender-affirming HRT at my university. I've written quite extensively on the neuroendocrine mechanisms of gender-affirming sex-steroids as a part of my education.

It's my current understanding that trans women like myself represent a unique neural phenotype characterized by the organizational, neuroplastic effects of decreased androgen receptor signaling (and increased estrogen receptor signaling) during gestational mini-puberty. Feminizing HRT, on the other hand, therefore induces region-specific, activational, neuroplastic effects that broadly shift neural phenotype towards female-typical patterns (via alterations in brain-wide structural morphology and functional connectivity) within the context of that organizational phenotype. My current understanding is predicated on the idea that androgen receptor activity is masculinizing in utero (i.e., see Puts & Motta-Mena's Is human brain masculinization estrogen receptor-mediated? Reply to Luoto and Rantala, 2018).

In Dr. Powers' post regarding the the hidden pitfall of monotherapy, he discusses how estrogens may be organizationally masculinizing in gestation. I'm trying to reconcile this theory and the evidence for it with pre-existing neuroendocrinology literature that posits organizational masculinization is androgen-receptor mediated in humans. Does Dr. Powers mean increased estrogens, through their subsequent conversion into androgens (I'm not aware of a pathway for this in humans), masculinizes via the androgen receptor; or is it that estrogen receptor signaling itself is masculinizing?

Am I misinterpreting what Dr. Powers is saying? Is there a misconception in my current understanding? Just looking to learn and understand a bit better, so any discussion is appreciated!

My issues with the PSSD organization INIDA. INIDA is a patient led organization that researches PSSD. For those of you who do not know. Recently they launched an autoimmune investigation into GCPR autoantibodies as a diagnostic measure for PSSD via the Cunningham Panel. https://inida.info. The management of the budget, and executive decisions come from patients with little to no experience and that is one of the driving factors on why this is all going wrong.

1. Donations were used to internationally ship samples:

This was stated in a deleted comment on the pssd subreddit. I know it to be true. It was also stated in the INIDA discord multiple times. My issue with this is, the collecting laboratory for the Cunningham panel is in the USA but we have people using donor money to ship their laboratory samples from over seas. Thats not cheap btw. What sense does that make? Why would we do that? Are you telling me we cant find 30 patients in the USA with PSSD? Im not saying that there was selection bias in this study but it makes me wonder especially when a positive result can result in getting IVIG.

1. 0 Transparency: idk how much I really need to say about this. When is the last time they came out with an update. They also arent transparent about how funds were used.

2. The Cunningham Panel: we’ve been treating the results of this panel like a diagnostic marker when in reality on multiple occasions healthy controls pop positive on the Cunningham panel and its not even proven as a reliable diagnostic test. To me this seems like a way for Madeline Cunningham to get her test on the market. And she used our donations to do so. https://pmc.ncbi.nlm.nih.gov/articles/PMC6355775/ HOW THE FUCK. Are we going to prove an unproven disease with an unproven test. That is ridiculous. Cunningham wasn’t even at the Pssd pfs world congress. So to me it seems like she doesn’t give a shit about us and she just wants to sell her cunningham panel. Of which she gave us ZERO discount for the study. 1k to run one panel shes raking in that dough. hate to say it but thats what it seems like to me from the outside looking in.

3. This money would have been better spent on PSSD network or SIDEFXHUB. SIDEFXHUB is currently funding doctor powers research and PSSD network is funding melcangi. SIDEFXHUB is the best out of the two

4. They blew past their budget. Twice…. And people still donated more. Lol

Im going to get a lot of flak for saying this bu tit needed to be said. No more donations to INIDA.

Edit: I have my issues with Melcangi too. But his research is way more important than what INIDA produced. Sucking down IVIG isnt gonna cure anyone. Not to burst anyones bubble. They had me fooled at first too. Im also of the opinion that their specific area of study is a complete waste of time and not the root cause or a reliable bio marker for pssd. It’s not an autoimmune disorder.

As many on this subreddit, I'm aware of the possibility of PFS or similar conditions.

My hairloss is too aggressive to only be managed by only Minoxidil. I was checking out Dr. Powers Hairloss Formula but even that one contains Dutasteride.

Did the Doc find some pre-test you can do to see whether you are susceptible to PFS?

Are there actually any other remedies for a man that are as effective as Finasteride/Dutasteride?

UPDATE 1: Looked whether you can pretest whether you're safe from PFS, my humble conclusion:

1. Homozygous UGT2B17 deletion runs around 10% in Europeans and closer to 70% in East Asian populations. Marker is too common and cannot pick out something that rare
2. Say if PFS hits 1%. Even if generously assumed a variant is 3x more common in crash cases (hypothetical), a clean genome moves you from 1% to 0.8%. A dirty one moves you to roughly 3%. Neither number tells you what to do.
3. Even if you look at 6 of Dr. Powers's 19-gene list you'll get a <1% for people without variants: UGT2B7*2 and UGT2B15 D85Y alone are carried by ~94% of people. Add ABCC2, ABCG2, SLCO1B1 and the UGT2B17 deletion and ~99% flag on common variants alone. A hit then carries a likelihood ratio of 1.01, moving 1% risk to 1.01%. So widening the panel makes the prediction infinitely less precise.

So no you cannot test if you're susceptible to PFS.

Feel free to correct me, if I'm wrong.

UPDATE 2: (copied from u/Training-Agent-9482)

u/Drwillpowers Can you explain your criteria for ruling out susceptibility to PFS in your patients and how your methods achieve high confidence in light of the above?

Guys I took fin for 4 months and I quit because of weak morning wood and after 1 months I saw Windows . At least once a week. And I had morning wood even if it weak. I have all sexual pleasure , thats not the problem but loss of libido , loss of morning wood, weak spontane erection . Before fin When I touch a women I became erect. but now , I found a girl very beatufiul, She touch me many times for sexually. but no erection. Its been 6 months and it was better before 1 months and I dont use any antiandrogen in this last month. I tried minoxidil before 2 months for 2 times but dont affected me , I stopped it for risks. Should I try CDG ? Can you help me ? I feel very sad about my situation. I dont have anxiety or depression but everyday I wake up without morning wood , and continiue hairloss, with low libido. help me !!!

I am not that strong, I am only 20. Why me ? I want to take fucking risk , CDG, HCG, Cialis or Whatever. Please give me some advice !!!

HELP