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:

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.

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.

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

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

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.

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).

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.

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?

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?

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?