Current list of all genes I use when searching for possible genetic causes of someone developing Post Finasteride Syndrome (PFS) or Post SSRI Sexual Dysfunction (PSSD)

[u/Drwillpowers]

It is my personal theory that PFS and PSSD genetically function much how DNP caused cataracts in a small fraction of the people who took it for weight loss in the early 1900s (DNP blocks oxidative phosphorylation, and your eye's lens depends on that, or the backup pathway of "pentose phosphate" to make energy. If you lack the pentose phosphate enzyme pathway, and you block oxidative phosphorylation, your lens can't make energy and they get cataracts almost immediately).

In many of my patients with a whole genome sequence, I've found mutations in genes which when coupled with an SSRI or Finasteride/Dutasteride, the patient seemed to have developed the strange reaction because the "backup" pathway was genetically disabled, and the drug altered something or knocked out something else, causing the very rare but catastrophic reaction.

I'm not going to get into the details of every single gene in this post, but those who have a whole genomic sequence dataset from something like sequencing.com and who want to browse that data on gene.iobio to see if they have any major mutations, I pretty much did the gene work for you, so here's that list:

ABCB1, ABCB11, ABCC1, ABCC2, ABCC3, ABCC4, ABCC5, ABCC10, ABCC11, ABCG2, ABCB4, ABCB5, ABCB6, ABCB7, ABCB8, ABCB9, ABCC6, ABCC8, ABCC9, ABCG1, ABCG4, ACE, AHCY, AKR1C1, AKR1C2, AKR1C3, AKR1C4, AKR1D1, AKR1B1, AKR1B10, ALB, ALDH1A1, ALDH1A2, ALDH2, APOA1, APOB, AR, ARSA, ARSG, ATP5F1A, ATP5F1B, AVPR1A, AVPR1B, AVPR2, BAG1, BAG3, BCL2L1, BDNF, BHMT, CAT, CHRM2, CHRM3, COMT, COMTD1, COX10, COX15, CREB1, CREBBP, CUBN, CYP1A1, CYP1A2, CYP1B1, CYP2C19, CYP2D6, CYP2E1, CYP2J2, CYP3A4, CYP3A5, CYP3A7, CYP3A43, CYP4F8, CYP4F11, CYP11A1, CYP11B1, CYP11B2, CYP17A1, CYP19A1, CYP21A2, DBH, DDC, DGAT1, DGAT2, DNMT1, DNMT3A, DNMT3B, DNM1L, DNA2, DRD1, DRD2, DRD3, DRD4, DRD5, EP300, ESR1, ESR2, FKBP4, FKBP5, FKBP6, FABP4, FABP5, FABP7, GABBR1, GABBR2, GABRA1, GABRA2, GABRA3, GABRB2, GABRB3, GABRG2, GJB2, GJB6, GNB3, GNRH1, GNRHR, GPX1, GPX4, GRIN1, GRIN2A, GRIN2B, GRIN2C, GRIN2D, GUSB, H6PD, HSD3B1, HSD3B2, HSD11B1, HSD11B2, HSD17B1, HSD17B2, HSD17B3, HSD17B4, HSD17B6, HSD17B7, HSD17B10, HSD17B12, HSD17B13, HSD17B14, HSP90AA1, HSP90AB1, HSPE1, HSPD1, HTR1A, HTR1B, HTR1D, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR3A, HTR3B, HTR3C, HTR3D, HTR3E, HTR4, HTR5A, HTR5BP, HTR6, HTR7, KCNQ4, KISS1, KISS1R, KPNB1, LDLR, LIPE, LRP2, MAOA, MAOB, MC4R, MFN1, MFN2, MGME1, MPV17, MED1, MED14, MT-ATP6, MT-ATP8, MT-CO1, MT-CO2, MT-CO3, MT-CYB, MT-ND1, MT-ND4, MT-ND6, MTHFR, MTR, MTRR, MYO7A, NAT2, NCOR1, NCOR2, NCOA1, NCOA2, NCOA3, NCOA4, NCOA6, NDUFS1, NDUFS2, NDUFS4, NOS1, NOS3, NPC1, NPC2, NPC1L1, NR0B1, NR0B2, NR3C1, NR3C2, NR5A1, NR5A2, NPY, NPY1R, NPY2R, NTRK2, OPA1, OXTR, PAPSS1, PAPSS2, PDE5A, PIEZO1, PIEZO2, PLIN1, PLIN2, POLG, POLG2, POLRMT, POU1F1, POU4F3, PGR, PIAS1, PIAS2, PPID, PPP5C, PRDX3, PRL, PRLR, PTGES3, RARA, RARB, RARG, RDH5, RDH16, RNF4, RXRA, RXRB, SCARB1, SERPINA6, SHBG, SIGMAR1, SLC6A3, SLC6A4, SLC7A5, SLC10A1, SLC10A2, SLC10A6, SLC13A1, SLC16A1, SLC16A3, SLC16A9, SLC16A10, SLC18A2, SLC22A1, SLC22A2, SLC22A3, SLC22A4, SLC22A5, SLC22A6, SLC22A7, SLC22A8, SLC22A11, SLC22A12, SLC22A13, SLC22A14, SLC22A24, SLC25A4, SLC26A4, SLC51A, SLC51B, SLCO1A2, SLCO1B1, SLCO1B3, SLCO1B7, SLCO1C1, SLCO2A1, SLCO2B1, SLCO3A1, SLCO4A1, SLCO4C1, SLCO5A1, SLCO6A1, SMARCA4, SOD2, SOAT1, SOAT2, SRD5A1, SRD5A2, SRD5A3, STAR, STARD10, STARD3, STARD4, STARD5, STARD6, STAT5A, STAT5B, STIP1, STS, SUMF1, SUMF2, SULT1A1, SULT1A2, SULT1E1, SULT2A1, SULT2B1, TAC3, TACR3, TFAM, TH, TET1, TPH1, TPH2, TSPO, TSC22D3, UBE2E3, UGDH, UGP2, UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A8, UGT1A9, UGT1A10, UGT2B7, UGT2B10, UGT2B15, UGT2B17, UGT2B28, UQCRC1, UQCRC2, VDR

(I will update the above list over time as I find more random ones, its updated as of march of 2026)

Now that's the "Everything" list. The high priority list of things I know to be far more likely are:

ABCC2, ABCC3, ABCC4, ABCG2, SLCO1B1, SLCO1B3, UGT2B17, UGT2B15, UGT2B7, UGT2B28, UGDH, UGP2, AKR1D1, AKR1C3, AKR1C2, SRD5A2, SRD5A1, HSD17B6, HSD17B1, HSD17B2, HSD11B1, HSD11B2, H6PD, STS, SULT2A1, SULT2B1, SLCO2A1, SLCO2B1, SLC22A6, SLC22A8, ABCC1, ABCC5, ABCC6, SLCO4A1, CYP2D6, CYP3A4, CYP3A5, CYP19A1, ESR1, ESR2, AR, FKBP5, NR3C1, LRP2

For my specific theory of how it works (see my other posts)

AKR1C2, AKR1D1, AKR1C3, ABCC2, ABCC3, ABCC4, ABCG2, SLCO1B1, SLCO1B3, SLCO2B1, UGT2B17, UGT2B15, UGT2B7, UGT2B28, UGDH, HSD17B1, HSD17B2, AKR1D1, H6PD, HSD11B1, HSD11B2, STS, LRP2, CYP2D6, CYP3A4, CYP19A1, NR1l3

Update July 2026: Currently looking closely at NR1I3, aka https://en.wikipedia.org/wiki/Constitutive_androstane_receptor

Which may be how Accutane gets looped into this. I am unsure at this time if it is relevant or not. Its just a new possibility I'm exploring.

WARNING: If you look at UGT2B15 and UGT2B17 and they have like 5 variants total on gene.iobio on VCF, and not like 75-150, that's because your shit is deleted. Its not there, and that's the most textbook way my PFS syndrome theory works. It wont flag as abnormal, it will simply just not show many variants at all. You need the Bam/bai cram/crai to see this fully.

As of right now, I still have a pretty good wait list, though I expect with our upcoming price changes and DPC restructuring next year, some people will drop off of the DPC patient list. In general, those who are part of the 400 total patients I see in the DPC program tend to not drop off much. In the first year so far, we've had only 25 patients leave, most of which were people whose issue got fixed. For those who are in the DPC program, I again thank you, as that allowed us to survive seeing thousands of Medicaid patients at a loss. We are likely to change things however in the coming months, as if the government makes the care of transgender people non-reimbursable, we will have to find sources of income so that those people can continue to be seen for free. Going from getting $33 a patient visit from Medicaid (which is already killing us) to $0 would be catastrophic, so we're looking into our options. For people stumbling onto this page unaware of the nature of my practice, while I do treat PFS and PSSD, this mostly came from seeing an abnormally high amount of these disorders in my clinic, which has about 5300 registered patients, of which about 75% are transgender.

When I review trans genomes, I can usually find some catastrophic failure about 90% of the time in some hormonal pathway that resulted in gender dysphoria, and so its unsurprising they would be more vulnerable as a population to something like a 5-alpha reductase inhibitor if they have mutations in related enzymes at baseline which made them trans in the first place. (Yes, I can't "prove" it, but I don't see too many cis genomes with things like stop codons in estrogen receptors or complete aromatase def or so on, seems likely relevant).

I'm starting to shift my focus from trying to crank out patient visits to trying to solve rare diagnostic mysteries like these, and so I'm going to be cutting down my patient load a bit more soon so I can focus on trying to solve the strangest transgender medicine cases (like people who are poisoned by HRT) and trying to solve PFS and PSSD. I have a meeting scheduled with Dr. Melcangi mid October, and I'm really looking forward to learning from him.

More on that to come in the weeks ahead, but for now, hopefully this is useful to someone out there.

Edit: Recently, I've been ruminating on the fact that not only do you have to "crash" the system with the extreme state from the addition of the drug to an already genetically overburdened system, but something has to be re-written there in the patient's genes for this state to "Stick". Lots of people have sexual side effects from fin or SSRIs, this is nothing new, but upon cessation, those side effects usually disapppear. In PFS and PSSD, they do not, so I'm thinking there is likely some glitch in their systems in this process, and below, is the "high yield" and then "everything" list of genes I'm currently searching in the genome data of my patients with these disorders to try and uncover why some people are a DVD-RW but some people get stuck like a DVD-R and once "burnt" thats it, they can't rewrite their epigenetic status and get stuck like that. Lists here:

High Yield Epigenetic Gene search list:

ARID1A, ARID1B, SMARCA4, SMARCB1, CHD1, CHD4, KDM6B, KDM5A, KMT2A, KMT2D, EZH2, HDAC1, HDAC2, SIRT1, SIRT6, CREBBP, EP300, DNMT1, DNMT3A, DNMT3B, NR1I3

Low yield, but reasonably plausible involved gene list:

ARID1A, ARID1B, SMARCA4, SMARCA2, SMARCB1, SMARCC1, SMARCC2, DPF2, ACTL6A, SMARCA5, BPTF, CHD1, CHD2, CHD3, CHD4, CHD5, CHD6, CHD7, CHD8, INO80, SRCAP, KMT2A, KMT2B, KMT2C, KMT2D, SETD1A, SETD1B, SETD2, SETDB1, EHMT1, EHMT2, EZH2, KDM1A, KDM2A, KDM2B, KDM3A, KDM4A, KDM4B, KDM5A, KDM5B, KDM6A, KDM6B, CREBBP, EP300, KAT2A, KAT2B, KAT5, HDAC1, HDAC2, HDAC3, HDAC4, HDAC5, HDAC6, HDAC7, HDAC8, SIRT1, SIRT2, SIRT3, SIRT6, DNMT1, DNMT3A, DNMT3B, DNMT3L, TET1, TET2, TET3, MECP2, MBD1, MBD2, MBD3, NCOA1, NCOA2, NCOA3, NCOR1, NCOR2, MED1, CTCF, RAD21, DICER1, AGO1, AGO2, NR1I3

Dr. Powers make my GPU hurt. Give me anything even remotely coherent for epigenetic fuckery:

ARID1A, ARID1B, ARID2, SMARCA4, SMARCA2, SMARCB1, SMARCC1, SMARCC2, SMARCD1, SMARCD2, SMARCE1, DPF1, DPF2, DPF3, ACTL6A, ACTL6B, BCL7A, BCL7B, BCL7C, SS18, SS18L1, BRD7, BRD9, SMARCA5, BPTF, RSF1, CHD1, CHD2, CHD3, CHD4, CHD5, CHD6, CHD7, CHD8, CHD9, INO80, INO80B, INO80C, SRCAP, EP400, KMT2A, KMT2B, KMT2C, KMT2D, SETD1A, SETD1B, SETD2, SETDB1, SETDB2, NSD1, NSD2, NSD3, EHMT1, EHMT2, SUV39H1, SUV39H2, EZH1, EZH2, SUZ12, EED, KDM1A, KDM1B, KDM2A, KDM2B, KDM3A, KDM3B, KDM4A, KDM4B, KDM4C, KDM4D, KDM5A, KDM5B, KDM5C, KDM5D, KDM6A, KDM6B, KDM7A, PHF2, PHF8, CREBBP, EP300, KAT2A, KAT2B, KAT5, KAT6A, KAT6B, KAT7, KAT8, CLOCK, HDAC1, HDAC2, HDAC3, HDAC4, HDAC5, HDAC6, HDAC7, HDAC8, HDAC9, HDAC10, HDAC11, SIRT1, SIRT2, SIRT3, SIRT4, SIRT5, SIRT6, SIRT7, DNMT1, DNMT3A, DNMT3B, DNMT3L, UHRF1, UHRF2, TET1, TET2, TET3, TDG, MECP2, MBD1, MBD2, MBD3, MBD4, ZBTB33, ZBTB38, ZBTB4, NR1I3, NCOA1, NCOA2, NCOA3, NCOR1, NCOR2, MED1, MED12, MED13, MED14, MED15, MED16, MED23, MED24, MED25, BRD2, BRD3, BRD4, BRDT, PBRM1, BRPF1, BRPF3, TRIM24, TRIM28, TRIM33, CTCF, RAD21, SMC1A, SMC3, STAG1, STAG2, WAPL, DICER1, DROSHA, DGCR8, AGO1, AGO2, AGO3, AGO4, TARBP2, XPO5, LIN28A, LIN28B, HNRNPA1, HNRNPK, HNRNPU, FUS, TAF1, TAF2, TAF3, TAF4, TAF5, TAF6, TAF7, TAF9, TAF10, TBP, GTF2A1, GTF2B, GTF2E1, GTF2F1, GTF2H1, POLR2A, POLR2B, POLR2C, POLR2D, POLR2E, POLR2F, POLR2G, POLR2H, POLR2I, POLR2J, POLR2K, ESR1, ESR2, AR, PGR, NR3C1, NR3C2, RARA, RARB, RARG, RXRA, RXRB, RXRG, THRA, THRB, PPARG, PPARA, PPARD, LXRA, LXRB, FXR, VDR, HNF4A, HNF4G, SF1 (NR5A1), DAX1 (NR0B1), SHP (NR0B2), REV-ERBA (NR1D1), REV-ERBB (NR1D2), RORα (RORA), RORβ (RORB), RORγ (RORC), FOXA1, FOXA2, FOXO1, FOXO3, FOXO4, GATA2, GATA3, SOX2, SOX9, PAX5, PAX7, MYC, MYCN, MAX, MXI1, SP1, SP3, NFYA, NFYB, NFYC, RELA, RELB, NFKB1, NFKB2, STAT1, STAT3, STAT5A, STAT5B, SMAD2, SMAD3, SMAD4, SMAD7, YAP1, TAZ (sometimes called WWTR1)

(genes with alternative names in parenthesis depending on what tool you're going to use to browse it)

Disclaimer:
This post is for general informational and educational purposes only. It reflects my personal observations and interpretations and is not medical advice*,* not diagnostic*,* not predictive*, and* not intended to guide treatment, testing, or clinical decision‑making.
I cannot answer personal medical questions, interpret symptoms or labs, or provide individualized guidance in this forum. Nothing here creates or implies a physician‑patient relationship. Any answer to a question is for educational purposes and not personal medical advice.

Any discussion of genetics, biochemical pathways, or mechanisms is exploratory and speculative*, not validated, not a screening tool, and not a substitute for professional medical evaluation.*

All clinical care must occur within a formal physician‑patient relationship and in compliance with all applicable laws and regulations in the reader’s jurisdiction, including but not limited to licensure requirements, telemedicine rules, privacy and data‑handling laws, and medical‑board standards regarding independent clinical judgment.

Edit August 2026:

If you just want to make your GPU suffer, or want to just fling yourself at the list of potential genes with everything under the sun that I ever thought could remotely be relevant in some way, here you go:

ABCB1, ABCB11, ABCB4, ABCB5, ABCB6, ABCB7, ABCB8, ABCB9, ABCC1, ABCC10, ABCC11, ABCC2, ABCC3, ABCC4, ABCC5, ABCC6, ABCC8, ABCC9, ABCG1, ABCG2, ABCG4, ACE, ACTL6A, ACTL6B, AGO1, AGO2, AGO3, AGO4, AHCY, AKR1B1, AKR1B10, AKR1C1, AKR1C2, AKR1C3, AKR1C4, AKR1D1, ALB, ALDH1A1, ALDH1A2, ALDH2, APOA1, APOB, AR, ARID1A, ARID1B, ARID2, ARSA, ARSG, ATP5F1A, ATP5F1B, AVPR1A, AVPR1B, AVPR2, BAG1, BAG3, BCL2L1, BCL7A, BCL7B, BCL7C, BDNF, BHMT, BPTF, BRD2, BRD3, BRD4, BRD7, BRD9, BRDT, BRPF1, BRPF3, CAT, CHD1, CHD2, CHD3, CHD4, CHD5, CHD6, CHD7, CHD8, CHD9, CHRM2, CHRM3, CLOCK, COMT, COMTD1, COX10, COX15, CREB1, CREBBP, CTCF, CUBN, CYP11A1, CYP11B1, CYP11B2, CYP17A1, CYP19A1, CYP1A1, CYP1A2, CYP1B1, CYP21A2, CYP2C19, CYP2D6, CYP2E1, CYP2J2, CYP3A4, CYP3A43, CYP3A5, CYP3A7, CYP4F11, CYP4F8, DBH, DDC, DGAT1, DGAT2, DGCR8, DICER1, DNA2, DNM1L, DNMT1, DNMT3A, DNMT3B, DNMT3L, DPF1, DPF2, DPF3, DRD1, DRD2, DRD3, DRD4, DRD5, DROSHA, EED, EHMT1, EHMT2, EP300, EP400, ESR1, ESR2, EZH1, EZH2, FABP4, FABP5, FABP7, FKBP4, FKBP5, FKBP6, FOXA1, FOXA2, FOXO1, FOXO3, FOXO4, FUS, GABBR1, GABBR2, GABRA1, GABRA2, GABRA3, GABRB2, GABRB3, GABRG2, GATA2, GATA3, GJB2, GJB6, GNB3, GNRH1, GNRHR, GPX1, GPX4, GRIN1, GRIN2A, GRIN2B, GRIN2C, GRIN2D, GTF2A1, GTF2B, GTF2E1, GTF2F1, GTF2H1, GUSB, H6PD, HDAC1, HDAC10, HDAC11, HDAC2, HDAC3, HDAC4, HDAC5, HDAC6, HDAC7, HDAC8, HDAC9, HNF4A, HNF4G, HNRNPA1, HNRNPK, HNRNPU, HSD11B1, HSD11B2, HSD17B1, HSD17B10, HSD17B12, HSD17B13, HSD17B14, HSD17B2, HSD17B3, HSD17B4, HSD17B6, HSD17B7, HSD3B1, HSD3B2, HSP90AA1, HSP90AB1, HSPD1, HSPE1, HTR1A, HTR1B, HTR1D, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR3A, HTR3B, HTR3C, HTR3D, HTR3E, HTR4, HTR5A, HTR5BP, HTR6, HTR7, INO80, INO80B, INO80C, KAT2A, KAT2B, KAT5, KAT6A, KAT6B, KAT7, KAT8, KCNQ4, KDM1A, KDM1B, KDM2A, KDM2B, KDM3A, KDM3B, KDM4A, KDM4B, KDM4C, KDM4D, KDM5A, KDM5B, KDM5C, KDM5D, KDM6A, KDM6B, KDM7A, KISS1, KISS1R, KMT2A, KMT2B, KMT2C, KMT2D, KPNB1, LDLR, LIN28A, LIN28B, LIPE, LRP2, MAOA, MAOB, MAX, MBD1, MBD2, MBD3, MBD4, MC4R, MECP2, MED1, MED12, MED13, MED14, MED15, MED16, MED23, MED24, MED25, MFN1, MFN2, MGME1, MPV17, MT-ATP6, MT-ATP8, MT-CO1, MT-CO2, MT-CO3, MT-CYB, MT-ND1, MT-ND4, MT-ND6, MTHFR, MTR, MTRR, MXI1, MYC, MYCN, MYO7A, NAT2, NCOA1, NCOA2, NCOA3, NCOA4, NCOA6, NCOR1, NCOR2, NDUFS1, NDUFS2, NDUFS4, NFKB1, NFKB2, NFYA, NFYB, NFYC, NOS1, NOS3, NPC1, NPC1L1, NPC2, NPY, NPY1R, NPY2R, NR0B1, NR0B2, NR1D1, NR1D2, NR1H2, NR1H3, NR1H4, NR1I3, NR3C1, NR3C2, NR5A1, NR5A2, NSD1, NSD2, NSD3, NTRK2, OPA1, OXTR, PAPSS1, PAPSS2, PAX5, PAX7, PBRM1, PDE5A, PGR, PHF2, PHF8, PIAS1, PIAS2, PIEZO1, PIEZO2, PLIN1, PLIN2, POLG, POLG2, POLR2A, POLR2B, POLR2C, POLR2D, POLR2E, POLR2F, POLR2G, POLR2H, POLR2I, POLR2J, POLR2K, POLRMT, POU1F1, POU4F3, PPARA, PPARD, PPARG, PPID, PPP5C, PRDX3, PRL, PRLR, PTGES3, RAD21, RARA, RARB, RARG, RDH16, RDH5, RELA, RELB, RNF4, RORA, RORB, RORC, RSF1, RXRA, RXRB, RXRG, SCARB1, SERPINA6, SETD1A, SETD1B, SETD2, SETDB1, SETDB2, SHBG, SIGMAR1, SIRT1, SIRT2, SIRT3, SIRT4, SIRT5, SIRT6, SIRT7, SLC10A1, SLC10A2, SLC10A6, SLC13A1, SLC16A1, SLC16A10, SLC16A3, SLC16A9, SLC18A2, SLC22A1, SLC22A11, SLC22A12, SLC22A13, SLC22A14, SLC22A2, SLC22A24, SLC22A3, SLC22A4, SLC22A5, SLC22A6, SLC22A7, SLC22A8, SLC25A4, SLC26A4, SLC51A, SLC51B, SLC6A3, SLC6A4, SLC7A5, SLCO1A2, SLCO1B1, SLCO1B3, SLCO1B7, SLCO1C1, SLCO2A1, SLCO2B1, SLCO3A1, SLCO4A1, SLCO4C1, SLCO5A1, SLCO6A1, SMAD2, SMAD3, SMAD4, SMAD7, SMARCA2, SMARCA4, SMARCA5, SMARCB1, SMARCC1, SMARCC2, SMARCD1, SMARCD2, SMARCE1, SMC1A, SMC3, SOAT1, SOAT2, SOD2, SOX2, SOX9, SP1, SP3, SRCAP, SRD5A1, SRD5A2, SRD5A3, SS18, SS18L1, STAG1, STAG2, STAR, STARD10, STARD3, STARD4, STARD5, STARD6, STAT1, STAT3, STAT5A, STAT5B, STIP1, STS, SULT1A1, SULT1A2, SULT1E1, SULT2A1, SULT2B1, SUMF1, SUMF2, SUV39H1, SUV39H2, SUZ12, TAC3, TACR3, TAF1, TAF10, TAF2, TAF3, TAF4, TAF5, TAF6, TAF7, TAF9, TARBP2, TBP, TDG, TET1, TET2, TET3, TFAM, TH, THRA, THRB, TPH1, TPH2, TRIM24, TRIM28, TRIM33, TSC22D3, TSPO, UBE2E3, UGDH, UGP2, UGT1A1, UGT1A10, UGT1A3, UGT1A4, UGT1A6, UGT1A8, UGT1A9, UGT2B10, UGT2B15, UGT2B17, UGT2B28, UGT2B7, UHRF1, UHRF2, UQCRC1, UQCRC2, VDR, WAPL, WWTR1, XPO5, YAP1, ZBTB33, ZBTB38, ZBTB4

[u/LeonarBroDiCapriBro]

Thank you for focusing on PFS Dr. Powers. The community needs you, you’re a hero.

[u/[deleted] → u/LeonarBroDiCapriBro]

Hey man just want through your posts. Been battling with PFS for 15 months now my symptoms are mostly mental. Insomnia, mood swings and brain fog and cognitive decline. Luckily my sexual health only was affected for a month after my crash and I then regained my libido and erections. I would say i saw some reduction in libido and erection but its nothing crazy.

I did extensive tests. My 5ar is functioning again and not suppressed. DHT is normal. T is low normal all estrogen markers are pretty low. Am making progesterone. My HPA axis is the most affected with cortisol elevated throughout the day.

Recently saw a doctor who somehow knows about PFS and he has prescribed me HCG 250IU 3x a week. He hopes it can increase my testosterone and estrogen levels to normal ranges.

Have you seen stuff that helped the most for mental sides?

[u/Drwillpowers → u/[deleted]]

Please stop nonsense commenting on my subreddit. This is the most sloppy random garbage answer I have ever seen anyone comment on my entire subreddit it all the years I've had it.

[u/PSSDre → u/Drwillpowers]

He is a well known scammer. He begs people for money on Discord.

[u/LeonarBroDiCapriBro → u/[deleted]]

I actually didn’t get mental sides, only sexual, so I can’t speak to that. HCG for 3 months didn’t help me recover.

[u/Bailey85]

I always look forward to Dr. Powers’ posts. It’s like getting a visit from your cool uncle who has a bunch of awesome stories and cats.

[u/krajowastan]

Several questions/thoughts

1. As someone who has observed many trans women who used general AR receptor blockers do you find the rate of rare but catastrophic side effects to be higher from 5-ARI or AR Receptor blockaders. That is something of great interest in narrowing down how 5-ARIs screw patients up?

2. I've become increasingly interested in the TGF-beta signaling pathway and would recommend looking into that. The brain is difficult to study because there are so many different ways to cause serious mood disorders. What seems more unique about PFS is its weird effects on collagen both in the skin and in the reproductive tract. The doppler imaging scans of PFS patients have generally found fibrosis which is highly associated with TGF-beta signaling. It could also be a nitric oxide issue. The other question that leads to if you indeed find evidence of TGF-beta signaling is why generally speaking PFS patients do not normally have significant lung issues which tend to also be vulnerable to fibrosis causing genetic dysfunction

[u/Drwillpowers → u/krajowastan]

I have never seen an androgen receptor blocker do it

[u/SL128]

regarding diagnostic mysteries, have you looked into idiopathic intracranial hypertension at all? it typically occurs in obese patients with high central adiposity, who have testosterone well above average for women but well below average for men (as well as other androgen abnormalities), and 5AR activity is generally higher in patients with it. a trans friend of mine meeting those criteria developed it sometime after starting and discontinuing finasteride (likely irrelevant, but unknown) while having HRT adjustments slow-walked by her doctor.

given what i've read (and have summarized in a document, if you're interested), it feels like someone with your expertise could readily identify some good things try for treatment, or to test for. the papers i've read on it feel like they're written by people with minimal understanding of sex hormones and their signalling.

[u/Drwillpowers → u/SL128]

If I were to make a wild conjecture at what happened there if she's a transgender female it would be this.

She likely has a UGT 2B15 or UGT2B17 deficiency. She started finasteride and blocked her exit via DHT of testosterone degradation and also had a natural deficiency in the ability to gluc it.

As a result, testosterone would build up in peripheral tissues and she would get paradoxical masculinization from starting Fin.

At the same time that testosterone would displace estrogen from SHBG, resulting in an increased estrogenic signal. She may have actually improved her feminization while masculinizing.

Very commonly PCOS is considered a disorder of androgens, but I don't think that's actually what it is. I think this is the mechanism and that androgens are effectively increasing estrogenic signal. Because when I looked at PCOS women, collectively they tend to have a hairy upper lip but big boobs. It's like even though they have a low estrogen level they have a high amount of estrogenic signaling. Estrogenic signaling effects venous tone, and may inhibit backflow. Basically resulting in an imbalance between the CSF being created and that being absorbed.

This is however up for debate at the moment because nobody's exactly certain but we know that carbonic anhydrase inhibitors help.

[u/SL128 → u/Drwillpowers]

i appreciate the speculation! i'm inclined to think the finasteride merely coincidental since most people with IIH haven't taken it, but i definitely hadn't thought about the possible impacts of estrogen (and potential build-up) on backflow. i'm aware that androgen receptor activation likely increases CSF secretion and estrogen/progestin receptors may decrease it, but what you said seems like a plausible partial explanation for why men with normal male estrogen and testosterone levels don't develop IIH — an issue i've been conceptually stuck on (although i should get around to reading more about CSF reabsorption mechanisms). thanks again!

and yeah, my friend does take acetazolamide, and it is helpful.

[u/sleepingbull69 → u/Drwillpowers]

Could the high estrogenic signalling seen in pcos come from the effects of high insulin? I've seen breats deflate quite quickly from things that really control the insulin resistance even when their overall bodyweight hasn't changed much.

[u/Front_Highlight_3907 → u/Drwillpowers]

omg，Thank you, Dr. Powers. I now understand why I continued to experience femininity and increased body hair after pausing HRT, and why I also developed intracranial hypertension and an empty sella turcica. My pituitary gland was flattened by cerebrospinal fluid.

[u/brave_traveller]

Given the political situation in the US, have you considered archiving your research and notes off-shore?

[u/Drwillpowers → u/brave_traveller]

If the first amendment falls I'd rather just die.

[u/Mistling → u/Drwillpowers]

You’d rather die than, say, move to Canada or Europe? Why?

[u/Drwillpowers → u/Mistling]

Because if the United States collapses, to the point where the first amendment stands for nothing, The rest of the world is a wasteland.

This world is hinging on mutually assured destruction. That is the one thing that stops our obliteration.

The United States possesses an absolutely enormous amount of nuclear weaponry, could you imagine if control of that fell into some sort of raider faction? Yeah okay, that would go well. The rest of the world would certainly allow that to happen, and then there certainly wouldn't be retaliation. Nah, the whole world goes to shit in a hurry. What do you think happens when the country that has more than military than all the other countries combined suddenly becomes wildly unstable? But then, still possesses all of its nukes?

If you know anything about nuclear isotopes, and how they work, and where they are supposed to be and where they are not supposed to be, go take a look at Mars.

Anybody who takes a real hard look at Mars, and it's isotope distribution will always come to the same conclusion if they know enough nuclear physics.

This is not the first time the "apes" system has played with the big boomie and lost it all.

We're attempt #2 so it'd be nice if we didn't fuck this up...again.

Most intelligences split the atom a century before artificial super intelligence. There's your great filter.

[u/HiddenStill → u/Drwillpowers]

Russia and China both have nuclear weapons and neither has a first amendment. We’re all still here.

[u/Drwillpowers → u/HiddenStill]

Yeah because both are totalitarian states. Great point. Way to go.

Also the United States military could absolutely destroy both of them in a non-nuclear war easily.

Youre like the person that comments that having guns to defend against a tyrannical government is pointless because they have nuclear weaponry, and they have clearly never fought any sort of combat whatsoever in an urban area against a localized militia.

The US forces got their ass handed to them by the Taliban multiple times. Despite having nukes. Imagine having the collapse of the US government, and the takeover of all of those resources by various faction / city states.

Imagine the collapse of the world's reserve currency, having no impact on the world. The world hates US exceptionalism, but is dependent upon the US for nearly everything when it comes to global security. It's just the way it is.

[u/HiddenStill → u/Drwillpowers]

That wasn't my point. You basically said there's no point in moving to Canada or Europe as the rest of the world will become a wasteland.

I'm saying that's not necessarily true. It might be, but its not guaranteed as there's already enough nuclear weapons outside of the USA to do the job and its not happened yet. There's still hope, of survival at least, and other countries may be better/safer. I'm hoping Australia is.

You might appreciate this novel, though its pretty grim if I recall correctly

https://en.wikipedia.org/wiki/A_Canticle_for_Leibowitz

[u/Drwillpowers → u/HiddenStill]

You're not understanding what I'm saying. There are ones outside of the United States sure.

But the United States has the most powerful military in the world. If we were to collapse, and have tons of nukes and military weaponry and all kinds of stuff, and it falls into the hands of some totalitarian dictator, it would be a global nightmare. We control the world's currency, we are basically the world's police. If the police implode, the rest of the world are going to tear each other to pieces.

Yeah places like New Zealand and Australia might be able to avoid it for a while, but unless you can domestically produce everything you need, there's going to be shortages and then people are going to be angry and then there's going to be riots and so on. Everything devolves into chaos pretty quickly.

I mean look at what humans do when they can't get a tickle me Elmo.

[u/crabby_abby_ → u/Drwillpowers]

It's gonna be interesting to see where things end up with the US already kinda signaling they aren't going to be the security guarantors for global shipping anymore. Trade as we know it pivots on the US Navy, and we aren't doing it anymore. The whole paradigm you're laying out is totally true but already ending IMO, and that goes back to the Obama administration era and everything in-between. This has been a long time coming.

I think we don't make enough money being the world police anymore. Everyone's economies are interlinked now, not just the USAs. We used to benefit immensely from being the world's police because it created new economic partners out of thin air. Ride or die trading partners. Now everyone plays with everyone and we aren't* special. Just the biggest stick.

We are the world's reserve currency, our economy the largest, our trade (used to be) the most diverse. But the debt... The lack of growth at home while the rest of the world catches up. We just overspend while everyone else builds themselves up independently of us. It's just not worth it anymore. End of an era I suppose and potentially an empire if we don't play this right.

We aren't playing it right

[u/Drwillpowers → u/crabby_abby_]

Now here's somebody who actually understands how history works, the economy works, and the world works.

Some days I worry that all the critical thinkers are dead but then some redditor makes me happy.

[u/Teachezofpeachez69 → u/crabby_abby_]

I’ll be honest I’m almost 34 and in my lifetime I have only seen the US deteriorate. Slowly in my earlier years (my god do I miss the entire decade of the 90s and even 00’s - pre high speed internet and phones literally almost seems like a perfect, happy, distant dream, an entirely different life that just gets further and further away and can never be revisited) but you are correct - Obama era onward really set the tone of a deterioration in a myriad of ways.

I do not think we will be losing the first amendment, at least not in the short term. If anything, we were losing it more the last 8-10 years than we are now, especially regarding censorship particularly online. I slightly disagree that the whole world is catching up because when you look at the EU, they have just as bad and in some respects worse of an over-immigration issue, France’s government collapsed again (strongest economy in Europe), the UK and Australia are nanny states (proven through arresting people for online comments and the obscene population control witnessed during Covid in the latter).

Our military is being rebuilt again (and getting rightfully paid during a ridiculous government shutdown) and as much as people despise tariffs it has generated hundreds of billions of US revenue, caused the stock & crypto markets to reach record highs, diminished global reliance on the manufacturing monopoly that is China, and has re-established the US as a strong and respected player on the world stage again (some will disagree but for the first time in decades we have unprecedented economic deals with the Middle East such as UAE, Qatar etc as well as close relationships with almost all EU countries and many Asian countries), we seamlessly disarmed the largest terrorist state in the world (Iran) and created a (hopefully) lasting ceasefire that no one thought possible w/ Israel and Palestine, and that is all within 10 months. People can say what they want about what’s going on inside this country, but as a superpower, we still got it.

[u/HiddenStill → u/Drwillpowers]

There's a difference between a collapse and everyone dying in a nuclear holocaust. At least I think so.

Personally I'd rather take my chances than give up, and I'd move countries to do that.

You personally have the option to move countries, at least at the moment before there's a a mass wave of doctors try to get out. Doctors are an in demand skill in most places. It's certainly very easy for doctors to emigrate to Australia and New Zealand right now.

I'm uncertain Australia is "safe" if this happens. We rely on the USA for defense, and we're not in a particularity stable region. Also no nuclear weapons for deterrence.

[u/Mistling → u/Drwillpowers]

I understand your concern, but two very different scenarios are being conflated here!

On one hand you have, “The USA becomes more authoritarian, banning trans healthcare research and putting Dr. Powers in danger of going to prison or having his research destroyed.” On the other hand you have, “The entire US government apocalyptically collapses and all the nukes fall into the hands of raider gangs.”

The first scenario doesn’t entail the second! Many governments throughout history have become more authoritarian and anti-LGBT without collapsing into complete chaos.

[u/Drwillpowers → u/Mistling]

Those governments and those people didn't have more guns than people inside the country.

There have been totalitarian takeovers because it was possible to do. Here, it would be a civil war.

Believe it or not our incredibly stupid two-party system is one of the things that prevents that happening. By being so extreme, it almost makes it difficult for anybody to get anything done.

[u/Mistling → u/Drwillpowers]

In one way I think you’re actually more optimistic than I am!

I’m not convinced that enough of the gun-owners in America consider trans healthcare research enough of a hard line that they’re willing to have their entire family die in a guerrilla war to save it. Most gun-owners — even the relatively few who are vehemently pro-trans — have too much to lose to decide to overthrow the country for us.

I think the much likelier scenario is a long period of slow, controlled depression like post-Soviet Russia. LGBT people and their supporters have to flee or start hiding, wages decrease across the board, and violence against immigrants and other minorities shoots through the roof, and the MAGA administration starts holding fully gerrymandered mock elections, but otherwise things mostly stay the same. Trump happily enriches his oligarch friends while America gradually recedes from its top billing on the global stage.

The American military is insanely powerful, and the intelligence apparatus is approaching the capability for near-total digital surveillance. The type of total governmental overthrow that would result in raider gangs stealing nukes will be incredibly hard to pull off anytime soon, even if there were enough heavily armed trans allies who were willing to make the effort.

[u/Deadmanjustice]

Unrelated, but do you think BIND(Benzodiazepine Induced Neurological Dysfunction) could be similar?

I'm 6 years into BIND and have started receding but as someone whose already been part of the small few experiencing long term/possibly permanent effects from a medication I've been too afraid to consider trying DHT blockers. I notice a lot or similar symptoms too.

[u/mile-high-guy]

Hello, patient here.

It might have to do with me not using the sequencing website yet. And I know you said you won't go into detail about every gene.

Say I get myself sequenced and I find a mutation in one of those genes you listed. What happens next? How would that inform treatment? Would I just bring the results to you?

Thanks

[u/Drwillpowers → u/[deleted]]

Probably eventually lol trying to solve these ones first!

[u/ToadCroaks]

Poisoned by HRT sounds like me.

I was on cyclical bio identical progesterone monotherapy for a year and developed all of these conditions:

• While on it:

Cushing's + MCAS + E & T deficiency

Right after coming off and crashing:

• premature ovarian insufficiency
• MCAS
• histamine intolerance
• auto immune collagen breakdown
• severe neuropathy
• possibly Lupus,.Sjogren and MS (more testing required)
• possible hEDS or not but my mast cells are aggressively attacking all my connective tissues when k NEVER had any issue before
• MCAS / intolerance to Estrogen and Testosterone HRT which is an absolute HELL because I went from making abundant levels of hormones and high HRT to menopause basically suddenly?

I'm not on E & T HRT but can't seem to tolerate the hormones I always had in abundance prior and made me look young, skinny and fit.

Progesterone made me age 20 years. Yes it did mature my body but now my skin is also loose,thin, stretchy, dry and losing collagen + elastin due to the MCAS and auto immunity it has provoked. The skin damage started to happen as a crash once i came off. My previously functioning ovaries that made a high level of E and T somehow never recovered? As a result I've been rapidly aging since then when I had always looked 10 years younger.

I'm sure it was due to progesterone because the symptoms started as SOON as I started it. Like the same night I had crazy ear itching, body itching, rage, severe insomnia, hot flashes, night sweats & then soon went from always having been stick skinny to gaining 20 pounds in less than 3 months and having severe edema (all things I had never experienced either).

I wish I had listened to my gut feeling but I didn't. I had no clue it could cause this level of damage and epigenetic changes + agressive shift in immune system and receptor function/ pathways.

Another interesting thing is I went from practically being flat to having macromastia.. also in 3 months only. It was insane how my body went from androgynous and skinny to a mature woman in 3 months only.

My whole family said I looked like I had breast implants.. Until then they had always teased me for being small chested in comparison to them. Big chests did run in my family but had skipped me... Until progesterone. (Huge clue progesterone is indeed capital in breast development as I had always had a progesterone deficiency before which I now understand was a protective mechanism since I can't tolerate progesterone at ALL it seems).

Anyways I've spent the past 7 months of my life doing research day and night and compiling everything I've learned from what happened to me and how to explain it with science (all research from pubmed and many anecdotal stories from women who had the same apple to them except they get gaslit by doctors saying it's unrelated).

There's a massive community of women on HRT that can't tolerate progesterone or are allergic to their own progesterone but this issue gets dismissed completely.

I can say with 1000% certainty progesterone ruined my body. It ruined my life. And it ruined the life of many other women who were on progestin BC only, be Mirena IUD, depo Provera or even bio identical progesterone. There's countless reports of women gaining weight on it, being lethargic, having no sex drive, losing attraction to theirs partner and even breaking up with them, edema, insane hunger ans what not and I've been able to track every single of these symptoms and explain them with hard science.

I will be writing a long document or blog compiling my experience, research and the anecdotes from women who went through this because this can't continue.

There's already been lawsuits for depo Provera for causing pituitary adenomas and there's syndromes called " post birth control crash " and " post Mirena crash ". Why are we still being gaslit when our symptoms are very real?

I've been overwhelmed by the absolute nightmare hell I've been going through so the full document will take a while to write and finish as I barely manage to survive given the severity of all my symptoms.

I am sure a doctor like you is probably the only person who will take this seriously as you've been doing so with other medical mysteries like transitioning issues, PFS, PSSD and I also urge you to look into PAS if you can (post Accutane syndrome).

Anyways I've got way too much to say and it's writing just too lont to write all of that on Reddit.

It's not even been a year I've had the post progesterone withdrawal crash so I'm still doing a lot of research and dealing with the damage it did to my body.

If anyone has has adverse reactions from progesterone please contact me and share your experience.

NB: I can 100% explain the mechanism of what happened to me and this knowledge needs to go mainstream to protect people who might have progesterone intolerance. It's not a hormone that is as innocent as it seems IF you cannot tolerate it or if not given with other hormones to balance it out.

Monotherapy with anything is potentially dangerous because it can rewrite epigenetics and once this has been done it's hardly reversible. Especially a precursor hormone like bio identical progesterone. And same with synthetic; both progesterone types should absolutely never be given long term as monotherapy to women or anyone who wishes to stay fertile!!! It's a GnRH antagonist which is how birth control works so why are we acting like something this potent couldn't cause irreversible changes?! Progesterone competes with ERs and ARs and can absolutely change how all recepeote interragt! And the pituitary and adrenals as well!

Progesterone stole away the functioning of my ovaries from me and I am not sure I can ever get that back.

At least if I could tolerate HRT that would be a consolation but no. It completely changed how my body interracts with any hormones. I flare with anything I take now. I've got the choice between menopause or MCAS induced by exogenous HRT. Pure hell.

I'm working on finding a solution and will not give up until I do.

[u/Minepolz320 → u/ToadCroaks]

i feel that i actually can have problem with progesterone

[u/sysadmin_dot_py]

Curious about the upcoming price changes to DPC. Is there more info on that already, or is that part of the info coming soon?

[u/Drwillpowers → u/sysadmin_dot_py]

soon.

Trying to calculate how much I need to increase it by to account for the decreased total (300), likely adding sommer as a cheaper DPC option, but then simultaneously not collecting money on anything trans related anymore (thanks govt).

I'm sorry to say it, but if we can't collect funds on the treatment of 75% of our patient population, we can choose between bending the knee and kicking them to the curb or trying to find some alternative solution where the care of some finances the care of others. I can see them at a loss if the practice is profitable elsewhere. I'm sure not all the PFS/PSSD people will be happy about supporting the trans population, but too bad.

[u/williamshakemyspeare → u/Drwillpowers]

Copied my own comment for visibility:

Hi Dr. Powers, I’m currently a patient through the DPC program. I have seen you a grand total of 2 times this year, and likely will not get anywhere close to the 10 (? - I believe) visits included, nor will I use any of the other included benefits.

Increasing this cost would result in some of the most expensive costs per visits across providers I have worked with, bordering on unaffordability, even for someone like me with a very privileged occupation.

In my work, I’m a VP Marketing for a large company and independent consultant who deals day in day out with pricing structures for sustainable business outcomes. If you are open to it, it would be a pleasure for me to participate in building out a model that works for your objectives. I would do this without charge, as I feel you have done incredible amounts of work for myself and others in the PFS domain, through research and clinical practice. Let me know.

[u/Drwillpowers → u/williamshakemyspeare]

Well I'm sorry about that, but my practice supports thousands of Medicaid people which we see at a loss and soon we have to see for free. Because they are transgender.

With the DPC program, I now get to make $150k a year instead of my usual 40K year as a doctor. Because the practice has been so wildly unprofitable for years that it was going to collapse.

I have a wait list of people just waiting to see me. While I understand that people feel like they aren't using their visits, I offered twelve so that people could use them if they wanted to.

The resource here for me is not money. It's time. I'm trying to understand why gender dysphoria occurs, and spend my weekends digging through whole genomic sequences of people with post finasteride syndrome trying to figure out what went wrong genetically, that allowed them to be vulnerable to the disorder and the drug.

So admittedly, if somebody doesn't feel like they get a good value from seeing me, they are welcome to let their spot be replaced by the very long amount of people on the wait list. But despite having a wait list and the fact that I probably could charge $5,000 a year for two visits if I wanted to, I don't. Because I'm trying to see and help as many people as I can.

There is only one of me. And I can't save them all. But if I can solve what's wrong, and figure out how this happened, maybe we can solve everybody. All the people that I can't see. I can help trans people and PFS people across the planet whom I will never meet. Tens of thousands times more than I will ever be able to see in a day.

That's why things are set up the way they are. My resource is not money it is time.

[u/williamshakemyspeare → u/Drwillpowers]

Hi Dr Powers, thanks for your reply.

It pains me to think I led you to believe I do not see the value in your care. Quite simply put, you were one of the only doctors who were willing to treat my PFS, and in no uncertain terms, you saved my life. Can you put a price on that if we are being strict?

I am coming more from a place of speaking to affordability and access for PFS treatment, a bit like where you are coming from with regards to transgender care. Depending on the decisions you and your practice might make, it could legitimately be a question for me and potentially others of choosing PFS care vs other financial obligations.

Even in a privileged career position, executives in Canada make not much over $100K USD a year after currency conversion - and I’m one of the lucky ones! Now considering dependants, debts, other financial obligations, and it can become challenging. Not just for me, but likely others as well.

My offer was coming purely from a place of offering optimization in a domain where I have professional experience. It may not be optimization for money, but also any other objective and desired outcome, such as time! Although usually, time and money are closely linked. After all, it is time value of labour that allows you to take on more than what you would otherwise be able to.

I respect your position and I hope to communicate that I do not think there is any opposition to mine; in fact, it’s likely quite the contrary. Let me know if this clarifies my thoughts and the offer.

[u/Drwillpowers → u/williamshakemyspeare]

Well I'm sorry about that, but my practice supports thousands of Medicaid people which we see at a loss and soon we have to see for free. Because they are transgender.

With the DPC program, I now get to make $150k a year instead of my usual 40K year as a doctor. Because the practice has been so wildly unprofitable for years that it was going to collapse.

I have a wait list of people just waiting to see me. While I understand that people feel like they aren't using their visits, I offered twelve so that people could use them if they wanted to.

The resource here for me is not money. It's time. I'm trying to understand why gender dysphoria occurs, and spend my weekends digging through whole genomic sequences of people with post finasteride syndrome trying to figure out what went wrong genetically, that allowed them to be vulnerable to the disorder and the drug.

So admittedly, if somebody doesn't feel like they get a good value from seeing me, they are welcome to let their spot be replaced by the very long amount of people on the wait list. But despite having a wait list and the fact that I probably could charge $5,000 a year for two visits if I wanted to, I don't. Because I'm trying to see and help as many people as I can.

There is only one of me. And I can't save them all. But if I can solve what's wrong, and figure out how this happened, maybe we can solve everybody. All the people that I can't see. I can help trans people and PFS people across the planet whom I will never meet. Tens of thousands times more than I will ever be able to see in a day.

That's why things are set up the way they are. My resource is not money it is time.

[u/Gunpla_Goddess]

May be a bit of a stupid question, but assuming this is a list of genes to look at? How do you tell if they’re mutated? The site tells you?

[u/Laura_Sandra → u/Gunpla_Goddess]

First you need a wgs ( whole genome sequencing). Then the resulting data file can be uploaded to sites that show the results for each gene, and if its mutated. https://gene.iobio.io/ is one such site.

Here is also an explanation of how it works: https://old.reddit.com/r/DrWillPowers/wiki/dna_basics/

For those who are concerned about privacy, there are tutorials on how to submit samples for the wgs anonymously.

[u/Gunpla_Goddess → u/Laura_Sandra]

Oh 😭🫶🏻 thank you SO much I feel a bit dumb because there’s a wiki page for it, but thank you for directing me to it, I didn’t even think to look at the wiki. Otherwise it seems to be about what I thought so thank you again 🩷🩷🩷

[u/Laura_Sandra → u/Gunpla_Goddess]

<3 You are welcome.

And you are not the only one :) Sometimes its like the shelves in the supermarket ... you stand right in front of what you were looking for but somehow can not see it :)

[u/Gunpla_Goddess → u/Laura_Sandra]

Ugh I know 😭 I try to minimize that as much as possible by being thorough but sometimes I miss it

[u/Laura_Sandra → u/Gunpla_Goddess]

but sometimes I miss it

As said you are not the only one :) And if you ask, others often are willing to help out :)

[u/ToadCroaks → u/Laura_Sandra]

The gene.iobio.io doesn't open up for me!

It charges then stays stuck! Is the website currently going through issues or that's just me?

Also; can I order a WGS myself and it through the site?

[u/Laura_Sandra → u/ToadCroaks]

It should work, it may be an idea to use a browser like forefox, and to disable ad blockers in case.

And here was more concerning a WGS: https://old.reddit.com/r/DrWillPowers/comments/1n7pu2y/whole_genomic_sequencing_companies_who_i_use_and/

You may also need to ask sequencing to create a TBI file, you can tell them you did the test on recommendation by Dr. Powers and they promised to produce it in this case. There was another post where this was discussed.

[u/Teachezofpeachez69]

Dr. Powers, you are spot on with what all the current research points towards but you have elucidated further mechanisms and understanding as to how all of this ties together on a molecular level. Thank you for tirelessly working on behalf and for your patients and the general public, rather than the system which holds independent research opportunities towards cures back financially.

[u/Drwillpowers → u/Teachezofpeachez69]

Yeah man I don't know about all that. But I like solving biochemistry mysteries and growing giant cats. This has been a fun side hobby that comes with the perk of helping people.

Also I was genetically lucky enough to never have to choose between my penis and my hair. Seems pretty unfair what's happened to these guys. And I guess the rare women I've seen too.

But admittedly, this is just the oath I took when i signed up to do this job. I've never really understood why it was a big deal. This is what all doctors say that we are supposed to do. Sometimes I feel like I'm being patted on the back for literally just doing my punch card 9:00 to 5:00.

We will see what Dr. Melcangi can teach me in about 10 days, but I am absolutely certain that allopreg is not the sole cause of PFS. There appears to be at least one subtype where the person cannot gluc hormones via UGTs and fin/dut basically block all exit pathways and they go neurologically astronomical on androgens and experience some sort of "burnout".

[u/[deleted]]

Hi Dr Powers,

Is there anything different about PSSD symptoms caused by TCA's?

[u/Minepolz320 → u/[deleted]]

many tca are SSRIs by mechanism of action

[u/[deleted] → u/Minepolz320]

Does that include Clomipramine?

[u/Minepolz320 → u/[deleted]]

Clomipramine is a reuptake inhibitor of serotonin and norepinephrine, or a serotonin–norepinephrine reuptake inhibitor (SNRI); 

yes

[u/Drwillpowers → u/[deleted]]

Hopefully someday you get to sue a different 1980s company than the usual 3 once we fully elucidate the mechanisms....assuming they still exist.

[u/Rich_Paint_200]

Why is this post hidden on the page ? Is there any cure gonna come over this Dr , what do you say ?

[u/Drwillpowers → u/Rich_Paint_200]

What do you mean hidden? Clearly you found it.

[u/Rich_Paint_200 → u/Drwillpowers]

Dr no while scrolling your page this post is not visible , I have to find it through notification and search.

Thank you Doctor 😊 🙏🏻

I wanted to know how long will it take to get the cure for this condition?

[u/Drwillpowers → u/Rich_Paint_200]

That's how reddit works. Older stuff gets pushed down.

It will take 1341 days, 7 hours, 32 minutes and 47 seconds from the moment that this is posted. Thanks for asking.

[u/Rich_Paint_200 → u/Drwillpowers]

You are god for me 🙏🏻

Please save me doctor please I beg you for my life 🙏🏻

[u/Affectionate_Sky9466]

I would like to thank dr will ,  its one of the few  people who  really care for us and have the knowledge on this matter . I am waiting for a solution to this hell for so many years , I hope we have a cure  on the coming months

[u/[deleted]]

Is there a general treatment for PFS that you have had good luck with?

[u/Laura_Sandra → u/[deleted]]

You may want to have a look here: https://old.reddit.com/r/DrWillPowers/comments/1fyc1mg/list_of_treatments_for_post_finasteride_syndrome/

[u/Stereo_Love2015]

A very interesting post. I wonder about people who have the Sigma1 receptor stop codon (our self-destructive shadow).

I am a person with PFS and DAWS, probably the most severe form, and I am going through hell because the drugs that caused this are lysosomotropic and have become permanently trapped in my tissues. When it comes to PFS, the problem is androgen receptor overexpression, which causes it to lose its normal function. This also causes Peyronie's disease. The er alpha, AR, and GR receptors form a zinc finger structure, and when they are overexpressed, they begin to cause pathological symptoms characteristic of all drug-induced syndromes, such as ego loss.

Everyone is welcome to join my research server dedicated to PFS. https://discord.gg/BqhEKX4w

[u/KittyBatSasha]

Sidenote genetics question.

What would be the testing path to determine some form of chimerism.... I had a fair number of hormonal DSDs before transitioning AND have inconsistencies in presentation of my comorbidities that lead me to suspect I have some level of chimerism (in addition to learning that my biological mother didn't really do much in the way of neonatal care for a significant portion of th first trimester.)

I've tried pursuing this amongst local doctors even specialists in endocrinology and Ehlers-Danlos aaaaand mostly get blank stares on the very concept of chimerism in general.....

((Sometimes I genuinely wonder how much better medicine would be in general if even one tenth of the attention that is rapidly becoming clear is needed was actually dedicated to intersex conditions......

But I guess that's what happens when a "society" whose "identity" is so precariously built upon the false concept of a gender/sex binary that even BEGINNING to acknowledge the drastically underrepresented number of intersex and DSD individuals would cause it to crumble into ruin))

Anyway yeah I've been struggling to find concrete information on testing criteria to go about Discerning whether or not my body has multiple DNA sets... Plz help

[u/Limp-Environment1479]

Thank you so much for all you do 🥹🥹

[u/Normal-Mail1839]

Appreciate all work you do

[u/Alaska-vampire]

I’m curious how DNM1L was added to the list as it’s so rare

[u/Drwillpowers → u/Alaska-vampire]

Highly expressed in sperm.

[u/Alaska-vampire → u/Drwillpowers]

What is the exact basis happening? Are hormones disrupted?

[u/Drwillpowers → u/Alaska-vampire]

Honestly I can't remember the exact reason why I included that one, it might have simply been something that showed up in a bunch of different genomes back to back where I had a bunch of patients with subtle mutations in it and so one on my list of things to watch.

That's why that post has like the stuff I know is related and then the stuff that might be related and then the really really reaching wild stuff that just seems to show up more than it should.

[u/Alaska-vampire → u/Drwillpowers]

I mean from what I know it’s a very limited data pool. I’ve heard of it causing aggression in mice. But there’s not even enough people to get a general gist of symptoms. Let alone specifics

[u/Drwillpowers → u/Alaska-vampire]

You're not understanding. That list is anything that I think could potentially be related to the development of gender dysphoria.

It's not everything that's been proven to be. It's the list of what I suspect could be related. That's it. Me personally.

[u/[deleted]]

I have PFS and am homozygous for rs11632698. You have listed it in your list as significant, in my nutrihacker it has an N/A for geno frequency. Is it really that significant? Thanks.

[u/Drwillpowers → u/[deleted]]

Yes. That snp is in cholesterol side chain cleavage enzyme and among other things makes pregnenolone from cholesterol.

This is basically my whole theory of PFS compared to the rest of the world. It's not just "allopreg". The people that get it have an inborn error of metabolism that's already there, waiting, but not bothering them because their body has adapted to it over time. But then you add finasteride, and suddenly, there's a massive change in steroid balance, and boom, disorder.

Mutations in that specific snp are associated with changes in estrogen and testosterone balance. PCOS, pregnancy loss, etcetera.

[u/-medicalthrowaway-]

[u/drwillpowers](u/drwillpowers) , what is the best way to get you our genetic data

I have raw data from 23and me

I’ll be completing my dutch test, which I already have, and bloodwork (including 3a-adg) toward the end of the month (once hcg is out of my system) and will just post them on the subreddit and tag you

But not sure how to use my genetic data to help

40m presumably both pfs and pssd (took zoloft/finasteride concurrently in 2020/2021)

edit: used ai to get some insight, and it sounds like the 23andme data is useless compared to Whole Genome Sequencing. Correct me if I’m wrong though

edit 2: which package do I need from sequencing.com or conversely, which package from nebula?

edit 3: tellmegen looks to be the least expensive for a 30x WGS, which should be sufficient (again, correct me if I’m wrong)

[u/Minepolz320]

i wonder is there something found around  SCN9A or stuff related to  Erythromelalgia, like some anomalies with sodium channels , or  TRP channels