- Messages
- 11
FOREWORD: I have 0 experience with anything medical, chemical, endocrinological, or otherwise. I am a bum with a computer and some dangerous ideas. Do not try anything in this post. It will probably worsen, permanently disable, or kill you. I’m just throwing shit at the wall here after staring at pubmed for too long.
I'm sure everyone has seen this post from Chemhead that has been making the rounds these past few months, if you haven’t I’d suggest giving it a read. How bad is finasteride?
After reading this I was particularly fascinated with it. A sufferer of almost a decade making a near miraculous recovery after a 4 year stint with the condition. I want to explore his musings, connect this to other anecdotes in the PFS sphere, and draw up a potential protocol I may try myself.
The core of Chemhead’s theory is that there is a codependent/reflexive relationship between the expression of 5 alpha reductase and some extra thyroidal elements including thyroid receptor beta (TRβ) and deiodinase 1. He posits that attacking from both ends of this, by supplementing both exogenous androgens (DHT) and including some sort of thyroid support in the form of heavy doses of cofactors (especially iodine) or thyroid hormones that one might be able to recover from PFS.
However so far despite some attempting this, including Chemhead himself, none have been able to replicate it. While this is often the case with PFS recoveries, I think Chemhead himself and everyone discussing this glosses over the most eye-catching fact that he only briefly mentions about his last successful recovery.. the use of an anti-androgen prior to recovery. Let’s explore.
Androgens and Thyroid, Best Buds
I think Chemhead’s theory about 5aR deficiency + lack of thyroidal support holds water. There is a lot of precedent in PFS recoveries already to support it. Some have made significant recovery progress citing androgens as a major column if not the primary reason for their recovery - pal[1], AlphaGels[2], FL1025[3], bear111[4], and hemingway[5] are just some examples. Though clearly this is only a piece of the puzzle, otherwise everyone could simply knock back some proviron for a week and move on with their life. Many have tried and failed.
In comes our friend Chemhead, now introducing us to the wonderful power of the thyroid with citations to boot. Clearly this too is a major piece of the puzzle. While Chemhead has now possibly shed light on a mechanistic understanding, many in the past have cited the thyroid as a major pillar in PFS and their own recovery. Josh, a science-minded former sufferer discusses the thyroid as a major pillar[6]. hCG, a commonly successful therapeutic is a known thyroid stimulating hormone[7]. Even the mighty androsterone, responsible for many a CDSNuts recovery, while also metabolizing to DHT, is a known thyroid hormone mimetic[8]. Even a urologist familiar with the condition seems to have independently adopted his own pet theory of “intracellular hypothyroidism”[9].
While there is a clear picture to be drawn here closely linking androgens and thyroid function.. we’re obviously still missing some pieces. Many in Chemhead’s thread including Chemhead himself have tried to replicate his results with no success thus far. This is where I would like to start building on Chemhead’s theory and discuss the one part of his final recovery that he didn’t.
Hair of the Dog
The last thing Chemhead mentioned was using a topical androgen receptor antagonist / SARM called RU58841 weeks before his recovery. I think this small crumb is more significant than he has let on. Let’s examine a few facts and anecdotes about PFS.
With these facts in mind we can start to expand this theoretical picture of PFS a little. I believe androgen receptor overexpression plays a huge role in driving the condition. Perhaps even *the* role. Even the folks over at the PFS Network have come to a similar conclusion[16]. They discuss the existence of an inverted U shaped or horseshoe shaped response curve of the androgen receptor to its ligands. Positing that an overexpressed AR with normal levels of androgens could in fact behave much like a normally expressed AR with low levels of androgens - exhibiting a lack of phenotypic expression and function. A la, your dick doesn’t work and you feel like dogshit.
Considering this it may make sense why a lot of these strange and often paradoxical things happen with PFS sufferers. Testosterone would push your androgenic stimulation on these already overexpressed receptors even higher to possibly cell toxic levels where signalling would shut down even more. 5aRis and AAs (anti-androgens) would however lower the overall levels of stimulation in some cases making people feel better. You however run the risk of worsening your PFS, presumably due to starving still healthy cells of much needed androgenic stimulation.
So the million dollar question then is.. can we lower the expression of these overexpressed receptors? Interestingly that has been the same question on the minds of those researching castration resistant prostate cancer. One of the primary treatments for prostate cancer is depleting the body of androgens by using drugs that prevent the body from delivering androgens to the AR.. sound familiar? In some cases they even do in fact use 5aRis like Finasteride. One of the problems they eventually run into is that in an androgen depleted environment, in the absence of being able to adjust androgen creation.. the body will adjust everything else to compensate. This means overexpressing the androgen receptor[17] to make prostate cells more sensitive to what little residual androgens are still available and downregulating the metabolism of these androgens by lowering glucuronidation pathways[18]. It is even possible this glucuronidation pathway is reflexive of AR expression[19]. These stories are starting to rhyme…
Unfortunately in the case of prostate cancer, once it becomes castration resistant, the prognosis for the patient is poor and the only tools left in the tool bag are radiation and aggressive chemotherapy. However there is one simple thing they cannot try in cancer therapy that we can… increasing androgens. Doing this in a prostate cancer therapy patient would cause it to quickly metastasize and kill them. However in our case we can do it easily and with comparatively less risk other than a “crash”.
But wait.. didn’t we just discuss raising androgens? Yes, in fact I believe that raising androgens is also the cause of the crash to begin with. Ie: When you stop the AA and androgen signalling rapidly returns to the AR. I suspect that it is the speed and metabolic circumstances in which androgens are raised that is the difference between a PFS sufferer and someone who used Finasteride, tossed it in the trash, and moved on with their lives. Raising these androgens “too fast” for the body to cope with causes some kind of maladapted homeostatic response where the AR gets stuck overexpressed.
This is where my theory breaks down into loose ends, “vibes”, and speculation (but hey that’s what this forum is for). I almost wonder if Chemhead stumbled on to some sort of bizarrely paradoxical therapeutic for PFS. PFS is filled with paradoxes and I wouldn’t be surprised to see yet another. So far I think some recovery factors we have found empirical evidence for are:
There are very likely more knobs and dials to look for here so I’m continuing to dig. The androgen receptor has possibly hundreds of coregulators, many of which are still under active research, so there is quite a sea of knowledge to explore. Some names I have seen pop up in the PFS/PSSD/PAS & COVID research spaces that are likely relevant to our quest are P53 (guardian of the genome), ACE2, TMPRSS2 (both responsible for COVID pathology)
Here are a few other challenging questions I have asked myself and I think the explanations for them that line up with the “AR” theory…
Isn’t 5aR downregulated / what about the lower neurosteroids in CSF?
> Yes I also think 5aR is downregulated but I don’t think it is the root cause. In fact if anything I think it is simply a knock on effect of the lack of androgen signalling. If you’ll remember, pure AR antagonists like RU58841 also induce this syndrome and even GnRH drugs like Lupron can cause similar symptoms. It is also notable that all isoenzymes of 5aR have an androgen response element (ARE) in the promoter region of their genes suggesting that adequate androgenic signalling is required for their expression. Yet another cylinder in Chemhead’s codependent “diesel engine” analogy.
Aren’t there *thousands* of genes misexpressed, why just the focus on AR?
> I suspect all of these misexpressed genes are also knock on effects of dysregulated AR signalling. The androgen receptor is a nuclear receptor responsible for coregulating a fat chunk of the genome including *other* regulatory genes like p53 which is the noted “guardian of the genome”.
Other loose but notable points of interest
A rough starter visual of Chemhead's theory of codependency... I'm gonna expand this later as I dig stuff up
Here’s a rough skeleton if like me you are reckless and have little regard for life. Just to spell it out THIS IS INCREDIBLY DANGEROUS AND COULD KILL YOU OR LEAVE YOU IN IMMENSE SUFFERING
Questions, thoughts, statements of disgust?
CITATIONS
I'm sure everyone has seen this post from Chemhead that has been making the rounds these past few months, if you haven’t I’d suggest giving it a read. How bad is finasteride?
After reading this I was particularly fascinated with it. A sufferer of almost a decade making a near miraculous recovery after a 4 year stint with the condition. I want to explore his musings, connect this to other anecdotes in the PFS sphere, and draw up a potential protocol I may try myself.
The core of Chemhead’s theory is that there is a codependent/reflexive relationship between the expression of 5 alpha reductase and some extra thyroidal elements including thyroid receptor beta (TRβ) and deiodinase 1. He posits that attacking from both ends of this, by supplementing both exogenous androgens (DHT) and including some sort of thyroid support in the form of heavy doses of cofactors (especially iodine) or thyroid hormones that one might be able to recover from PFS.
However so far despite some attempting this, including Chemhead himself, none have been able to replicate it. While this is often the case with PFS recoveries, I think Chemhead himself and everyone discussing this glosses over the most eye-catching fact that he only briefly mentions about his last successful recovery.. the use of an anti-androgen prior to recovery. Let’s explore.
Androgens and Thyroid, Best Buds
I think Chemhead’s theory about 5aR deficiency + lack of thyroidal support holds water. There is a lot of precedent in PFS recoveries already to support it. Some have made significant recovery progress citing androgens as a major column if not the primary reason for their recovery - pal[1], AlphaGels[2], FL1025[3], bear111[4], and hemingway[5] are just some examples. Though clearly this is only a piece of the puzzle, otherwise everyone could simply knock back some proviron for a week and move on with their life. Many have tried and failed.
In comes our friend Chemhead, now introducing us to the wonderful power of the thyroid with citations to boot. Clearly this too is a major piece of the puzzle. While Chemhead has now possibly shed light on a mechanistic understanding, many in the past have cited the thyroid as a major pillar in PFS and their own recovery. Josh, a science-minded former sufferer discusses the thyroid as a major pillar[6]. hCG, a commonly successful therapeutic is a known thyroid stimulating hormone[7]. Even the mighty androsterone, responsible for many a CDSNuts recovery, while also metabolizing to DHT, is a known thyroid hormone mimetic[8]. Even a urologist familiar with the condition seems to have independently adopted his own pet theory of “intracellular hypothyroidism”[9].
While there is a clear picture to be drawn here closely linking androgens and thyroid function.. we’re obviously still missing some pieces. Many in Chemhead’s thread including Chemhead himself have tried to replicate his results with no success thus far. This is where I would like to start building on Chemhead’s theory and discuss the one part of his final recovery that he didn’t.
Hair of the Dog
The last thing Chemhead mentioned was using a topical androgen receptor antagonist / SARM called RU58841 weeks before his recovery. I think this small crumb is more significant than he has let on. Let’s examine a few facts and anecdotes about PFS.
- FACT - PFS sufferers have overexpressed androgen receptors in specific tissues[10]
- ANECDOTE - PFS sufferers often report that anti-androgenic substances, like 5aRis/AAs/etc can paradoxically provide temporary but acute reprieve from symptoms despite their implicit danger[11][12][13]
- ANECDOTE - PFS sufferers often report that administering exogenous androgens, or TRT, can make them paradoxically feel worse[14][2]
- FACT - PFS sufferers exhibit many of the signs of hypogonadism, or low androgens, while testing with sufficient or even high serum levels of androgens[15]
With these facts in mind we can start to expand this theoretical picture of PFS a little. I believe androgen receptor overexpression plays a huge role in driving the condition. Perhaps even *the* role. Even the folks over at the PFS Network have come to a similar conclusion[16]. They discuss the existence of an inverted U shaped or horseshoe shaped response curve of the androgen receptor to its ligands. Positing that an overexpressed AR with normal levels of androgens could in fact behave much like a normally expressed AR with low levels of androgens - exhibiting a lack of phenotypic expression and function. A la, your dick doesn’t work and you feel like dogshit.
Considering this it may make sense why a lot of these strange and often paradoxical things happen with PFS sufferers. Testosterone would push your androgenic stimulation on these already overexpressed receptors even higher to possibly cell toxic levels where signalling would shut down even more. 5aRis and AAs (anti-androgens) would however lower the overall levels of stimulation in some cases making people feel better. You however run the risk of worsening your PFS, presumably due to starving still healthy cells of much needed androgenic stimulation.
So the million dollar question then is.. can we lower the expression of these overexpressed receptors? Interestingly that has been the same question on the minds of those researching castration resistant prostate cancer. One of the primary treatments for prostate cancer is depleting the body of androgens by using drugs that prevent the body from delivering androgens to the AR.. sound familiar? In some cases they even do in fact use 5aRis like Finasteride. One of the problems they eventually run into is that in an androgen depleted environment, in the absence of being able to adjust androgen creation.. the body will adjust everything else to compensate. This means overexpressing the androgen receptor[17] to make prostate cells more sensitive to what little residual androgens are still available and downregulating the metabolism of these androgens by lowering glucuronidation pathways[18]. It is even possible this glucuronidation pathway is reflexive of AR expression[19]. These stories are starting to rhyme…
Unfortunately in the case of prostate cancer, once it becomes castration resistant, the prognosis for the patient is poor and the only tools left in the tool bag are radiation and aggressive chemotherapy. However there is one simple thing they cannot try in cancer therapy that we can… increasing androgens. Doing this in a prostate cancer therapy patient would cause it to quickly metastasize and kill them. However in our case we can do it easily and with comparatively less risk other than a “crash”.
But wait.. didn’t we just discuss raising androgens? Yes, in fact I believe that raising androgens is also the cause of the crash to begin with. Ie: When you stop the AA and androgen signalling rapidly returns to the AR. I suspect that it is the speed and metabolic circumstances in which androgens are raised that is the difference between a PFS sufferer and someone who used Finasteride, tossed it in the trash, and moved on with their lives. Raising these androgens “too fast” for the body to cope with causes some kind of maladapted homeostatic response where the AR gets stuck overexpressed.
This is where my theory breaks down into loose ends, “vibes”, and speculation (but hey that’s what this forum is for). I almost wonder if Chemhead stumbled on to some sort of bizarrely paradoxical therapeutic for PFS. PFS is filled with paradoxes and I wouldn’t be surprised to see yet another. So far I think some recovery factors we have found empirical evidence for are:
- Sufficient support of extrathyroidal function (TRβ and deiodinase 1) via iodine & cofactors
- Sufficient function of glucuronidation / metabolic clearance of androgens, no idea how or if we can modulate this.. may be partially driven by thyroid and AR which is a catch 22, I am still trawling pubmed
- Sufficient feedback regulation of 5αR by DHT (SRD5A1 and 5A2 are supposedly positively regulated but SRD5A3 appears to be negatively regulated)
There are very likely more knobs and dials to look for here so I’m continuing to dig. The androgen receptor has possibly hundreds of coregulators, many of which are still under active research, so there is quite a sea of knowledge to explore. Some names I have seen pop up in the PFS/PSSD/PAS & COVID research spaces that are likely relevant to our quest are P53 (guardian of the genome), ACE2, TMPRSS2 (both responsible for COVID pathology)
Here are a few other challenging questions I have asked myself and I think the explanations for them that line up with the “AR” theory…
Isn’t 5aR downregulated / what about the lower neurosteroids in CSF?
> Yes I also think 5aR is downregulated but I don’t think it is the root cause. In fact if anything I think it is simply a knock on effect of the lack of androgen signalling. If you’ll remember, pure AR antagonists like RU58841 also induce this syndrome and even GnRH drugs like Lupron can cause similar symptoms. It is also notable that all isoenzymes of 5aR have an androgen response element (ARE) in the promoter region of their genes suggesting that adequate androgenic signalling is required for their expression. Yet another cylinder in Chemhead’s codependent “diesel engine” analogy.
Aren’t there *thousands* of genes misexpressed, why just the focus on AR?
> I suspect all of these misexpressed genes are also knock on effects of dysregulated AR signalling. The androgen receptor is a nuclear receptor responsible for coregulating a fat chunk of the genome including *other* regulatory genes like p53 which is the noted “guardian of the genome”.
Other loose but notable points of interest
- All 3 classes of drugs that appear to cause similar if not the same syndromes (5aRis, SSRIs, tretinoins) have now all been discovered to cause dysregulation to common cellular proteins like ACE2 and p63[20]. Whether this is exerted by a common rallying point like dysregulated AR I do not know
- All 3 classes of these same drugs have all been discovered to reduce mortality of and protect against COVID[21][22][23]. COVID mortality has been positively correlated with androgen load in the body[24][25] and these drugs may have common effects on proteins COVID uses as it’s infection vector such as ACE2 and TMPRSS2
- The AR is known to modulate immune function. Increased signalling is negatively correlated with immune activity. Anecdotally this may be why you typically see more autoimmune diseases in women and higher COVID severity in men.
- Gbold himself discussed the AR sensitivity and glucuronidation theories back in the day[26][27][28], there may be more knowledge nuggets we can dig up from him
A rough starter visual of Chemhead's theory of codependency... I'm gonna expand this later as I dig stuff up
Here’s a rough skeleton if like me you are reckless and have little regard for life. Just to spell it out THIS IS INCREDIBLY DANGEROUS AND COULD KILL YOU OR LEAVE YOU IN IMMENSE SUFFERING
- hCG 250IU EOD to maintain steroidogenesis
- DHT topically 50-240mg/day depending on tolerance to attempt to begin stimulating AR and upregulating 5aR - unsure if a smooth or spiky saw wave type dosing pattern is more preferable here
- Diet sufficient in thyroid cofactors + supplemental high dose iodine (in the mg range?)
- RU58841 or some kind of androgen receptor antagonist for a few weeks, very low dose.. maybe something like bicalutamide or spiro would be “safer”? This is the part that can and will likely fuck you up
- I imagine you’d wanna start hCG+DHT, give it a week, start the AA v low dose, run this for a few weeks, drop the AA on a taper (you would want something with a linear dose response curve unlike fucking fin), then wait a couple of weeks and drop the hormones
Questions, thoughts, statements of disgust?
CITATIONS
- Cured after 11 years, PropeciaHelp, <Cured after 11 years>
- AlphaGels replies, Reddit, < >
- Post Finasteride Syndrome, iSARMS, <Post Finasteride Syndrome>
- Post finasteride syndrome, iSARMS, <Post finasteride syndrome>
- Using steroids in the right combination has brought me back to 90% within a week (UPDATED), PropeciaHelp, <Using steroids in the right combination has brought me back to 90% within a week (UPDATED)>
- Post-Finasteride Syndrome and The Thyroid Gland: What you may not know, Web Archive, <Post-Finasteride Syndrome and The Thyroid Gland: What you may not know>
- Kennedy, R L, and J Darne. “The role of hCG in regulation of the thyroid gland in normal and abnormal pregnancy.” Obstetrics and gynecology vol. 78,2 (1991): 298-307., <The role of hCG in regulation of the thyroid gland in normal and abnormal pregnancy - PubMed>
- The Thyromimetic Mechanism Of Androsterone (and Other Androgens), Ray Peat Forum, <The Thyromimetic Mechanism Of Androsterone (and Other Androgens)>
- “FINASTERIDE DEPRESSION”, cbhrt.ca, <FINASTERIDE DEPRESSION>
- Howell, Skyler et al. “Differential Gene Expression in Post-Finasteride Syndrome Patients.” The journal of sexual medicine vol. 18,9 (2021): 1479-1490. doi:10.1016/j.jsxm.2021.05.009, <Differential Gene Expression in Post-Finasteride Syndrome Patients - PubMed>
- Jack17 log, Hackstasis, <Jack17 PFS log>
- PFStinks log, Hackstasis, <PFS almost cured>
- Therapeutic responses to androgens and antiandrogens in PFS, PFS Network, <PFS: Manifestation of a Post-Androgen Deprivation Syndrome following exposure to substances with antiandrogenic effects - propeciahelp.com>
- “RWAC's PFS log (on the TEI train)”, Hackstasis, <RWAC's PFS log (on the TEI train)>
- Pereira, Ana Francisca Junqueira Ribeiro, and Thaissa Oliveira de Almeida Coelho. “Post-finasteride syndrome.” Anais brasileiros de dermatologia vol. 95,3 (2020): 271-277. doi:10.1016/j.abd.2020.02.001, <Post-finasteride syndrome - PubMed>
- Induced Wild Type AR Overexpression and the potential relevance of SBMA to PFS, PFS Network, <PFS: Manifestation of a Post-Androgen Deprivation Syndrome following exposure to substances with antiandrogenic effects - propeciahelp.com>
- Kawata, Hiromitsu et al. “Prolonged treatment with bicalutamide induces androgen receptor overexpression and androgen hypersensitivity.” The Prostate vol. 70,7 (2010): 745-54. doi:10.1002/pros.21107 <Prolonged treatment with bicalutamide induces androgen receptor overexpression and androgen hypersensitivity - PubMed>
- Grosse, Laurent et al. “Androgen glucuronidation: an unexpected target for androgen deprivation therapy, with prognosis and diagnostic implications.” Cancer research vol. 73,23 (2013): 6963-71. doi:10.1158/0008-5472.CAN-13-1462 <Androgen glucuronidation: an unexpected target for androgen deprivation therapy, with prognosis and diagnostic implications - PubMed>
- Zimmer, Brenna M et al. “Altered glucuronidation deregulates androgen dependent response profiles and signifies castration resistance in prostate cancer.” Oncotarget vol. 12,19 1886-1902. 14 Sep. 2021, doi:10.18632/oncotarget.28059 <Altered glucuronidation deregulates androgen dependent response profiles and signifies castration resistance in prostate cancer - PubMed>
- A Cure for PSSD, PFS and Post-Isotretinoin Syndrome, Rxisk, <A Cure for PSSD, PFS and Post-Isotretinoin Syndrome | RxISK>
- Goren, A et al. “Anti-androgens may protect against severe COVID-19 outcomes: results from a prospective cohort study of 77 hospitalized men.” Journal of the European Academy of Dermatology and Venereology : JEADV vol. 35,1 (2021): e13-e15. doi:10.1111/jdv.16953, <Anti-androgens may protect against severe COVID-19 outcomes: results from a prospective cohort study of 77 hospitalized men - PubMed>
- Abdelmaksoud, Ayman et al. “Could isotretinoin be a protective agent against COVID-19?: A dermatologist perspective.” Journal of cosmetic dermatology vol. 20,8 (2021): 2394-2395. doi:10.1111/jocd.14239, <Could isotretinoin be a protective agent against COVID-19?: A dermatologist perspective - PubMed>
- Foletto, Vitória Segabinazzi et al. “Selective serotonin reuptake inhibitor (SSRI) antidepressants reduce COVID-19 infection: prospects for use.” European journal of clinical pharmacology vol. 78,10 (2022): 1601-1611. doi:10.1007/s00228-022-03372-5, <Selective serotonin reuptake inhibitor (SSRI) antidepressants reduce COVID-19 infection: prospects for use - PubMed>
- Moradi, Fatemeh et al. “The role of androgens in COVID-19.” Diabetes & metabolic syndrome vol. 14,6 (2020): 2003-2006. doi:10.1016/j.dsx.2020.10.014, <The role of androgens in COVID-19 - PubMed>
- John, Jeff, and Ken Kesner. “COVID-19: the androgen hypothesis.” African journal of urology : the official journal of the Pan African Urological Surgeons' Association (PAUSA) vol. 26,1 (2020): 55. doi:10.1186/s12301-020-00075-0, <COVID-19: the androgen hypothesis - PubMed>
- Gbold discusses methylation / AR silencing as a possible maladaptation to protect over exposed ARs post-finasteride, Hackstasis, <PFS almost cured>
- Gbold posits a grand molecular theory of PFS, Hackstasis, <FINASTERIDE: PFS MECHANISM (detailed)>
- Gbold discusses glucuronidation as a cog in the PFS machination, Hackstasis, <PFS almost cured>
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