Hi I’m Australian and 35 years of age. My story is below my theory for anyone that would like to read that also. Please be aware this is a running theory and I will continuously change it, due to ongoing understanding of our condition. If you do take any information from here, please check back in, as my theory and any information may have changed. I believe a full recovery needs to be where the body is back to complete homeostasis and continues to be without supplemental modifications and homeostasis stays stable under any circumstance (pre-fin homeostasis). In my opinion I do not believe this will be attained, until a root cause is found to allow for a direct and specific reversal of PFS.
Just briefly I was hit 100% with PFS 2 years ago start of 2018 after taking Finasteride for 8 years. I’ve gone from 30% bodily functions to where I’m at today, which is on the way to recovery. I am not a medical professional, but as many of us on here, I have also spent hours upon hours researching to find answers, I am also:
- Very OCD
- Positive
- Always knew that I can pull myself out of this
- Was fit and healthy beforehand as a Crossfitter and Rugby player
- Was always curious about health being a Physical Education Teacher
- Mentally very strong before crashing
- Could/had to see the funny side of this condition to mentally get through
- Looked at this as a character building experience
I have used all my research along with observing my condition and symptoms to find clues that have led to this ongoing theory. I believe many of the conversations on here are on the right track, but I believe many are pinpointing specific symptoms and supplementing to seek progress, I believe this is a holistic approach and all symptoms that have been discussed can and do fit into this theory. You can also see why this is such a holistic approach to heal…if this theory is correct!. I believe PFS has a simple beginning, but turns very holistic as the domino affect spreads through multiple pathways of the body, trying to compensate for the many imbalances…hence why you are so confused with this condition. I hope my theory sheds some light on PFS and answers some questions you may have been pondering over. I’m not 100% cured, but I’m sure once my body reaches complete homeostasis and balance I will be back to normal.
I believe focusing on one particular area, be that methylation, steroids, inflammation, sleep, erections, so on and so forth, can waste valuable time and potentially exacerbate the condition. Believe me, I was one of these blokes for 1.5 years. I have a box full of supplements, I’ve literally made over 20 different word documents trying to get to the bottom of this and thousands of hours of researching and tweaking in this crazy mind-set we find ourselves in during this imbalance. On the most part, I started making progress when I began to realise that there is multiple pathways that have been affected. This is what I call the DOMINO effect! In my opinion you cannot just treat the initial cause, you have to support all systems that have either been down-regulated, deficient or in a negative loop due to the initial cause.
All the information below comes from scholarly medical papers, but due to time restraints, I’ll leave it up to you guys to do further research to make connections to what I’m saying. It will just take too long to link studies to everything within this post. I also understand that each section of my theory has been spoken about in individual posts previously, but it’s connecting all the dots that I’m interested in and figuring our what the root cause is that has caused a domino affect throughout of body.
My theories…which has and may continue to change as further study and information comes to light, as you’re aware PFS is a tricky one to figure out, but right now at this moment, this is where I’m at! Please don’t be alarmed by the length of this theory, as I said, it has caused multiple pathway dysfunctions! I am also aware that this theory could be completely incorrect… I’d be more than happy for studies, scientist or individuals to prove it wrong, for the benefit of all of us! Let’s face it, it’s about recovering, nothing else! In saying that, I do believe I am on the correct path, which is leading me on the road to recovery.
****Theory currently in DRAFT as of 12:29pm 17/11/19. Sorry for continuously tweaking this theory, but as I get closer to recovery things become clearer. Please be aware that I’m currently editing the information below to try and make it easy for you to understand.
- While on finasteride 5a-reductase is decreased lowering DHT levels
- Androgen receptors become hypersensitive due to Amplification of the androgen receptor gene to low DHT levels and increased levels of mRNA along with upregulation of enzymes involved in steroidogenesis
- Cessation of Propecia/Finasteride
- DHT increases dramatically due to 5a-reducatse inhibition now lifted. Depending on your dosage, this could be 100-150% increase in DHT
- The hypothalamus sees the hormonal imbalance as a stressor and releases ACTH to keep producing androgens
- Adnrogens increase due to
- Increase in Adenylyl Cyclase expression (Finasteride reduces Adenylate cyclase expression)
- Increase in cAMP due to the increase in Adenylate cyclase
- Cytochrome P450c17 phosphorylation increases due to PKA activation
- Androgen receptors are still hyposensitive/overexpressed during the influx of adrogens on cessation of finasteride for the set period of time before we crash
- The body is now in a constant stress response due to an imbalance of androgen’s
- The sudden increase in androgen and overexpressed receptors causes oxidative stress
I believe it’s the timeframe while you’re hyper sexual during overexpression of receptors that sends our body into a cytokine storm and sending out REDOX system out of balance, which in turn literally switches of P450c17 phosphorylation. This is what we all speak about as the feeling of a switch turning off and on. I was so happy when I read this term in a scholarly article. Phosphorylation by PKA of P450c17 happens instantaneously. Where P450c17 from enzymatic cofactors is a slower process
Now the question is how does oxidative stress caused by the sudden influx of DHT and over active androgen receptor turn the phosphation of P450c17 switch off.
I believe there is a negative regulatory response causing gene silencing of the receptor signal through the downregulation of cAMP pathway preventing the cAMP activated PKA to phosphorylate P450c17 - P450c17/P45017A is responsible for all androgen production by regulating the synthesis of target genes. P450c17 regulates the activation of ligand binding by either formation or degradation of ligands on the adnrogen receptor for translation to it’s target genes.
I believe P450c17 deficiency/down regulation may have been caused by one or all of the potential options below.
- cAMP/PKA deficiency due to the influx of DHT and increased phosphorylation
- cAMP pathway altered due to cytokine storm (altered REDOX) decreasing MSH halting the Adenylaye Cyclase pathway
- Increase in Methyltransferase and HDACs methylating P450c17 caused by altered REDOX balance
- Altered G protein
Please disregard anything below until as the above theory has been adjusted
- NAPDH is also an electron donor to P450c17. P450c17 receives it’s electrons via POR. POR has two distinct domains FAD and FMN which receive electrons from NADPH.
- NADPH protects against redox stress by providing reducing equivalents to antioxidants such as glutathione and thioredoxin. I believe NADPH is reduced in our condition.
- Hypersensitive/overexpression of receptors and the influx of DHT drain the cells of antioxidants causing Oxidative Stress, leading to endothelial dysfunction and an imbalance of bioavailabilty of ROS causing altered REDOX signaling, causing Endoplasmic Reticulum Stress due to unfolded proteins
- Altered REDOX balance between ROS and Antioxidants
- Oxidative stress plays a critical role in endothelial dysfunction with superoxide reacting with nitric oxide forming peroxynitrite and reducing bio-availability of NO which has anti inflammatory and vasodilatory properties
- Peroxynitrite oxidises small-molecule antioxidants such as glutathione and tetrahydrobiopterin
1st* cause of gene silencing - Increase in Methyltransferase and HDACs cause gene silencing as a protective response. I believe Oxidative Stress has initiated Hypomethylation of cytosine at CpG Lenths on a gene promotor causing gene silencing through the increase in classes of histone methyltransferases and HDACs consequently inhibiting P450c17 isoforms
2nd cause of gene silencing - Oxidative Stress leading to deficiency in MSH, down regulated adenylate cyclase, deficiency in cAMP (transcriptional co-factor) leading to deficiency in P450. P450 isoforms catalyse the formation and degredation of these ligands. Ligand binding is unable to activate the adrogen receptor causing silencing
10) CRASH due to androgen receptor silencing. I do not believe this happens like a switch, more over the course that your hyposexual during the time after quitting finasteride, while your receptors and sensitised to DHT influx causing oxidative stress in multiple ways. Oxidative stress causes - glutathione depletion, cytokine release, methylation block, lepton resistance, MSH deficiency, cAMP deficiency and P450 inhibition due to the domino affect below
11) HPG/HPA axis dysfunction due to increase in androgens causing oxidative stress
- The unfolded protein response initiates apoptosis leading to the cell death which is seen in our narrowing of the penis and shrinking of the testes. The Ying Yang balance of cell survival has been changed and ROS (reactive oxygen species over power antioxidants in cells)
- Endoplasmic reticulum stress causes decrease in Leydig cells further lowering T levels
- Adrenals stressed causing pregnanalone steal, decrease in androgens, high estrogen and low testosterone
- Increases estrogen to combat Testosterone levels and DHEA in the absence of progesterone
- Testosterone plummets and estrogen dominance
- Cortisol drops and oxidative stress increases
- Inflammation
- Glutathione depletion decreases NO and causes methylation block trying to deal with excessive inflammation due to ER stress and oxidative stress.
- Methylation block
- Pro inflammatory cytokines increase
- Cytokines block leptin receptor in hypothalamus
- Leptin resistance (pituitary gland needs leptin to produce MSH to be cleaved form COMP)
- MSH decreases dramatically with all MSH properties decreased
- Cytokines and low MSH keep oxidative stress, ER stress happening
- MSH receptor downregulates
- Adenylate cyclase decreased (melanin decreases hence change in skin pigmentation, exposed veins, light sensitivity and inflammation to skin when in the sun)
- cAMP decreases (downregulated immune response. Histamine problems and all the symptoms that come with histamine). P450 decreases
- ER stress, oxidative stress, inflammation, increased cytokines and decreased antioxidants
- Leydig cells decrease due to ER stress
- Apoptosis of cells due to REDOX imbalance
- A complete negative pathway cycle keeps you in this state or slows your recovery
What is the root cause?
Hypermethylation of histones due to an increase in classes of transcriptional regulatory enzymes protein Methyltransferases (PMT’s) and Histone Deacetlylases (HDAC) causing histone acetylation and gene silencing due to a sudden increase of DHT. I believe oxidative stress is the regulatory response that has caused the increase in transcriptional regulatory enzymes, the decrease in the transcriptional co-factor cAMP, both leading to the decrease in P450, causing androgen receptor silencing as P450 can no longer activate ligand binding preventing adrogens capability to regulate their target genes.
Can you reverse the root cause?
- Histone acetylation status is a reversible process of placing and removing covalent acetyl groups that can improve or reduce the AR transcriptional activity, respectively.
- REDOX balance can be relieved
How do we do this?
- Demethylation and re-expression of the AR gene by modulating the acetylation profile of AR genes using specific classes of histone acetylase inhibitors (HDACi) and protein methlltransferase inhibitors. This can be a little tricky as foods, herbs and supplements either increase or decrease the 18 HDAC enzymes and the numerous Methyltransferase enzymes. This will be something I may continue to play with.
- Lower oxidative stress to increase REDOX balance, NAPDH and cAMP and P450
- Lower oxidative stress to switch off the regulatory effects it’s having on the transcriptional regulatory enzymes
- Avoid P450 inhibitory substances
- Eat food that induce P450
- Increase cAMP with Forskolin. I need to figure out the best cycle to prevent the HPA axis from lowering LH due to forskolin use
- Increase foods that produce butyrate to have an inhibiting effect on Methyltransferases and HDACs
- Avoid foods that increase DHT dramatically
- Avoid food that increase estrogen dramatically
- Avoid foods that decrease 5a-reductase dramatically
- Increase androgen receptor density and function through resistance training, l-carnitine (red meat)and potentially Tribulus (I’m et to take this)
Ok…so what should you do to recover faster? There are many studies to back these dietary foods up, with their direct pathways to our recovery. In my opinion everyone on here will be at a different level of recovery and your homeostasis with all the affected pathways will be somewhat different.
Below is my protocol right now. This is just about two years after my crash. Please do your own research as what you don’t put in your diet is just as important as what you put in. My belief is fresh food will heal us, so we have to trust some foods!
Forskolin:
- Increase Adenylate Cyclase which increases cAMP due to low MSH Low cAMP in my opinion is causing multiple debilitating affects. It is a key link to why I believe P450 inhibition has caused our problems.
-Forskolin literally removes brain fog within hours for me along with increases melanin in my skin back to near normal levels.
-Many of my severe symptoms have now gone completely because of Forksolin.
Ashwagandha:
- Many benefits! lowers cytokines
- Lowers inflammation
- Increases leptin sensitivity
- Lowers oxidative stress and many other benefits directly linked to our condition.
Demethylating agents:
- You need to decrease classes of methytransferases and of HDAC’s to resensitise the receptors. These may change as I learn more about what increases and decrease specific classes of enzymes. Also to make sure these foods are not inhibiting C450 or decreasing 5AR
- Chamomile tea (contains Apigenin HDAC inhibitor)
- Cruciferous veggies - contain sulphoraphane a HDAC inhibitor (cabbage, broccoli and cauliflower the main 3).
- Garlic contains organosulfur a HDAC inhibitor
- Increase dietary fibre through oats and veggies to allow gut biome to produce butyrate a HDAC inhibitor
Lower inflammation:
- Stay away from gluten and Lectins (nightshades). MSH has an immune protecting response and due to it being low you will be susceptible to inflammation, where previously this would not have affected you.
- Limit alcohol (as people have said they feel recovered the day after drinking, that’s because it inhibits HDAC, methyltransferase and increases P450). But the inflammation alcohol causes will further increase oxidative stress
- Increase cAMP as it is a natural histamine regulator
- Focus on things that make you happy
- Don’t stress on this site too much
- Believe you will get better
- Limit sugar
- Don’t over train
- Will add to this list soon
Depending on your recovery progress:
- Supporting your methylation cycle will help decrease oxidative stress as your glutathione has been depleted… Remembering that excess of any amino acid/vitamin and also certain genetic variances will cause a negative effect as seen by many on here. A prime example is B12 variants
- Vitamin C, Methyl folate, B6, Vitamin D3 and magnesium helped me get through when my glutathione was depleted and inflammation was at its worst
- NAC the precursor to glutathione also helped and is also a HDAC inhibitor. NAC mad me need to urinate to frequently, so I stopped this about a year ago.
Exercise:
- I’ve just started back at Yoga and started some resistance training no more than 30min at a time
- People do feel better after exercise, but you have to weigh up the inflammation it causes. I’d stay to 30min or under only a few times a week. Focus on full body movements like squats, deadlifts, chins, push-ups and dips. You do not want to cause extra stress on your body that will slow your progress, but I do believe exercise will help stabalise our androgen receptors.
In regard to diet. Below is what I find works for me. As you will see, nothing processed and all natural…that’s the key! Every food listed either is a demethylating agent, antioxidant, anti inflammatory, increases P450 AND cAMP or healthy fats to line cell walls
My diet and supplements
- 3-4 cups of organic chamomile tea in hot water a day. Use plastic free tea bags.
- Organic walnuts and pecans 1 or two hand fulls a day. Powerhouse antioxidant and alpha lipoid acid. 2 x Brazil nuts for selenium a day.
Breakfast
- 60g Hemp protein with 250ml water…amazing stuff!
- Gluten free oats 1 cup (fermented in your gut produces butyrate HDAC inhibitor)
- Organic almond milk
- 3 capsules of HCL for digestion of proteins. Digestive enzymes will be fine if acid reflux isn’t a concern for you.
- 1 x Ashwagandha tablet standardised to withanoides 30mg - dried root extract 600mg
Lunch and dinner the same meals for both
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100g grass fed red meat or organic free range chicken or quality fish
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A mix of raw broccoli, raw cabbage, raw cauliflower, spinach, rocket and Brussels sprouts (can be lightly steamed, but will reduce its demethylation agent properties, I would suggest raw)
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Freshly cut organic garlic 3-4 cloves (amazing!)
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A choice of white or sweet potato around 200-250g or 1/3 cup low GI white rice. Either steamed or sliced/diced and fried in olive oil
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3 capsules of HCL for digestion of proteins (low cAMP and MSH causes low release of digestive enzymes)
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1 x Forskolin tablet at dinner 125mg 20% forskolin
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Plenty of filtered water!
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I only use olive oil
Natural products
My thalate levels were through the roof 15,500, due to glutathione depletion. So I remove all chemicals, weLL I try to anyway from my diet to further increase the methyl cycle and lower inflammation.
- natural toothpaste miessence
- natural body wash Bosisto’s
- bamboo toothbrush
- natural laundry liquid organic choice nusa Indah
- natural deodorant NO PONG
- natural tooth floss
- remove plastic containers
- steel water flask
- stainless steel cookware
- will be looking into organic chemical free clothing from either hemp or cotton sources
This list may not need to be followed by you, but I was sort of heading down this path anyone before PFS. Once you realise how your body is susceptible to tiny imbalances, you begin to want to put only the best in your body and remove all toxins from your life. This is another positive I see from PFS!
I think all these foods are powerhouses to heal our condition. I believe you need to focus on lowering inflammation, increasing antioxidants and inhibiting methytransferase and HDAC to recover. It’s definitely working for me and is the only holistic theory that I’ve seen on here that connects all our symptoms to a specific cause and secondary affects.
I’d like to make an info graph, as I do understand if you haven’t done your research it may not make the most sense, so I’m sorry for that.
My back ground
- 35 years of age
- Started Finasteride in 2010 and quit Jan 2018
- Had the intense sex drive for a number of weeks
- Had dead skin in chunks fall off my scrotum
- Had sever acid reflux (still take HCL with every meal to make sure all food is digested. Digestive enzymes are also good due to low cAMP)
- Heart palpitations and irregular heart rhythms (crazy!). Mostly due to high histamine!
- Become massively histamine intolerant and allergies to gluten (gluten allergies due to low MSH)
- Had Chronic Fatigue and Adrenal fatigue symptoms (causing deficiencies in vitamin C)
- Super tired (pass out at anytime during the day)
- Loss of feeling to genitals (rubber and cold)
- Rotation on axis of penis head (still rotated. My opinion I’m not sure that will rectify itself)
- Scrotum colour change to darker red with a distinct line. Scrotum also has a mind of its own, like it’s alive!
- Loss of skin pigmentation. I have a really good tan and at my worst my skin went just about clear.
- Small bumps on knob
- Increased veins all over body and on penis and scrotum.
- Scrotum moving continuously
- A ring of smooth skin around my shaft below my knob. I believe due to apoptosis where cells have died, which also causes the narrowing of the top of the shaft and the axis rotation.
- Small hard white spots on scrotum only 3 of them. Look like calcium deposits
- Penis decreased dramatically in size as did testes. Was around 7cm on flaccid and went to around half that.
- scrotum was like a 1/3 of the size .
- Insomnia
- Speech impediment
- Memory loss
- Anxiety
- Frustration
- Extremely irritated
- Could not look people in the eye
- Found myself starring at the TV and into no man’s land
- Could not retain an erection
- Lost all attraction and libido
- Would get out of breath easy
- Muscle soreness and pain due to low MSH
- Chin bone structure decreased
- loss of hair on body and face
- severe ringing in ears
- stopped producing sperm
- I’d say more that I just can’t think of right now.
I believe at my worst I was at 30% functioning and I’m on the road to recovery and believe I’ll get back to 100% with more time. Where I’m at right now feels amazing! Once you go though what we’ve been through when you get back to 80-90% you feel like a new person. Even though I feel close to recovered, I still have a way to go, but I would not say I’m going through PFS now. More just trying to balance my methylation of my androgen receptions to bring them back to their normal expression. While supporting all the systems that were affected along the way.
This is where my body is at in regard to recovery.
- Scrotum colour is still not back to 100%
- Scotum still has a slight mind on its own
- Still taking HCL for low hydrochloric acid release, but could be better. I just haven’t stopped since I started. I think recovering MSH to its optimal will take a bit of time and will need all inflammation in the body to cease.
- Penis is still curved on the axis, but length and girth are back to normal. On flaccid it still has a bit to go to gain full length and girth, but very happy with where it’s at.
- Slight ring below knob, which I believe was from apoptosis of this area and may not fully recover. We did go through extreme decrease in T levels and decrease in Leydig cells. I believe you will recover down there, but may not go back 100%
- libido has increased dramatically and erections hard and full. Having some amazing sex. Recovery time is getting better and can go every other day.
- recovery of T levels after sex isn’t taking so long.
- still feel that slight clarity issues, but nothing worth worrying about.
- Everything else has recovered! Which to me is a 90% recovery. 10% doesn’t sound like much, but it will still take a while to get back to homeostasis.
I would suggest a very refined diet like mine. I don’t think it will not give you histamine our immune responses, it will help lower inflammation, lowers cytokines, increases antioxidants, and most of all directly inhibits the enzymes that caused our condition. I would also suggest you remove foods that lower 5ar. I think when finasteride lowered your DHY it actually made your receptors more sensitised. If you lower your DHT with food, it may feel a little better, but you’re being counterproductive. I found that green tea would make my scotum and penis feel better, but once you have too much and go to low with DHT it would be worse. So there are demethylating natural foods and herbs like green tea, but if they also lower DHT stay away from them.
With recovery I don’t believe you can recover overnight.
I think many systems are imbalanced due to this domino affect. You could try some chamomile tea and fresh organic garlic. See what happens! Both very good demethylating agents.
I do not believe there is an instant recovery! I think it will take a bit of time to recover and balance out. Hence why people are recovering after 5 years. I want to recover faster than that, and I think this protocol will do that.
I will start an instagram channel at some point so you can see my face and hear my voice. I’ve found it hard to make his sound how I wanted it to, but I hope you gain something from it.
I wish you all the best and happy to help out and answer any questions. If you think this discussion needs anything removed please let me know, I’m not here to offend anyone or make rash comments. Purely my thoughts and feelings on the issue.
Further notes
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Not a bad table in this study with dietary compounds and their affect on acetylation
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6115944/ -
Great study on butyrate, gut biome and its HDAC inhibitory ability
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4903954/ -
Antibiotics and antifungals are just a few more HDAC inhibitors DYOR
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Oxidative stress directly increases HDAC and mehtyltransferase
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Broccoli Sprout extract is an option if a higher inhibition of HDAC and Methyltransferase is needed
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Demethylating should also increase 5a-reductase
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Demthylating is a balancing act…as foods, herbs and supplements either increase or decrease one or a combination of the 18 HDAC enzymes and Methyltransferase enzymes. Hence why we fluctuate between unknowingly increasing or decreasing HDAC, 5a-reductase and adrogens.
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The specific HDAC and Methyltransferase enzymes that cause our condition need to be studied and what regulatory function has triggered these enzymes to cause hypermethylation