FINASTERIDE: PFS MECHANISM (detailed)

[IHateFin]

man we are light years ahead of all other forums! @gbolduev you are the fucking man! my dick is forever in your debt lol

 

[IHateFin]

@gbolduev @TubZy I am actually in the middle of doing a protocol that falls in line with this.

Electrolyte protocol daily and cycle zinc with cofactors EOD.

Run 3 days of RU with progesterone. I assumed the prog helped make sure RU antagonized prog receptors but in reality progesterone inhibits 5 alpha while RU gets 5 beta working again. I just finished my first day of this.

My question is, should I run low dose prog for a while after RU or jump on r andro, or just refeed? @IHateFin and @bruschi11 both have experience with prog and RU

my vote is for not hoping on prog rn and instead do a refeed of cofactors and hop on Randro

 

[IHateFin]

Finasteride is a progestin which does not convert to cortisol or metabolites like progesterone does. Since it does not convert to metabolites as progesterone it lowers NADPH. This takes down 5 alpha reductase. Also since progestin does not convert into cortisol, it puts pressure on cortisol and this weakly inhibits the enzyme that breaks down cortisol which is 5 beta reductase. Most of the symptoms while on fin are coming from inhibiting 5 beta reductase enzyme. the higher dosage of Fin , the more you inhibit this enzyme. and the higher cortisol goes.. 5 beta reductase is the enzyme which is responsible for bile acids. This is why progestins stop bile production. Actually progesterone in certain cases could do the same.

So while you are taking finasteride, you lower NADPH and you lower NADP , you stop 5alpha reductase and you stop 5 beta reductase. Most of the symptoms come from 5 beta reductase . And the higher fin dose the more you inhibit this enzyme. This is why if you found the optimal dosage not to inhibit this enzyme you would be only inhibiting 5 alpha reductase and would not have problems while on fin.


Now. After you come off fin. I assume. your NADPH production spikes back up really high. Since fin was blocking it. while you were on it. . This is why you see high DHT in some of the PFS guys. This high NADPH inhibits 5 beta reductase even further. Since 5 alpha reductase works on NADPH, but 5 beta reductase's end product is NADPH. SO when you come off fin, your NADPH production is high , and 5 beta gets inhibited even more. Your bile acids are zero now. your fat solubles are zero, and also your cortisol is high and aldo is high , since 5 beta reductase does not break them down. You are in alkalosis. and your fat digestion is zero.

So once again. When you are on fin , since fin raises metabolism but does not convert to cortisol like progesterone should have. It lowers both 5 alpha and 5 beta reductase.

But when you go off fin, this increases 5 alpha back to normal and beyond , but it totally inhibits 5 beta even more since NADPH decreases 5 beta


This is why andro works( inhibits 5 alpha) , 5 alpha inhibitors work, licorice works( increases cortisol) and this pushed 5 beta higher, dexamethasone , and progesterone. amino acids, zinc finger , RU lowers metabolism and increases cortisol and 5 beta increased . they all decrease need for cortisol and this increases 5 beta reductase.

So PFS is a imbalance between NADP and NADPH after you come off FIN. NADPH is what 5 alpha works on, and NADP is what 5 beta works on. NADPH is also made out of NADP. So this makes 5 beta and 5 alpha 2 enzymes that go opposite of each other. NADP to NADPH ratio. when NADP high 5 beta is higher, when NADPH is high , 5 beta is lower.


We will be trying many things to put 5 beta back online.





This is basically more precise explanation of the receptor theory but from enzymes view.

For those who are still taking fin, you can always adjust dosage so you dont inhibit 5 beta reductase too much , and this way you will be on fin with minimal sides . If you adjust the dosage lower, this will grow even more hair since you wont be experiencing protein wasting hairloss like in hyperthyroidism. Fin is just uncontrollable progesterone. Fin does not convert to cortisol, but causes the rise of metabolism. When metabolism rises progesterone converts to cortisol to make more sugar and aminos. But fin cant convert , and if you take too high of a dose it is like being hyperthyroid. Puts too much pressure on cortisol and closes down 5 beta reductase with bad sides coming from 5 beta reductase

IF you test your 5 beta reductase and make sure it is good, you can stay on fin without sides


For people who went off the fin . @TubZy and I are trying different protocols to fix this situation more precise. But you have many ways to manipulate NADP NADPH ratio, knowing this mechanism that we outlined above

I hope this explains why people feel bad on anything that increases 5 alpha reductase.

and for those who still think what andro does - just look a this chart. Hormonal Charts & Pathways
as you can see andro inhibits 5 alpha reductase. Because androstenedione converts to androsterone via 5 alpha reductase.


@mattyb

so what you are saying is that androsterone decreases 5AR due to needing it to convert into DHT?

so the trick to curing PFS is actually in making sure that 5 BR is upregulated.
does 4andro do anything for this? i guess we could look up things that increase 5beta reductase to help our situations?
Randro does increase 5beta by reducing 5alpha, but also increases metabolism since its a thyroid mimic so maybe thats why it takes several cycles?

would a RU low dose 5 to 10mg with high dose Randro be of benefit? i feel like it would but i would like to hear your thoughts on this.

 

[IHateFin]

Brain 5beta-reductase: a correlate of behavioral sensitivity to androgen

"Testosterone is converted in the dove (Streptopelia risoria) brain to 5 beta-reduced metabolites that do not affect behavior. In long-term castrated birds, which are relatively insensitive to the behavioral effects of testosterone, the activity of preoptic 5 beta-reductase is increased. The increase, which is specific to the preoptic area, is reversed by estrogen. Inactivation of testosterone by 5 beta-reduction may be involved in the control of brain sensitivity to androgen."


Changes in 5 alpha- and 5 beta-reductase pathways of aldosterone metabolism by dietary sodium. - PubMed - NCBI

"The effects of dietary Na+ on 5 alpha- and 5 beta-reductase pathways of aldosterone metabolism in the liver were studied in male rats maintained on low, control, and high Na+ diets. A high Na+ diet caused significant increases in the synthesis of 5 beta-reduced metabolites, primarily 3 alpha, 5 beta-tetrahydroaldosterone; whereas a low Na+ diet stimulated the 5 alpha-reductase pathway causing increases in the synthesis of 5 alpha-dihydroaldosterone and 3 beta 5 alpha-tetrahydroaldosterone, as well as certain polar, hydroxylated metabolites of aldosterone. These studies demonstrate that dietary Na+, a known regulator of aldosterone synthesis, may also regulate enzymes involved in aldosterone metabolism in peripheral tissues."

is this why licorice root works? it increases aldosterone and sodium/ water retention thus increasing 5beta reductase?

 

[MNK99]

Just read that abstract too @IHateFin
I like that bird study. I'll see if I can still read thru my school's e-resources/library all of these.

Re: Testing 5beta-reductase. Endo's order this test right?

I'm not sure how helpful these ones are to our cause:

Effects of glycyrrhetinic acid and its derivatives on delta 4-5 alpha- and 5 beta-reductase in... - Abstract - Europe PMC
Abstract:

The effect of glycyrrhetinic acid (GA) and its derivatives on delta 4-5 alpha- and 5 beta-reduction of cortisol, aldosterone and testosterone was investigated on rat liver preparations. In vitro studies demonstrated that GA and its derivatives inhibited 5 beta-reduction to a much greater extent than 5 alpha-reduction. When GA or glycyrrhizin (GL) were administered, 5 beta-reductase activity was significantly suppressed. On the contrary, 5 alpha-reductase was markedly increased though its meachnism remains to be clarified. In human beings 5 beta-reductase is quantitatively the major enzyme and plays an important role in the regulation of cortisol and aldosterone metabolism. Thus from the studies presented here, it can be presumed that the suppression of 5 beta-reductase activity by GA or GL administration may delay the clearance of corticosteroids and prolong the biological half-life of cortisol resulting in the synergism of these steroids and GA or GL.

Evidence for independent modulation of human 11-HSD and 5 alpha/5 beta reductase activities. - PubMed - NCBI
Abstract:

The increased ratio of 5 alpha to 5 beta reduced steroids associated with apparent mineralocorticoid excess (AME) may be a necessary consequence of altered 11 beta-hydroxysteroid dehydrogenase (11-HSD) activity. In order to test this hypothesis we have compared changes in 11-HSD activity and 5 alpha/5 beta reduction in a variety of clinical and experimental conditions. The ratio of 11-oxo/11 beta-hydroxy metabolites of cortisol (11-oxo/11-OH FM) was used as an index of 11-HSD activity and the ratio of allotetrahydrocortisol/ tetrahydrocortisol (allo THF/THF) was used as an index of 5 alpha/5 beta reduction. Ratios were derived from 24 hour urinary steroid profiles measured by high resolution gas chromatography. The clinical conditions studied were Cushing's Syndrome, Major Depression and hirsutism. In each study, the patient group were compared with age-matched healthy controls. For the experimental conditions, subjects treated with either hydrocortisone, dexamethasone, metyrapone or finasteride acted as their own controls. No consistent relationship was found between changes in the ratios of 11-oxo/11-OH FM and allo THF/THF. We conclude that there is no evidence of consistent metabolic interaction between 11-HSD and 5 alpha/5 beta reductase activities under a wide range of conditions. Furthermore, the patterns of metabolic changes seen in these conditions are no less characteristic, although more subtle, than the well-documented metabolic changes seen in inborn errors of steroid metabolism.

 

[IHateFin]

Metabolic regulatory effects of licorice: A bile acid metabonomic study by liquid chromatography coupled with tandem mass spectrometry

"Particularly, the plasma levels of cholic acid (1465.33 ± 915.93–7156.46 ± 3490.49 ng/mL, p = 0.0027) and β-muricholic acid (228.19 ± 163.95–1284.40 ± 775.62 ng/mL, p = 0.0045) increased significantly 48 h after administration. As licorice is widely used as a detoxifying drug, the regulation of plasma bile acids may be an important evidence to interpret its mechanism."

licorice may help, but maybe in a morning low dose one time and not spread through out the day? one dose up regulates bile secretion 48 hours later

 

[expendable]

Man am I glad to see licorice root research, myself being forever a proponent of it.

Remember the one recovery where the guy got better ~3 days after taking licorice root every time he did it!

 

[Helen]

I was thinking. in the body to make xylitol you need NADPH. I'm wondering if you take xylitol , would this inhibit g6pd a little, I am not sure about this. Just throwing it out there.. this should decrease NADPH, and increase NADP and cause bile to flow. Lower cortisol and aldosterone . this can work exactly like Finasteride. Only without side effects. I remember I heard somewhere they use xylitol against candida. Well that would makes sense. Bile flow kills SIBO

Just an idea. not sure if anyone try this

There is a woman who claims she started to live on xylitol and she is ageless .

 

[Chapman]

Brain 5beta-reductase: a correlate of behavioral sensitivity to androgen

"Testosterone is converted in the dove (Streptopelia risoria) brain to 5 beta-reduced metabolites that do not affect behavior. In long-term castrated birds, which are relatively insensitive to the behavioral effects of testosterone, the activity of preoptic 5 beta-reductase is increased. The increase, which is specific to the preoptic area, is reversed by estrogen. Inactivation of testosterone by 5 beta-reduction may be involved in the control of brain sensitivity to androgen."


Changes in 5 alpha- and 5 beta-reductase pathways of aldosterone metabolism by dietary sodium. - PubMed - NCBI

"The effects of dietary Na+ on 5 alpha- and 5 beta-reductase pathways of aldosterone metabolism in the liver were studied in male rats maintained on low, control, and high Na+ diets. A high Na+ diet caused significant increases in the synthesis of 5 beta-reduced metabolites, primarily 3 alpha, 5 beta-tetrahydroaldosterone; whereas a low Na+ diet stimulated the 5 alpha-reductase pathway causing increases in the synthesis of 5 alpha-dihydroaldosterone and 3 beta 5 alpha-tetrahydroaldosterone, as well as certain polar, hydroxylated metabolites of aldosterone. These studies demonstrate that dietary Na+, a known regulator of aldosterone synthesis, may also regulate enzymes involved in aldosterone metabolism in peripheral tissues."

is this why licorice root works? it increases aldosterone and sodium/ water retention thus increasing 5beta reductase?

Would a diet high in Sodium chloride also work?

 

[RebelWithACause]

Tomato juice the cure of PFS?

Most of tomato juices contain high sodium + lycopene (lowers 5a-reductase).

Like I said in my log. I felt close to pre-fin days (high libido, strong erections) when I was doing zinc finger + tomato juice + beet juice. I am back on that now. Testing things out.

 

[Helen]

I rec'd tomato juice for that reason in the diet. Wrote extensively about it in Q an A section

 

[Helen]

Also we could consider that the oxidation of mitochondria could lead to extra need for NADPH and this causes low NADP. So by increasing antioxidants we could spare this conversion . Since fin is a progestin, it raises metabolism without zinc. Zinc should have done that not fin. But people did it with fin / When zinc is raised usually it puts tons of pressure on SOds and especially manganese SODS , since that is the the SOD inside of the mitochondria. So when you go off fin , NADPH cant be downregulated back down, since antioxidant systems are all down. And this causes NADP to stay down. since NADP converts to readily to NADPH . and this NADPH is used heavily for GSH redox. to protect mitochondria.

This is one possibility. May be use of turmeric with ginger can help this situation. Turmeric is very high in manganese iron and ginger is high in potassium

 

[Potion]

I rec'd tomato juice for that reason in the diet. Wrote extensively about it in Q an A section

Though it contains no potassium, could the antiandrogen properties of spearmint tea perform as well as those of tomato juice?

 

[TubZy]

I was thinking. in the body to make xylitol you need NADPH. I'm wondering if you take xylitol , would this inhibit g6pd a little, I am not sure about this. Just throwing it out there.. this should decrease NADPH, and increase NADP and cause bile to flow. Lower cortisol and aldosterone . this can work exactly like Finasteride. Only without side effects. I remember I heard somewhere they use xylitol against candida. Well that would makes sense. Bile flow kills SIBO

Just an idea. not sure if anyone try this

There is a woman who claims she started to live on xylitol and she is ageless .

Taurine and TUDCA stimulate bile as well, I doubt they effect 5b though, they have been used by many ppl before

 

[RebelWithACause]

Though it contains no potassium, could the antiandrogen properties of spearmint tea perform as well as those of tomato juice?

Not sure if you want to lower all androgens. Your testosterone will go down too. Lowering 5AR has side effects but less than lowering free testosterone.

 

[supernature]

...

 

[barbaar]

Turmeric - Iron, Potassium - 100gr

Ginger - Manganese - 100gr

Nice, where did you find this? Is this about fresh or dried/powdered?

 

[joekool]

@supernature awesome info... I've seen 'fasting' drinks with Tumeric & such ... like Ginger and ACV... but I like this info so we know...

@Goose12 how long are you into that protocol ?? I didn't have luck with progesterone but that was before my RU run. I can say I'm more receptive to R-Andro after RU... but it's also my 3rd cycle of it, 2 prior to RU so that could be another reason... but I'm glad you're on a protocol... ensure we hear your results... even small improvements add up for everyone

 

[IHateFin]

I consume ginger in my oatmeal and Greek yogurt breakfast every day. I've never had bowls this perfect. Sometimes I go 2 to 3 times a day now and they are solid and sometimes barely registers wiping haha
Maybe low dose licorice in the morning 2 days a week could be of benefit too

 

[Goose12]

@supernature awesome info... I've seen 'fasting' drinks with Tumeric & such ... like Ginger and ACV... but I like this info so we know...

@Goose12 how long are you into that protocol ?? I didn't have luck with progesterone but that was before my RU run. I can say I'm more receptive to R-Andro after RU... but it's also my 3rd cycle of it, 2 prior to RU so that could be another reason... but I'm glad you're on a protocol... ensure we hear your results... even small improvements add up for everyone

This is my second day of RU and prog and I have been doing the electrolyte protocol for over two months, and cycling zinc finger ever other day consistently for the last 2 weeks.

This is my 4th cycle of RU, but this is my first time taking progesterone. I don't want to speak to soon because I know how things go up and down but I feel great on prog and ru already. This is probably the best thing I have tried so far and I feel really close to prefin. I just hope it doesn't backfire but I am reaching new highs already.