THEORY - PAS and Progesterone/Progestin - Unlikely

flynn

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Feb 28, 2018
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#1
One theory put forth for post finasteride syndrome (PFS) by a well known online user called Gbolduev, proposes that Finasteride (FIN) acts as progestin (interacts with the progesterone receptor). Put very simply, the basics of the theory are that progesterone receptors are either up or downregulated by FIN usage, upon stopping FIN. These receptors remain up or downregulated depending on the mineral balance of the cells such as levels of potassium etc. This leads to issues with progesterone sensitivity and problems with associated enzymes etc.

As far as I can find there isn't much evidence to support the idea that progesterone receptors will remain up or downregulated depending on mineral level of the cell. However, Gbolduev raises an interesting point in relation the effect of progesterone on libido/sex drive.

"Deca dick" is a condition which some bodybuilders who use Deca-Durabolin (Deca) (chemical name: Nandrolone-Decanoate) who develop sexual problems such as erectile dysfunction and libido problems. Its believed these effects are caused by the progestin activity of these types of steroids. Its widely thought that running compounds such as Deca alongside Testosterone avoids deca dick. However I've seen numerous accounts of people who reported developing Deca dick despite using testosterone. Interestingly, users report sexual problems such as low libido persisting long after stopping Deca, despite normal androgen levels.

This is interesting, as its a case of persisting sexual dysfunction despite people having normal androgen levels, as is the case with PAS.

Another progestin which is capable of reducing sex drive/libido is Depo Provera, its been looked at for use in sex offenders to reduce sex drive - https://pdfs.semanticscholar.org/ac4b/8e66cffb81b27254e96d69a8f12ef3794c9e.pdf

Given this, is it possible Accutane has some kind of progestin activity or alters progesterone levels in the body enough to alter progesterone sensitivity/activity? Rather than write a piece, I will summarise a few articles of interest:

This study showed that in rats both retinol and retinoic acid significantly increased the accumulation of progesterone in rats granulosa cells compared to controls - https://www.ncbi.nlm.nih.gov/pubmed/3036474

This study showed that retinoic acid appears to significantly reduce progesterone receptor expression in human breast cancer cells, which indicates that it's possible that it could have a similar effect in other tissues -
https://www.ncbi.nlm.nih.gov/pubmed/2373707

In female mice, the PR appears to play a crucial role in facilitating dopamine induced sexual behaviour. Mice without the PR receptor appeared to show markedly reduce sexual behaviour following a dopamine agonist as compared to wild type - http://citeseerx.ist.psu.edu/viewdo...947B19E?doi=10.1.1.322.7661&rep=rep1&type=pdf

This study looks into the role of progesterone in androgen dependent sexual behaviour, shows that progesterone plays an important role in sexual behaviour in some male reptiles and mammals. It appears that very high doses of progesterone are bad for sexual behaviour but some low levels can be beneficial - http://sites.utexas.edu/crewslab/files/2016/06/psyneuro.pdf

Essentially, progesterone plays a role in sexual behaviour. Now here is where the studies get particularly interesting.

The striatum is a key component of the dopamine dependent reward system (1). Estrogen and progesterone receptors are highly expressed in dopaminergic neurons of the midbrain and other areas of the reward system such as the striatum and amygdala. A study of female brain activity showed that activity changed depending on estrogen and progesterone levels. indicating that brain activity is influenced by the current levels of sex steroids such as Estrogen and Progesterone. Preclinical data show that estrogen and progesterone interact with affect neuronal signalling and the effects of estrogen differ in the presence of progesterone (2).

Essentially estrogen and progesterone both influence dopaminergic activity in the reward circuitry of the brain. Given this, its plausible that changes in progesterone activity and/or progesterone receptors could be affecting our dopaminergic system, leading to PAS. As a theory, I know this is a bit of a long shot but any and every theory/treatment option is worth investigating and reviewing.

Treatment options:

1. Several PFS sufferers have reported improvements in sexual side effects and mood by taking the birth control pill Mifepristone or RU-486. It acts primarily as a progesterone receptor antagonist but also works as an anti-glucocorticoid. The idea behind this, is that by blocking the receptors, the body will up/downregulate progesterone receptors making the body more or less sensitive to progesterone. Most users report benefits appearing several days after stopping RU-486 as a sort of rebound effect. Most people try dosages around 50mg each day for 3-4 days and then stop. Now it's possible that this dosage and time frame isn't enough for PAS users and they need to try taking it for a longer period. Below I will post an account of a person who gained benefits only after 12 days of RU.

Unfortunately, I know of two PAS users with sexual sides who have experimented with RU-486 and gained no improvement so far. This doesn't mean its a lost hope, but dosages which seem to help PFS people, don't seem to help PAS people.

2. Another option may be to experiment with progesterone itself, to see if it alters symptoms.



- Flynn


(1) - https://books.google.co.uk/books?id=bCXcf0Dp62UC&pg=PA310&lpg=PA310&dq=progesterone+receptors+dopamine+neurons+male&source=bl&ots=zsd3jeFeL7&sig=JqMUIGydnw7f4h1Sw_eb2TqCcOU&hl=en&sa=X&ved=0ahUKEwjlgvqJ8-7YAhVCF8AKHWtRDrA4ChDoAQg2MAQ#v=onepage&q=progesterone receptors dopamine neurons male&f=false
(2) - http://www.pnas.org/content/104/7/2465.full
(3) - https://www.ncbi.nlm.nih.gov/pubmed/15863802
 

flynn

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#2
Here is an anecdotal report of someone who used RU which was a repost on another forum by a user. I don't believe this person took Accutane or Deca, the trigger was strep throat. What is interesting is that a guy can suffer some sexual issues despite taking TRT and then recover from RU-486. This shows how powerful progesterone can be for sexual health:

"5-6 years ago (age 18) i came down with strep throat. i was sick for about 2 weeks. within the first week i started to notice e.d. problems. now that i look back at it, a lot like what ppl complain of after using deca (deca **** aka zero libido and **** ifeels like its not even there). i also began to notice all of the symptoms of low testosterone (fatigued, loss of strength/energy, no concentration, zombie-ish, depression, etc, etc).

i went to like 4-5 different doctors, tons of bloodtests with little to no clarity. doctors all thought i was crazy. the one thing that i did notice was that for my age my testosterone was low (always ranged from in the 200's-400's). so i "knew" that was the problem. i also noticed that my progesterone was high, but none of the dr's commented on it and i had no idea what it meant....

so i went on trt..standard test cyp and hcg. i noticed some help in areas, but nothing huge and no improving in sex drive and erection strength. i then spent the next 4 years w out having sex a single time or any girlfreind, mainly because i didnt want to deal with the sex problem.

over this time i had continued and continued doin research on my own over the net. i began to read about deca ****/high progesterone, etc. i noticed that all of my tests over these years have shown high progesterone, often times over the range. more and more research into it and i came to my own conclusion that high progesterone was my problem and was also causing low t. a very good dr in this field agreed that seems like it may be my problem. but he said there is nothing he can do for me as very little is actually known about the effect of high progesterone in men.

so again more research and i noticed that winstrol (stanzolol sp?) and ru486 are some of the few known anti-proesterones out there. i couldnt get a script for either of them. i didnt know any steroid dealers so i wasnt going to be able to get ahold of winsrol. so i bought some mifeprex/ru486 from an online pharmacy. i took 50mg for 12 days. during this time, and for the first time in 5-6 years, i noticed morning wood, 100% hard erections, and i actually had a sex drive. i could actually "feel" my ****.

this lasted (finally feeling like a normal 23 yr old) for about a 5-6 weeks. i should have stopped trt at that point, but i didnt and my e2 began to raise, and i started to notice gyno-ish signs. thats where i am right now...."
 
Likes: Lost
Mar 10, 2018
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#3
I'm not sure on this one, I think the theory Gbol puts forward makes a lot of sense. I've only seen 3 people with PAS who've had progesterone tested and in all cases it's either high or low, none were normal. Of all the people who've tried RU though (PFS and PSSD) nobody has made a full recovery from it, although it does seem to have led to some improvements. Definitely keeping an open mind about this theory.
 
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flynn

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Feb 28, 2018
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#4
I'm not sure on this one, I think the theory Gbol puts forward makes a lot of sense. I've only seen 3 people with PAS who've had progesterone tested and in all cases it's either high or low, none were normal. Of all the people who've tried RU though (PFS and PSSD) nobody has made a full recovery from it, although it does seem to have led to some improvements. Definitely keeping an open mind about this theory.
Agreed, I don't have much confidence in this theory but thought it was worth putting forward any and every possible theory to be scrutinised. I still plan to get my progesterone tested. I did however find a very interesting piece of research related to progesterone today. If you go on the 5AR theory and read the bit under the heading More Evidence. In my opinion this provides potentially one of the first strong bits of evidence that PAS involves a downregulation of 5AR in the brain.

Yeah another thing about RU is that not all PFS people get much of a benefit from it. So just because PAS people don't seem to get a benefit from RU its doesn't mean PAS and PFS are completely unrelated.
 

Lost

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Mar 10, 2018
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#5
I would suggest you guys to try RU. I had v minimal improvements but it was something.

The improvements (again , minimal but definitely noticable) came during my second run in which I took 100 mg for 3 days, and then spread out 1 100mg half pill over 4 5 days (dont remember exact no of days).

If I had to guess, the high dosage days benefited me more. So please try Ru, we need more data on this. At most I got dry lips for which I could have prog cream but I didn't, thinking at that time that its no use buying the cream for one day ( I hadnt planned that time to take the last 100 mg over many days).

Sorry if my language is unclear I m typing as thoughts come to me on mobile. If any part is unclear please do ask.
 
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