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
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
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