I should start by stating that I am a Biology Graduate, and I have no vested interest in the following theory I'm about to present.
I have read a lot of things about finasteride. Some of them good, some of them bad, some of them just plain ridiculous.
I went on the alarmist website 'Propeciahelp', and there is no doubt in my mind that the plight of a small subset of men they present is a serious one, but I must say they do themselves no favours with the way they present things. If you want to be taken seriously by the scientific community, don't use words like 'devastating effect' to describe something. I suppose that's easy for me to say though saying as I don't suffer PFS. Anyway, onto my theory about PFS.
We all know that within Homo Sapiens there is a lot of genetic variation. This genetic variation has many far reaching effects, such as determining your colour, creed, eye colour, baldness, infertility etc. But what a lot of people don't realise is that certain people will respond different to drugs than others based upon their genes too. It has sparked a whole new field which is only really starting to take off now, Pharmacogenomics.
While reading around finasteride I stumbled accross this study (http://www.ncbi.nlm.nih.gov/pubmed/21386657). It showed that finasteride had an effect on a mutant (but functional) form of the androgen receptor in cultured cells IN VITRO above and beyond what you would expect from inhibition of DHT alone. They went on to conclude that this AR, which contained a point mutation (T877A) could be competitively inhibited by finasteride, which could actually act directly at this AR and prevent DHT from binding.
One could perhaps see a situation where, in a population, there is a certain percentage of people who have a mutant form of the AR receptor susceptible to this type of inhibition. The trouble arises because if it blocks the AR, it would not just block DHT, it would block T too. This would of course lead to side effects the likes of which are seen with oral spironolactone treatment (a direct inhibitor of the AR). This would explain some of the stories of testicular hypotrophy and other feminizing effects sometimes reported by people claiming to have so-called 'PFS'.
This would go hand in hand with the fact that, for the majority of people, finasteride treatment is an effective hair-loss weapon. It would also perhaps explain why some people appear to have very serious complications from it. Further research into those people (unfortunately only people with obvious physical effects i.e. things that are measurable like loss of testicle size etc.) would perhaps lead to established exactly what genotype of person is susceptible to this. This would lead to improving the outcomes for everyone with finasteride. Those without risk could take it without having to worry about PFS, and those who are susceptible would have to move on from the idea of finasteride.
Of course, this is just a theory, and it should NOT be taken as fact as it has NOT been scientifically tested or proven, and there are zero results indicating that this is the case.
What are your thoughts?
I have read a lot of things about finasteride. Some of them good, some of them bad, some of them just plain ridiculous.
I went on the alarmist website 'Propeciahelp', and there is no doubt in my mind that the plight of a small subset of men they present is a serious one, but I must say they do themselves no favours with the way they present things. If you want to be taken seriously by the scientific community, don't use words like 'devastating effect' to describe something. I suppose that's easy for me to say though saying as I don't suffer PFS. Anyway, onto my theory about PFS.
We all know that within Homo Sapiens there is a lot of genetic variation. This genetic variation has many far reaching effects, such as determining your colour, creed, eye colour, baldness, infertility etc. But what a lot of people don't realise is that certain people will respond different to drugs than others based upon their genes too. It has sparked a whole new field which is only really starting to take off now, Pharmacogenomics.
While reading around finasteride I stumbled accross this study (http://www.ncbi.nlm.nih.gov/pubmed/21386657). It showed that finasteride had an effect on a mutant (but functional) form of the androgen receptor in cultured cells IN VITRO above and beyond what you would expect from inhibition of DHT alone. They went on to conclude that this AR, which contained a point mutation (T877A) could be competitively inhibited by finasteride, which could actually act directly at this AR and prevent DHT from binding.
One could perhaps see a situation where, in a population, there is a certain percentage of people who have a mutant form of the AR receptor susceptible to this type of inhibition. The trouble arises because if it blocks the AR, it would not just block DHT, it would block T too. This would of course lead to side effects the likes of which are seen with oral spironolactone treatment (a direct inhibitor of the AR). This would explain some of the stories of testicular hypotrophy and other feminizing effects sometimes reported by people claiming to have so-called 'PFS'.
This would go hand in hand with the fact that, for the majority of people, finasteride treatment is an effective hair-loss weapon. It would also perhaps explain why some people appear to have very serious complications from it. Further research into those people (unfortunately only people with obvious physical effects i.e. things that are measurable like loss of testicle size etc.) would perhaps lead to established exactly what genotype of person is susceptible to this. This would lead to improving the outcomes for everyone with finasteride. Those without risk could take it without having to worry about PFS, and those who are susceptible would have to move on from the idea of finasteride.
Of course, this is just a theory, and it should NOT be taken as fact as it has NOT been scientifically tested or proven, and there are zero results indicating that this is the case.
What are your thoughts?
