Spencer Kobren Speaks With Dr. Michael S. Irwig About Post Finasteride Syndrome (PFS)

[River]

My issue with this study is that an underlying assumption of the stated aim is that otherwise healthy men do not spontaneously develop permanent sexual dysfunction. Sexual dysfunction is relatively common, and it can strike at random. It does not necessary have to result from a drug, and in fact it often happens for no apparent reason.

The only way to show that these men actually developed persistent sexual side effects from propecia is to compare the percentage of users reporting persistent sexual side effects to the percentage of men in general who spontaneously develop the sexual side effects randomly during the duration of the study.

Ie, if a study shows that 2% of men who take propecia for 12 months develop persistent sexual side effects, but 1% of men develop the same side effects independently without using propecia, then propecia actually causes Post finasteride syndrome. If this were reversed, then propecia actually exerts a protective effect (and this is possible!).

It is claimed by Irwig that he can't do a proper study which actually demonstrates that persistent sexual side effects result form the use of propecia for MPHL, because it would require substantial resources. In fact, this is not the case. Below I present an experimental design that would answer this question once and for all. It would not require extensive resources, and one researcher could complete this quickly.


What Irwig should of done was interview 400 people who reported any sexual side effect whilst using propecia. Out of those 400, he should have made a note of those whose side effects continued after stopping the drug.

Let the variable X = (the number of propecia users experiencing PFS) / (the number of propecia users who have had any sexual side effect)


Since other studies have already indicated that there is about a 2% rate of sexual side effects, Irwig would have been able to use a statistical method to estimate the rate of Post Finasteride Syndrome to a reasonable degree.

The estimated rate of PFS = X / (2/100)
= X / 50


Since the rate of spontaneous sexual dysfunction is known through other studies, it is possible, and fairly easy to verify the hypothesis that propecia causes Post Finasteride Syndrome. You just compare the percentage of users reporting persistent sexual side effects to the percentage of men in general who would be expected to spontaneously develop the sexual side effects randomly during the duration of the study.


If the estimated rate of PFS is greater than the expected rate of sexual side effects during period covered by study, and this can't be accounted for by chance, then the hypothesis is proved. Otherwise it is disproved.

This is not that hard to do, and I highly encourage researchers in the field to either take this approach or try something similar.

[PropeciaVictim]

River - Your proposed research design is not viable for several reason. I will list the most important.

1. The rate of spontaneous development of ED is not known, especially within men in their 20's. I have only seen one study that examined young men in Japan and it showed the frequency of moderate to severe ED in men in their 20s was 0.0%. It was slightly higher for mild cases. Feel free to prove me wrong if you can find any study that proves otherwise as I have been vigorously looking for this myself.

2. You cannot combine figures from one study and use them in another. All studies have intrinsic biases and borrowing from several studies would make the conclusion false. Not just weak as in Irwig's study, but false. The clinical trials put the rate of sexual AEs at 2%, but other studies have this number well into the double digits.

3. There is a concurrent emergence of cognitive problems that emerges with PFS that makes it not equivalent to normal ED. There is also the emergence of the common complaint that semen volume is significantly decreased with a decrease in viscosity and increase in transparency. You could not compare these to your generic complaints of attempting to achieve an erection.

Your thought process was logical, but the idea is not completely practical for those reasons plus more.

[Mens Rea]

My issue with this study is that an underlying assumption of the stated aim is that otherwise healthy men do not spontaneously develop permanent sexual dysfunction. Sexual dysfunction is relatively common, and it can strike at random. It does not necessary have to result from a drug, and in fact it often happens for no apparent reason.

The only way to show that these men actually developed persistent sexual side effects from propecia is to compare the percentage of users reporting persistent sexual side effects to the percentage of men in general who spontaneously develop the sexual side effects randomly during the duration of the study.

Ie, if a study shows that 2% of men who take propecia for 12 months develop persistent sexual side effects, but 1% of men develop the same side effects independently without using propecia, then propecia actually causes Post finasteride syndrome. If this were reversed, then propecia actually exerts a protective effect (and this is possible!).

It is claimed by Irwig that he can't do a proper study which actually demonstrates that persistent sexual side effects result form the use of propecia for MPHL, because it would require substantial resources. In fact, this is not the case. Below I present an experimental design that would answer this question once and for all. It would not require extensive resources, and one researcher could complete this quickly.


What Irwig should of done was interview 400 people who reported any sexual side effect whilst using propecia. Out of those 400, he should have made a note of those whose side effects continued after stopping the drug.

Let the variable X = (the number of propecia users experiencing PFS) / (the number of propecia users who have had any sexual side effect)


Since other studies have already indicated that there is about a 2% rate of sexual side effects, Irwig would have been able to use a statistical method to estimate the rate of Post Finasteride Syndrome to a reasonable degree.

The estimated rate of PFS = X / (2/100)
= X / 50


Since the rate of spontaneous sexual dysfunction is known through other studies, it is possible, and fairly easy to verify the hypothesis that propecia causes Post Finasteride Syndrome. You just compare the percentage of users reporting persistent sexual side effects to the percentage of men in general who would be expected to spontaneously develop the sexual side effects randomly during the duration of the study.


If the estimated rate of PFS is greater than the expected rate of sexual side effects during period covered by study, and this can't be accounted for by chance, then the hypothesis is proved. Otherwise it is disproved.

This is not that hard to do, and I highly encourage researchers in the field to either take this approach or try something similar.

This is ANYTHING but simple buddy.

It's not even about percentages or numbers. Irwig hasn't even attempted to try ascertain how big or large this subset is. Too difficult at this moment in time.

Also, you think a simplistic calculation of comparing pecentages of non-finasteride users vrs finasteride users having spontaneous sexual dysfunctinon would suffice...

Reality: There are FAR too many variables: For example, in many cases these guys who develop these "spontaneous" issues had just happened to be on finasteride for a month. Some longer. How one could begin to calculate the liklihood of one individual developing sexual dysfunction in the same time frame (as i said, sometimes days or weeks) as finasteride treatment, i just don't know. A study without this type of information would be massively inaccurate.

This doesn't even account for types of sexual dysfunction. In finasteride cases there seems to be a strange trend emerging where many guys are presenting with unique symptoms such as low FSH, low 3-adiol-G, Vitamin D deficiency and seemingly androgen resistent (i.e. very low response to high doses of TRT: unprecedented!!). These thing are entirely different than the average case so for one to lump all cases of sexual dysfunction together would be completely misguided...


The prevailing reality that many top endos are now finding out is that guys who have taken 5AR inhibitors such as Finasteride, Dustasteride, Accutane and even Saw Palmetto, are in a whole different bracket than the normal guy complaining of ED. Therefore, the devil lies in the detail. I would also add - the TRUTH lies in the detail. These patterns prove PFS and I've no doubt they'll emerge over the next decade as accepted facts.

[PropeciaVictim]

TO KAYPEEOH

In case you see this message which I hope you do, SSRIs are not necessarily the answer to solving the neurosteroid imbalance caused by finasteride. SSRIs typically have very common sexual side effects as well, but they tend to be reversible much more often than from finasteride. Please be sure to consult with a trusted doctor before you experiment with this type of thing on your own, even though I know you are a veterinarian.

[River]

1. The rate of spontaneous development of ED is not known, especially within men in their 20's. I have only seen one study that examined young men in Japan and it showed the frequency of moderate to severe ED in men in their 20s was 0.0%. It was slightly higher for mild cases. Feel free to prove me wrong if you can find any study that proves otherwise as I have been vigorously looking for this myself.

Perhaps you should read this article on the prevalence and medical management of erectile dysfunction in Asia. (Shows prevalence rate of 2 to 88% of men, depending on age/ and other factors)
http://www.ncbi.nlm.nih.gov/pubmed/21460862

2. You cannot combine figures from one study and use them in another. All studies have intrinsic biases and borrowing from several studies would make the conclusion false. Not just weak as in Irwig's study, but false. The clinical trials put the rate of sexual AEs at 2%, but other studies have this number well into the double digits.

Actually, you can combine figures from one study and use them in another. It's done all the time, and it is regarded as scientific if it is done right. The science of epidemiology, or population health, is completely dependent on this. For example, read "Asthma and Risk of Erectile Dysfunction-A Nationwide Population-Based Study", and examine how they derive their data. (http://www.ncbi.nlm.nih.gov/pubmed/21426497)

3. There is a concurrent emergence of cognitive problems that emerges with PFS that makes it not equivalent to normal ED. There is also the emergence of the common complaint that semen volume is significantly decreased with a decrease in viscosity and increase in transparency. You could not compare these to your generic complaints of attempting to achieve an erection.

I'm not concerned about the types of permanent ED resulting from the use of propecia, only determining whether it actually occurs.

This is ANYTHING but simple buddy.

It's not even about percentages or numbers. Irwig hasn't even attempted to try ascertain how big or large this subset is. Too difficult at this moment in time.

Also, you think a simplistic calculation of comparing pecentages of non-finasteride users vrs finasteride users having spontaneous sexual dysfunctinon would suffice...

Reality: There are FAR too many variables: For example, in many cases these guys who develop these "spontaneous" issues had just happened to be on finasteride for a month. Some longer. How one could begin to calculate the liklihood of one individual developing sexual dysfunction in the same time frame (as i said, sometimes days or weeks) as finasteride treatment, i just don't know. A study without this type of information would be massively inaccurate.

You would be surprised how easy it is to calculate the liklihood of one individual developing sexual dysfunction in the same time frame as finasteride treatment. That is really not an issue at all.

Your assertion that there are too many variables relates to the problem of the perfect being the enemy of the good. It would be great to have a double blind control trial, but it is not necessary to characterize every case of ED suffered by every propecia patient to investigate this issue. It is only necessary to have a sufficient population size such that you can test your hypothesis to a reasonable confidence level.

[Mens Rea]

Perhaps you should read this article on the prevalence and medical management of erectile dysfunction in Asia. (Shows prevalence rate of 2 to 88% of men, depending on age/ and other factors)
http://www.ncbi.nlm.nih.gov/pubmed/21460862



Actually, you can combine figures from one study and use them in another. It's done all the time, and it is regarded as scientific if it is done right. The science of epidemiology, or population health, is completely dependent on this. For example, read "Asthma and Risk of Erectile Dysfunction-A Nationwide Population-Based Study", and examine how they derive their data. (http://www.ncbi.nlm.nih.gov/pubmed/21426497)


I'm not concerned about the types of permanent ED resulting from the use of propecia, only determining whether it actually occurs.


You would be surprised how easy it is to calculate the liklihood of one individual developing sexual dysfunction in the same time frame as finasteride treatment. That is really not an issue at all.

Your assertion that there are too many variables relates to the problem of the perfect being the enemy of the good. It would be great to have a double blind control trial, but it is not necessary to characterize every case of ED suffered by every propecia patient to investigate this issue. It is only necessary to have a sufficient population size such that you can test your hypothesis to a reasonable confidence level.

Some of the bloods manifested in PFS are so unique a cross study isn't even necessay.

[PropeciaVictim]

Perhaps you should read this article on the prevalence and medical management of erectile dysfunction in Asia. (Shows prevalence rate of 2 to 88% of men, depending on age/ and other factors)
http://www.ncbi.nlm.nih.gov/pubmed/21460862

This article is not useful at all. Contrary to what you say, what you have presented does not control for age.

Actually, you can combine figures from one study and use them in another. It's done all the time, and it is regarded as scientific if it is done right. The science of epidemiology, or population health, is completely dependent on this. For example, read "Asthma and Risk of Erectile Dysfunction-A Nationwide Population-Based Study", and examine how they derive their data. (http://www.ncbi.nlm.nih.gov/pubmed/21426497)

Due to the sparse data on PFS and finasteride clinical trials, this is not possible. The study borrows a figure from another study of 17,000 patients but this is still problematic.

I'm not concerned about the types of permanent ED resulting from the use of propecia, only determining whether it actually occurs.

This one figure is of utmost importance. Finasteride doesn't merely cause a different 'type' of ED, it causes a unique syndrome. You would have to match up the other miscellaneous symptoms in order to even think of comparing independent studies.

There have been some extremely smart people investigating this problem for several years. Its a bit humorous that you believe you can come up with a rock-solid research design in about 10 minutes that will solve the problem entirely.

[Mens Rea]

There have been some extremely smart people investigating this problem for several years. Its a bit humorous that you believe you can come up with a rock-solid research design in about 10 minutes that will solve the problem entirely.

LOL

Cyber-scientists!

[the_charger]

In case you see this message which I hope you do, SSRIs are not necessarily the answer to solving the neurosteroid imbalance caused by finasteride. SSRIs typically have very common sexual side effects as well, but they tend to be reversible much more often than from finasteride. Please be sure to consult with a trusted doctor before you experiment with this type of thing on your own, even though I know you are a veterinarian.

To the contrary of what you said, SSRI's have been shown to cause persistent sexual dysfunction, and there are a number of studies to actually back it up with too! I think I remember seeing this happening in more than 1% of people taking them... Just google "post-ssri sexual dysfunction".

add that to the fact that SSRI's can cause sexual problems in as much as 20% of people taking them, have way way more other awful symptoms over finasteride, and people even have terrible withdrawl symptoms when stopping them. not to mention there is an increased suicide risk for some people that take them!

My point is, SSRI's are way more popular than propecia, and prescribed to way more people and have been shown to cause just as many, and even more severe problems. They are really shown to be MUCH more dangerous than propecia is. But it's weird, where are all the forums dedicated to people with problems, and where is all the public outrage and the lawsuits?


But yeah, you said

"SSRIs typically have very common sexual side effects as well, but they tend to be reversible much more often than from finasteride"

but that really isn't true. SSRIs appear to cause persistent sexual problems in a much higher percentage than propecia does, but people take these without a second thought. Propecia is so much more safer than SSRI's, which is why I would never subject my body to taking them, no matter how depressed I got!


Its pretty obvious to me that this PFS is real, but it looks like a bunch of you are trying to convince everyone how big of a risk it is. It sounds to me like its so rare that the average guy really shouldnt worry, and im glad spencer is trying to find out really how common it is! Because that number is what guys like me will use to decide if we should keep taking it or not. No way i would keep taking it if it was a 1/100 chance, but its sounding to me more like less than 1/1000 and seriously, i wouldnt mind taking that risk.

[PropeciaVictim]

Charger you aren't right. There is no established frequency for Post-SSRI syndrome and there really is no way of telling if it is more common than finasteride. Because the symptoms are very similar to PFS and both circumstances involve the introduction of a foreign pharmaceutical chemical it has been hypothesized that they cause persistent problems using the same mechanism of action. There is still a lot that is unknown about both conditions. According to this blog, it appears that there are only 9 cases of post SSRI dysfunction officially in the literature and there are now 71 cases for PFS.

http://blog.alanjacobsmd.com/alan-ja...sm-puzzle.html

The major difference between finasteride and SSRIs is that they serve two completely different functions. Restoring or preserving hair is completely cosmetic where depression is a very serious medical condition.

You are in fact delusional if you think we are trying to convince everybody it is a huge risk. No reasonable PFS advocate will tell you it is common and nobody knows the prevalence. At this point, nobody can confidently and truthfully tell you if the risks are 1% of 0.1% so just be happy that you are aware of 'some' risk before you make your decision.

PS Anti-depressants have not been show to be more dangerous than finasteride. Speaking intuitively, adjusting one's hormone balance would be a lot riskier than preventing the reuptake of a given neurotransmitter. I do also think that there should be fair warning for SSRIs as well.