Guest Post – Analyzing the Recent Finasteride / Persistent Side Effect Study

Note: This post comes from one of our favorite readers (he has requested to remain anonymous), who has contributed posts in the past about FDA and clinical trial issues. Some of his previous contributions are here, here, here, and here.

He has broken down the latest finasteride side effect study for our readers and explains why interpreting the data is problematic:

Post by Guest Writer

    This month an article appeared in a medical journal (Irwig MS. Journal of Sexual Medicine, 2012 Epub ahead of print) that relates to persistent sexual side effects of finasteride and has generated discussion in your blog from both posters and commenters. An abstract of the paper can be found at: Persistent Sexual Side Effects of Finasteride: Could They Be Permanent?

    I am a physician scientist (MD-PhD) who spent over 20 years conducting clinical trials and interpreting clinical data. Because I believe this is an important issue, I wish to summarize this study (and discuss its strengths and limitations) for your readers. Two biases that I am disclosing: (1) I believe that persistent sexual side effects of finasteride exist, and (2) I also believe that well-done published scientific investigations on this phenomenon are lacking and readers (most who are unfamiliar with scientific investigations) historically come to form impressions from magazine and newspaper articles, lawyer-run web sites, and blogs… none of which are ideal to better define and understand this phenomenon.

    Method:
    Fifty-four men were recruited. Most men (undefined number) were recruited from an internet site that focuses on sexual side effects from Propecia. Other men (number undefined) were recruited from the author’s clinical practice. To participate in the study, all men were required to have had their finasteride use before age 40 and (by their self-report) and have no history of sexual dysfunction, medication use (other than antibiotics), or significant medical or psychiatric conditions at the time that they began taking finasteride. Initial information for the study was collected by telephone or Skype. Info on sexual dysfunction, medication use, significant medical or psychiatric conditions, etc before and after finasteride use was collected. Follow-up emails were sent to the participants 9-16 months after initial interview (average 14 months). Multiple valid questionnaire scales of sexual dysfunction were used.

    Results:
    The average age of the men at time of initial interviews was 31 years, and the average age when finasteride was begun was 26 years. Average duration of finasteride use was 23 months. Most of the subjects lived outside of the United States. At the time of the interviews, duration of persistent side effect ranged from 3-6 months (7% of subjects), 7-11 months (9%), 1-2 years (44%), 3-5 years (19%), and 6 or more years (20% of subjects). Most men had sexual dysfunction scale scores that showed significant greater dysfunction following initiation of finasteride.

    My impressions:
    This study confirms prior reports of persistent sexual dysfunction in men using finasteride. The study also has significant methodological limitations. These limitations do not invalidate the phenomenon, but make interpretation challenging: men (mostly from outside the US) were recruited by an internet site to self-report historical (and some prospective) data. While the author notes that some patients are recruited from his own practice, he does not report (or perhaps have access to) medical records for most of the recruited men and no information is available on their medical work-up. Thus, the reader is left wondering what sort of evaluation for differential diagnosis (and what medical evaluations) these men received.

    The author doesn’t describe the countries that these men are from (which can affect their level of medical evaluation). This is not the author’s fault; this is a single author, single site, questionnaire/telephone/email study relying on the subject’s self-report and not presented as otherwise. The author should be commended for doing this study. As the author notes (page 5) “an important limitation to this study is selection bias, in that the most affected by finasteride are more likely to participate in a study such as this one.” I would also add that bias exists in that a study relying on “self-report” in the absence of medical records introduces potential error.

    Finally, a prospective study in larger numbers of men would be able to better define the incidence of such events, obtain detailed medical evaluations that can rule out other causes of the dysfunction (psychologic, hormonal, vascular, etc), and perhaps identify factors at initiation of drug use that increase the probability of getting these effects. I am hopeful that such studies – considerably more expensive and involved – be conducted. I am also hopeful that the “pro-Propecia permanent sexual dysfunction” group understands that anecdotes and surveys pale in comparison to more robust and well done scientific investigations, which should be conducted, appear in top journals, and are ultimately in their best interest.

Tags: fda, clinical trials, propecia, finasteride

9 thoughts on “Guest Post – Analyzing the Recent Finasteride / Persistent Side Effect Study

  1. This is a fantastic post, and I thank the author for bringing some rational thought and critical thinking to the table.

    Hopefully some people take the time to read this and understand what’s really going on. Too many people have been hailing this study as the word of god.. I am willing to bet the majority of these people haven’t even read it.

    What’s most refreshing is the author believes persisting side effects are real, but doesn’t let the fact that this study supports his belief dictate his ability to remain objective and identify the weaknesses.

    One further point to expand on (the author touched on this) is that since the majority these men were recruited from a website dedicated to helping people with these issues, it introduces another level of bias into the study, further skewing the results. All members from this website believe finasteride is the sole cause of their symptoms, so it is reasonable to conclude these men might exaggerate their symptoms in order for the results to look more shocking and furthering their cause. There is no way to verify that these reports are accurate, so it’s yet another unknown that needs to be addressed.

    One more point that wasn’t discussed is the fact that the baseline sexual function scores (from before they took the drug) were not actually conducted at this time, but the individuals were asked to remember back and try to recall what their sexual function was like before. This would be difficult for anyone to do accurately, so the data obtained from this study were inaccurate to begin with.

  2. Self reported levels are always going to be a problem in any study. Especially with something as esoteric as sexual desire levels. Most men are always convinced they are highly sexual animals when they might be relatively low on the libido scale naturally.

    I’m well aware that reductions in DHT can cause some reduction in sex drive (i’ve experienced this myself and had regular blood tests for my own athletic career so I can see and feel the difference) but I’m also aware that reduction in sex drive is very often linked to many other factors which our self-selected group might commonly be part of.

    Sex drive often diminishes slowly from the late 20s (in some men) and almost certainly into the 40s and 50s it will be reduced (although clearly not eradicated). Still most men taking propecia will do so at a time of life when they are getting older and sex drive will naturally be slightly lower than the teens, early twenties phase of your life.

    Next hairloss, in general, is known to cause depression and stress. Ask any Doctor specialising in ED and they’ll tell you 9 times out of 10, stress and depression are the primary cause, not illness or drug reactions or injury. I recall my sex drive was lower (at least in my own biased recollection) when my hair started to recede slightly. As soon as Propecia not only stopped the loss but then later regrew all the lost hairline (I’ve been one of the lucky ones in that regard) my sex drive was as high as ever. Likely confidence, reduced stress and success of a medical intervention was as much as factor as the DHT levels rebalancing.

    I’m glad people are looking into Propecia. I feel sorry for anyone who’s suffered severe reactions to any drug (or feels they have). I’m not in any way defending drug companies – I am perfectly aware of their dubious practices and profit driven need to bury bad news, but I also hate to see hysteria drive men who could have successful hair regrowth and minimal side effects into avoiding a treatment through lack of information.

    When proper large scale studies are done into this phenomena I think everyone will be much happier. Although hopefully the cure comes out before then and Propecia is obsolete for baldness anyway (hey I guess optimism helps!)

  3. This article is more reasonable than the majority that I have seen on this blog in recent weeks.

    Dr. Irwig’s article (and its follow-up) provide strong evidence that Post-Finasteride-Syndrome exists but it cannot accurately tell us the prevalence of these side effects or the severity in the average sufferer. I have never seen anybody praise the articles as being delivered from the divine, but Dr. Irwig has been very brave and a hero to those who are suffering. In the past Merck has gone after doctors who have spoken out about the safety of their drugs and they are quite a goliath, to say the least.

    Dr. Irwig’s article, is certainly not the only evidence that finasteride causes irreversible side effects as it has shown up in clinical trials, the gold-standard of clinical science. For obvious reasons Merck was not so keen on highlighting this information.

    Paul – Your sympathy is appreciated, but I would like to add that PFS is not something that will be mistaken for even pre-mature aging. When one has PFS, it is very clear that some of the biological machinery just simply is not working in the way that it is designed to and is not a product of stress or aging. When recalling how things used to be – the distinction is as clear as driving a fully functioning car vs trying to start up an vehicle with a sputtering engine.

  4. As some philosopher once said ” All drugs are poison, what matters is the dose” No doubt a small minority of the hundreds of thousands/millions of takers have experienced Side effects, but sifting through and finding the real cases will be tough. It’s swings and roundabouts. One has to weigh up the chance that you may be one of the 2% who experience sides and unlucky still a smaller percentage who are possibly permanent

  5. “(1) I believe that persistent sexual side effects of finasteride exist, and (2) I also believe that well-done published scientific investigations on this phenomenon are lacking and readers (most who are unfamiliar with scientific investigations) historically come to form impressions from magazine and newspaper articles, lawyer-run web sites, and blogs… none of which are ideal to better define and understand this phenomenon.”

    Doesn’t this say it all? the phenomenon does exist! When you are growing up and are experiencing the world, you learn rather quickly that certain things have certain reactions eg. milk made me get stomach discomfort. It was only after many years that a proper diagnoses of lactose intolerance clarified what was happening to me. But before this diagnosis, it was still rather obvious that there was correlation btwn milk and stomach discomfort for me.

    The problem is the evidence is clear and present. The arguments against the facts are just like a lawyers argument for getting a murderer off of death row. People with vested interests, like to find technicalities and doubt to disprove the facts. a lot ‘like if the glove doesn’t fit we must acquit.’

    The problem with this is that the reality, at the end of the day, whether properly proven or dis-proven, remains at the end of the day.

    I read tons of commentary on studies done on smoking, that find holes in the stats and use them to justify my desire to continue smoking cigarettes.

    Finally, how many doctors such as rassman, and other hairloss specialists and dermatologists are well studied in the endocrine system?

    bottom line, there are very few drugs in this world that can cause permanent side effects. Any drug that has this potential should be treated with the utmost caution and care… and most likely only used when extremely necessary, which IMHO hairloss does not fit that bill.

  6. Oh, and lastly, and please leave this up doc…

    My physician once said to me, “2% or not for the population of users, for you it is 100% or not”. Meaning i will either get the side effects, or I wont. The risk for me individually is inherent.

  7. Andrew
    In science, observation and self-report (“something exists because I know it exists”) is a little different than scientific explanations that try to understand risk factors, differential possibilities, and quantify the phenomenon. They are not mutually exclusive.

  8. PFS is real my friends. I decided to stop this drug after 14 years of use (with NO side-effects) after seeing Irwig’s study. I quit because the possiblity worried me so much and I thought 3 months off would prove/disprove what these sufferers are saying. I, like many of you used to laugh at the riduclousness of such claims that propecia could cause this.

    I regret to say my problems began at about 9 weeks off the drug and have persisted now for what will be 1 year in 15 more days. The sydnrome (which obviously occured for me AFTER stopping) has MANY debilitating effects other than just erection issues. The tissues of my penis have actually changed physically in shape and size!! Physical damage to the genitals is what caused my erection issues. I also have experienced symptoms of low-testosterone even though my levels are normal. I am in total shock that this could have ever happened, but it did just as the PFS desctiption outlined.

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