Talk:Finasteride/Archive 3

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Also, Type III

this should be here: Finasteride (brand names Proscar and Propecia by Merck, among other generic names) is a synthetic type-2 and 3 5α-reductase inhibitor. This enzyme converts testosterone to dihydrotestosterone (DHT). Finasteride is approved for the treatment of benign prostatic hyperplasia (BPH) and male pattern baldness (MPB).

Finasteride, a 4-azasteroid and analogue of testosterone, works by acting as a potent and specific, competitive inhibitor of one of the two ( there are 3 knowen) subtypes of 5α-reductase, specifically the type II and type III isoenzyme.

As you can see here

No one here of the people, who can do such change this? I realy wonder, who the english wikipedia works. All seems to be bussy with other discussions. This need to be changed. source see above link. --Brainbug666 (talk) 22:29, 6 October 2012 (UTC)

I would love to know, why no one here wants to add this important information in the article. The source can be found here Finasteride also inhibits the 5AR type III what is an important fact fo this entry. The fact, that this information is not added and so keepet back shows for me that this entry is fully controled by people, who dont want to give all information about this drug.--Brainbug666 (talk) 12:33, 11 October 2012 (UTC)

still Ignored. the source is here.

--Brainbug666 (talk) 19:36, 11 October 2012 (UTC)

Post-Finasteride Syndrome

The Post-Finasteride Syndrome should also added to the side effects of finasteride.

That depends on Wikipedia:Articles for deletion/Post-Finasteride Syndrome, in my opinion. Biosthmors (talk) 16:05, 4 October 2012 (UTC)

So, I would now like to see if the admins here are also so fast in changing this entry, on the AS than on the dicusion about the deletion. of the post-finasteride syndrome. Everbody, who wonders, why the article has been deleted can read all here Wo is still want to read the article about the post-finasteride syndrome, can find it here.--Brainbug666 (talk) 00:13, 11 October 2012 (UTC)

DHT

Seems to be a contidiction?? at start:"converts testosterone to dihydrotestosterone" (DHT) near bottom of article states: works "By blocking DHT production" which is correct?? Davidrogerc (talk) 02:50, 19 November 2012 (UTC)davidrogerc

See the next section. Adrian J. Hunter^{(talk•contribs)} 11:15, 2 January 2013 (UTC)

Edit request on 2 January 2013

The line "This enzyme converts testosterone to dihydrotestosterone (DHT). " is wrong & is supposed to be "This enzyme PREVENTS conversion of..."

Hope you change it or allow me.

Zoeyetra (talk) 03:35, 2 January 2013 (UTC)

The enzyme 5α-reductase does the conversion. Finasteride inhibits the enzyme, thus preventing the conversion. I've reworded the lead for clarity. The wording is a bit awkward but it retains the highly relevant wikilinks. Adrian J. Hunter^{(talk•contribs)} 11:15, 2 January 2013 (UTC)

Edit request on 3 January 2013

Please add the following to the "History" section: Dr. Reddy’s Laboratories announced today that is has launched Finasteride Tablets (1 mg), a bioequivalent generic version of Propecia® (Finasteride) Tablets in the US market on January 02, 2013. Dr. Reddy’s ANDA for Finasteride 1 mg Tablets has been awarded a 180-day period of marketing exclusivity in the U.S. on 2 Jan, 2013.

Digitalpharmacist (talk) 14:36, 3 January 2013 (UTC)

Not done: mainly because the source provided is a wiki and a press release. Also the proposed text reads like a press release. Please provide reliable, third-party sources to support this claim and reword the proposed text to an encyclopedic tone and I might be willing to entertain this request. —KuyaBriBri^Talk 15:38, 3 January 2013 (UTC)

Jenny McCarthy

On the Howard Stern show Jenny McCarthy claimed that propecia has the side effcts of erectile disfunction. http://howardstern.com/ (go to wensday's show, March 13, 2013) I think its an interesting bit of information for the article, adding a cultural dimension. — Preceding unsigned comment added by 97.107.215.232 (talk) 08:01, 15 March 2013 (UTC)

It is already discussed in extenso. Jenny McCarthy is not a medical authority. JFW | T@lk 21:52, 17 March 2013 (UTC)

Edit request

Merck warned about persistent Finasteride side effects in the early 1990's on the Proscar label. This means they showed up in the clinical trials. The article as it currently is indicates that only Internet hysteria caused a wave of post-marketing case reports, mandating a label change. When in fact, side effects that persist after discontinuation was first on the label nearly two decades ago. The warning was only omitted on one Finasteride brand (Propecia). The Australian Financial Review mentioned this in a piece on finasteride. Australian Financial Review — Preceding unsigned comment added by Gilmour1201 (talk • contribs)

As I explained on your talk page, this cannot be discussed without a WP:MEDRS-compatible secondary source. JFW | T@lk 11:53, 20 February 2014 (UTC)

Both labels have been cited. The reader can verify the incongruity. — Preceding unsigned comment added by Gilmour1201 (talk • contribs) 08:28, 21 February 2014 (UTC)

JfdWolff, you can even read the label in your native tongue. See the Dutch label warning of persistent side effects here.

ETA: Copy and Paste if the linke won't work from Wikipedia.

http://www.dokteronline.com/pils/nl/patient_information_leaflet-760-proscar_5_mg,_filmomhulde_tabletten-nl.pdf-1326804181.pdf

"Als de verschijnselen bleven aanhouden, verdwenen ze meestal bij het stopzetten van de inname van PROSCAR."

Gilmour1201 The situation hasn't changed. You are engaging in investigative journalism rather than writing an encyclopedia. There is already a section that discusses very clearly the nature of sexual AEs and the fact that they might persist. You are now adding some weak sources (that definitely fail WP:MEDRS) to suggest that the package inserts didn't always discuss this side effect. The only benefit that I can see is an implied accusation of bad faith on behalf of the manufacturer. For such a claim you need very strong sources, quite the opposite of what you're doing. :::I really think you should have a look at dispute resolution rather than repeatedly adding the same stuff. Alternatively, you could try the reliable sources noticeboard to see whether the community has particular views on the quality of your sources. Good luck. JFW | T@lk 12:31, 21 February 2014 (UTC)

JDWolff , your latest post is so absurd I don't even know where to begin. You say, "there is already a section that discusses very clearly the nature of sexual AE's and the fact that they might persist." I already told you why an addendum is necessary. The article as is indicates that ONLY POST-MARKETING CASE REPORTS of persistent sexual AE's have been reported. But not only was persistent side effects warned about when Proscar hit the market, but persistent AE's were also picked up in the PLESS trials.

"You are now adding some weak sources (that definitely fail WP:MEDRS) to suggest that the package inserts didn't always discuss this side effect."

I don't even know what you mean here. When discussing the package insert, how can you call citing the package insert itself a "weak source?" Please answer

"To suggest that package inserts didn't always discuss this side effect?" lol, WHAT? I said one of them discussed "this" side effect (side effects that persist after discontination) and the other omitted it

Proscar label: If side effects persist, they USUALLY resolve upon discontinuing 'Proscar'

Propecia label: These side effects went away in men who stopped taking PROPECIA

Clearly, one label indicates side effects can persist after discontinuing the drug, the other label indicates it cannot. This is information Wikipedia readers need to know about. Doctors look at these labels for information on how to treat patients.

ETA: These aren't the updated labels based on case reports. These were the original labels in the 1990's, as you would be easily able to verify in the sources I gave.

"Can you please tell me the where exactly it states the Propecia trials were double-blind?" - Go to site http://www.accessdata.fda.gov/drugsatfda_docs/nda/97/020788_propecia_toc.cfm. Open part one of the medical review, go to page 28. Then open part 2 and and go to pages 42 and 92. These are the page numbers of the original document, and not PDF numbering.

The last page of Part 3 of the medical review discusses findings that unlike the 5 mg dose, the 1 mg dose "had little effect on semen production". and that there "appears to be a dose-dependent effect on ejaculate volume". So I believe the normal observation of a dose response relationship holds here.

I'm a little surprised by your comment that patients began experiencing sexual side effects for the first time after stopping the drug. Do you have a reference? What would be the proposed mechanism for this?

Its hard for me to evaluate stuff on chat boards that comes from outside of a double blind RCT. For a 60 year old to report falling sex drive and ability to perform is not unusual in any way. Especially when followed over a 6 year period. In some studies the prevalence of impotence in this age group is above 40%.

Many thanks Formerly 98 (talk) 09:02, 23 February 2014 (UTC)

Suggested edits for clarity

One fairly important and one minor suggestion for better clarity in the article. I am not addressing the content, which I'm not at all qualified to do.

The intro says: "Finasteride (brand names Proscar and Propecia by Merck, among other generic names)..." This is unclear, to a layman at least. "Brand names" are not "among" other generic names -- they are a separate category. If there are other generic names for this drug, I don't see them listed; there is one note, however, of a related 5α-reductase inhibitor. So is it that there are other brand names for this drug? Or other generic names?

More important, I think, is the arrangement of the section on prostate cancer. The opening sentence gives the important point, I agree, but because you have to go to the footnote to find out when the FDA required a label change, it's not clear whether this whole section is written in chronological or reverse-chronological style. The result, after reading through the entire section, is deep confusion. The two paragraphs seem to contradict one another sharply; while there is some justification for the FDA's decision given in the first paragraph, there is a great deal more justification given in the second paragraph for the 2005 study's conclusion that the drug does not cause high-grade cancers. It takes a careful reading to see that the FDA's decision is based on a fear that the drug may mask the emergence of new cancers and (apparently) that doesn't conflict with the 2005 study's conclusion that it doesn't cause new cancers. (It does appear to contradict the earlier study's conclusion that the smaller prostate size makes new cancers easier to detect.)

This section could very usefully be recast, I think.Tito john (talk) 05:01, 24 February 2014 (UTC)

Adverse Events

I don't think it makes much sense to include information in the article about theoretical concerns about long term effects that were raised 17 years ago (BEFORE any long term safety data existed) and then exclude actual data about long term safety from two large, multi-year trials that were designed precisely to address long term safety questions. Whatever your feelings about adding data "from a single trial" (actually it was 2 and they were big stuides), data always outweighs theoretical concerns that were voiced before data was available.

I'd suggest deleting the theoretical concerns (as I did in the first place) and keeping the discussion focused on actual safety data. The actual data consists mainly of

• The results of the 5 year safety trials conducted post-approval. These are rigorous but not powered to detect rare side effects
• The case reports that formed the basis of regulatory warnings of long term sexual effects. These are less rigorous, but strongly suggestive of long term effects in a small minority of patients.

The latter of these is already incorporated in the article. The former should be too though its not a deal breaking issue from my point of view. What makes no sense is to raise the theoretical concerns from 1997 and then deliberately leave out the data from the trials that were designed to address those concerns.

I'm also modifying the language describing the AdCom meeting for now. In contrast to the current language stating that the panel "refused to approve" Propecia, both the official transcript of the meeting and a Chicago Sun article indicate that no vote was taken. Formerly 98 (talk) 14:38, 22 February 2014 (UTC)

Formerly 98 Why leave out the data from safety trials that show side effects can be persistent? As I stated before, this article as is indicates that the only evidence of persistent side effects is post-marketing case reports, when that isn't the case. Doctors can read this article and come to the conclusion that Finasteride cannot cause persisent side effects based on the omitted evidence. They may be unaware that Merck warned about a causal relationship between Proscar and persistent side effects when Proscar first hit the market*. The (pre-Wikipedia) paradigm only shifted when Propecia hit the market and the warning was "these side effects went away in men who stopped taking PROPECIA." Wikipedia shouldn't help to propagate this myth, when the data are right here. I agree with you 100%, let's not deliberately leave out any datum.

• Copy and paste for original label: mcs.open.ac.uk/nlg/old_projects/pills/corpus/pil/doc/proscar.doc

I don't fully agree with you since I feel there is a contradiction in your response. You mention the 5 year safety trials were deliberately designed to address those concerns but also mention that while these are rigorous they are not designed to detect rare side effects. On the contrary, this was an industry funded study and would have only been publicly released if it revealed data that was favorably to the manufacturer. This publishing phenomena has been well documented but really is part of another discussion.

I do agree that we should restructure the section on adverse side effects. As a compromise, I suggest we move mention of the advisory panel's discussion to the history section which talks about the drug discovery and approval process in more depth. The transcript of the advisory meeting does not include the outcome of the vote or the committee's recommendation but that is not the equivalent of saying it indicates no vote was taken. I do think it is worth including in the history section since as you probably know the FDA most often accepts the AdCom's suggestion especially when they do not suggest approval. I'll moderate the language about the committee's recommendation. So far, the news article I have provided is the only source to directly reference the committee's recommendation (or lack thereof). It would be appreciated if you would provide the Chicago Sun article for purposes of comparison since I was unable to locate this on my own. Thanks and I'm happy to discuss further if you feel these edits merit additional change. Doors22 (talk) 19:53, 22 February 2014 (UTC)

Hi Doors:

Thanks for your thoughtful response. I am aware that some of these issues have been discussed at great length, and I am not really the person to talk to about reversing decisions made previously. Frankly, I'm not that influential.

The language difference you note is intriguing, but I don't think it rises to the level of evidence required by WP:MEDRS. I do not know the detailed history of the package inserts, but I wonder if any of the following are relevant to your observation.

• Propecia is a 1 mg tablet and Proscar is 5 mg.
• The clinical trials were performed in different populations.

I looked into this by digging into the FDA approval summary for Propecia http://www.accessdata.fda.gov/drugsatfda_docs/nda/97/20788_PROPECIA%20TABLETS,%201MG_MEDR_P3.PDF My reasoning is as follows:

• The publications may not be reliable sources of AE information, but the FDA approval summaries probably are
  • The FDA requires submission of raw data from individual patients. One cannot simply omit data, it would be necessary to actively submit fraudulent data
  • This would put the individual responsible at high risk of jail time
  • There is reasonable evidence that these submissions are accurate. Most of the expose papers that revealed selective publication by pharma companies came from comparing published results to data obtained in Freedom of Information requests to FDA
• The Approval Summary for Propecia explicitly states: "Eleven patients (1.2%) on finasteride and 8 patients (0.9%) on placebo discontinued due to a drug related sexual adverse event. All of them had resolution of their sexual adverse events"

You are correct in that there is an intrinsic contradiction between doing a long term safety study and then stating that it was not powered to see an effect. But some side effects are just too rare to readily pick up in trials. The approval summary notes that only 1.2% patients discontinued due to sexual side effects. Assuming that 10% of those stopping due to sexual side effects find that they continue after stopping, that's only 0.1%. You'd need to do a trial in 10,000 patients (5,000 treatment, 5,000 placebo) to reliably see even one or two examples pre-approval. Based on the 700 spontaneous reports described by the FDA in their announcement, the usual assumption that only one in 10 to 20 unexpected adverse events is reported, and peak Finasteride sales of $1.2 billion, I think a rate of about 1 in a few thousand is probably a reasonable estimate of the actual rate. So there is no contradiction between saying that this was not seen in clinical trials but that it is probably a real effect of the drug.

As for a compromise:

• I've read a lot of these transcripts, and I disagree with your comment that a vote would not be shown. The transcript begins with the committee members introducing themselves and ends with adjournment of the meeting. The Chicago Tribune article specifically states that "The committee did not vote on Propeicia's safety or effectiveness".

• Generally I'd like to stick with the data and not with concerns voiced before data was available. Lets just state what the data shows.

• We know that the incidence of permanent sexual dysfunction is low (from the clinical trials), but it probably does occur (from the spontaneous reports and the FDA warning).

• Can we just state the above in the Sexual Side Effects section?

Also, I really don't want to go on record as recommending a rehash of anything that has been extensively discussed already. Please take any prior discussions of this issue into account.

Best Regards Formerly 98 (talk) 21:10, 22 February 2014 (UTC)

OK, after reading the Chicago Sun article it does change my understanding of the meeting. There is already mention of the persistent sexual side effects listed elsewhere in the article. The new interpretation of the AdCom meeting doesn't really make sense to include at the top of the side effects section so I think it makes sense to remove that whole paragraph entirely. Please let me know if you disagree.Doors22 (talk) 21:54, 22 February 2014 (UTC)

No objection here. Thanks for a good exchange of ideas. Formerly 98 (talk) 22:20, 22 February 2014 (UTC)

Formerly 98 You seem to be cherry-picking data. For the Propecia trials, you cite the following:

"Eleven patients (1.2%) on finasteride and 8 patients (0.9%) on placebo discontinued due to a drug related sexual adverse event. All of them had resolution of their sexual adverse events"

You call the 3040 Randomized Control Trial as rigorous, but fail to cite the results of persistent sexual Adverse Events

"Only 4% of finasteride and 2% of placebo patients discontinued the study because of sexual AEs. In men who discontinued with a sexual AE, 50% and 41% experienced resolution of their sexual AE after discontinuing finasteride or placebo therapy, respectively."

Please note that the PLESS study was a double-blind, while the Propecia trial was not. The PLESS is more robust and more up-to-date than the Clinton era Propecia trial data. As you stated, let's stick with the data, giving favor to the most robust. The PLESS results of persistent sexual side effects deserves a place in the Sexual Side Effects section. They also corroborate post-marketing data. Once again, as the page currently is, the reader is led to believe that only the only evidence of persistent sexual side effects is case reports, and that isn't the case.

Also, it was me, not Doors, who was concerned about the incongruity of the two warning labels for the same drug. I'd like to discuss your points, but I think we should come to an agreement on the PLESS data first.

And your assumptions for your long-term Propecia side effects estimation are wrong, but more on that later.

Hi whoever wrote that. (You didn't sign your comment).

I found the reference for the PLESS Proscar results:"Only 4% of finasteride and 2% of placebo patients discontinued the study because of sexual AEs. In men who discontinued with a sexual AE, 50% and 41% experienced resolution of their sexual AE after discontinuing finasteride or placebo therapy, respectively." I'm not deliberately cherry picking, but this study did not come up in a Pubmed search for phase 3 studies of finasteride. The difference is as you have reported it, and appears statistically significant. But the FDA reported in 2012 that "In controlled clinical trials, these side effects resolved in patients who stopped finasteride, as well as in most patients who continued therapy." I'd like to understand this a bit better, which will likely mean going to the library to see what was seen in the other trials.

I've provided the reference to my quote from the Propecia development program "Eleven patients (1.2%) on finasteride and 8 patients (0.9%) on placebo discontinued due to a drug related sexual adverse event. All of them had resolution of their sexual adverse events" above. Its on page 76 of the document I linked to above.

I disagree with your assessment that the PLESS trial is of higher quality than the Propecia trials. The FDA approval summary describes all of the Propecia trials as double blind, in contrast with your statement. The Propecia trials were performed in 1993-4, and the PLESS trial initiated around 1995-6 or so. The designs of the trials, which were set before the trials started and not when they ended, would presumably be of similar sophistication. Any difference in the results of the two trials is best attributed to the fact that they looked at drmatically different doses of finasteride.

What specifically about my assumptions do you think is are incorrect? The standard pharmacoepidemiology assumption is that 5-10% of unexpected adverse events of new drugs are reported. That would mean the 700 cases reported to the FDA corresponds to about 15,000 cases over 12 years, or a little over 1000 per year. Given that this was a billion dollar drug that sold for about $1000 for a year's therapy, one can calculate an incidence of about one per thousand patient years. This is a pretty good fit to the numbers I derived from the discontinuation rates in the FDA doc.

Thanks Formerly 98 (talk) 03:42, 23 February 2014 (UTC)

Hi Formerly 98. Can you please tell me the where exactly it states the Propecia trials were double-blind? Thanks.

I beg to differ that the different results were from "Dramatically different doses of Finasteride." Finasteride has a flat-dose response rate. 1mg of Finasteride inhibits nearly the same amount of DHT as 5mg. There was a study linked on this on the University of Pennsylvania website, but it was taken down late 2012. Suspicious. The dead link is here: http://www.physics.upenn.edu/facultyinfo/frankel/papers/propeciafda2/index.html

It's not that you're wrong regarding your estimation of what % of men experience persistent side effects, it's just that you weren't given the proper tools. The only information you are given on those who didn't experience persistent side effects are the patients who discontinued therapy. For those who finished the trial, there is a cutoff date when you are allowed to report an Adverse Event. So we have no measurement of the 900 other men who finished the trial. Going by case reports, the side effects start after quitting the drug. When disclosing to shareholders why they're being sued, Merck explained that patients experienced a range of sexual side effects upon cessation of Propecia.

As for going by case reports, we have no idea how many reports the FDA has received. They said they reviewed close to 700 reports, but it doesn't say how many they've received. Admittedly, the FDA doesn't review every report. Many of them are thrown out for a variety of reasons. So it's unreasonable to base an estimate on the case reports.

In the abstract of the paper I cited, it doesn't say how many men were in the Finasteride group. But if there were 1,500, 4% or 60 of them quit Finasteride due to a sexual AE. 50%, or 30, did not experience resolution of their sexual AE's. So that's 30 out of 1,500. And that's only measuring those who quit the trial. My estimation has it at 2%, yours at .01%. Either way, it's a moving target.

Also, I don't think the persistent sexual side effects in the PLESS trials was statistically significant. But I don't know if an ANOVA was done or they left it as is.

As for the FDA stating "In controlled clinical trials, these side effects resolved in patients who stopped finasteride, as well as in most patients who continued therapy," that's nothing but meaningless PR chatter. They don't like to admit that their studies fail to predict what is seen in the real-world. The evidence cited in this thread shows they're wrong. Like I've shown many times, the original Finasteride consumer label warned of persistent side effects. So the FDA was communicating nothing, just doing some face-saving PR vernacular. It's silly to think the FDA would admit the trials didn't properly screen for the withdrawal effect, admit patients weren't properly followed-up on after the trial was over, or cite a study that showed the label they approved was wrong the entire time. There's even more in the medical literature that say Finasteride side effects don't always resolve, but I'd like to finish with the PLESS and original Proscar label discussion before moving on.

Which label more accurately describes what's being seen in the real world?

Proscar label: If side effects persist, they USUALLY resolve upon discontinuing 'Proscar'

Propecia label: These side effects went away in men who stopped taking PROPECIA

Thanks for researching this important public health matter.

ETA: Formerly 98, if you're interested, there are people in forums. who claim they were involved in Finasteride clinical trials and experienced severe sexual problems after the trial concluded. Obviously, this would never make it to a Wikipedia page, but for academic reasons, if you're interested in hearing trial patients in their own words, here's one such patient:

"I signed up for the Prostate Cancer Prevention Trial at about the age of 50. Took Proscar 1mg daily for six years, followed by a prostate biopsy. When the test was unveiled, I was informed that I had been taking finasteride and not a placebo. Around the time the trial concluded, I began to notice ED problems, primarily loss of sensitivity. It became harder and harder to achieve an orgasm and ejaculate. After five years had elapsed, I was no longer able to achieve an intravaginal orgasm and had to masturbate. I was 60 years old by then. Since then, it has been a steadily downward slope. I no longer have morning erections and haven't been able to ejaculate for about a year."

"Can you please tell me the where exactly it states the Propecia trials were double-blind?" - Go to site http://www.accessdata.fda.gov/drugsatfda_docs/nda/97/020788_propecia_toc.cfm. Open part one of the medical review, go to page 28. Then open part 2 and and go to pages 42 and 92. These are the page numbers of the original document, and not PDF numbering.

The last page of Part 3 of the medical review discusses findings that unlike the 5 mg dose, the 1 mg dose "had little effect on semen production". and that there "appears to be a dose-dependent effect on ejaculate volume". So I believe the normal observation of a dose response relationship holds here.

I'm a little surprised by your comment that patients began experiencing sexual side effects for the first time after stopping the drug. Do you have a reference? What would be the proposed mechanism for this?

Its hard for me to evaluate stuff on chat boards that comes from outside of a double blind RCT. For a 60 year old to report falling sex drive and ability to perform is not unusual in any way. Especially when followed over a 6 year period. In some studies the prevalence of impotence in this age group is above 40%.

I noticed that one case of sexual dysfunction that did not resolve upon ceasing treatment was observed in phase 2 according to these docs.

The Canadian Adverse Event database http://www.hc-sc.gc.ca/dhp-mps/medeff/databasdon/index-eng.php which is more accessible than the US one seems to show about 145 "not recovered/not resolved" reports of sexual dysfunction associated with finasteride over the same time period as the FDA review. Correcting by the size of the two national populations, I get an estimated number of AE reports for the US of about 1330, which is about twice the number mentioned in the FDA press release.

Many thanks Formerly 98 (talk) 09:08, 23 February 2014 (UTC)

Formerly 98 The higher reduction of ejaculate volume for 5mg dose patients has nothing to do with why a warning of persistent side effects would be on the Proscar label, but omitted on the Propecia label. The reduction of DHT for 1mg--what we're most interested in--is exactly one page above the page you cited. It's nearly identical to what 5mg reduces ~65% of serum DHT. As it stands, 1 mg and 5mg of Finasteride has nearly the same effect on the male endocrine system.

The Orignal Proscar label should be discussed in the Finasteride Wikipedia page. It is what most accurately describes what's seen in the real world. No one has given a reasonable explanation why the Original Proscar label warning of persistent sexual side effects shouldn't be on the Finasteride Wikipedia page.

I understand Internet forums don't serve as a basis for an encyclepedia. I provided that report for you because a patient IN A CLINICAL TRIAL experienced a range of sexual side effects UPON CESSATION of Finasteride. I can direct you to literally thousands of other patient reports--ranging from ages 17 to 70--with similiar post-drug reactions.

My point was that the withdrawal effect was never properly screened for, and the paradigm that "side effects always go away" was based on the reports 11 PATIENTS who did not complete the Propecia study. For a description of the post-drug reaction, please see http://propeciahelp(DOT)com/symptoms If you're the type to demand only published literature, see the first Dr. Irwig study on Finasteride. He says something like 67% of patients he interviewed reported worsening of side effects upon cessation.

As for a mechanisms to explain why side effects get worse after quitting: that's is currently being studied at Brigham and Women's Hospital and Baylor College of Medicine. It's been demonstrated in animals that Androgen Ablation leads to permanent Androgen Receptor hypersensitivity, making symptoms worse after a return of baseline DHT. From my understanding, this is the leading hypothesis.

In any event, it's well-established that Finasteride does cause permanent sexual side effects. As shown in case reports, clinical trials, and other studies in the medical literature. That's why it's imperative Wikipedia put the PLESS trial results showing persistent Finsateride sexual side effects. No one has even offered a rebuttal for why it shouldn't be, and quite frankly, it's looking awefully suspicious. Many influential people are looking into and reporting these machinations by Wikipedia. (ETA) These suspicions grow by the minute when Wikipedia puts a "protection filter" on PropeciaHelp. It's as if Wikipedia encourages ignoring real-world patients. Sad.

And thanks for citing the page # where it says it's a double-blind placeo study. However, the studies were both single-blind and double-blind.

"The higher reduction of ejaculate volume for 5mg dose patients has nothing to do with why a warning of persistent side effects would be on the Proscar label, but omitted on the Propecia label. The reduction of DHT for 1mg--what we're most interested in--is exactly one page above the page you cited." - I'm not at all sure I agree with that. What is the source of your number for the DHT reduction caused by the 5 mg dose? We both need to be careful about drawing broad conclusions based on cross-trial comparisons.

"No one has given a reasonable explanation why the Original Proscar label warning of persistent sexual side effects shouldn't be on the Finasteride Wikipedia page." - We're discussing that now, though I'll be upfront and say I agree with a previous comment that Wikipedia is not an investigative journalism venue. I've never run across a case where the frequency of side effects is not dose-dependent upon a 5x change, and a priori am deeply skeptical that there is any need to invoke any other explanation for the difference in the labels.

"It's been demonstrated in animals that Androgen Ablation leads to permanent Androgen Receptor hypersensitivity, making symptoms worse after a return of baseline DHT." - I'd be interested in reading about this if you have a ref. Wouldn't androgen hypersensitivity have exactly the opposite effect?

"In any event, it's well-established that Finasteride does cause permanent sexual side effects...I can direct you to literally thousands of other patient reports" - Based on what I've seen so far I'm inclined to agree that the higher dose probably does have this effect in a very small fraction of men (which given the very large number of men who have taken the drug would in fact correspond to "many thousands of case reports". I'd like to understand the FDA's comments better and see what was observed in other Propecia trials, which will require a trip to the library.

I suppose we should talk about what the goals of this discussion are. I know that there has been a lot of discussion of this topic before, and I am certainly not influential enough to reverse decisions that were made previously after extensive discussion. What reason has been given previously for not including the observations from the PLES trial? Formerly 98 (talk) 12:03, 24 February 2014 (UTC)Thanks

Edits of September 28

(Moving this discussion from User Talk pages to this page.)

Several changes made on September 11 were reverted with the explanation "Please don't remove sections that have been discussed and agreed upon months/years earlier - Discuss further on talk page if you wish)". First I'd say that I don't see anything on the Talk page clearly indicating that the language you have reverted back to is "consensus". The discussion ended on February 24, with me asking you a series of questions that you never responded to.

• "In December 2008, the Swedish Medical Products agency concluded a safety investigation of finasteride and advised that finasteride may cause irreversible sexual dysfunction. The Agency's updated safety information lists difficulty in obtaining an erection that persists indefinitely, even after the discontinuation of finasteride, as a possible side effect of the drug"

As my edit summary explains, the quoted insert only says that there have been case reports and causation is unestablished. It is WP:UNDUE to call this a "warning". I've literally come across AERS reports in which people have reported "death of pet" as a side effect of medication. If we included every spontaneous adverse event report as a "warning" for other drugs we'd need several hundred thousand KB just to list them out. This is not meaningful evidence in support of a causative relationship. Furthermore, the link does not work, making this claim unverifiable and subject to immediate removal under WP:VERIFY

I am not the person with whom you were conversing on February 24th. I am not sure if you were aware of that or not but either way this discussion does not involve the PLESS trial. I have updated the reference with a live, verifiable link. These AERS cannot be compared to reports indicating "death of pet". The relevant regulatory bodies discovered a sufficient number of reports and decided it warranted including a statement on their respective labels. Your reference to "death of pet" is potentially misleading too as a pet could have accidentally consumed the medication, leading to death, which makes the report completely valid not so humorous. Doors22 (talk) 06:39, 21 October 2014 (UTC)

• "The UK's Medical and Healthcare Products Regulatory Agency (MHRA) cites reports of erectile dysfunction that persists once use of finasteride has stoppedIn April 2011 Merck revised the United States' warning in consumer and medical leaflets to include erectile dysfunction that may persist after stopping finasteride."

As noted in my edit summary, the cited document from MHRA appears to say nothing about sexual dysfunction. Being unverifiable, it is subject to immediate deletion per WP:VERIFY. You've restored this material without addressing my explanation for the edit, and in contrast to your comment, there is no consensus on the Talk page for including this material. Even if there were, it would violate WP:CONEXCEPT as the material is unverifiable.

• In April 2012, the warning label was further strengthened to include reports of persistent libido disorders, ejaculation disorders, orgasm disorders, and decreased libido. According to FDA, these warnings were added as precaution after reviewing 678 case reports of post-treatment sexual dysfunction received over an 18 year period. The Agency further stated that "despite the fact that clear causal links between finasteride (Propecia and Proscar) and sexual adverse events have NOT been established, the cases suggest a broader range of adverse effects than previously reported in patients taking these drugs."

This is probably an acceptable source as the FDA issued a release around the label changes.

I've deleted the Swedish Medical Agency and MHRA references and left the FDA one in place.

• "regulatory authorities have listed mood disorders as among the possible adverse effects of finasteride,"

As I noted in my edit summary, the cited reference does not support the statement "regulatory authorities have listed mood disorders as among the possible adverse effects of finasteride". You reverted my deletion of this material without commenting on the reason for the deletion. "Prior Consensus", which I see no evidence for on the Talk page, is insufficient to overcome the fundamental pillar of Wikipedia that all content must be sourced.

I've deleted the reference to "regulatory authorities" as unverifiable.

• "Some studies have shown that the dose of finasteride needed to treat male pattern baldness may be smaller than 1 mg.[44] Petitions to the FDA to re-examine the approved dosage in light of the statistical evidence and possible long-term risks,[45] were met with the response that a study had shown increased effect of a 1 mg dose compared to 0.2 mg without added risks; the same study also concluded that doses of 0.01 mg per day were found to be ineffective in treating hair loss.[45]"

Once again you've reverted me without responding to the reasons in my edit summary and appealing to a "consensus" for which there is no evidence on the Talk page. As I noted in the edit summary, this petition is non-notable. I could write a petition to the FDA tomorrow requesting that they re-examine the dosage for Lipitor. But I am not a well known expert in the field of cardiology, so its really not notable unless the FDA actually acts on it.

The statement that doses needed may be less than 1 mg cites an FDA document, in which I can find no discussion of dosing issues. Like any other statement without verifiable sources, it can and should be deleted. Verifiability is one of the 3 pillars of Wikipedia. I've deleted the paragraph. Formerly 98 (talk) 11:10, 28 September 2014 (UTC)

You posted on my talk page that the most recent edits on the talk page were you asking questions to which I didn't not respond. This isn't correct for two reasons. First, your comments were directed at an entirely separate editor and secondly, you were asking questions about the PLESS study which has already been removed from the article. You even mention you aren't influential enough to reverse decisions made after extensive discussion, but several months later this is exactly what you did.

"I suppose we should talk about what the goals of this discussion are. I know that there has been a lot of discussion of this topic before, and I am certainly not influential enough to reverse decisions that were made previously after extensive discussion. What reason has been given previously for not including the observations from the PLES trial? Formerly 98 (talk) 12:03, 24 February 2014 (UTC)Thanks"

The previous consensus was attained much earlier in the history of the talk page or in the direct notes of the edits. Some of your points are valid - I did not notice that some people had given incorrect references or maybe the reference links had broken, since as I mentioned, the edits were made a long time ago. I will take your comments into consideration and try to fix the reference links where possible. Doors22 (talk) 14:54, 28 September 2014 (UTC)

@Doors22: I don't think a consensus reached a year or so ago is necessarily still consensus, and my general openness to your concerns about AEs was not intended as agreement to use poor sources. But I don't want to have a huge argument over this, I'll be satisfied for the most part if you fix the sourcing. Prefer that we drop the FDA petition from a physicist. Thanks. Formerly 98 (talk) 15:05, 28 September 2014 (UTC)

I'm getting a sense of deja vu. Didn't we agree that we needed to be very selective about sources in this highly disputed area? Doors22 isn't anything if not persistent. JFW | T@lk 22:41, 6 October 2014 (UTC)

I'm really not sure to what your comment pertains. The edits have used sources that high quality according to the Wiki community. This problem has been visible for a long time now and as a consequence several of the links have died after a period of years. They have been updated accordingly. I am not sure if your suggestion that I am nothing if not persistent is some failed attempt at humor given the discussion on persistent side effects of the drug, but in any case it is in very poor taste. The Wikipedia community should expect and require more from members it makes administrators. Doors22 (talk) 06:46, 21 October 2014 (UTC)

Doors22 No, my comment about "persistence" relates to the fact that you've been editing Wikipedia as a single-purpose account since February 2011. During that time we have had repeated discussions about using Wikipedia to promote awareness of a phenomenon that has been very poorly studied. Without wanting to be particularly patronising, I think your time might be better spent by collaborating with academic andrologists on improving the pathophysiological understanding and documenting the phenomenon using validated objective measures. JFW | T@lk 13:20, 21 October 2014 (UTC)

Regarding today's change, if you look at your recent statement you said you would be mostly satisfied so long as sourcing is fixed which is done. To reach a consensus, I have left out the commentary on dosing and I hope you are not going back on your word. It isn't compatible with your statement that you chose to reverse the edit. However, I have revised the statements to make them much less wordy. Side effects that are non-life threatening are not the only side effects worthy of mention. The outcome leads to permanent injury and a significantly reduced quality of life, which on the occasion unfortunately has led to suicide. The outcome is not as infrequent as you suggest although frequency has not yet been discussed in peer-reviewed medical journals. As mentioned in the article, more than 600+ accounts were reported to FDA which is a very small subset of those living with side effects. Thanks. Doors22 (talk) 01:52, 22 October 2014 (UTC)

Its WP:UNDUE Doors. There is no evidence of causation (FDA comments to this effect seem to have been the main thing removed in your edit "to make the section less wordy".

You re-added the WP:OR assertion "Despite updating European information leaflets, Merck left the US label unchanged until April 2012" even though the first FDA reference at the end of that sentence states that "persistent erectile function was added to the label in 2011". I have adjusted that sentence and will make other changes later if needed.Formerly 98 (talk) 11:40, 22 October 2014 (UTC)

I have provided two additional sources which show the statements were not original research. I get the sense that you are engaging in a revert war as you have reverting edits nearly a dozen times over the past couple of months. In the future, please abide by Wikipedia regulations and edit rather than revert to avoid giving off a sense of hostility. WP:ROWN Thanks Doors22 (talk) 03:13, 23 October 2014 (UTC)

I added another meta analysis draws the opposite conclusion. They both look at a similar number of studies, but one journal is of a higher quality than the other. Formerly 98, are you getting paid to edit Wikipedia? It seems to be a full time endeavor for you since you are editing at all hours of the day. The majority of your edits involve reversions about side effects or information that is not favorable to pharmaceutical companies. Doors22 (talk) 00:28, 24 October 2014 (UTC)

Doors, please take a look at WP:GF, and when you have done so, strike your remark above. Disagreeing with you does not constitute evidence of COI. Formerly 98 (talk) 00:43, 24 October 2014 (UTC)

I am familiar the concept of assuming good faith and would like to refer you to WP:AAGF. I don't think you are malicious or even that you disagree with me. I am just inquiring about your background since you are a very prolific editor on Wikipedia. By the way, I happened to realize you added the reference to the meta analysis without having ever read the study - I saw this on JFDWolff's talk page. Will you please explain why you are adding references without having fully read them? I personally have read the article and can vouch that it is not a very high quality article in a not highly respected journal. An answer to my previous question would be appreciated as well. 01:47, 24 October 2014 (UTC)

Yes, I read the abstract and the article was summarized in other articles. I felt that the abstract and these additional descriptions provided sufficient understanding of the material to add it. Judging from your edit, you interpreted it differently than I did (may I assume you read the entire article before writing your own summary?) and I did not think it appropriate to challenge your interpretation without reading the entire text.

Are you aware of quality secondary sources that support your contentions? I believe that the 5-10% of this article that is spent on this subject is undue weight. I further believe that the article is written in a way that implies that this is well-established science, when it is actually quite speculative. The highest quality sources I have found either refute this hypothesis or give it only passing mention.

1) The FDA safety announcement that said that information was being added to the Propecia label as a precaution in spite of lack of proof of causation.

2) The label itself, which dedicates one half of a sentence out of 18 pages of text to this putative side effect.

3) The Swedish and MHRA labels. The British package insert contains one sentence on this subject.

4) The meta analysis which I added and which I will refrain from modifying your interpretation of until I see the full text.

5) The American Urology Association treatment guidelines for BPH, which refers to sexual side effects as follows: "These events are reversible and uncommon after the first year of therapy."

6) The guidelines of the European Association for Urology contain 2 paragraphs on adverse effects of finasteride. Sexual dysfunction persisting after discontinuation of therapy is not even mentioned.

And no, I will not respond to your completely inappropriate question. I find it remarkable that you would direct me to WP:AAGF after point-blank suggesting that I am performing undisclosed paid editing. Formerly 98 (talk) 04:00, 24 October 2014 (UTC)

Reading the abstract of a meta study or any article is not sufficient. You, yourself, have posted that you don't like meta studies on your own talk page because you can't understand why the author drew conclusions even AFTER reading the article, let alone from a quick abstract. While it is inappropriate that you are asking me if I read the article because it is a minimum standard of editing, I will let you know that I did in fact read both meta studies. The one you quote narrowed hundreds of articles down to 12 and did not explain how it concluded that active intervention did not increase risk of sexual dysfunction. A rather ridiculous interpretation coming from a low quality journal, especially when industry sponsored studies indicate otherwise. Nonetheless I kept your inclusion, even though you should have never added this edit without opening the source, and added another higher quality meta study that concludes the opposite. Yes, I have read both.

Your commentary that the Wiki article should reflect the PI is not a valid statement. If it had any relevance, Wikipedia articles on drugs would just reiterate the PIs. Drug companies argue with the FDA for months over single words which they deem to be critical so your response is irrelevant.

I also never "suggested" you were performing undisclosed paid editing. I did not express any certainty this was a fact, but just asked a question since there is more than enough evidence this is a possible, and just expected an honest answer. Had you truthfully responded something like 'no, I am not paid for my engagement on Wikipedia' the issue would have been over. Your refusal to answer and even your defensiveness raises additional questions.

My question was had little to do with your disagreement with me but rather your being very quick to revert edits, your very extensive history of diminishing commentary on pharmaceutical side effects, and reverting comments on litigation against pharmaceutical companies. In fact, I have rarely seen you add information rather than remove it. Additionally found evidence of administrators and other scientists concerned with your edits. http://wp.rxisk.org/post-ssri-sexual-dysfunction-wikipedia-falls/

While much less significant, I also noticed you live in San Diego, where a lot of pharmaceutical/biotech companies are located and you have referred to yourself as an "industry guy". For all I know, you could simply own Merck stock and nothing more. Do you have any conflicts of interest that would affect your edits on this article? Doors22 (talk) 11:00, 25 October 2014 (UTC)

Please note that Formerly98 has privately refused to disclose any conflicts of interest, whether or not they exist, and admonished me for discussing this on the talk page. Prior to filing a formal investigation, this really is an appropriate place to bring this up. I suggest that he treads carefully, as long as he abides by Wikipedia norms there won't be any troubles but if he continues with excessive reversions rather than editing and referencing sources without having read them additional action will be taken. Healthy discussion and dissonance can improve the quality of Wikipedia articles so the norms and values of the community are upheld. Doors22 (talk) 15:17, 25 October 2014 (UTC)

Doors22 It is a sadly typical mistake to personalize disputes over content. I suggest that you tread very carefully to avoid violating WP:AGF and WP:NPA. You have zero evidence of a COI. If you want to run the risk to your reputation and run the risk of a WP:BOOMERANG you are of course free to file a case at COIN. Outside of that, per WP:TPG please comment on content, not contributor. Jytdog (talk) 15:54, 25 October 2014 (UTC)

Worked this over today

i worked the article over today. Brought it into compliance with WP:MEDMOS in terms of sectioning, level of detail, and putting things into plain English as much as possible. Fixed a bunch of dead refs or bare URL refs. Seems like it is in decent shape now. Happy to discuss any of the changes. Jytdog (talk) 20:37, 25 October 2014 (UTC)

Post-Finasteride Syndrome Foundation

I reviewed the talk page and I think I see what some of the struggle is about. A group called the Post-Finasteride Syndrome Foundation formed in 2012 and appears to be trying to establish the validity of this syndrome, to educate folks about it, and to work toward a cure for it. My sense is that the arguments over sexual side effects stem from this foundation's efforts, or folks aligned with them. I searched pubmed and there no reviews on this Syndrome yet, so it appears not to be accepted by mainstream medicine, yet. So the syndrome should not be mentioned per se in the side effects part of the article as there are no MEDRS-compliant sources for it. Yet. As for the organization itself, there are few indepedent secondary sources about it (you can see that the source I found - the best one I could find - is something called the "Australian Financial Review"), so per WP:NPOV the foundation should get little weight in this article. With this kind of thing, I think it is useful to give a mention, but the mention should not be used to coatrack content into the article about their agenda. This is an effort to "give an inch" - I hope no one takes a mile. Jytdog (talk) 21:25, 25 October 2014 (UTC)

Thanks, I think it is sensible to have a blurb about the PFSF in the society and culture section. If I recall, I tried putting that in awhile ago with a similar type of news source but it seems like everything is met with a lot of resistance. By the way, "post finasteride syndrome" is a little bit of a colloquial phrase which is why it more likely belongs in society and culture. If you search the terms "finasteride" and "persistent" on pubmed you will see maybe a dozen articles from different doctors describing things like hormone/semen levels, neurosteroid levels, and several case series.Doors22 (talk) 23:09, 25 October 2014 (UTC)

Thanks Jytdog for your input. And Doors22 - without a strong secondary source it will not be appropriate to work PFSF into the article, even the "society and culture" section. Until stronger sources exist, it has the same level of importance as any random theory. Can I once again suggest you stimulate the work of academic andrologists to demonstrate or disprove the syndrome along the lines of formal scientific enquiry? JFW | T@lk 21:28, 26 October 2014 (UTC)

This has been several years in the works already. As an MD, I am sure you are more than acquainted with the timelines associated with conducting medical research. If you look through the foundation's website a bit more thoroughly, you will see a couple globally respected institutions have already taken up this task while a handful of doctors have already published on the subject. Baylor College of Medicine is the first and Harvard's Brigham Women's Hospital. Very different than any random theory which hasn't been tested. A substantial amount of data has been collected and a couple lab assays have been published on patients. I also think its very unlikely any random theory would attract the attention of a Harvard teaching hospital. Doors22 (talk) 01:50, 27 October 2014 (UTC)

Doors22 you took the bait. may i ask you guys to take this elsewhere? this is not a forum for discussing the topic; the key thing for Wikipedia and this article is that there are no strong secondary sources yet, so per WP:MEDRS (and RS for that matter) we shouldn't discuss it in the article. thanks. Jytdog (talk) 08:55, 27 October 2014 (UTC)

Jytdog This is not a matter of "bait". I've been trying to explain this to Doors22 for some time. As it is relevant to the article it does not necessarily violate WP:TALK. Until there is sufficient evidence, this remains a "random theory". JFW | T@lk 09:02, 27 October 2014 (UTC)

As we have additional eyes on the article now, I've added a proposed modification to the text for consideration.

• We formerly had one sentence to describe the fact that there were case reports of persistent sexual dysfunction, a second sentence to describe the fact that the Europeans had added mention of these to their package inserts, and a third sentence stating that the U.S. had done so as well. I've collapsed these to a single sentence. I find it difficult to believe that adding a separate sentence for each place the report appeared would be considered acceptable if we were discussing, for example, a preliminary positive result seen in a single arm phase 1 trial.
• I moved the meta analyses on sexual dysfunction during treatment to the beginning of the paragraph to avoid the impression that they dealt with post-treatment effects.

You guys can decide. I think I've made my position pretty clear, and if there is no support among those with an outside perspective I will drop this, as I've spent far too much time on it already.Formerly 98 (talk) 10:00, 27 October 2014 (UTC)

I am fine with your changes. Jytdog (talk) 11:24, 27 October 2014 (UTC)

Agree. JFW | T@lk 21:39, 27 October 2014 (UTC)

Breast cancer

I've simplified the discussion. This is an Adverse Events section, and the focus should be on assessing these. We don't really need to discuss each regulatory agency adding the same warning to the label in separate sentences, which seems to be a common method used for adding undue weight to the discussion of rare adverse events of unknown causation.

Also, the sentence that Merck modified the label to "give warning of increased risk of breast cancer" is incorrect. The label refers to a "possible increased risk" and specifically states that causation has not been established. The prior wording very much left the impression that both an increased incidence of breast cancer among finasteride users and a causative relationship have been established. I don't see anything in the label stating that either has been. Formerly 98 (talk) 14:14, 15 January 2015 (UTC)