Finasteride [5ARI] Induced/Associated Effects

[visionquest99]

Re: Mainstream media finally realizing Propecia can make you impotent

The special relationship is this; Finasteride inhibits 5beta-Reductase (not just 5Alpha-Reductase). 5beta-Reductase controls the CYP450 3A4 enzyme responsible for the metabolization of both xenobiotics and sex steroids.

Finasteride is a xenobiotic (and also a synthetic androgen). Theoretically Finasteride could even inhibit its own metabolism.

When Finasteride usage ends, 5beta-Reductase will regenerate, there will therefore be 'more' CYP450 3A4. I would suggest that the increase in an enzyme that has been both inhibited and heavily taxed to metabolize an androgen could lead to its permanant induction/up regulation. (---remember, something has been permanantly changed---)

If CYP450 3A4 is now metabolizing more testosterone, the effect will not be more testosterone urinated out but more weak/deactivated testosterone in the blood. Enough deactivated testosterone is a natural anti-androgen as it will impede the androgenic activity of normal testosterone by competing for the Androgen Receptor and binding/not binding to SHBG etc.

The result may be a new form of hypogonadism.

This validity of this theory is easy to determine via a blood/urine test.

You sound very knowledgeable. Any suggestions for those suffering these effects?

 

[zkt]

Re: Mainstream media finally realizing Propecia can make you impotent

But many common drugs inhibit 3A4 as well as the other ones in the family.
Wish I could find the link to the general Cyp drug interatcions topic I posted.
You havent soecified anything other than F inhibits its own metabolism.
This is true for many drugs and obvoiusly for drug combinations.
You fail to identify anything specific to F.
With all due respect.

The special relationship is this; Finasteride inhibits 5beta-Reductase (not just 5Alpha-Reductase). 5beta-Reductase controls the CYP450 3A4 enzyme responsible for the metabolization of both xenobiotics and sex steroids.

Finasteride is a xenobiotic (and also a synthetic androgen). Theoretically Finasteride could even inhibit its own metabolism.

When Finasteride usage ends, 5beta-Reductase will regenerate, there will therefore be 'more' CYP450 3A4. I would suggest that the increase in an enzyme that has been both inhibited and heavily taxed to metabolize an androgen could lead to its permanant induction/up regulation. (---remember, something has been permanantly changed---)

If CYP450 3A4 is now metabolizing more testosterone, the effect will not be more testosterone urinated out but more weak/deactivated testosterone in the blood. Enough deactivated testosterone is a natural anti-androgen as it will impede the androgenic activity of normal testosterone by competing for the Androgen Receptor and binding/not binding to SHBG etc.

The result may be a new form of hypogonadism.

This validity of this theory is easy to determine via a blood/urine test.

 

[xeno]

Re: Mainstream media finally realizing Propecia can make you impotent

As I understand it, Finasteride's inhibition of 5beta-Reductase is unique, (see Inhibition of Human Steroid 5?-Reductase (AKR1D1) by Finasteride and Structure of the Enzyme-Inhibitor Complex — JBC)

"(inhibition of 5beta reductase) by high dose finasteride would also deprive PXR of its natural 5?-pregnane ligands, resulting in diminished CYP3A4 induction. This could result in significant drug-drug interactions"

So rather than inhibit CYP3A4 directly like many, many drugs do, Fin inhibits the regulator of CYP3A4 the PXR (see [ame="http://en.wikipedia.org/wiki/Pregnane_X_receptor"]Pregnane X receptor - Wikipedia, the free encyclopedia@@AMEPARAM@@/wiki/Filerotein_NR1I2_PDB_1ilg.png" class="image"><img alt="" src="http://upload.wikimedia.org/wikipedia/commons/thumb/0/0e/Protein_NR1I2_PDB_1ilg.png/250px-Protein_NR1I2_PDB_1ilg.png"@@AMEPARAM@@commons/thumb/0/0e/Protein_NR1I2_PDB_1ilg.png/250px-Protein_NR1I2_PDB_1ilg.png[/ame]).

In experiments, scientists have shown that over expression of PXR is an effective means of androgen deprevation, as it will increase CYP3A4 and therefore the metabolism of testosterone - even in rats being injected with supra-physiological doses of test (see Pregnane X receptor as a therapeutic target to inh... [Endocrinology. 2010] - PubMed result)

I suggest that after quitting Fin there is a reflex-type over expression of 5beta-reductase/PXR that now leads to increased testosterone metabolism. This leads to higher levels of deactivated hydroxy-testosterones in serum, which compete for the androgen receptor, and thus a state of androgen deprevation - despite normal-ish blood work.

 

[zkt]

Re: Mainstream media finally realizing Propecia can make you impotent

I`m sure that if I studied your references sufficiently I would reach the same conclusion.
Thanks for posting here.

As I understand it, Finasteride's inhibition of 5beta-Reductase is unique, (see Inhibition of Human Steroid 5?-Reductase (AKR1D1) by Finasteride and Structure of the Enzyme-Inhibitor Complex — JBC)

"(inhibition of 5beta reductase) by high dose finasteride would also deprive PXR of its natural 5?-pregnane ligands, resulting in diminished CYP3A4 induction. This could result in significant drug-drug interactions"

So rather than inhibit CYP3A4 directly like many, many drugs do, Fin inhibits the regulator of CYP3A4 the PXR (see Pregnane X receptor - Wikipedia, the free encyclopedia).

In experiments, scientists have shown that over expression of PXR is an effective means of androgen deprevation, as it will increase CYP3A4 and therefore the metabolism of testosterone - even in rats being injected with supra-physiological doses of test (see Pregnane X receptor as a therapeutic target to inh... [Endocrinology. 2010] - PubMed result)

I suggest that after quitting Fin there is a reflex-type over expression of 5beta-reductase/PXR that now leads to increased testosterone metabolism. This leads to higher levels of deactivated hydroxy-testosterones in serum, which compete for the androgen receptor, and thus a state of androgen deprevation - despite normal-ish blood work.

 

[James23]

Re: Mainstream media finally realizing Propecia can make you impotent

When we're talking about the effects of Propecia, are we talking about complete ED and totally absent libido?

Or, are we just talking about noticeably diminished libido and occasional ED?

 

[Deadballs]

Re: Mainstream media finally realizing Propecia can make you impotent

What is this joke man?? People loose their testicles, penises and mind after finasteride use. Where is the difficulty to prove it??

I have blood tests that show a wacked system after using finasteride - or do you think that someone that converts almost no T to dht is normal ?? (unless we belong to this caribbean tribe that have congenital androgen resistance and still don't know it)
I can bring 7-8 ex girlfriends i had in the court to assure that before fin i was a perfect male and now a limp. In all aspects.
.

Same!!

 

[Deadballs]

Re: Mainstream media finally realizing Propecia can make you impotent

When we're talking about the effects of Propecia, are we talking about complete ED and totally absent libido?

Or, are we just talking about noticeably diminished libido and occasional ED?

Both and everything in between as well as a smorgasbord of other ailment for the unlucky few!

 

[xeno]

Re: Mainstream media finally realizing Propecia can make you impotent

When we're talking about the effects of Propecia, are we talking about complete ED and totally absent libido?

Or, are we just talking about noticeably diminished libido and occasional ED?

Go to PROPECIAHELP: Unresolved Finasteride Propecia Proscar side effects info & forum to find out.

The side effects are the same as hypogonadism/androgen deprevation, to varying degrees, but with normal testosterone.

 

[zkt]

Re: Mainstream media finally realizing Propecia can make you impotent

This belongs here:
http://www.edhayes.com/CYP450-4.html
I dont understand Zeno`s theory well enought yet to grasp all the implications of it.
If ever a thread needed to stay on the first page, this is it.
Anyone else got enough background to analyze it ?

 

[Michael Scally MD]

Re: Mainstream media finally realizing Propecia can make you impotent

Does anyone have access to the filed complaint?

[UPDATED: COMPLAINT ATTACHED]

Lawsuit Blames Hair Loss Drug For Sexual Dysfunction And Mental Problems
http://www.courant.com/health/connecticut/hc-buck-propecia-lawsuit-0304-20110303,0,205650.story

By RINKER BUCK
The Hartford Courant
March 3, 2011

A Connecticut law firm has filed a lawsuit against pharmaceutical manufacturer Merck & Co. on behalf of men who have taken Propecia, a prescription drug that combats hair loss but, its critics say, can also cause severe side effects such as sexual dysfunction and mental impairment.

Attorney Edward Jazlowiecki of Bristol has joined two other firms, in New Jersey and New York, in filing the suit, which alleges that Merck has failed to fully disclose the serious side effects of Propecia and failed to adjust its warnings in the American market even after European regulators forced the company to carry a stronger warning label.

Propecia, which is also marketed under the brand name Proscar, was originally introduced to treat men with enlarged prostates, but it won FDA approval in 1997 for the treatment of male pattern hair loss after patients noticed its restorative powers with hair. The drug's active ingredient is finasteride, which can help reduce the levels of the substance on the scalp that leads to hair loss.

But in many men, Jazlowiecki said, finasteride also reduces sexual function and leads to mental and emotional symptoms like anxietyattacks and insomnia that do not go away years after men stop using the drug.

"The same mechanism in the hormone system that controls hair loss also controls sexual function and a patient's mental state, and this drug has had devastating effects and destroyed the lives of men who have taken it," Jazlowiecki said. "Merck knew this, and their claims that the negative effects of the drug go away once you stop using it are false. The damage to these men appears to be permanent, even after five years of taking the drug."

When contacted by The Courant, Merck released a statement that said, "The company intends to vigorously defend against the lawsuit."

Jazlowiecki said that one of the plaintiffs in his suit suffered such severe symptoms that his wife left him, and that another plaintiff suffered from a loss of concentration that forced him to drop out of law school. Jazlowiecki's complaint, filed in U.S. District Court in New Jersey, where Merck's U.S. headquarters are located, also quotes American and European doctors who have passionately argued against the drug, citing many of the severe side effects listed in the lawsuit.

Similar experiences are described on a website devoted to men who have suffered side effects from the drug, PROPECIAHELP: Unresolved Finasteride Propecia Proscar side effects info & forum.

One Connecticut patient, who plans to join the lawsuit as soon as lawyers finish examining his medical records, said that he stopped taking Propecia three years ago after experiencing trouble breathing, sexual dysfunction, anxiety attacks and memory loss. He asked not to be named because his mother still does not know of the severe side effects the drug caused.

"I was a happy, athletic person before I started taking this drug, but now it has ruined my life," the plaintiff said. "The hardest part is going to doctors and describing my condition and they don't believe me. They believe all of the material that has been sent out by the FDA and Merck and just send me home with a prescription for anti-depressants."

On its Propecia website, under "possible side effects," Merck does have a warning, which reads:

"A small number of men had sexual side effects, with each occurring in less than 2% of men. These include less desire for sex, difficulty in achieving an erection, and a decrease in the amount of semen. These side effects went away in men who stopped taking PROPECIA because of them."

But doctors that Jazlowiecki quotes in his lawsuit insist that symptoms persist after patients stop using Propecia, and might be permanent.

 

[Structure]

Re: Mainstream media finally realizing Propecia can make you impotent

Does anyone have access to the filed complaint?

[UPDATED: COMPLAINT ATTACHED]

Lawsuit Blames Hair Loss Drug For Sexual Dysfunction And Mental Problems
http://www.courant.com/health/connecticut/hc-buck-propecia-lawsuit-0304-20110303,0,205650.story

By RINKER BUCK
The Hartford Courant
March 3, 2011

A Connecticut law firm has filed a lawsuit against pharmaceutical manufacturer Merck & Co. on behalf of men who have taken Propecia, a prescription drug that combats hair loss but, its critics say, can also cause severe side effects such as sexual dysfunction and mental impairment.

Attorney Edward Jazlowiecki of Bristol has joined two other firms, in New Jersey and New York, in filing the suit, which alleges that Merck has failed to fully disclose the serious side effects of Propecia and failed to adjust its warnings in the American market even after European regulators forced the company to carry a stronger warning label.

Propecia, which is also marketed under the brand name Proscar, was originally introduced to treat men with enlarged prostates, but it won FDA approval in 1997 for the treatment of male pattern hair loss after patients noticed its restorative powers with hair. The drug's active ingredient is finasteride, which can help reduce the levels of the substance on the scalp that leads to hair loss.

But in many men, Jazlowiecki said, finasteride also reduces sexual function and leads to mental and emotional symptoms like anxietyattacks and insomnia that do not go away years after men stop using the drug.

"The same mechanism in the hormone system that controls hair loss also controls sexual function and a patient's mental state, and this drug has had devastating effects and destroyed the lives of men who have taken it," Jazlowiecki said. "Merck knew this, and their claims that the negative effects of the drug go away once you stop using it are false. The damage to these men appears to be permanent, even after five years of taking the drug."

When contacted by The Courant, Merck released a statement that said, "The company intends to vigorously defend against the lawsuit."

Jazlowiecki said that one of the plaintiffs in his suit suffered such severe symptoms that his wife left him, and that another plaintiff suffered from a loss of concentration that forced him to drop out of law school. Jazlowiecki's complaint, filed in U.S. District Court in New Jersey, where Merck's U.S. headquarters are located, also quotes American and European doctors who have passionately argued against the drug, citing many of the severe side effects listed in the lawsuit.

Similar experiences are described on a website devoted to men who have suffered side effects from the drug, PROPECIAHELP: Unresolved Finasteride Propecia Proscar side effects info & forum.

One Connecticut patient, who plans to join the lawsuit as soon as lawyers finish examining his medical records, said that he stopped taking Propecia three years ago after experiencing trouble breathing, sexual dysfunction, anxiety attacks and memory loss. He asked not to be named because his mother still does not know of the severe side effects the drug caused.

"I was a happy, athletic person before I started taking this drug, but now it has ruined my life," the plaintiff said. "The hardest part is going to doctors and describing my condition and they don't believe me. They believe all of the material that has been sent out by the FDA and Merck and just send me home with a prescription for anti-depressants."

On its Propecia website, under "possible side effects," Merck does have a warning, which reads:

"A small number of men had sexual side effects, with each occurring in less than 2% of men. These include less desire for sex, difficulty in achieving an erection, and a decrease in the amount of semen. These side effects went away in men who stopped taking PROPECIA because of them."

But doctors that Jazlowiecki quotes in his lawsuit insist that symptoms persist after patients stop using Propecia, and might be permanent.

Wow, how evil is Merck? This is really great news though. I hope Merck soon finds itself with a few new assholes torn in it...

 

[dfein]

Re: Mainstream media finally realizing Propecia can make you impotent

Landes Bioscience Journals: Cancer Biology & Therapy

Apparently it's no coincidence that the side effects are the same as flutamide, because it has been found to partially bind to and deactivate the androgen receptor. This may be why it ruins libido.

 

[Structure]

Re: Mainstream media finally realizing Propecia can make you impotent

More coverage: Baldness Drug Sexual Effects - ABC News

 

[Structure]

Re: Mainstream media finally realizing Propecia can make you impotent

Study Coming Out This Week Should Make Issue Legitimate, Author Says

Dr. Michael Irwig, an endocrinologist at George Washington University, interviewed 100 healthy men, aged 21 to 46, in the past year who took finasteride for hair loss and reported sexual side effects or depression after they stopped the drug. He tracked down the men, half of whom live overseas, through the Propeciahelp.com Web site, which has been visited by more than 1,700 men with problems following finasteride use.

"This will finally give evidence that this exists and will make this legitimate and doctors won't blow these patients off," Irwig said. "And now, most importantly in terms of prevention, we can have an informed discussion; men contemplating using this medicine and doctors prescribing it."

Irwig said he has seen men "who have actually been suicidal; some who have lost their jobs" because of psychological and physiological fallout after using the medication. "I had one guy in his early 20s fly all the way from Australia, who is that desperate," he said.

Irwig said there was "strong evidence" that finasteride interferes with hormones in the brain, called neurosteroids, which in turn alter levels of important chemicals called neurotransmitters that affect mood and thinking, among other critical functions.

Irwig said he was surprised at the dearth of published material, given that finasteride has been around for 10 years and "there have been guys who have had persistent side effects for 5 and 10 years already."

Although reversible effects have been well-known, he attributed the scant knowledge about persistent effects to their relative absence in medical literature until now. "A guy will go to a doctor and will say, 'I think this medicine has caused ED [erectile dysfunction] that hasn't gone away," he said.

But because the doctor hasn't been exposed to such cases, he or she will tell the patient it's supposed to go away and refer the patient to a psychiatrist.

The Journal of Sexual Medicine will publish Irwin's research this Friday (tomorrow).

 

[Michael Scally MD]

Re: OnLine First

Irwig MS, Kolukula S. Persistent Sexual Side Effects of Finasteride for Male Pattern Hair Loss. The Journal of Sexual Medicine. Persistent Sexual Side Effects of Finasteride for Male Pattern Hair Loss - Irwig - 2011 - The Journal of Sexual Medicine - Wiley Online Library

Introduction.? Finasteride has been associated with reversible adverse sexual side effects in multiple randomized, controlled trials for the treatment of male pattern hair loss (MPHL). The Medicines and Healthcare Products Regulatory Agency of the United Kingdom and the Swedish Medical Products Agency have both updated their patient information leaflets to include a statement that “persistence of erectile dysfunction after discontinuation of treatment with Propecia has been reported in post-marketing use.”

Aim.? We sought to characterize the types and duration of persistent sexual side effects in otherwise healthy men who took finasteride for MPHL.

Methods.? We conducted standardized interviews with 71 otherwise healthy men aged 21–46 years who reported the new onset of sexual side effects associated with the temporal use of finasteride, in which the symptoms persisted for at least 3 months despite the discontinuation of finasteride.

Main Outcome Measures.? The types and duration of sexual dysfunction and the changes in perceived sexual frequency and sexual dysfunction score between pre- and post-finasteride use.

Results.? Subjects reported new-onset persistent sexual dysfunction associated with the use of finasteride: 94% developed low libido, 92% developed erectile dysfunction, 92% developed decreased arousal, and 69% developed problems with orgasm. The mean number of sexual episodes per month dropped and the total sexual dysfunction score increased for before and after finasteride use according to the Arizona Sexual Experience Scale (P < 0.0001 for both). The mean duration of finasteride use was 28 months and the mean duration of persistent sexual side effects was 40 months from the time of finasteride cessation to the interview date. Study limitations include a post hoc approach, selection bias, recall bias for before finasteride data, and no serum hormone levels.

Conclusion.? Physicians treating MPHL should discuss the potential risk of persistent sexual side effects associated with finasteride.

 

[Madlib]

Re: Low Libido, numbing, aching and sleeping problems - I quit finasteride 4 months a

I am really getting desperate now guys. I used pregnenolone and had a brief recovery, I could masturbate 3-4 times a day like normal but it lasted only 4 days.

Is there anything else that I could try on my own without paying a fortune for a doctor?

 

[Deadballs]

Re: Help me please -- Finasteride-induced secondary hypogonadism, low T/LH/FSH, high

Just wanted to revive this thread!

 

[Deadballs]

Re: Mainstream media finally realizing Propecia can make you impotent

I told you!

lol/cry

 

[beverwykella]

I've seen the same story in a number of patients (I'm a clinical researcher). Firstly you should know that your problem is by no means unique and in fact there is a class action suit against the maker of this drug (not including the name for legal reasons) for men that have experienced permanent side effects like the ones you described after finasteride adm. Anendotal evidence also suggests that these effects could be triggered by less than a 3-month regimen. I would urge you to look for details of the class-action online and contact the legal group that is presenting the suit. Signup is relatively simple and there is no real associated cost.


Mental fog and fatigue are frequently reported; sometimes for years after finasteride discontinuation. I would suggest that you ask for a prescription for a drug called monadafil which is essentially one of the new 'smart drugs' giving increased focus, increased mental acuity, reduction or elimination of mental fog and fatigue. The pill is now generic so the costs are somewhat reduced. There are few side fx and it is not habit forming. Several physicans prescribe it to combat chronic fatigue syndrome (CFS); the CFS symptoms are very similar to the post-finasteride complaints.


Secondly. TRT is also recommended. There is no known interaction between these substances.

Lastly, hcg and clomid should work to restore the hypogonadism in a short period of time. HCG is only taken for 3 weeks and can be repeated in 6-8 months if necessary. The clomid should be taken along with the hcg but should be continued for at least 2-3 weeks after the hcg regimen is over. Not only should these restore gonadal size but offset any potential testicular atrophy from the TRT.

 

[Madlib]

Anyone on these boards seeing improvements on there finasteride nightmare?

I have been off a year and a month now, and no improvement.