PFS study released from Italy (2017)


Peripheral Nervous System Involved in Post-Finasteride Syndrome Patients with Severe Erectile Dysfunction, New Study Demonstrates for the First Time

Condition also has ‘broad consequences’ on plasma and cerebrospinal fluid neuroactive steroid levels

SOMERSET, N.J., April 18, 2017 – Post-finasteride syndrome (PFS) patients suffer from altered levels of critical brain-function regulators, including neuroactive steroids, according to a new clinical study published in The Journal of Steroid Biochemistry and Molecular Biology.

Titled Neuroactive Steroid Levels and Psychiatric and Andrological Features in Post-Finasteride Patients, the three-year study also uncovered evidence of neuropathy of the pudendal nerve among those with severe erectile dysfunction.

In all, 16 men with PFS and 25 control patients were evaluated in the study conducted at the University of Milano’s Department of Pharmacological and Biomolecular Sciences by a team of 12 researchers led by Roberto Cosimo Melcangi, Ph.D. The PFS patients had discontinued finasteride for a median of 5.4 years at the time of evaluation, and had no prior history of erectile dysfunction or depression prior to finasteride use.

Key findings of the study include broad effects on plasma and cerebrospinal fluid (CSF) neuroactive steroid levels observed in 14 PFS patients, as compared to 25 controls. Statistically significant decreased levels of DHT, pregnenolone, progesterone, 17-beta estradiol and dihydroprogesterone (DHP), and increased levels of DHEA, testosterone and 3-alpha diol were observed in the CSF of PFS patients.

In plasma, statistically significant decreased levels of DHP and allopregnanolone, and increased levels of pregnenolone, DHEA and testosterone were observed.

Decreased plasma levels of allopregnanolone and decreased CSF levels of progesterone are common features of anxious/depressive symptomatology. Important physiologic effects of neuroactive steroids on brain function include neuroendocrine control of reproduction and sex behavior, synaptic plasticity, morphology of neurons and astrocytes, maintenance of cytoskeleton proteins and myelin, adult neurogenesis, and cognition-related functions.

The study also identified, in 25 percent of PFS patients, the first objective evidence of abnormal somatosensory evoked potentials (SSEP) of the pudendal nerve. Abnormal SSEP findings were observed in PFS patients with severe ED.

Peripheral neuropathy of the pudendal nerve, the major nerve supplying the genitals that is critical for peripheral neurogenic control of erection, in PFS patients is a novel finding that demonstrates for the first time involvement of the peripheral nervous system in PFS patients with severe ED.

Additionally, 50 percent of the PFS patients were diagnosed with major depression based on the results from validated questionnaires, the Mini-International Neuropsychiatric Interview, the Beck Depression Inventory and the Beck Anxiety Inventory.

Such depression represents the first confirmation of findings in research led by Shalendar Bhasin, MD and published last year in The Journal of Clinical Endocrinology & Metabolism (Characteristics of Men Who Report Persistent Sexual Symptoms after Finasteride Use for Hair Loss), which suggested that men who experience persistent sexual dysfunction after discontinuing finasteride have “neurobiological abnormalities.”

“Among the most important milestones of Professor Melcangi’s research is that it builds directly on Dr. Bhasin’s work,” said Dr. John Santmann, CEO of the Post-Finasteride Syndrome Foundation, which sponsored the study.

“Medical science is now one step closer to characterizing the underlying biologic mechanisms of PFS, which in turn promises to pave the way for the development of effective therapies,” he added.

The full JSBMB study is available here.

Not only did this study find major differences in neurosteroid levels in CFS & plasma…

But it also found pudendal nerve issues in the men that had the worst erectile dysfunction. That is very ground breaking.

Great news…Wonder if the physical sides like I have stem from the Neuro steroids or just the hormone imbalance? I didn’t get sexual sides only physical and mental…seems they never even mention the physical symptoms usually in these studies and descriptions of pfs…Always sexual and mental.

Thaunks for posting moonman1. Is this the study funded by the PFS foundation or a separate study?

For me the following statement seems most significant:

"Peripheral neuropathy of the pudendal nerve, the major nerve supplying the genitals that is critical for peripheral neurogenic control of erection, in PFS patients is a novel finding that demonstrates for the first time involvement of the peripheral nervous system in PFS patients with severe ED. "

This seems like me. I’ve had a tingling in the back of my scrotum since I got pfs. It seems like the the signal from my brain to my dick is attenuated 90%.

Anyway seems like we are making some progress on the scientific front. I wonder if the researchers are trying any treatments on the patients to see if this crap can ever be reversed. I’ve aged so much from this I feel like a different person anymore.

Yeah you’re telling me…Hair thinner and greying, body and facial hair almost completely whit, hugh body compostion change to fat and water retention…Its like your go from 36 years old in my case when I started to a damn old man over several months…

Just be aware that grey hair has been linked with an increased risk of heart disease. … sease.html

I’m very excited to read about this. Been away for the last 6 months or so just trying to forget about pfs and take care of the rest of my life. But there is no escaping the fact that reproducing/having a wife and kids is ultimately the thing I want most in the end, and until I get healed those things are off the table.

The fact these studies are coming in is extremely encouraging. I feel like we might have turned the corner from moaning on the internet unable to really go anywhere, to finally possibly taking real steps toward the development of treatments.

Anyone else feel the same way? Anyone have a sense of what the rough timeframe might be on when ideas might start arriving on specific things we can do to treat our symptoms?

Not being a biology person I think my spin on the Italian study is as follows:

  1. Confirmed what we already knew, that there are multiple facets to the pfs problem including nerve damage to the pudendal nerve and numerous biological markers, many of them neurosteroids, that are affected by pfs.

  2. Item one above probably accounts for most of our symptoms including ED and numerous mental issues including depression, brain fog, anxiety, insomnia, etc.

  3. Unfortunately the Italians were not able to determine what caused the chain reaction that caused our bodies to change from taking finasteride. Nor did they offer a guess in their paper although I would speculate that the authors have a general idea of what they think the cause is.

  4. We have one more study to be released yet, the Baylor study. I believe it is focused on genetics/epigenetic changes due to finasteride. It’s possible that they could come up with results that would indicate how the issues the Italians found occurred. In that case we could start trying to find a solution. If they find no genetic abnormalities then we will be left primarily with the Italian results since the Harvard study really didn’t provide too much insight. In that case more studies, probably several years in duration would be required.

I’m again surprised there has been almost no discussion of the Italian results on the board. Comments anyone?

I’ll have to go read the Italian study myself then. I suspect the reason the studies aren’t discussed more is that few of us have the medical background to really be able to understand what they report. That’s certainly the case with me.

Do you have a sense of how many of the things revealed by the Italian study might be treatable vs how many of them might be permanent and untreatable? For example, I imagine that some changes in hormones might be permanent but treatable, via hormone replacement therapy, perhaps. However, nerve damage seems like it’s more likely to be untreatable.

This syndrome is horrific. I do wish there were more people here with the background to understand and process the content of the studies. I also wonder how significant a number of such people exist anywhere, as well as what motivations exist for seeing their efforts dedicated toward it.

Do you have a link to the full paper?

Here is the full Italian study. KeepingHard posted it in the Research Initiatives section.

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