Epigenetic Effects of Finasteride on Human Leydig Cells

Abstract

Finasteride is a synthetic 4‐azasteroid, used in the treatment of both androgenetic alopecia and benign prostatic hyperplasia. In some men, its use is associated with persistent erectile dysfunction, ejaculatory dysfunction, loss of libido, altered sperm counts and infertility ‐ even after cessation of the drug. This condition has been termed “Post‐finasteride Syndrome” (PFS). We want to understand the underlying biochemical mechanisms that govern the development of this condition. Therefore in this experiment we tested the effects of exposure of finasteride on human Leydig cells, the main hormone‐producing cell of the testis, to identify epigenetic changes in the cells that could be at least partially responsible for PFS. We cultured human Leydig cells in the presence of 0.5 μM finasteride for 14 days and performed whole‐genome DNA methylation analysis using the NimbleGen Human DNA Methylation 3×720K Promoter Plus CpG Island Array and Ingenuity Pathway Analysis. Here we describe initial identification of specific genes and pathways involved that may ultimately lead to treatments to reverse PFS.

Abstract published a few days ago, reading the full study will be interesting

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I can’t open it via sci-hub, unfortunately. Has anyone had more luck/a different route to the full study?

It’s only an abstract the full article isn’t published yet. Likely a submitted abstract for a conference of some description.

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You are right. It’s an abstract for the Experimental Biology 2020 Meeting, which was cancelled.

Csoka is an interesting guy. I knew I had heard this name before.

He authored the paper “Epigenetic side-effects of common pharmaceuticals: a potential new field in medicine and pharmacology” and was also involved with a study that assessed the effects of an AD on DNA methylation…

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i’m a bloody genius!

Has the foundation or the admins engaged him on any level[quote=“axolotl, post:9, topic:43221”]
it is unlikely the normal tissue response to finasteride will reveal the pathological epigenetic effect in PFS patients.
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My thoughts exactly. After all only a tiny minority of people develop PFS symptoms.

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This sounds super interesting but is giving me blue balls. “Here we discuss how we can reverse your hellish otherwise permanent condition - just kidding, nothing’s here.”

Interesting, will have a read.

An important thing for future research towards these aims is a case control study in highly androgen-dependent cells with patient tissue vs normal people, as obviously it is unlikely the normal tissue response to finasteride will reveal the pathological epigenetic effect in PFS patients. This was something proposed to us by a molecular biology centre at the end of last year.

We’re familiar, cited a paper or two in the document recently published on our website. I’ll reach out shortly. Hopefully we can practically collaborate.

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That’s what I was thinking. Only a small minority of people who take Finasteride go on to develop PFS. Not sure what this paper could reveal…

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Could potentially serve as comparative data for further study, even if nothing directly itself. I personally believe it’s very likely the condition could represent an aberrant expression of conserved mechanisms, so it may be intriguing anyway - will have to read.

At least it’s heartening to see some movement with regard to using modern whole-genome analysis/bioinformatic approaches! Not simply the same old weekly hand-wringing “is it real” commentaries, and the occasional rat drowning…

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Csoka has also been researching for PSSD for years .

[Persistent Sexual Side Effects after SSRI Discontinuation]
Antonei B. Csoka, Stuart Shipko, 2006 http://www.ncbi.nlm.nih.gov/pubmed/16636635

[Persistent Sexual Dysfunction after Discontinuation of Selective Serotonin Reuptake Inhibitors] Antonei Csoka, Audrey Bahrick, Olli-Pekka Mehtonen, 2008
https://www.researchgate.net/publication/228667893_Persistence_of_Sexual_Dysfunction_Side_Effects_after_Discontinuation_of_Antidepressant_Medications_Emerging_Evidence

[Epigenetic side-effects of common pharmaceuticals: A potential newfield in medicine and pharmacology]
Antonei B. Csoka e Moshe Szy, Medical Hypotheses 73 (2009) 770–780 http://www.ncbi.nlm.nih.gov/pubmed/19501473

[Post-SSRI Sexual Dysfunction: Clinical Characterization and Preliminary Assessment of Contributory Factors and Dose-Response Relationship]
Ben-Sheetrit J, Aizenberg D, Csoka AB, Weizman A, Hermesh H., 2015 http://www.ncbi.nlm.nih.gov/pubmed/25815755

[The Effect of Citalopram on Genome-Wide DNA Methylation of Human Cells]
Kanherkar RR, Getachew B, Ben-Sheetrit J, Varma S, Heinbockel T, Tizabi Y, Csoka AB, 2018 https://www.ncbi.nlm.nih.gov/pubmed/30148158

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