Research Forum for Enduring Sexual Dysfunction

Introduction

A number of treatments that inhibit serotonin reuptake – antidepressants, antibiotics, antihistamines and analgesics – along with retinoids used for skin and other problems, and finasteride and related drugs for hair loss, can cause enduring sexual dysfunctions.

These conditions include post-SSRI sexual dysfunction (PSSD), post-retinoid sexual dysfunction (PRSD), also called post-Accutane syndrome (PAS), post-finasteride syndrome (PFS) and persistent genital arousal disorder (PGAD). Once triggered they can persist for years or decades after stopping treatment.

There are thousands of recorded cases, almost certainly tens of thousands of people affected, and in all probability hundreds of thousands affected. At least 15% of the 1 billion people living in the ‘West’ (150 million) are on drugs known to cause the problem, most of whom expect that everything will revert to normal when their current treatment stops, but for many it won’t.

These devastating conditions, lack of hope for an imminent cure or even understanding of the problem, and in some cases the failure of doctors to recognize these disorders, lead people to take their own lives.

Many doctors, PhDs and others suffering these conditions have engaged in forums and other settings and done a lot of work to track down a cause and possible remedy – at present to no avail. Efforts to date have focused on the brain and obvious targets like serotonin, dopamine systems and the effects of neurosteroids.

Novel perspectives

This Research Forum hopes to open novel perspectives on the problems and perhaps on ways to do clinical research.

Over the last decade, RxISK has made it very clear that people affected by treatment induced alcoholism, suicide or sexual dysfunction have a motivation to solve problems that is often worth more than any academic expertise. Motivated folk with no background in the issues can sift through and master astonishing amounts of complex information. We want to mobilize a collective effort to turn up new leads on PSSD and related conditions and to draw the conditions to the attention of researchers.

The focus in this forum is on the body not the brain, and on proteins, especially regulatory proteins, and enzymes rather than on amines like serotonin. The enduring sexual dysfunctions don’t just involve an action of drugs on sexual function but what looks more like the flipping of a switch so that a particular effect stays locked in place. This is more likely to involve a protein than an amine.

At the core of these syndromes are changes in genital skin sensation. We usually say genitals become numb, but it is likely more complex than this with affective touch being lost. And genitals can also become irritable as in PGAD. So it makes sense to look at things like skin and even hair.

Finasteride restores hair, while SSRIs, isotretinoin and Covid cause hair problems, and all four act on skin and cause sexual dysfunction.

Researchers are more likely to engage if the research holds out a prospect of future cures for other conditions rather than shedding more light on sexual function alone.

SSRIs, isotretinoin and other retinoids appear useful in Covid and other viral infections. In addition to preventing infection, retinoids can reverse the anosmia that Covid causes. Besides Covid, all of these drugs also look like they have an anti-cancer effect.

Added to these findings, it appears thalidomide can treat Covid. Thalidomide also causes sexual dysfunction, and like SSRIs and retinoids it can be helpful for cancer. It is most famous for causing birth defects, which SSRI and isotretinoin also cause.

In the case of birth defects, many seem linked to switches being flipped at the wrong time. In the case of cancer, the treatments seem to flip a switch at the right time. It also appears that thalidomide and related drugs can treat some cancers.

Solving what causes an alteration in genital sensation to endure is likely to shed a great deal of light also on what causes suicide on a range of drugs, both through akathisia which is like PGAD, or emotional numbness which is like genital numbness.

It will also shed light on what causes dependence on many drugs, as the enduring sexual dysfunctions typically show up in withdrawal states.

In addition, this research seems likely to open up a potential for new antiviral and anti-cancer agents.

It is important for any letters sent to researchers to emphasize possible breakthroughs in treating viruses like Covid or cancers as it is to focus on solving a treatment induced problem.

How can you contribute?

Hunting

Just googling some of the details listed here will throw up some fascinating nuggets of information. There is a lot to unearth simply by looking for links between serotonin and ACE-2 receptors, or links between retinoids and finasteride on the one side with skin keratin on the other (keratin is an extraordinary molecule) or linking any of these drugs to promising proteins listed here like kisspeptin, prokineticin and others.

We invite you to play around with things. Almost all of the interesting target proteins we know about to date have come from people like you – not from experts.

There is a set of links at the top of this page which take you to other pages for each of the target proteins. They contain lists of articles that can be explored, and you can add comments at the bottom. We will add further pages as more targets and information becomes available.

It would be great if any of you who find interesting articles can write a short set of notes as to why this article might offer ways forward.

If you have suggestions for new targets, please leave a comment with details of how you think it might fit in and what to say about it.

Contacting

If finding and reading articles is not for you, the articles that will hopefully accumulate on these pages always have at least one email address – sometimes emails for all authors.

Someone needs to draw the attention of these researchers to PSSD, PFS, PRSD and PGAD, to the terrible toll of suffering these conditions cause, and how a breakthrough might dramatically shift the way we view ourselves, as well as lead to possible cancer and Covid treatments.

The researchers also need to hear about the RxISK Prize. This $100,000 Prize for someone who makes a truly significant contribution toward solving these problems shows researchers that people with these conditions are serious and want someone to find answers.

The hope is that some researchers are already working on something that could provide an answer. The Prize offers them an incentive to consider whether they might have the answer to our problem and didn’t realise it because they hadn’t heard of it.

There are template emails below which you can use or adapt.

Please leave a comment afterwards about anything useful that came from any contact you have managed to make.

Expert input

As material on the forum builds up, hopefully researchers will come to visit the site to get articles from us, to contribute more articles, and to engage further.

In your email/letter, especially if there is some interest, it would be wonderful if you could invite a member of the prokineticin or p73 or other research teams to write a short piece about their protein/target to tell all of us about their area of research and any possibilities they can envisage for how some aspect of what they are doing might help.

If we get discussions going between those affected and researchers working on possibly related areas we may end up creating a new way to do research.

Template email

Subject: Possible role of [insert here] in enduring sexual dysfunctions

Dear Dr X,

I am writing with regard to your recent work on [insert here]. Your work opens up the possibility that you have an answer to a problem you didn’t know existed.

A number of treatments that inhibit serotonin reuptake – antidepressants, antibiotics, antihistamines and analgesics – along with retinoids used for skin and other problems, and finasteride and related drugs used for hair loss, can cause enduring sexual dysfunctions.

These devastating conditions, lack of hope for an imminent cure or even understanding of the problem, and in some cases the failure of doctors to recognize these disorders, lead to people taking their own lives.

For over a decade, doctors and PhDs among other people with the condition have focused on brain research and serotonin, dopamine systems or neurosteroids, but these drugs affect the body from skin and hair to blood and guts more than the brain.

You work opens up new perspectives. I am inviting you to explore these conditions and would like to make you aware there is prize of $100,000 for anyone who establishes what is happening and what might be done to remedy the problem – see RxISK Prize.

In addition to this, recent work on thalidomide, SSRIs, and isotretinoin points to both anti-cancer and anti-Covid effects for all these treatments.

If there are any ways in which your research might map onto some aspect of these problems, please let me know. If there are any articles you think might be helpful for me or others to read, it would be good to get these references. Similarly, if you have any colleagues working on this or in related areas, I’d appreciate getting their contact details.

Template email to epigeneticists

[Very few people are called epigeneticists. Googling though does throw up research groups in which epigeneticists play a part. Departments of Genetics may be able to offer leads and it may also be worth emailing folk who give their background as Genomics.]

Dear Dr X,

Given your background as having worked on epigenetics, I am writing to draw your attention to recent epigenetic studies on finasteride, two on Citalopram an SSRI – Cit A and Cit B, and two linked to isotretinoin – Iso A and Iso B.

These studies were undertaken because a number of treatments that inhibit serotonin reuptake – antidepressants, antibiotics, antihistamines and analgesics – along with retinoids used for skin and other problems and finasteride and related drugs used for hair loss can cause enduring sexual dysfunctions.

For over a decade people with the condition have focused on brain research. Researchers have focused on predetermined changes – for instance linked to neurosteroids on which finasteride unquestionably works, or systems linked to depression on which SSRIs work. But these drugs affect the body from skin and hair to blood and guts more than the brain.

There has been a more recent epigenetic turn to the research as well as a switch to looking at regulatory proteins like p63 and related proteins, and proteins like prokineticin and kisspeptin in functions like affective touch.

To the untrained eye the biggest effects in these epigenetic studies appear to be on things related to skin and proteins that are not usually linked to the clinical actions of finasteride, SSRIs or isotretinoin.

Along with colleagues, none of whom have any knowledge of epigenetics, I was wondering how these studies might look to an epigeneticist who has no preconceived ideas about how these drugs must be working.

What might be of even greater importance than skin or sex might be some evidence of an effect on something that could have a switch function – something that might lead to a function like sex or touch being shut down rather than just influenced.

Another angle is that all the treatments that cause these problems seem to be beneficial in the treatment of Covid and cancer, and the key events may lie in this area also.

I am inviting you to explore these conditions and would like to make you aware there is prize of $100,000 for anyone who establishes what is happening and what might be done to remedy the problem – see RxISK Prize.

If there are any ways in which your research might map onto some aspect of these problems, please let me know. If there are any articles you think might be helpful for me or others to read, it would be good to get these references. Similarly, if you have any colleagues working in the epigenetic area who might be interested, I’d appreciate getting their contact details.