Someone, who regularly emails breaking research that I haven’t spotted or don’t have time to spot, got in touch recently with great insights on an article about Kisspeptin that I had seen. But I had managed to miss several things he spotted that may be important to anyone thinking about PSSD.
A Kiss Before Sex
The article reported a clinical trial on the Effects of Kisspeptin on Libido and Penile Tumescence. It increases libido and penile tumescence.
The problem was it was done in men with Hypoactive Sexual Desire Disorder, which is very different to PSSD.
Another problem was that before this article came out we had been in touch with its key authors Alexander Comninos and Waljit Dhillo from UCL in London and had a long discussion and several emails with them. They were intrigued to hear about PSSD but made it clear that running a trial would need a lot of money and ethics approval and was not going to happen any time soon – unless someone stepped up with the money.
Following the publication my source spotted that one of the authors was David Goldmeier, who has recently retired but was one of the leading experts on PSSD and PGAD and thought it might be worth contacting him.
DG’s view was that Kisspeptin was more likely to help people with an endocrine problem rather than people with a neuropathy and he didn’t think it was likely to halp conditions with a genital neuropathy. It can for instance induce ovulation.
DG’s view on kisspeptin then comes closer to the more endocrine ideas about enduring sexual dysfunction that Roberto Melcangi and his group have been chasing.
David G had another proof of concept suggestion. Get some Kisspeptin and try it out in 5 volunteers. This is the kind of view you are more likely to hear from a medical person than from researchers not used to giving drugs in clinical practice.
So Kisspeptin-54 is synthesized and purified by Bachem (Bachem Holding AG). Sterile vials of kisspeptin-54 were produced by Bachem (Clinalfa; Bachem Distribution Services GmbH). See A Kiss Before Conception. (Great title for an article).
Before rushing into this, it should be noted that Kisspeptin is an injection not a tablet and its not clear how many injections would be needed.
Kisspeptin and the Penis
My researcher colleague spotted other things that escaped me (his ghostwriter) – Kisspeptin genes are not only expressed in the hypothalamus but also in peripheral areas of the body, such as the liver and gonads.
Researching this further he found that blocking the sympathetic nervous system, which is part of the autonomic system, can block the production of Kisspeptin in the ovaries of female rats so that they don’t ovulate.
Perhaps related to this, in males Kisspeptin has been thought to play a part in penile tumescence and the UCL Kisspeptin Trial seems to prove this.
This all fits in with an observation from people with PFS, in particular, and PSSD where people report decreased penile size – a shrinkage. Those who seem to be recovering slowly sometimes report that one of the things they notice is that their penis seems less shrunken.
To my great shame I have been inclined to dismiss this – as I’m sure pretty well all psychiatrists have – as a ‘mental’ problem. This is probably because I like pretty well everyone in training hear about Koro.
The books all firmly say that Koro is a delusional disorder found mostly in Asian men who claim their penis is shrinking and may disappear. The silent response of young medical men in the West is probably mostly – ‘thank God this doesn’t happen over here’,
But have we got Koro completely wrong?
One of the shocking things about PSSD is several people I know of have been told by doctors that their ideas about numb genitals being caused by the drugs they were on are delusional – its a somatic delusion they are told.
In this case the deluded people are the doctors – their patients are entirely sane. Have doctors been deluded about Koro also? Have people with Koro got something in common with people with PFS, PSSD and other neuropathic or endocrine conditions?
Treating PSSD and PFS
How might this fit in with PFS and PSSD? Possibly in a few ways.
If PSSD and PFS are neuropathies, the knock-on effects may lead to endocrine problems. I lean this way rather than saying they are endocrine problems which cause a neuropathy in that hormones are not normally a primary cause of neuropathy. Diabetes can lead to neuropathy but this is from glucose toxicity.
Many people with PSSD, maybe most, figure it is not just a genital neuropathy and they are right to think so. There are problems all around the body – in our skin, in our eyes, and definitely in the autonomic system.
An anticholinergic drug called pirenzepine is currently in clinical trials for diabetic neuropathy – aimed at restoring the sensation lost in the peripheral nerves to our lower legs and feet that leads to abnormally low Small Fibre nerve endings on an ankle biopsy.
Pirenzepine is being applied as a paste to legs, and could be given as drops into eyes where diabetics can be shown to lose nerve endings also. The problem is with PSSD, while it might restore some genital sensation, it likely cannot solve all neuropathic problems because it is not absorbed into the body and therefore won’t get to the autonomic nervous system and correct the POTS like problems people with PSSD or SSRI withdrawal have or whatever it is that has turned off Kisspeptin production and caused the penis to shrink and perhaps libido also.
Perhaps Kisspeptin receptors play a part in the additional sensitivity, the pleasurable sensations, found in genitals compared to others areas of the body.
One of the greatest movies I have seen is The Intouchables – in which a quadriplegic man with no sensation below the neck finds his earlobes become intensely pleasurable.
There is so much we just don’t know – so much to find out – so much we will only learn from listening to the people affected and not dismissing them as deluded.
All of this plays into another point that will be picked up in a following post – that one of the things that could be happening in PSSD is that small fibres are affected but primarily those that mediate affective touch using proteins like Prokineticin – See The Holy Grail and RxISK Research Fund.
If this were the case, the ambiguous results on Small Fibre Biopsies in PSSD might be explained – there could be a low normal density of most Small Fibres but a distinctive set of Small Fibres that mediate affective touch could be missing.
These issues all need exploring.