Very promising theory on PSSD being caused by changes in Kisspeptin expression

This is for hypothesis and even educated speculation.
Brain food
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Re: Very promising theory on PSSD being caused by changes in Kisspeptin expression

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anacleta wrote: Mon Aug 29, 2022 10:17 am
Brain food wrote: Sat Aug 27, 2022 4:37 pm So I have done some more research and have further refined my theory. I think that it's likely that if Kisspeptin causes PSSD, it does so by causing damage to the testicles (in men at least, in women it would be another part of the body). This study from Imperial College London shows that Kisspeptin at high doses causes testicular degeneration in rats. It showed that the rats treated with Kisspeptin experienced damage to their seminiferous tubules. There are several studies in rats that show that SSRIs and Finasteride damage the seminiferous tubules. In review that I mentioned above, the study #92 shows that escitalopram greatly increases kisspeptin levels in certain areas of the brain in rats. This could be causing damage to their testicles and might be the biological mechanism behind PSSD and PFS.

Kisspeptin-54 at high doses acutely induces testicular degeneration in adult male rats via central mechanisms

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2697701/

https://bpspubs.onlinelibrary.wiley.com ... 08.00061.x

thanks for the research. i haven't read in detail (i don't have the head to do that right now) but i read about possible "testicular degeneration" so i wonder if it results in reduced male fertility, if so would it be interesting to do a semen analysis? maybe a study comparing sperm quality between men with pssd and without pssd (I think it would also be pretty easy and cheap!)
Here’s a 2019 review from University of Southern California that summarizes all of the studies into antidepressants and male fertility. The evidence does show that reduce fertility.

Effect of antidepressant medications on semen parameters and male fertility
https://onlinelibrary.wiley.com/doi/ful ... /iju.14111

Here’s a 2016 study from Denmark. They also found that SSRIs reduce fertility.

Use of selective serotonin reuptake inhibitors reduces fertility in men

https://onlinelibrary.wiley.com/doi/ful ... #d26151074
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anacleta
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Re: Very promising theory on PSSD being caused by changes in Kisspeptin expression

Unread post by anacleta »

Brain food wrote: Mon Aug 29, 2022 10:55 am
Here’s a 2019 review from University of Southern California that summarizes all of the studies into antidepressants and male fertility. The evidence does show that reduce fertility.

Effect of antidepressant medications on semen parameters and male fertility
https://onlinelibrary.wiley.com/doi/ful ... /iju.14111

Here’s a 2016 study from Denmark. They also found that SSRIs reduce fertility.

Use of selective serotonin reuptake inhibitors reduces fertility in men

https://onlinelibrary.wiley.com/doi/ful ... #d26151074
studies on reduced male fertility caused by SRI administration have been around for a long time, but studies revealing persistent infertility caused by SSRIs are not around, and if this were related to those who report having PSSD it would be super interesting (and something outrageous and alarming!)

I imagine a study comparing the sperm quality of:
- ten healthy 20/30-year-old men
- ten 20/30-year-old men who are taking SSRIs
- ten 20/30-year-old men who took SSRIs but are not complaining of PSSD
- ten 20/30-year-old men complaining of PSSD
KnockyBird
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Re: Very promising theory on PSSD being caused by changes in Kisspeptin expression

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Last edited by KnockyBird on Sat Feb 11, 2023 10:02 am, edited 1 time in total.
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anacleta
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Re: Very promising theory on PSSD being caused by changes in Kisspeptin expression

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KnockyBird wrote: Mon Aug 29, 2022 11:38 am My fertility is above average and I have full-blown PSSD.
thank you for saying that
Whereas semen analysis can be done by each person
we can collect the results of those who have done it
because if you don't see any significant mean abnormality, then there is no point in proceeding with that study
I will do a survey on reddit
rmichaelballow
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Re: Very promising theory on PSSD being caused by changes in Kisspeptin expression

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Kisspeptin is not behind PSSD. But interesting theory.
Brain food
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Re: Very promising theory on PSSD being caused by changes in Kisspeptin expression

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rmichaelballow wrote: Tue Aug 30, 2022 1:45 pm Kisspeptin is not behind PSSD. But interesting theory.
How do you know this for certain? It is just a theory at this point. I would guess that multiple hormones are involved, I don’t think that just administering external Kisspeptin would be a cure for PSSD.
defmyst
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Re: Very promising theory on PSSD being caused by changes in Kisspeptin expression

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If testicular health is part of the problem, apparently fish oil supplements help for that.

https://www.healio.com/news/endocrinolo ... upplements

We found that intake of fish oil supplements during the past 3 months was associated with higher semen volume, total sperm count and testis size; lower follicle-stimulating hormone and luteinizing hormone levels; and a higher free testosterone to luteinizing hormone ratio among young men compared with no supplement intake,” the researchers wrote. “Interestingly, a dose-response association was found, as men with intake of fish oil supplements on 60 or more days had higher semen volume, higher total sperm count, lower luteinizing hormone level, higher free testosterone level and a lower free testosterone to luteinizing hormone ratio than men with fish oil intake on fewer than 60 days.”

Has anyone tried fish oil supplements?

In general, I eat a lot of seafood which is also good for the brain, so I am not sure if there is something else in the fish oil that isn't present in regular seafood that could help with the problem.
Brain food
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Re: Very promising theory on PSSD being caused by changes in Kisspeptin expression

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Here’s another study which shows that shows a relationship between Kisspeptin and SSRIs.

Kisspeptin and RF9 prevent paroxetine-induced changes in some parameters of seminal vesicle fluid in the male rats

First published: 12 February 2020

https://onlinelibrary.wiley.com/doi/abs ... /and.13538
Brain food
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Re: Very promising theory on PSSD being caused by changes in Kisspeptin expression

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So I emailed the doctors from Baylor Medical School who did the study on the tissue of the PFS patients. Here is what they said about the Kisspeptin genes:

The data showed there are no significant difference on the expression levels of both KISS1 and KISS1R between patient’s group and control group
Brain food
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Re: Very promising theory on PSSD being caused by changes in Kisspeptin expression

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Here is a comment with a link to an article that a user name Serguei Novitchok posted on the RxISK Research Forum. I copied and pasted his comments below:

This study seems interesting in explaining genital numbness in PSSD/PFS/PRSD and persistent genital arousal in PGAD, in case Kisspeptin is involved. Here is the study: https://doi.org/10.1186%2F1744-8069-7-90

Study Summary:
Adult mice were used to assess pain sensitivity after administration of Kisspeptin or p234 (GPR54/KISS1R antagonist) in the right hind paw. A hot plate and formalin test were performed to assess pain sensitivity.
Immunohistochemistry was also performed to identify GPR54/KISS1R in the plantar surface of the hind paws.

Results:
-Peripheral or intrathecal injection of kisspeptin induced hyperalgesia.
-GPR54 was localized in “sensory fibers that ascend vertically between keratinocytes to reach the stratum corneum of the epidermis”.
-Kisspeptin injection induced hyperalgesia in the first and second phase of the formalin test.
-“Intrauterine injection of the GPR54 antagonist, p234, induced robust analgesia in the formalin test, suggesting that endogenous kisspeptin acts extracellularly to activate GPR54 receptors GPR54 during inflammatory pain.”

Conclusion:
Modulation of Kisspeptin and its receptor activity may explain the reported sensory symptoms. Analgesia may explain the numbness in PSSD/PFS/PRSD while hyperalgesia may explain the symptoms in PGAD

https://journals.sagepub.com/doi/10.1186/1744-8069-7-90
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