If you have questions

[Meso]

Hey guys & gals!

If you have any questions regarding anything PSSD related, please start a thread instead of sending me PMs as I very rarely check my inbox. This is also for the benefit of everyone here since others will also benefit from answers, right?

I know that I don't respond as quickly as I used to, but please be patient. My time is divided between:
- Researching symptoms and coming up with effective novel treatment options for PSSD.
- Consultations with patrons, which is also very time consuming.

I believe that spending my time on reading studies and research papers is the most beneficial thing for the community overall since we will keep getting closer to more profound relief and more options for achieving that.

Thanks for understanding!

[tenacity]

Understood! Apologies.

[Meso]

Understood! Apologies.

No need for apologies. It's not specific to you. I still answer PMs from time to time, but I want the Q/A to get more exposure as to benefit everyone and avoid repeating questions.

[GIXXER]

What do you know about Kisspeptin?

[afx]

Mesolimbo, I do have a question. I see the main focus in PSSD is dominately on brain-serotonin-neurotransmitters in general. My big question is - is there a link between PFS and PSSD? Some more or less direct link? I do ask, because PFS sufferers do have a lot of things they do avoid that is androgenic-antiandrogenic, reductases and aromatases, 5ar... I mean things like everyday foods, spices, herbs.. Phenols, polyphenols. The list can become insane, literally almost like only water is ok. They took 5AR inhibitor, we took serotonin drug. Is that all around hormones, 5AR, aromatase,.. our big worry too? Ofcourse, we have to be careful about everything that messes with anything, but I just wonder if PSSD sufferer should really focus high priority on PFS as well (behave like if PSSD sufferer also has PFS, although PSSD is the true condition he suffers). Hope my question makes sense l, I simply dont know if I should behave like I not only have PSSD but PFS as well, it makes things much more complicated. Btw, I give You an example - I saw somewhere You recommended ALA - alpha lipoic acid, it does have lots of benefits, but someone with PFS avoids it, because it is 5ar inhibitor (some even crashed badly on it). Olive oil, coconut oil, any oils, teas, beans.. Could give You literally tens, hundrets of examples with common beneficial substances, vegetables, herbs, spices,.. how paranoid things can become.. I get that amounts in food are ok, but how about herb extracts, oils - e.g. like green tea extract (just a micro example, I could name many things). List is extensive and makes a lots and lots of limitations. And thanks a lot in advance, even really simplified answer without deep explanations will sure help to make things a little more clear

[Meso]

What do you know about Kisspeptin?

I have read positive studies on it. I'll touch more on Kisspeptin in my next article.

Mesolimbo, I do have a question. I see the main focus in PSSD is dominately on brain-serotonin-neurotransmitters in general. My big question is - is there a link between PFS and PSSD? Some more or less direct link? I do ask, because PFS sufferers do have a lot of things they do avoid that is androgenic-antiandrogenic, reductases and aromatases, 5ar... I mean things like everyday foods, spices, herbs.. Phenols, polyphenols. The list can become insane, literally almost like only water is ok. They took 5AR inhibitor, we took serotonin drug. Is that all around hormones, 5AR, aromatase,.. our big worry too? Ofcourse, we have to be careful about everything that messes with anything, but I just wonder if PSSD sufferer should really focus high priority on PFS as well (behave like if PSSD sufferer also has PFS, although PSSD is the true condition he suffers). Hope my question makes sense l, I simply dont know if I should behave like I not only have PSSD but PFS as well, it makes things much more complicated. Btw, I give You an example - I saw somewhere You recommended ALA - alpha lipoic acid, it does have lots of benefits, but someone with PFS avoids it, because it is 5ar inhibitor (some even crashed badly on it). Olive oil, coconut oil, any oils, teas, beans.. Could give You literally tens, hundrets of examples with common beneficial substances, vegetables, herbs, spices,.. how paranoid things can become.. I get that amounts in food are ok, but how about herb extracts, oils - e.g. like green tea extract (just a micro example, I could name many things). List is extensive and makes a lots and lots of limitations. And thanks a lot in advance, even really simplified answer without deep explanations will sure help to make things a little more clear

I think PSSD and PFS have a couple of pathways in common, but not everything overlaps. For example, in both conditions neurosteroid synthesis is disrupted through either inhibition that seems permanent (PFS) or tolerance to their effect after long-term potentiation (PSSD). I talked a bit about this in my allopregnanolone article:
on-progesterone-allopregnanolone-s-effect-on-the-brain

Androgen receptors upregulate in presence of androgens, as such androgens are potent regulators of their very own receptors. When you take Finasteride, you are significantly reducing DHT, so I would expect that AR expression would also be reduced. Perhaps that's why some PFS sufferers found relief on tribulus terrestris - since it upregulates AR expression a little. Another way to upregulate AR is through TRT that puts your testosterone along the upper limit. After several months, AR expression would be elevated.

So, an important similarity between PSSD and PFS is how elevated serotonin can depress androgen receptor (AR) expression directly. Some SSRIs also lower testosterone through non-serotonergic pathways (i.e. Sertraline, Venlafaxine), so you end up with reduced androgens (even if temporarily) and reduced AR expression. I find PSSD more complex though, since many other pathways are affected. I'll go more in-depth in my next article.

[afx]

Thanks a lot for Your answer, I hopefully am right if I translate it as I, a PSSD sufferer (although took almost all types of Ssris/Snris/Saris.. over years), I am still more safe around those PFS to-avoid substances compared to true PFS sufferer.. (endless minefield of things to avoid or lottery to better avoid - that ends with almost better do nothing and wait for Baylor study)

Funny thing is that on PFS forum the most strong theory is about that their AR receptors are -overexpressed- so the opposite of Your conclusion, they seem to follow the path trend of effort to reduce their AR receptors.. (But maybe I am understanding it wrong somehow, I did not exactly looked into too much details, I will, but anyway they do tend say their ARs are overexpresses, too much upregulated).

[AnhedonicApe]

What do you know about Kisspeptin?

I have read positive studies on it. I'll touch more on Kisspeptin in my next article.

Mesolimbo, I do have a question. I see the main focus in PSSD is dominately on brain-serotonin-neurotransmitters in general. My big question is - is there a link between PFS and PSSD? Some more or less direct link? I do ask, because PFS sufferers do have a lot of things they do avoid that is androgenic-antiandrogenic, reductases and aromatases, 5ar... I mean things like everyday foods, spices, herbs.. Phenols, polyphenols. The list can become insane, literally almost like only water is ok. They took 5AR inhibitor, we took serotonin drug. Is that all around hormones, 5AR, aromatase,.. our big worry too? Ofcourse, we have to be careful about everything that messes with anything, but I just wonder if PSSD sufferer should really focus high priority on PFS as well (behave like if PSSD sufferer also has PFS, although PSSD is the true condition he suffers). Hope my question makes sense l, I simply dont know if I should behave like I not only have PSSD but PFS as well, it makes things much more complicated. Btw, I give You an example - I saw somewhere You recommended ALA - alpha lipoic acid, it does have lots of benefits, but someone with PFS avoids it, because it is 5ar inhibitor (some even crashed badly on it). Olive oil, coconut oil, any oils, teas, beans.. Could give You literally tens, hundrets of examples with common beneficial substances, vegetables, herbs, spices,.. how paranoid things can become.. I get that amounts in food are ok, but how about herb extracts, oils - e.g. like green tea extract (just a micro example, I could name many things). List is extensive and makes a lots and lots of limitations. And thanks a lot in advance, even really simplified answer without deep explanations will sure help to make things a little more clear

I think PSSD and PFS have a couple of pathways in common, but not everything overlaps. For example, in both conditions neurosteroid synthesis is disrupted through either inhibition that seems permanent (PFS) or tolerance to their effect after long-term potentiation (PSSD). I talked a bit about this in my allopregnanolone article:
on-progesterone-allopregnanolone-s-effect-on-the-brain

Androgen receptors upregulate in presence of androgens, as such androgens are potent regulators of their very own receptors. When you take Finasteride, you are significantly reducing DHT, so I would expect that AR expression would also be reduced. Perhaps that's why some PFS sufferers found relief on tribulus terrestris - since it upregulates AR expression a little. Another way to upregulate AR is through TRT that puts your testosterone along the upper limit. After several months, AR expression would be elevated.

So, an important similarity between PSSD and PFS is how elevated serotonin can depress androgen receptor (AR) expression directly. Some SSRIs also lower testosterone through non-serotonergic pathways (i.e. Sertraline, Venlafaxine), so you end up with reduced androgens (even if temporarily) and reduced AR expression. I find PSSD more complex though, since many other pathways are affected. I'll go more in-depth in my next article.

I think the common believe on the propecia forum is that they have AR overexpression, not under. Also because this was shown in DNA taken from the skin.

[Meso]

Thanks a lot for Your answer, I hopefully am right if I translate it as I, a PSSD sufferer (although took almost all types of Ssris/Snris/Saris.. over years), I am still more safe around those PFS to-avoid substances compared to true PFS sufferer.. (endless minefield of things to avoid or lottery to better avoid - that ends with almost better do nothing and wait for Baylor study)

Funny thing is that on PFS forum the most strong theory is about that their AR receptors are -overexpressed- so the opposite of Your conclusion, they seem to follow the path trend of effort to reduce their AR receptors.. (But maybe I am understanding it wrong somehow, I did not exactly looked into too much details, I will, but anyway they do tend say their ARs are overexpresses, too much upregulated).

It's possible that they have misinterpreted studies relative to AR expression. These studies show that AR over-expression is tissue-specific, mostly along the human foreskin (stromal and epithelial cells) as well as the cortical regions. Androgen receptors in the normal prostate can be downregulated by Finasteride, while upregulated in the hyperplastic prostate. [link][link2]

When it comes to neural AR expression, androgens can upregulate them while Finasteride can partially block this effect, except for cortical neurons. [link3][link4]

In the penis smooth muscles (not foreskin), T and DHT actually upregulate AR expression. Only when 5-alpha reductase is blocked does testosterone downregulate AR there (through aromatization to estradiol)
[link5].

Finally, it's important to determine which cell types are affected by Finasteride-induced AR over-expression instead of generalizing this to all tissue types. It's also important to take into consideration auto-regulation and cross-regulation of nuclear receptors, especially the interaction between estrogen and androgen receptors (and different interactions across different cell types)

[Koivukovy]

Why Antidepressants Cause Sexual Dysfunction
May 9, 2016 by admin
By Dr.Richards.MD

There are several types of anti-depression drugs. Widely used are SSRIs (Selective serotonin reuptake inhibitors) and SNRIs (Serotonin-norepinephrine reuptake inhibitors). Usually, anti-depression drugs lead to excessive chronic prolactin production – a condition called Hyperprolactinemia (can best be described as a functional disorder). Excessive prolactin in the bloodstream reduces the testosterone and DHT release from the testicles, resulting in bone and muscle weakness.

SSRIs tend to block dopamine nervous functions in the hypothalamus-pituitary axis, which are responsible for the release of oxytocin, known as the emotional and orgasm hormone. The drugs also tend to indirectly interfere with all the neurotransmitter systems and the production of various hormones, usually by overloading the liver P450 detoxification system. They also block the spinal nervous transmissions in the synapses with a flooding of serotonin through a reuptaking inhibition. The gene expressions of D2 dopamine receptors, acetylcholine receptors, and 5-HT (Serotonin) 2C receptors are also being alternated.

SSRIs will destroy the pituitary and liver functioning, burdening your endocrine system. SSRIs not only inhibit the reuptaking of serotonin, but actually lower the natural levels of serotonin due to the destructive effects on the liver P450. SSRIs drugs usually reduce the serotonin nervous action in the neuromuscular ending receptors all over the body.

The blocking of dopamine and acetylcholine transduction, accompanied with the high level prolactin (being dumpled into the bloodstream), disables the nervous function in the penis and seminal production, and if taken systematically, can completely desensitize the penile nerves, prostate and seminal vesicles. Furthermore, SSRIs drugs tend to block hypothalamic/adrenal – dopamine – norepinephrine conversion and oxytocin release (essential to activation of orgasmic contractions).

SSRIs anti-depression drugs cause neuroplasticity, a term used in this particular context to describe deformation of synapses and outgrowth of serotonin neurons. This neuroplasticity is known to cause addiction and severe withdrawal symptoms. SSRIs will inhibit the reputaking of serotonin in the nervous synapses by blocking the serotonin transporter, thus allowing the serotonin neurotransmitter to continue influencing the postsynaptic neurons. However, SSRIs are not increasing neurotransmitter synthesis, on the contrary – they are cutting down the natural serotonin release from the nervous terminals, it is just that SSRIs stimulate more serotonin neurons. SSRIs antidepressants also tend to alter the relationship between dopamine and serotonin signaling in the striatum, which will receive moderate serotonergic and rich dopaminergic innervation. This can be extremely harmful and may lead to irreversible damage. Due to the inhibition of serotonin transporters, the dense striatal Dopamine Transporters may uptake serotonin into the dopamine terminals, which will destroy the dopamine nervous function responsible for the release of oxytocin, LH and FSH. Also, a weak dopaminergic function will result in heightened pituitary release of prolactin and disable sexual function completely.

What do you think of this Meso? It's suggesting that at least some of the damage is irreversible