Post Orgasmic Illness Syndrome (P.O.I.S.)

General Category => Poll Center => Topic started by: b_jim on June 03, 2011, 04:08:23 AM

Title: Premature ejaculation
Post by: b_jim on June 03, 2011, 04:08:23 AM
I wanted to create it long time ago but I only remember today.
Title: Re: Premature ejaculation
Post by: Daveman on June 03, 2011, 09:58:00 AM
I put "normal", but it's more like "sometimes".

If I would put 100 events on a statistical curve, the curve would probably peak on slightly better than normal (40%), but with a range that varies from severe to not at all (P<2%).

Title: Re: Premature ejaculation
Post by: Starsky on June 03, 2011, 12:37:11 PM
How quick is Premature Ejakulation? 2 minutes? Davemen did you have that problem before POIS?
Title: Re: Premature ejaculation
Post by: Willem on June 03, 2011, 01:02:49 PM
I don't know about you guys, but for me, this is all a question of frequency.  When I was first married this wasn't an issue at all, and those times that I have an O too often it's also not an issue.  What do you guys think?  Is there some other correlation besides just having to hold off for so long? 
Title: Re: Premature ejaculation
Post by: Daveman on June 03, 2011, 01:30:22 PM
How quick is Premature Ejakulation? 2 minutes? Davemen did you have that problem before POIS?

No problem whatsoever before. I was even proud of my longevity!!

2 minutes inside would be pretty good I think, maybe my average. Sometimes I can go 5 to 7, sometimes barely scratch the surface!!

Strangely, when I tend to be most sensitive, I can't hardly even get it up, yet just about anything will set it off.

If I'm really "hot" and "hard" (excuse the graphic nature), I will usually last longer.

Weird huh?

Title: Re: Premature ejaculation
Post by: Daveman on June 03, 2011, 01:36:38 PM
I don't know about you guys, but for me, this is all a question of frequency.  When I was first married this wasn't an issue at all, and those times that I have an O too often it's also not an issue.  What do you guys think?  Is there some other correlation besides just having to hold off for so long? 

I've thought the same..... I think it has to have something to do with it.

I imagine if I was doing it every other day, it would be a different story.

There are things like in my last post here though that make me feel as though there is someting else involved too.... but can't really put my finger on it. (else it goes of heh, heh)

Title: Re: Premature ejaculation
Post by: Vandemolen on June 03, 2011, 06:11:31 PM
I am happy that I don't have PE. It must be hard for the guys who have PE.

I think there is a link between abstinence and PE. I also read it in an article about POIS.
Title: Re: Premature ejaculation
Post by: Daveman on July 20, 2011, 08:41:20 AM
Strange, isn't it, since PE is a particular interest of his!
Title: Re: Premature ejaculation
Post by: omen on July 20, 2011, 06:24:02 PM
I am happy that I don't have PE. It must be hard for the guys who have PE.

I think there is a link between abstinence and PE. I also read it in an article about POIS.
yeah cause when i am absistence from an O for a long time i tend to PE but if i have an O regularly then there is no PE....
Title: Re: Premature ejaculation
Post by: MrMoonJr on September 15, 2011, 01:13:14 PM
I have severe PE. It is hard, really it is. Im not sure how niacin will effect this... Now. Is it possible PE is caused by my subconcious anxiety over POIS? it would be something interesting to looking into... I may experiment with this to see if i Can discover something more about my PE and PE in general
Title: Re: Premature ejaculation
Post by: Daveman on September 15, 2011, 02:47:29 PM
I have severe PE. It is hard, really it is. Im not sure how niacin will effect this... Now. Is it possible PE is caused by my subconcious anxiety over POIS? it would be something interesting to looking into... I may experiment with this to see if i Can discover something more about my PE and PE in general

Yes, I think it has a lot to do with anxiety. There are a lot of factors.

Maybe the most important is that we don't have as much sex as we could. Before I had POIS, when I was about 35, my personal prime, I had three girlfriends at a time and usually had sex with them all regularly. So it wouldn't be unusual to be "doing it" A LOT. On weekends, I could hardly keep up. But when i was doing it a lot, I never had problems with PE, almost the opposite. It got sore from trying and trying, not able to have the orgasm. I guess they liked it!

But when you do it once every two weeks, just "getting it to the surface" is enough to set you off. Sometimes you are so worried about POIS that you can;t even get it up, but even then, the slightest stimulation and POW. Believe me, you don't need an erection to have an orgasm.

Somehow with masturbation there is less PE. I think that has to do with the less intimate character, les stimulation and less "responsibility".

The stress of responsibility seems to work against us, especially if we are "hot".

Sometimes, before POIS, if I wanted to be sure I could last for a new hottie, I'd masturbate beforehand, so that I could last longer. We can't do that now.  We'd be so POISed out afterwards!!

Title: Re: Premature ejaculation
Post by: Observer on September 17, 2011, 09:53:52 AM
I have found that garlic helps against PE.

My case is rare, because there are times that i control effectively the impulse of eyaculating and there are times that i just can´t. I remember that after 20 days without any ejaculation i was able to have sexual intercourse and not orgasm, and some days i don´t last enough.

Be relaxed, not tired, not eat heavy food, take garlic... are the best tips i could suggest. It seems that the niacin is helping too, but if i have an orgasm every day, that would take a toll on the quality of sexual intercourse the following days(erections, PE). I realized that it is better to have some day of rest following 3-4-5 days of daily intercourse to not have PE, because i have the feeling of being somewhat "sexually exhausted"(I feel great, but i just don´t want to have sex or masturbate). Maybe this is because i have never get used to have an O. so repeatedly. I am going to rest more than a week and i will report later with my next experiences.
Title: Re: Premature ejaculation
Post by: b_jim on September 20, 2011, 11:25:54 AM
If garlic help you I'm ok to test it but I'm sceptic  :) Why not.
Title: Re: Premature ejaculation
Post by: FloppyBanana on July 26, 2012, 12:42:53 PM
I know this is a pios from but I think this relevant, it has been of use for me. There are some delay creams out and some are fake however; there is one Chinese balm called Pau Yuen Tong. This helped because I could have a goos sex session without shooting the gun. Gun sometimes fired by mistake thuo. this is more likely to happen if I have not had sex for a month.
Title: Re: Premature ejaculation
Post by: slugishdragonn on January 22, 2014, 04:09:57 PM

well if you guys are still interested on the PE topic.
From my research, what I understand is following:
1. The allergen in the semen, causes the Mast cells to release histamine.
2. This histamine builds up over time in our body causing inflammations. I have gingivitis, sinusitis, UTI, Acne and nerves.
3. Histamine is also responsible for vasodilation of capillaries.
4. Histamine quickens ejaculation/reach orgasm. Some doctors prescribe histidile tablets to women who cant reach orgasm.
5. People with low histamine have difficulty reaching orgasm.

If that is true, than most likey people who have Positive skin prick test, must be experiencing PE.
For myself, I have positive and PE.. 5-10 strokes in and am set off :(

Any thoughts on this ?

Cheers,
slugishdragon

Title: Re: Premature ejaculation
Post by: b_jim on January 23, 2014, 07:43:06 AM
Yes, that's a good hypothesis.
Title: Re: Premature ejaculation
Post by: slugishdragonn on January 23, 2014, 04:50:50 PM

Further, we are most probably Histadials - Body with higher side of the regular histamine levels.
Do a research on this topic, it is pretty interesting.

MTFHR:
There are some people with Gene mutation (MTFHR, if am not wrong) who have problem with Histamine synthesis, because they cannot express Methyn, which is essential for synthesis of Histamine through the process called Methylation.

Under methylers
People with high histamine are ambitious, achievers, pushers, successful.. that explains why most of us are engineers and researchers :P

Anti histamines like citrizine blocks the H1 receptions, might be to an extent H2, out of (H1, H2, H3, H4 Receptors), but the histamine in body remains, and needs to be synthesized into something (Himocysteins) and excreted gradually. And only with Methyn could we synthesize histamine in brain... Anti-histamines either ways dont cross the blood brain barriers.

Recovery time:
I suspect the time we take to recover from the POIS (1-15 days roughly speaking), is directly proportional to Histamine released due to allergic reaction by the Mast cells, and inversely proportional to the Methylation ability of the person..

To test this hypothesis, I have started taking Methonine - 500 mg, Magnesium - 400 mg (Magnesium, Zince are essential in the Methylation process) to get rid of the excess Histamine in me. I might also start taking Vitamin B3 and B6 to prevent building excess Himocystines (which cause several cardiac diseases etc).

If I could delay my ejaculation in any measure or better see some improvements with Gingivitis/UTI/Acne , this hypothesis will be proved right ;)


Cheers,
slugishdragon
Title: Re: Premature ejaculation
Post by: Stef on January 24, 2014, 06:09:50 PM

Further, we are most probably Histadials - Body with higher side of the regular histamine levels.
Do a research on this topic, it is pretty interesting.

MTFHR:
There are some people with Gene mutation (MTFHR, if am not wrong) who have problem with Histamine synthesis, because they cannot express Methyn, which is essential for synthesis of Histamine through the process called Methylation.

Under methylers
People with high histamine are ambitious, achievers, pushers, successful.. that explains why most of us are engineers and researchers :P

Anti histamines like citrizine blocks the H1 receptions, might be to an extent H2, out of (H1, H2, H3, H4 Receptors), but the histamine in body remains, and needs to be synthesized into something (Himocysteins) and excreted gradually. And only with Methyn could we synthesize histamine in brain... Anti-histamines either ways dont cross the blood brain barriers.

Recovery time:
I suspect the time we take to recover from the POIS (1-15 days roughly speaking), is directly proportional to Histamine released due to allergic reaction by the Mast cells, and inversely proportional to the Methylation ability of the person..

To test this hypothesis, I have started taking Methonine - 500 mg, Magnesium - 400 mg (Magnesium, Zince are essential in the Methylation process) to get rid of the excess Histamine in me. I might also start taking Vitamin B3 and B6 to prevent building excess Himocystines (which cause several cardiac diseases etc).

If I could delay my ejaculation in any measure or better see some improvements with Gingivitis/UTI/Acne , this hypothesis will be proved right ;)


Cheers,
slugishdragon

Slugishdragonn,

How were you tested for excess histamine -- what lab tests were performed?

Stef

Title: Re: Premature ejaculation
Post by: FloppyBanana on January 25, 2014, 05:19:37 AM
... Anti-histamines either ways dont cross the blood brain barriers.
Hi Slugishdragonn,
This is not true. Some antihistamines cross the brain barrier and some do not. Some antihistamines which people use for POiS do cross the brain barrier.
FB
Title: Re: Premature ejaculation
Post by: slugishdragonn on February 28, 2014, 02:35:51 PM
@Stef
I havent tested histamine levels in my blood. The various inflammations (sinus, nerves, Gingivitis, UTI) goes to show that.
They worsen soon after ejaculation. I cant think of anything else which causes inflammations. In addition, antihistamines, quercetin seems to help a lot.

In my latest research, I tried taking Calcium (400mg). Calcium is supposed to release(eventually to excrete out of body) Histamine from the mast-cells into Blood.
And I could say that after 3-4 hours of taking calcium my Gingivitis gets bad, untill I take Methionine and Magnesium. BTW Magnesium (helps in mythlation) helps me a lot.


BTW, my doctor has prescribed me Mast-Cell Stabilisator Allegroval (Cromoglicic acid). 200mg 2 times a day.
Am taking this since a month, I feel very good. But not sure, if its this Mast-cell Stabilisator or my 4 times/per week Fitness studio + Magnesium supplements doing the trick :(
I will take the medicine another one month and report to the doctor. And a couple of weeks before that, stop taking any Magnesium and Neem (Quercitin) supplements.

I know am messing up with too many things (Neem, Mast-cell stabilisator, Work out, Magnesium, Zinc, Calcium supplements)
But hey I was diagnosed positive with POIS just a month ago after 15 years of suffering!! I am excited, happy, sad, impatient, stronger, hopeful, nervous all at once.

Title: Re: Premature ejaculation
Post by: Starsky on March 07, 2014, 03:43:54 PM
Check your copper levels. Most of POISers have low ceruloplasmin which is bioavaliable copper. Low copper=high histamine.  I am working to have more bioavailable copper and so far i have good results.

My ceruloplasmin levels were 0,13 Range 0,20-0,60.

I reached now 0,21.

I did not take copper. It seems that i had copper stored in tissues which is really disturbing on the body.

This is the histamine metabolism. You need copper to produce DAO. If you have good amounts of copper and still high histamine than its a methylation issue. But please check your copper in blood.

(https://ainotes.wikispaces.com/file/view/histamine_metabolism.png/204439802/720x315/histamine_metabolism.png)
Title: Re: Premature ejaculation
Post by: Stef on March 07, 2014, 10:13:22 PM
Hi, Slugishdragonn (and everyone else!),

It's great to hear that you're feeling better on your current regimen. POIS is such a miserable, awful condition. When something actually helps -- it's like a miracle has occurred! I don't say that lightly.

As you stated, you're doing several different things to find some relief -- neem (an herb -- I'm not clear about what it does), regular exercise, magnesium supplements, cromoglicic acid ("cromylyn" in the US --  an over-the-counter mast cell inhibitor that is used to treat allergies and asthma).

It could be that the combination of therapies -- or even just one -- is helping you. There's no way to know what's providing the relief.

The most important thing is that you're being followed by your physician...this can't be emphasized enough!!

We're all wishing you the best of luck!

As an aside, Starsky -- there's no research or documentation, anywhere, reflecting that men with POIS have low ceruloplasmin levels.  This is a theory that some forum members subscribe to -- but it is not fact. It might be worthy of formal scientific research at some point.

Stef   




Title: Re: Premature ejaculation
Post by: b_jim on March 10, 2014, 05:20:38 AM

My ceruloplasmin levels were 0,13 Range 0,20-0,60.

I reached now 0,21.



Does it really improve your pois symptoms ?
Title: Re: Premature ejaculation
Post by: slugishdragonn on March 10, 2014, 01:07:22 PM
Hi all,
thanks for your replies.

My entire regime seems to help just accelerate the Histamine excretion.
However, I still do feel POIS symptoms after Orgasm. I suspect the Auto Immune reaction still exist, whenever I ejaculate the body histamine level increases and after taking Magnesium, Methionine, Neem, Calcium, Vitamin C the Histamine level comes down waiting for the Orgasm to start it all over again !

By the way, I also feel pain in my Hands and Legs during sex (Even before ejaculation... when my Penis is erect and I get pleasure vibes).
I could imagine it to be my prostate, which is inflammed (due to exposure of semen all this long), and on erection/ejaculation, it is squeezed/tensed whatever, and the pain trickles all through the limbs.

Do you guys experience the same pain ?
I also have pain in mild pain in my lower back on the day of Orgasm.

Your expereinces/views are higly appreciated.

Thanks in advance.
slugishdragonn
Title: Re: Premature ejaculation
Post by: berlin1984 on May 24, 2020, 01:51:53 PM
Cross posting:

Premature ejaculation seems to be very common in the 'nofap' community, so it might be a general body (mal)adaption and not related exclusively to POIS.

Taking Tryptophan, 5HTP or Slow-Release 5HTP can help some people with premature ejaculation. It's also a side effect of SSRIs (anti depressants).

I've also seen that the above amino acids can help a bit with slow transit contipation (https://poiscenter.com/forums/index.php?topic=3293.0).
Title: Re: Premature ejaculation
Post by: berlin1984 on June 07, 2020, 10:20:05 AM
See also this thread:

* During an orgasm, histamine is released, and has been connected to the sex flush among women. However, men with high histamine levels may suffer from premature ejaculations.

And this one:
...
My thought: Person consumes too much histamine via food and also histamine liberators. Has problems with DAO (histamine intolerance (https://poiscenter.com/forums/index.php?topic=2061.0)). Has leaky gut (https://poiscenter.com/forums/index.php?topic=3098.0), making histamine passing through to bloodstream. Then: Histamine is released at orgasm. Virus is somehow re-activating and does it's thing, maybe involving more histamine.
All this histamine overload leads to problems.
...
Title: Re: Premature ejaculation
Post by: Muon on August 02, 2020, 10:19:39 AM
See also this thread:

* During an orgasm, histamine is released, and has been connected to the sex flush among women. However, men with high histamine levels may suffer from premature ejaculations.

Glans Penis Augmentation Using Hyaluronic Acid Gel for the Treatment of Premature Ejaculation (https://www.jsm.jsexmed.org/article/S1743-6095(20)30393-3/abstract)

Guess what, HA inhibits histamine (from mast cells)
https://sci-hub.se/https://www.sciencedirect.com/science/article/pii/S0161589008000151

Mast cell mediated premature ejaculation?

Association of NE, leptin, and 5‐HT with electrophysiological parameters in patients with primary premature ejaculation (https://poiscenter.com/forums/index.php?topic=139.msg34761#msg34761)
Title: Re: Premature ejaculation
Post by: Iwillbeatthis on February 16, 2021, 02:03:26 PM
When I last had sex a few years ago I had premature ejaculation before penetration even, I was also under the influence of alcohol. The times I've had sex since I devoloped POIS I've had premature ejaculation every time, apart from one time where I wasn't drinking alcohol - this time the first the first O was premature however the second O wasn't.

Before I had POIS my experience was that the more times I had sex the premature ejaculation got better every time which is the case with most men who have PE.

Now I can't tolerate alcohol at all so maybe I won't have PE the next time I have sex.

If you have PE issues cutting out Porn is probably the most helpful thing you can do. Porn is instant gratification which messes up the circuits in your brain causing PE.
Title: Re: Premature ejaculation
Post by: Cursed on February 17, 2021, 04:45:30 PM
How quick is Premature Ejakulation? 2 minutes? Davemen did you have that problem before POIS?

Strangely, when I tend to be most sensitive, I can't hardly even get it up, yet just about anything will set it off.

If I'm really "hot" and "hard" (excuse the graphic nature), I will usually last longer.

Weird huh?

I feel exactly the same. In fact, it's very strange that sometimes I feel that I just need to masturbate because I have this feeling of stimulation, even though I have no erection unless I actually start masturbating and then I would finish very quick. Also, this isn't really real horniness, I think it's more similar to what's called restless genital syndrome or something like that. I get this often the next day after ejaculation. Then it goes away.

At leaat for me, it is all depends very much on what I eat and how my GI tract is doing, but I haven't found anything that really works. I'm playing around with fecal transplants, hoping to fix the microbiome.

To add: these symptoms got better after I began using taurine, b2, b6, TMG, zinc,selenium and occasionally some methylfolate.
Title: Re: Premature ejaculation
Post by: VSmasher on July 15, 2021, 05:45:52 PM

well if you guys are still interested on the PE topic.
From my research, what I understand is following:
1. The allergen in the semen, causes the Mast cells to release histamine.
2. This histamine builds up over time in our body causing inflammations. I have gingivitis, sinusitis, UTI, Acne and nerves.
3. Histamine is also responsible for vasodilation of capillaries.
4. Histamine quickens ejaculation/reach orgasm. Some doctors prescribe histidile tablets to women who cant reach orgasm.
5. People with low histamine have difficulty reaching orgasm.

If that is true, than most likey people who have Positive skin prick test, must be experiencing PE.
For myself, I have positive and PE.. 5-10 strokes in and am set off :(

Any thoughts on this ?

Cheers,
slugishdragon

You can have high histamine WITHOUT having an allergic reaction. Histamine is used in your body for a ton of natural daily reactions. For instance, your body histamine increases in the morning to wake you up. (I think that's why I cum so quick with morning sex). Also, you don't need mast cells to release histamine. Your brain makes histamine inside the CNS as it acts as a neurotransmitter. You can have no mast cell release of histamine, and still have high brain histamine. I agree 100% that brain histamine may be our problem though.
Title: Re: Premature ejaculation
Post by: VSmasher on July 16, 2021, 02:14:42 PM

well if you guys are still interested on the PE topic.
From my research, what I understand is following:
1. The allergen in the semen, causes the Mast cells to release histamine.
2. This histamine builds up over time in our body causing inflammations. I have gingivitis, sinusitis, UTI, Acne and nerves.
3. Histamine is also responsible for vasodilation of capillaries.
4. Histamine quickens ejaculation/reach orgasm. Some doctors prescribe histidile tablets to women who cant reach orgasm.
5. People with low histamine have difficulty reaching orgasm.

If that is true, than most likey people who have Positive skin prick test, must be experiencing PE.
For myself, I have positive and PE.. 5-10 strokes in and am set off :(

Any thoughts on this ?

Cheers,
slugishdragon

Also, Opioids like oxycotin stop me from having an orgasm. Opioids release tons of histamine. Maybe our histamine is to low..?
Title: Re: Premature ejaculation
Post by: Muon on July 20, 2021, 06:52:12 AM
Note that a couple of women here with POIS suffer from premature orgasm.
Title: Re: Premature ejaculation
Post by: Progecitor on March 25, 2022, 02:03:57 PM
There is a product called a delay spray which can be bought in sex shops. Has anyone considered trying it to reduce PE? I don’t have endurance issues, but it may still work for those who have more severe problems in this regard.
Title: Re: Premature ejaculation
Post by: berlin1984 on March 25, 2022, 02:52:52 PM
I've tried the condoms with probably the same delay medicine inside. I don't really like it (=> getting problems keeping stiff).

I've tried for fun the stack of Magnesium, Zinc, Tribulus, Rosea Rhodiola, Ashwagandha before and it seems to help.

But my PE is not severe so that's more for experimentation and because of my finding that generic muscle building or masculinity supplements (claiming to help with sexual performance or testosterone) also help for POIS and/or general fatigue issues..
Title: Re: Premature ejaculation
Post by: Progecitor on April 12, 2022, 11:08:01 AM
Earlier I discussed the possible involvement of 5-HT2A in depression, but 5-HT2C is also worth more investigation due to its proposed roles in sexual functions.
The present findings suggest that 5-HT2A/5-HT2C receptors may be involved in the neural control of male sexual motivation and arousal, presumably by exerting reciprocal facilitative (5-HT2A) or suppressive (5-HT2C) influences.
https://www.karger.com/Article/Abstract/63681

5-HT2C was mentioned before in a different context, however its role in ejaculation was not discussed.
Some effects of 5-HT1A receptor activation include decreased aggressive behavior/ideation, increased sociability, and decreased anxiety and depression. 5-HT2C activation blocks dopamine and inhibits norepinephrine release. Blockade of the 5-HT2C receptor increases serotonin, releasing norepinephrine and dopamine within the brain.

"5-HT2C agonism has been demonstrated to induce anorexia via enhancement of serotonergic neurotransmission via activation of 5-HT2C receptors"
https://en.wikipedia.org/wiki/Aripiprazole#Pharmacodynamics

Indications are present for 5-HT2 receptors to modulate dopaminergic activity. Moreover, 5-HT2A receptors and 5-HT2C receptors exert opposite effects on dopamine release. Evidence has been provided that 5-HT2C receptors inhibit dopamine pathways and that 5-HT2A receptors enhance dopamine release.
http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.972.6802&rep=rep1&type=pdf

SSRIs were extensively discussed, however one SSRI called Dapoxetine (Priligy) is specifically indicated for the treatment of PE. Interestingly it increased POIS symptoms for some members.
Dapoxetine is used for the treatment of premature ejaculation. It’s a selective serotonin reuptake inhibitor. Ejaculation is controlled by both serotonin, dopamine, primarily the 5-HT1a and 5-HT2c receptors. It works by inhibiting the reuptake of the serotonin transporter. It inhibits the reuptake transporters of dopamine and norepinephrine.
http://ijpdt.com/File_Folder/86-89.pdf

Tramadol has been used with varying results by members and I think opioids shouldn't be considered as a sole reason for its effects. Folic acid may also effect PE. There are numerous other ideas for PE management in this review so it is a recommended reading.
Also check out Table 1 and Figure 1! Attached image: Table 1. Premature_ejaculation_guidelines
Although the pathophysiology of PE is relatively unknown, one hypothesis behind the etiology of PE is the dysfunction of 5-HT receptors. Elevated concentrations of 5-HT are present at many receptors that have been found to be involved with ejaculatory control, and activation of the central 5-HT mediated system has an overall inhibitory effect on ejaculation. Specifically, activation of 5-HT1B and 5-HT2C receptors has been shown to have inhibitory effects on the ejaculation pathway, delaying ejaculation, whereas activation of 5-HT1A receptors has been found to precipitate ejaculation.
Waldinger et al. proposed that the pathophysiology of PE could possibly be a result of hypofunction of the 5-HT2C receptor and/or hyperfunction of the 5-HT1A receptor. This hypofunction of the 5-HT2C receptor, as well as low levels of 5-HT transmission in general, is thought to be associated with a low threshold for sexual arousal and ejaculation. SSRIs can activate 5-HT2C receptors and raise this threshold, subsequently increasing the IELT.
The effect of SSRIs on PE has been seen as early as a few days after starting the medication; however, most patients notice a significant increase in ejaculatory time 1–2 weeks after beginning the medication, strengthening the thought that SSRIs treat PE through receptor desensitization. Furthermore, because 5-HT receptor desensitization can cause the body to upregulate the production of 5-HT receptors, the efficacy of SSRIs might decrease after 6–12 months of consistent use.
Tramadol exerts its analgesic effects by binding to centrally located mu opioid pain receptors, and by inhibiting the reuptake of both serotonin and norepinephrine. Interestingly, tramadol has also been shown to act as a 5-HT2C receptor antagonist. It is thought that tramadol’s effectiveness in the treatment of PE is due to the neuromodulation of serotonin and norepinephrine receptors. Tramadol has shown promising results in multiple studies examining its use in the medical management of patients with PE.
Folic acid is water soluble and readily available over the counter. The vitamin's cheap cost and absence of negative side-effects makes it an ideal pharmacological treatment for PE. Folic acid levels have been found to be negatively correlated with PE, with folic acid deficiency being considered a risk factor for decreased ejaculatory latency. Additionally, folic acid supplementation has been shown to improve erectile function when given concomitantly with a phosphodiesterase inhibitor. Although folic acid appears to play more of a role in ED, the vitamin's cheap and benign nature necessitates thorough study in association with PE.

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/iju.13202

Anyone who had success with tramadol should also try bacopa to see if there is a correlation.
Upregulation of 5-HT2C receptors in hippocampus of pilocarpine-induced epileptic rats: Antagonism by Bacopa monnieri. Our results showed upregulation of 5-HT2C receptors with a decreased affinity in hippocampus of pilocarpine-induced epileptic rats. Carbamazepine and B. monnieri treatments reversed the alterations in 5-HT2C receptor binding, gene expression, and inositol triphosphate content in treated epileptic rats as compared to untreated epileptic rats.
https://www.sciencedirect.com/science/article/abs/pii/S152550500900420X

Contrary to this at one time with Bacopa I felt some warmness, although this was not consistent. As a reference I have cold-type POIS.
The activation of 5-HT2C inhibits neurotransmitter (dopamine) release, thus reducing dopaminergic inhibition of the NRP and increasing activation of sympathetic structures. The activation of 5-HT2C thus inhibits vagal activity and favors hyperthermia. Antagonism (5-HT2C inhibition) is, however, apparently not so sufficient as to induce hypothermia.
https://www.mdpi.com/1422-0067/23/6/3365/htm

Lorcaserin (Belviq) has been recently withdrawn due to potential carcinogenicity, so it can't be tested anymore. However it still holds some theoretical value.
Lorcaserin, a selective 5-hydroxytryptamine (5-HT)2C receptor agonist, reduces body weight. It is unclear whether weight loss is due to reduced energy intake or also to enhanced energy expenditure. Lorcaserin is a potent and selective 5-HT2C agonist that decreases food intake and body weight in a dose-dependent fashion in rodents.
https://academic.oup.com/jcem/article/96/3/837/2597055?login=true

One particular lorcaserin side effect:
Rarely, males may have a painful or prolonged erection lasting 4 or more hours. If this occurs, stop using this drug and get medical help right away, or permanent problems could occur.
https://www.webmd.com/drugs/2/drug-164439/belviq-oral/details

Lorcaserine is pro-ejaculatory which seems contrary to what have been discussed for SSRIs. This may also indicate a potential role for 5-HT2C in nocturnal emissions.
Lorcaserin is an anti-obesity drug whose weight loss effect results from 5-hydroxytryptamin (5-HT)2C receptors activation. The 5-HT2C receptor was shown to participate in the physiological control of ejaculation, but no data addressing a putative effect of lorcaserin on ejaculation exist.
Lorcaserin (1.0 nM to 1.0 mM) had no significant effects on the in vitro contractility of seminal emission organs smooth muscle (cauda epididymis, vas deferens, and seminal vesicles). On the other hand, lorcaserin administration (0.3–1.0 mg/kg, intravenous) induced ejaculation in anesthetized rats, which was prevented by the 5-HT2C-selective antagonist SB 242084 (0.1 and 0.3 mg/kg, intravenous). Single-dose treatment of non-anesthetized male rats with lorcaserin (1.0, 4.0, or 10 mg/kg, per os) induced non-copulating ejaculations in sexually naive rats. Lorcaserin also had pro-ejaculation effects by decreasing the ejaculation threshold of copulating rats by half. The pro-ejaculatory effects of lorcaserin were reversible as the ejaculation threshold of treated rats recovered after a 1-week washout period.

https://www.sciencedirect.com/science/article/abs/pii/S1743609520301326

Ritalin and fluoxetine were also mentioned many times on the forum with varying outcomes.
Drugs like ritalin (methylphenidate): Actions may involve 5-HT2C-receptor stimulation. In addition, there are multiple subtypes of DA receptors and especially 5-HT receptors, allowing complex interactions between drugs and monoaminergic systems. 5-HT2C (formerly termed 5-HT1C) receptors, possibly in the hypothalamic appetite centre, may be involved in decreasing appetite, as demonstrated in knockout mouse models and it has been suggested that fenfluramine and other anti-appetite agents act at 5-HT2C receptors. Both 5-HT2C receptor and alpha2A-adrenoceptor are candidate genes for weight gain in patients on antipsychotics. Agonists at 5-HT2C receptors may also be useful in attention deficit and depression. Fluoxetine (prozac), in addition to serotonin re-uptake transporter blockade has high affinity for 5-HT2C receptors.
https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1038/bjp.2008.124

The 5-HT2C receptor has been suspected to be involved in neuropathic pain; an increase in the spinal 5-HT2C receptor density has been observed in different animal pain models. The antagonism of agomelatine on 5-HT2C receptors also induces an increase of noradrenaline in limbic areas. Noradrenaline has been involved in the pathophysiology of neuropathic pain and SNRIs are effective in neuropathic pain while selective serotonin reuptake inhibitors (SSRIs) are not recommended. According to these data, the melatonergic agonist and 5-HT2C antagonist properties of agomelatine could be responsible for an analgesic effect and potentially have an effect on neuropathic pain.
https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Agomelatine%3A+a+new+opportunity+to+reduce+neuropathic+pain%E2%80%94preclinical+evidence&btnG=
Title: Re: Premature ejaculation
Post by: Muon on April 12, 2022, 01:41:05 PM
Premature Ejaculation Articles --> https://poiscenter.com/forums/index.php?topic=3127.msg31516#msg31516
Reminder: Summary can be made from articles.

PE and weight?:
"5-HT2C agonism has been demonstrated to induce anorexia via enhancement of serotonergic neurotransmission via activation of 5-HT2C receptors"
https://en.wikipedia.org/wiki/Aripiprazole#Pharmacodynamics

Novel Marker for Premature Ejaculation: Serum Leptin Level (https://www.sciencedirect.com/science/article/pii/S205011612200023X) (2022)
"There was a statistically significant relationship between serum leptin levels and patients with PE. In addition, serum leptin levels in patients with PE decreased significantly after 8 weeks of treatment with SSRIs."

"Increased levels of melatonin causes a downregulation of leptin"
https://en.wikipedia.org/wiki/Leptin

Histamine (receptors) and PE?:
Involvement of Histamine H3 Receptor Agonism in Premature Ejaculation Found by Studies in Rats (https://www.mdpi.com/1422-0067/23/4/2291) (2022)

https://poiscenter.com/forums/index.php?topic=139.msg35655#msg35655
Title: Re: Premature ejaculation
Post by: Muon on April 12, 2022, 02:46:03 PM
Is there a correlation between (lifelong) Premature Ejaculation, primary and secondary POIS?

The epidemiology of premature ejaculation (https://tau.amegroups.com/article/view/10575/11762)
Title: Re: Premature ejaculation
Post by: Progecitor on April 24, 2022, 03:57:39 PM
I didn't know that delayed ejaculation (DE) was also considered a problem. Although not an issue with my POIS, but its understanding could be still informative in the management of PE.
Table 3 provides a comprehensive list of medications that may delay ejaculation. These are also possible treatments for PE.
Table 4 provides a list of medications that may treat delayed ejaculation or anejaculation. Interestingly some of these also help in POIS management.
https://synapse.koreamed.org/articles/1088855