POISCENTER

General Category => POIS Research => Topic started by: Muon on March 13, 2021, 04:07:11 PM

Title: POIS Theory Master List
Post by: Muon on March 13, 2021, 04:07:11 PM
Post theories/ideas regarding the Pathophysiology (https://en.wikipedia.org/wiki/Pathophysiology) of POIS. This thread can function as a central hub. You may dump links to threads from other members in the comment section. The numbers (in parentheses) are not refering to a list of references, these are just names for related hyperlinks.

Rudimentary version
Or a combination of more than one of the above.

What else?

Comorbidities:

Premature Ejaculation:

Increased APP, AB42 in seminal plasma. Abnormal PSSR (https://www.sciencedirect.com/science/article/pii/S1743609516304842) (lifelong PE)
Low Serotonin
Low serotonin + High Interferon gamma (https://www.neliti.com/publications/224850/flouxetine-improved-intravaginal-ejaculatory-latency-time-through-decreased-leve)
Low serum BDNF
High Leptin/5-HT ratio
Low seminal plasma magnesium
Low NO
Imbalance between excitatory and inhibitory signals in the brain
Altered serotonin receptor activity
Hyperexcitability of penile sensory receptors
Changes in the neural processing of sensory signals
PIEZO2 (https://onlinelibrary.wiley.com/doi/full/10.1111/andr.12779)
H3R (https://www.sciencedirect.com/science/article/abs/pii/S1743609522010190)
ANS dysfunction (https://pubmed.ncbi.nlm.nih.gov/23102443/) (lifelong PE)
TRP ion channels (https://www.sciencedirect.com/science/article/abs/pii/S0091305713003389)
weakened connectivity between the inner brain regions in the dopamine system and strengthened connectivity between the dopamine system and other brain areas (https://www.sciencedirect.com/science/article/pii/S2213158218301712#s0085)
Decreased TPH2 expression in brain (https://onlinelibrary.wiley.com/doi/full/10.1111/andr.13135).
Altered ALFF of frontal, parietal cortex, and putamen (https://academic.oup.com/jsm/article-abstract/17/12/2331/6973777?login=false)
Caudate nucleus volume (https://academic.oup.com/jsm/article-abstract/16/7/992/6980594?login=false)
Dopamine autoreceptors (https://www.sciencedirect.com/science/article/abs/pii/0091305784901035)
DAT1 polymorphism (https://academic.oup.com/jsm/article-abstract/7/4_part_1/1538/6848914?login=false)
Increased Norepinephrine firing? Low Norepinephrine? (https://sci-hub.se/10.1097/MJT.0000000000000863)
Medial preoptic area in the rostral hypothalamus and nucleus paragigantocellularis in the ventral medulla (https://www.sciencedirect.com/science/article/abs/pii/S0022534705641468)
Increased nerve fibers (NGF?)
Dynamic changes of brain activity (https://www.researchsquare.com/article/rs-4015150/v1) (Lifelong PE)

Hormonal Risk factors (https://sci-hub.se/10.1007/s12020-014-0520-7): High Testosterone, High Estradiol, Low Prolactin, High oxytocin, High FT3, High FT4, High Leptin.

Exercise intolerance

Histamine depletion (https://www.mastattack.org/2015/05/histamine-depletion-in-exercise/)
Histamine response
MCAS
Natural Killer cell response (https://poiscenter.com/forums/index.php?topic=2373.msg46892#msg46892)
Post-exertional Malaise
PSN/SNS tone
Gut and plasma microbiome (https://poiscenter.com/forums/index.php?topic=2373.msg35929#msg35929)
S100B compromised (https://poiscenter.com/forums/index.php?topic=2373.msg36204#msg36204)
Testosterone and Heat shock protein response (https://rcm.mums.ac.ir/article_12100.html)
Impaired microcirculation/deficient action of NO (https://sci-hub.se/10.1016/j.mehy.2005.11.028)
Defective Growth Hormone response (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2868257/)
Elevated Cytokines
Decreased rate of ammonia clearance: Amino acids: Aspartic acid deficiency (https://poiscenter.com/forums/index.php?topic=3669.msg47124#msg47124)
Dysfunctional increase in WASF3 protein (https://www.nih.gov/news-events/nih-research-matters/protein-may-be-linked-exercise-intolerance-me-cfs?)
 Dopamine beta hydroxylase deficiency (https://en.wikipedia.org/wiki/Dopamine_beta_hydroxylase_deficiency)
Uhthoff’s phenomena (https://en.wikipedia.org/wiki/Uhthoff%27s_phenomenon), 2 (https://pmc.ncbi.nlm.nih.gov/articles/PMC5152601/)

Headache inducers

Prostaglandins
CGRP
Histamine
TNF-alpha
Serotonin

Non-IgE mediated food hypersensitivity

The cholinergic tone as a modulator of Food Allergy (https://kuleuven.limo.libis.be/discovery/fulldisplay?docid=lirias2798215&context=SearchWebhook&vid=32KUL_KUL:Lirias&search_scope=lirias_profile&adaptor=SearchWebhook&tab=LIRIAS&query=any,contains,LIRIAS2798215&offset=0&lang=en)
Central sensitization
MCAS
Gustatory rhinitis
Eosinophil/ECP (ECP is a better marker for allergic activation than IgE, need source)
Type IV hypersensitivity
MRGPRX2 mediated pseudo-allergy
Intestinal B cell activating factor
Tregs
Intestinal epithelial barrier disruption

Weakness

Muscle hypoperfusion
INSL3/RXFP2 signaling (https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2018.00562/full)
Decreased nerve conduction velocity

Ocular itch
Gastrin-releasing peptide receptors in trigeminal sensory system (https://www.frontiersin.org/articles/10.3389/fnmol.2023.1280024/full)

Itch

Histamine
IL-31

(Sudden) Muscle wasting/weight loss not reversed by nutrition

Heat intolerance
Uhthoff’s phenomena (https://en.wikipedia.org/wiki/Uhthoff%27s_phenomenon), 2 (https://pmc.ncbi.nlm.nih.gov/articles/PMC5152601/)
MCAS
 Dopamine beta hydroxylase deficiency (https://en.wikipedia.org/wiki/Dopamine_beta_hydroxylase_deficiency)

Low blood pressure & wakefullness
Histamine
Prostaglandin E2
Title: Re: POIS Theory Master List
Post by: Muon on March 13, 2021, 04:07:56 PM
Reminder: Some ideas might be left inside other threads like POIS paper treatment summary (https://poiscenter.com/forums/index.php?topic=3551.0) etc.
Title: Re: POIS Theory Master List
Post by: Muon on March 13, 2021, 04:09:02 PM
Reserved 2
Title: Re: POIS Theory Master List
Post by: Muon on March 13, 2021, 04:10:24 PM
Reserved final
Title: Re: POIS Theory Master List
Post by: Muon on March 19, 2021, 07:42:34 AM
POIS Patients are rarely tested for DAMPs:
https://en.wikipedia.org/wiki/Damage-associated_molecular_pattern#Overview
Title: Re: POIS Theory Master List
Post by: Muon on April 20, 2021, 07:23:55 AM
Running nose and nasal congestion can be related to vasomotor dysfunction (ANS, endothelial dysfunction?) which is unrelated to allergy, people might not be aware of this:

Vasomotor rhinitis (https://www.wikidoc.org/index.php/Vasomotor_rhinitis)

https://en.wikipedia.org/wiki/Nonallergic_rhinitis
Title: Re: POIS Theory Master List
Post by: Muon on April 22, 2021, 06:51:26 AM
Fox (https://poiscenter.com/forums/index.php?topic=3098.0):
Gluten sensitivity
Improves on Niacin rich food
Slight blood pooling upon standing (Sympathetic activation? Vasomotor function?)

I do remember that a certain subset of Tregs plays a role in gluten sensitivity, it was the CD39 subset if I'm not mistaken (paper needed for confirmation). Now throw Niacin into the mix and combine it with the following post, see pic: https://poiscenter.com/forums/index.php?topic=3765.msg40413#msg40413

Could Niacin intake affect Tryp/5HT pathway and improves vasomotor function, thus blood pooling?

What does Testosterone therapy have to do with this?---> T is able to increase Treg population directly. POISers who improved on antibiotics could have altered Treg populations. Treg increase can also be seen in some individuals who have done allergic desensitization therapy with succesful outcome (generally speaking that is, but could play a role in desensitized POISers). These points can be used to support MCAS theory as well. Tramadol--->Tregs?
Title: Re: POIS Theory Master List
Post by: Muon on June 03, 2021, 02:20:20 PM
 An Overview of Seminal Plasma Hypersensitivity and Approach to Treatment (https://sci-hub.se/https://www.sciencedirect.com/science/article/abs/pii/S2213219820304682#)

Can’t copy stuff from tablet. Read part about: PAR2 and dust mite. Possible protease-activated receptor-mediated epithelial barrier dysfunction.

 Systemic and localized seminal plasma hypersensitivity patients exhibit divergent immunologic characteristics (https://www.jacionline.org/article/S0091-6749(14)00715-5/fulltext)

Proteases constitute more than 8% of all SPPs in WSP8 and can augment IgE-independent inflammatory responses by disrupting the epithelial permeability barrier and activating protease-activated receptors (PARs) on epithelial cells.9 PAR-2 activation, which has been demonstrated in response to proteases from dust mite and cockroach and in seafood workers exposed to high aerosolized levels of proteases, can augment epithelial barrier dysfunction and localized mucosal inflammation independent of specific IgE responses.9,  10 Moreover, it has been demonstrated that semen proteases such as PSA can activate PAR-2 on spermatozoa cell membranes.11 We have recently confirmed the presence of PAR-2 receptors on vaginal keratinocytes by using western blotting and flow cytometry as well as calcium influx in SPP-stimulated vaginal keratinocytes using confocal microscopy, which was blocked by a protease inhibitor (unpublished data; Ghosh D and Bernstein JA, 2014, manuscript in preparation).

Thus, PAR-2 activation in vaginal epithelium might contribute to localized SPH, although other possible mechanisms such as IgE-independent mast cell activation and neurogenic responses involving bradykinin-mediated inflammatory/pain pathways should be investigated. In addition, prostaglandins (present in a considerable amount in WSP), which can cause antigen presenting cells to release proinflammatory cytokines, may also contribute to localized vaginal inflammation, as we have observed in some cases of women with localized SPH who experience attenuation of their symptoms if they take a nonsteroidal anti-inflammatory agent before unprotected intercourse (unpublished data). Thus, these mechanisms, summarized in Fig E2 in this article's Online Repository at www.jacionline.org, could potentially explain reactions observed in women with localized SPH in which specific IgE does not play a critical role. To conclude, our data demonstrate that although women with systemic and localized SPH have similar clinical outcomes, the mechanism(s) of action for these responses is distinctly different. Further investigation of the mechanism(s) related to localized SPH is warranted.

(https://els-jbs-prod-cdn.jbs.elsevierhealth.com/cms/attachment/ce66e83f-fbfa-4cc3-b34a-d896f68c8a27/fx2.jpg)

Fig E2Postulated mechanisms for localized SPH: Although women with systemic SPH sensitized to PSA can induce a specific serum IgE response through the classical TH2 pathway, women with localized SPH may exhibit symptoms as a result of seminal plasma proteases causing degradation of mucosal tight junctions, leading to the activation of PAR-2 receptors on epithelial cells that results in the release of proinflammatory cytokines and localized inflammation. Seminal plasma also contains high levels of prostaglandin E2 (PGE2), which can activate antigen-presenting cells (APCs) lining the inner face of the vaginal epithelium, leading to the release of proinflammatory cytokines, causing localized mucosal inflammation.

Table 2:
https://sci-hub.se/10.1111/jsm.12813#

HDM, cockroach allergens or seminal protease—>PAR2–>leakage of PGE2 and other stuff. MCA is another possibility.
Title: Re: POIS Theory Master List
Post by: Muon on June 16, 2021, 01:53:26 PM
Quote from: Muon on April 22, 2021, 06:51:26 AM
Fox (https://poiscenter.com/forums/index.php?topic=3098.0):
Gluten sensitivity

Gluten-->zonulin-->PAR-2 activation? See previous post.
P0517 ZOT/ZONULIN-MEDIATED REGULATION OF INTESTINAL TIGHT JUNCTIONS INVOLVES THE PROTEINASE-ACTIVATED RECEPTOR 2 (PAR-2) (https://journals.lww.com/jpgn/Fulltext/2004/06001/P0517_ZOT_ZONULIN_MEDIATED_REGULATION_OF.641.aspx)
Title: Re: POIS Theory Master List
Post by: Muon on March 28, 2022, 12:49:50 PM
https://twitter.com/scubatropin/status/1319398186708942848
" Its a class 6 allergy to semen. Precoital prednisone is pretty effective when given sufficient time to affect the multiple areas where the immune system attack. Avoiding omega-6 and other inflammatory fats is crucial to tx. "

Antibody Dependant Cell Mediated Cytotoxicity (ADCC) Type VI Hypersensitivity (https://www.hon.ch/Library/Theme/Allergy/Glossary/type6.html)
Title: Re: POIS Theory Master List
Post by: Muon on April 07, 2022, 07:00:43 AM
Quote from: Iwillbeatthis on April 07, 2022, 05:49:55 AM
Also in most cases I don't think the cause of POIS is mast cell related, its mainly neurotransmitter dysfunctions: imbalanced Glutamate/Gaba ratio causing excitotoxicity, low dopamine, low DBH activity, low BH4, high epinephrine, low norepinephrine, any mast cell symptoms are secondary to the neurotransmitter issues. Correcting gut microbiome imabalances/gut infections, mineral imbalances, methylation impairments, removing heavy metals you will see the neurotransmitter issues correct themselves.

Improving dopamine synthesis, normalising DBH, correcting an imbalanced gaba glutmate ratio will all also help.

This Post from an ME/CFS researcher has a lot of useful information.

https://bornfree.life/experimental-treatment-methodology/7/blood-ph-ion-channel-disturbances-neurotransmitters-and-mineral-deficiencies/37/

A preferred approach (after confirming noradrenaline is low and/or vanillylmandelic acid is low on urine tests), is to normalise DBH, thereby correcting the downstream cascade. This would be best mediated by removing any/all "low-hanging fruit", such as:

1. Quantifying and remediating deficiencies of vitamin C, copper, manganese, magnesium, zinc, lithium, riboflavin and potassium. (PQQ may also be helpful.)
2. Quantifying and remediating interstitial and blood pH. Confirming by blood smear that red blood cell morphology is normal. Any clumping or rouleaux may act to limit other interventions.
3. Quantifying and remediating pulmonary respiration function.
4. Antagonising a2-adrenergic receptors, using a suitable intervention. (At this time, appropriate a2-antagonists may include small doses of yohimbe / yohimbine, rauwolscine and phenoxybenzamine. This is a WIP)
5. Further reducing NLRP-3 using eg. hesperidin.
6. Removing / remediating any detected pathogens that impair DBH - this can be a long process.
7. Investigating a BH4 deficiency - this is difficult to measure directly. This may appear as low levels of neurotransmitters, low ferritin, low intracellular riboflavin, low 5-MTHF / folinic acid, low citrulline.
Title: Re: POIS Theory Master List
Post by: Muon on June 13, 2022, 06:11:49 AM
Silodosin could be used for research to make a distinction between subgroups by blocking ejaculation.
Title: Re: POIS Theory Master List
Post by: Muon on June 13, 2022, 10:00:37 AM
Quote from: demografx on June 13, 2022, 09:18:35 AM
Quote from: Muon on June 13, 2022, 06:11:49 AM
Silodosin could be used for research to make a distinction between subgroups by blocking ejaculation.
Good idea. And Rapaflo?
Anything that fully blocks ejaculation. You could end up with 4 groups if the block is successfull:
1) POIS free
2) Diminished symptoms
3) Increased symptoms
4) No effect in symptoms

Group 1 and 4 could be isolated and investigated further.
Title: Re: POIS Theory Master List
Post by: Muon on June 13, 2022, 05:38:14 PM
Type IV of hypersensitivity and its subtypes (https://europepmc.org/article/med/18409354)

Classification of hypersensitivity reactions (https://allergolyon.fr/wp-content/uploads/2020/08/0.4-Classification-of-hypersensitivity-reactions-2019.pdf)

"It should be noted that some disorders are caused by IgE-independent, nonspecific activation of mast cells, which could be considered to be a subset of type I hypersensitivity reactions."

 Perspective of Delayed Hypersensitivity: A review  (http://www.newinera.com/index.php/JournalLaMedihealtico/article/view/623/547)

"There is an increase in  leukocyte  concentration  in  tissues  where  immunological  and  inflammatory  responses  are occurring  in  response to  external  antigens  because  of  the  upregulation  of  endothelial  cell adhesion  molecule  expression."

Why haven't these Type IV subtypes been explored already? The mediators are shown for each subtype.
Title: Re: POIS Theory Master List
Post by: dylanmurphy on June 14, 2022, 01:56:35 AM
Pulsatilla 200c works well so far for me for stopping Ne's (touch wood) !!
Title: Re: POIS Theory Master List
Post by: Muon on September 15, 2022, 08:24:49 PM
Men versus women on sexual brain function: Prominent differences during tactile genital stimulation, but not during orgasm (https://onlinelibrary.wiley.com/doi/abs/10.1002/hbm.20733)

"The only prominent gender difference during orgasm was male-biased activation of the periaqueductal gray matter."

Periaqueductal Gray (https://sci-hub.se/https://www.sciencedirect.com/science/article/pii/B9780123742360100100)
Title: Re: POIS Theory Master List
Post by: Muon on April 23, 2023, 06:06:08 AM
Are we dealing with inflammatory exosomes (20-100 nm) in POIS? Crossing all kinds of biological barriers?

 Exosomes in inflammation and role as biomarkers (https://www.sciencedirect.com/science/article/abs/pii/S0009898118305813)

The advantage of using exosomes as a biomarker vehicle consists of their ease of collection from body fluids such as urine and saliva as they may represent a non-invasive means for screening human pathology.

 Unlocking the Power of Exosomes for Crossing Biological Barriers in Drug Delivery (https://pubmed.ncbi.nlm.nih.gov/33477972/)

Recent emerging studies have shown numerous critical roles of exosomes in many biological barriers, including the blood-brain barrier (BBB), blood-cerebrospinal fluid barrier (BCSFB), blood-lymph barrier (BlyB), blood-air barrier (BAB), stromal barrier (SB), blood-labyrinth barrier (BLaB), blood-retinal barrier (BRB), and placental barrier (PB), which opens exciting new possibilities for using exosomes as the delivery platform.
Title: Re: POIS Theory Master List
Post by: Progecitor on April 23, 2023, 02:04:06 PM
Quote from: Muon on April 23, 2023, 06:06:08 AM
Are we dealing with inflammatory exosomes (20-100 nm) in POIS? Crossing all kinds of biological barriers?

 Exosomes in inflammation and role as biomarkers (https://www.sciencedirect.com/science/article/abs/pii/S0009898118305813)

The advantage of using exosomes as a biomarker vehicle consists of their ease of collection from body fluids such as urine and saliva as they may represent a non-invasive means for screening human pathology.

 Unlocking the Power of Exosomes for Crossing Biological Barriers in Drug Delivery (https://pubmed.ncbi.nlm.nih.gov/33477972/)

Recent emerging studies have shown numerous critical roles of exosomes in many biological barriers, including the blood-brain barrier (BBB), blood-cerebrospinal fluid barrier (BCSFB), blood-lymph barrier (BlyB), blood-air barrier (BAB), stromal barrier (SB), blood-labyrinth barrier (BLaB), blood-retinal barrier (BRB), and placental barrier (PB), which opens exciting new possibilities for using exosomes as the delivery platform.

Exosomes are also involved in SASP signaling.

Additionally, small exosome-like extracellular vesicles have recently emerged as key components of the senescent cell secretome to enable more distal functions, such as enhancing cancer cell proliferation, an intriguing topic requiring further investigation.
Senescent cells can communicate with the surroundings through juxtacrine NOTCH/JAG1 signaling or ROS secretion or cargo transfer by formation of cytoplasmic bridges or release of extracellular vesicles such exosomes.
https://www.frontiersin.org/articles/10.3389/fcell.2021.645593/full
Title: Re: POIS Theory Master List
Post by: Muon on May 31, 2023, 06:55:07 PM
Input from nurse Claire is appreciated. She tries to describe the cause of POIS with an autoimmune approach.

May 19, 2023
Equal Parts Derogatory Dismissal and Powerless Exasperation (https://autoimmunedx.substack.com/p/equal-parts-derogatory-dismissal)

May 26, 2023
Find the Antigen(s), Define the Disease (https://autoimmunedx.substack.com/p/find-the-antigens-define-the-disease)

Reminder to incorporate it into the list.
Title: Re: POIS Theory Master List
Post by: demografx on June 01, 2023, 09:09:07 AM
Quote from: Muon on May 31, 2023, 06:55:07 PM

Input from nurse Claire is appreciated. She tries to describe the cause of POIS with an autoimmune approach.

May 19, 2023
Equal Parts Derogatory Dismissal and Powerless Exasperation (https://autoimmunedx.substack.com/p/equal-parts-derogatory-dismissal)

May 26, 2023
Find the Antigen(s), Define the Disease (https://autoimmunedx.substack.com/p/find-the-antigens-define-the-disease)

Reminder to incorporate it into the list.

Sent to POIS Research Team. Thanks.
Title: Re: POIS Theory Master List
Post by: Muon on October 02, 2023, 08:06:03 AM
Quote from: Muon on September 15, 2022, 08:24:49 PM
Men versus women on sexual brain function: Prominent differences during tactile genital stimulation, but not during orgasm (https://onlinelibrary.wiley.com/doi/abs/10.1002/hbm.20733)

"The only prominent gender difference during orgasm was male-biased activation of the periaqueductal gray matter."

Periaqueductal Gray (https://sci-hub.se/https://www.sciencedirect.com/science/article/pii/B9780123742360100100)

 The neurobiology of central sensitization (https://onlinelibrary.wiley.com/doi/full/10.1111/jabr.12137)

We have similarly shown that decreased connectivity to antinociceptive brain regions, such as the periaqueductal gray (PAG - a critical locus of descending analgesic pathways), predicts responsiveness to milnacipran, a serotonin norepinephrine reuptake inhibitor. https://poiscenter.com/forums/index.php?topic=3312.0

Quote from: Muon on October 26, 2023, 08:38:59 AM
Quote from: Muon on December 09, 2020, 07:40:28 AM
Quote from: J.G
It's worth noting that observations regarding POIS in / and / or MECFS go back (at least) some 25 years. Noted ME specialist Dr. Jay Goldstein in his 1996 Betrayal by the Brain (https://me-pedia.org/wiki/Betrayal_by_the_Brain):

"Several of my male patients have complained that they feel exhausted for several days after ejaculating. Although little is known about the central neurochemistry of orgasm, it appears that NE [norepinephrine] facilitates it, and that NE is depleted after ejaculation. If a male neurosomatic patient were deficient in NE prior to sexual activity, ejaculation could thereby worsen his symptoms" (Goldstein 1996: 63).

Quote from: Poiscurse on March 20, 2024, 11:13:12 PM
I took an epipen injection after a NE and it made things worse, my usual extreme headaches that comes with pois were mush worse and throbbing in my head, when the effect of the shot wore off i was dreadfully tired and fatigued. Sleeped for days
Title: Re: POIS Theory Master List
Post by: Muon on October 26, 2023, 02:24:52 PM
https://en.wikipedia.org/wiki/Norepinephrine
"Brain areas containing noradrenergic neurons"
(https://upload.wikimedia.org/wikipedia/commons/0/04/Noradrenergic_neurons.png)
Title: Re: POIS Theory Master List
Post by: Muon on November 24, 2023, 06:52:33 AM
Table 2: Potential biomarkers for the AIT efficacy, stratification and efficacy prediction.
Table 3: Biologicals used to support AIT.
Hot topics in allergen immunotherapy, 2023: Current status and future perspective (https://onlinelibrary.wiley.com/doi/full/10.1111/all.15945)
Title: Re: POIS Theory Master List
Post by: Muon on December 07, 2023, 06:38:39 AM
https://www.reddit.com/r/POIS/comments/18clapc/comment/kcc2rrg/

Quote
Guys this Tachycardia is killing me, can't concentrate, can't study ,have exams in a month.Have muscle pain,some cognitive symptoms,no brain fog though, can cope with them all except that disturbing tachycardia which gets better after ejaculation for about 6 to 8 hrs and then sets again despite plenty of rest.Fexo has little to no effect and also makes me dizzy.Only ibuprofen worked so far.

Quote from: Stef on December 15, 2015, 04:33:04 PM
Hi All,

Demo and Daveman just received the public portion of Dr. Komisaruk's interim report from NORD. Here it is --

"A preliminary interpretation of our current data is that POIS symptoms are accompanied by a lowered heart rate and heart rate variability (HRV), and that vagal stimulation may produce a beneficial effect on POIS symptoms (increased heart rate and HRV) as a 're-bound' from the vagal stimulation. These are very preliminary findings and continued research with additional participants is underway, to assess the reliability of these findings."

Stef

Heard someone talking in this video that antihistamines can act negatively/positively depending on how the autonomic system behaves: https://www.youtube.com/watch?v=U0s26KdDDdU
His HR lowers after ejaculation.
Title: Re: POIS Theory Master List
Post by: b_jim on December 28, 2023, 05:52:37 AM
Wrong transsulfuration pathway.
Title: Re: POIS Theory Master List
Post by: Muon on December 28, 2023, 11:16:39 AM
(236) Flibanserin for Post-Orgasmic Illness Syndrome: A Case Report
https://academic.oup.com/jsm/article/20/Supplement_1/qdad060.222/7164839

Aside from raising brain levels of NE and DA:
Quote from: Muon on December 28, 2023, 11:03:34 AM
ChatGPT 3.5

Q: What 5-HT receptor subtypes are present on human mast cells?

Human mast cells express various subtypes of serotonin (5-HT) receptors, and the activation of these receptors can influence mast cell function and mediator release. The specific subtypes of serotonin receptors found on mast cells include:

5-HT1 Receptors:
Subtypes: 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E, and 5-HT1F.
Function: Activation of 5-HT1 receptors on mast cells may inhibit the release of histamine and other inflammatory mediators.

5-HT2 Receptors:
Subtypes: 5-HT2A, 5-HT2B, and 5-HT2C.
Function: Activation of 5-HT2 receptors on mast cells can enhance the release of histamine and other proinflammatory mediators.

5-HT3 Receptors:
Subtypes: 5-HT3A and 5-HT3B.
Function: 5-HT3 receptors are ligand-gated ion channels. Activation of these receptors on mast cells may contribute to the release of histamine and other mediators, and their blockade is associated with antiemetic effects.

5-HT4 Receptors:
Subtypes: 5-HT4A and 5-HT4B.
Function: Activation of 5-HT4 receptors on mast cells may influence the release of various mediators, including histamine.

5-HT6 Receptors:
Subtype: 5-HT6.
Function: 5-HT6 receptors are primarily found in the central nervous system, and their role on mast cells is not as well-characterized.

5-HT7 Receptors:
Subtype: 5-HT7.
Function: Activation of 5-HT7 receptors on mast cells may influence the release of histamine and other inflammatory mediators.

The functional outcomes of serotonin receptor activation on mast cells can vary depending on the specific receptor subtype and the context of the immune response. For example, some receptor subtypes may promote the release of histamine and other proinflammatory mediators, while others may have inhibitory effects.

The modulation of serotonin receptors on mast cells is an active area of research, particularly in the context of allergic and inflammatory conditions. Understanding the specific roles of serotonin receptor subtypes on mast cells may contribute to the development of targeted therapies for conditions associated with mast cell activation, such as allergic diseases and mastocytosis.

Q: What is the potential effect of flibanserin with 5-HT receptors on mast cells?

The specific effects of flibanserin on mast cells would depend on several factors, including the distribution of serotonin receptor subtypes on mast cells, the concentration of flibanserin reaching peripheral tissues, and the overall pharmacological profile of the drug.

In general, the potential effects of flibanserin on mast cells could include:

5-HT1A Receptor Activation: Flibanserin acts as a 5-HT1A receptor agonist. Activation of 5-HT1A receptors on mast cells may have inhibitory effects, potentially reducing the release of histamine and other inflammatory mediators.

5-HT2A Receptor Antagonism: Flibanserin acts as a 5-HT2A receptor antagonist. Antagonism of 5-HT2A receptors may counteract some proinflammatory effects associated with serotonin receptor activation.
Title: Re: POIS Theory Master List
Post by: hurray on December 28, 2023, 05:21:20 PM
Quote from: Muon on December 28, 2023, 11:16:39 AM
(236) Flibanserin for Post-Orgasmic Illness Syndrome: A Case Report
https://academic.oup.com/jsm/article/20/Supplement_1/qdad060.222/7164839

Very interesting, Muon. This would be top of my list of potential anti-POIS drugs to try because of its novel mechanism of action:

Quote
flibanserin has been described as a norepinephrine–dopamine disinhibitor (NDDI)
https://en.wikipedia.org/wiki/Flibanserin

Quote
Norepinephrine and dopamine disinhibitors (NDDIs) are a class of drugs which act at specific sites to disinhibit downstream norepinephrine and dopamine release in the brain
https://en.wikipedia.org/wiki/Norepinephrine%E2%80%93dopamine_disinhibitor

It's a drug designed to increase libido (for women!), you would expect it to have some kind of effect on male sexual function too. It worked for the one person in the case study, obviously that's no guarantee that it would work long-term or for a larger number of people, but it's still a starting point. I wonder if anyone else has attempted to copy the study?
Title: Re: POIS Theory Master List
Post by: Muon on December 30, 2023, 10:00:30 AM
Another case can be made for mast cell involvement. It seems to point in the direction of mast cells. Many treatments that are effective in POIS patients are able to block mast cell directly or indirectly. If true, then the mast cell needs to be played like a piano hitting the right tone(s) for each patient.

https://poiscenter.com/forums/index.php?topic=4375.msg47757#msg47757
Title: Re: POIS Theory Master List
Post by: Muon on January 28, 2024, 05:07:58 AM
Food for thought: How will low-dose IL-2 therapy affect POIS?
Targeting IL-2: an unexpected effect in treating immunological diseases (https://www.nature.com/articles/s41392-017-0002-5)
Title: Re: POIS Theory Master List
Post by: Muon on January 31, 2024, 09:37:16 AM
Quote from: Progecitor on January 30, 2024, 03:41:06 PM
The case mentioned here is termed leukocytospermia, which may be indicative of ongoing inflammation due to ROS (e.g. prostatitis). Such a test may not necessarily reveal the root of POIS, but it may be a potentially useful biomarker. I wish some upcoming POIS study would address this issue.
https://poiscenter.com/forums/index.php?topic=3374.msg39428#msg39428

Lotti, F., & Maggi, M. (2013). Interleukin 8 and the male genital tract. Journal of reproductive immunology, 100(1), 54-65. (https://sci-hub.se/10.1016/j.jri.2013.02.004)

"thus suggesting that sIL-8 could be a marker not only of inflammation of the prostate, but also of other organs of the MGT, including the epididymis"

There are a couple of cases with epididymitis in POIS literature. I haven't seen ROS being measured in POIS studies.
Title: Re: POIS Theory Master List
Post by: Muon on February 11, 2024, 06:52:10 PM
I wonder whether injecting cromolyn sodium into the urethra would help some patients.
Title: Re: POIS Theory Master List
Post by: Muon on February 14, 2024, 02:08:19 PM
Quote from: Warrior on February 10, 2024, 11:44:44 PM
POIS inflammation depletes methyl groups. POIS mental symptoms are a result of depleted neurotransmitters, from depleted levels of SAMe. SAMe (S-Adenosyl-L-methionine) is required for the brain to synthesize the neurotransmitters norepinephrine, dopamine, and serotonin (https://www.researchgate.net/figure/S-Adenosyl-L-methionine-SAMe-and-synthesis-of-neurotransmitters-The-neurotransmitter_fig2_11044923#:~:text=SAMe%20(S%2DAdenosyl%2DL,Mischoulon%20%26%20Fava%2C%202002)%20.). SAMe is a universal methyl group donor. In addition to SAM-e, methyl B12, methylfolate (if tolerated), choline, and TMG (trimethylglycine) are all methyl donors, and should help to replace lost methyl groups from POIS, and thus help to fix POIS mental symptoms.

Evidence for S-Adenosyl-L-Methionine (SAM-e) for the Treatment of Major Depressive Disorder (https://www.psychiatrist.com/jcp/evidence-s-adenosyl-l-methionine-sam-e-treatment-major/)

Quote from: Warrior on March 12, 2024, 05:08:50 AM
AFAIK, the body utilises two main pathways for methylation:

1) B12 & folate dependent (you need adequate status of both nutrients for this pathway to work)

2) choline (if B12 or folate is low, then body will switch to choline pathway)

Ideally you have adequate status of all nutrients B12, folate, choline, for optimal functioning.

Those that respond to choline with an improvement with POIS symptoms may have a folate or B12 deficiency.
Title: Re: POIS Theory Master List
Post by: Muon on February 23, 2024, 06:09:30 AM
https://www.reddit.com/r/POIS/comments/1axrtdh/cure_or_not/
Quote
I was on risperidone (an atypical antipsychotic drug) for 4-5 months and when I ejaculated, I felt no pois symptoms.

Anyone from medicine back can help me to understand this.

I have discontinued this medicine.

https://en.wikipedia.org/wiki/Risperidone#Pharmacology
Title: Re: POIS Theory Master List
Post by: Muon on March 02, 2024, 07:45:46 AM
Multiplex cytokine assays can be used for research to investigate (dynamic) cytokine ratio’s.
Title: Re: POIS Theory Master List
Post by: Muon on March 04, 2024, 07:32:08 AM
https://www.reddit.com/r/POIS/comments/1b66yvv/pois_following_vaccines/
Quote
Has anyone noticed the onset of POIS or its severity increasing significantly following vaccination?

I can’t recall ever having these horrific hangover type effects from ejaculating prior to receiving two Moderna jabs during Covid.

My symptoms will sound familiar to all I am a sure - crushing fatigue and brain fog, swollen glands, insomnia, pale skin and an inability to concentrate.

I am going to try grounding and fasting to try and clear my body. I literally cannot ejaculate without wanting to spend the next 3 days in bed afterwards in a flu like state. Needless to say I now try to abstain 100%.
Title: Re: POIS Theory Master List
Post by: Muon on March 07, 2024, 06:31:16 PM
Quote from: thephantom504 on January 05, 2024, 05:14:50 AM
I should mention that when I abstain for at least a week and do an extended water fast I get the same exact effect that I do from methylene blue. I feel like there is a connection there but I don't know what it would be.
Title: Re: POIS Theory Master List
Post by: Muon on March 15, 2024, 11:38:48 AM
Quote from: Ani1946 on March 15, 2024, 06:21:40 AM
I couldn't find pseudoephederine, so decided to try a beta 2 agonist before orgasm. Beta 2 agonists are potent mast cell stabilizer. I took 10mg terbutaline oral 1 hour before orgasm. Unfortunately it didn't work and now I'm exhausted like never before with exteme anxiety brainfog and doom like feeling and also palpitations and joint pain.

I think pseudoephederine worked for some not because it works on mast cell but because it affects central nervous system. Terbutaline can't cross blood brain barrier so may be that's why it didn't work for me.
Title: Re: POIS Theory Master List
Post by: Muon on March 21, 2024, 12:58:36 PM
Methylene Blue is an inhibitor of sGC and NOS, this would increase GTP. Cialis inhibits PDE5 which would increase cGMP. What does this mean? Cialis is also a PDE11 inhibitor.
(https://assets.cureus.com/uploads/figure/file/250676/lightbox_67697440fd9911eb86476362164ea84b-Screenshot-57-.png)
Title: Re: POIS Theory Master List
Post by: Progecitor on March 21, 2024, 01:44:16 PM
Quote from: Muon on March 21, 2024, 12:58:36 PM
Methylene Blue is an inhibitor of sGC and NOS, this would increase GTP. Cialis inhibits PDE5 which would increase cGMP. What does this mean? Cialis is also a PDE11 inhibitor.
(https://assets.cureus.com/uploads/figure/file/250676/lightbox_67697440fd9911eb86476362164ea84b-Screenshot-57-.png)

Alternatively tadalafil can also down-regulate Rho-kinase activity, which should reduce calcium ion intake, circumventing a possible Ca2+ overload, similarly to PMCA activation by methylene blue.
Actually amyloid beta-peptide (Abeta) and neurofibrillary tangles of tau inhibit PMCA. Furthermore lipid peroxidation and 4-hydroxynonenal, which are the most likely and direct causes of POIS also inhibit PMCA.
https://www.sciencedirect.com/science/article/abs/pii/S0304394017306419
Title: Re: POIS Theory Master List
Post by: Muon on March 29, 2024, 12:04:47 PM
Quote from: demografx on March 29, 2024, 09:28:46 AM
The NP-C explained to me that Cialis IMPROVES NERVE CONDUCTION!
Nerve conduction study for POIS?

Edit:
Plus VTA (https://poiscenter.com/forums/index.php?topic=4375.msg48523#msg48523)?
Title: Re: POIS Theory Master List
Post by: demografx on March 30, 2024, 11:49:05 AM
Quote from: Muon on March 29, 2024, 12:04:47 PM
Quote from: demografx on March 29, 2024, 09:28:46 AM
The NP-C explained to me that Cialis IMPROVES NERVE CONDUCTION!

Thanks for putting this in your Theory thread (and thank you for organizing it!)
Title: Re: POIS Theory Master List
Post by: Muon on April 03, 2024, 08:27:55 AM
Quote from: less_fogged on April 03, 2024, 03:36:46 AM
I've been diagnosed with ME/CFS. I'm stunned as I've always considered myself a pretty fit person! Just feel like huffing and puffing while in POIS!

I was diagnosed after a CT scan for the brain together with Neurospect.

I don't think it would influence my test results but just in case; I had 3 ejaculations in the 2 days before the scan test. Apparently there is no blood circulation in the front of my frontal lobe!
Title: Re: POIS Theory Master List
Post by: Muon on April 09, 2024, 05:43:45 AM
Quote from: Muon on February 29, 2020, 06:56:19 AM
Other ways to observe mast cell activity

"Single cell laser microcapture and qRT-PCR should be used to identify mast cell phenotype variability and mediator synthesis/release in situ." Ref (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7003574/)

"Electron microscopy using time lapse photography on bladder biopsies from IC/BPS patients and controls to see if the mast cells in the biopsies of IC/BPS patients are degranulating at a more frequent rate, or releasing inflammatory mediators without degranulating compared to the control group."Ref (https://tau.amegroups.com/article/view/8090/8845)
Title: Re: POIS Theory Master List
Post by: Muon on April 16, 2024, 05:46:17 AM
Spermine/Spermidine depletion theory for POIS:
https://www.mdpi.com/2073-4409/10/8/1867

https://www.sciencedirect.com/science/article/abs/pii/S0031942206002251
Quote
S-Adenosyl-l-methionine (AdoMet or SAM) is a substrate in numerous enzyme-catalyzed reactions. It not only provides methyl groups in many biological methylations, but also acts as the precursor in the biosynthesis of the polyamines spermidine and spermine
Title: Re: POIS Theory Master List
Post by: Progecitor on April 16, 2024, 07:50:09 AM
Quote from: Muon on April 16, 2024, 05:46:17 AM
Spermine/Spermidine depletion theory for POIS:
https://www.mdpi.com/2073-4409/10/8/1867

https://www.sciencedirect.com/science/article/abs/pii/S0031942206002251
Quote
S-Adenosyl-l-methionine (AdoMet or SAM) is a substrate in numerous enzyme-catalyzed reactions. It not only provides methyl groups in many biological methylations, but also acts as the precursor in the biosynthesis of the polyamines spermidine and spermine

In this relation it may be worthwhile to supplement ornithine as well:

Spermidine, a polyamine synthesized in vivo from ornithine, has been reported to induce autophagy through epigenetic regulation of autophagy genes.
https://www.frontiersin.org/articles/10.3389/fcell.2022.811701/full

I have to say though that I have already taken a box of spermidine without much benefit. I took only 1 per day, which was below recommendation, however I took it for two months this way, which makes a deficiency situation less likely.
Title: Re: POIS Theory Master List
Post by: Muon on April 17, 2024, 02:25:22 PM
Quote from: less_fogged on April 17, 2024, 08:49:29 AM
In my case I believe it's a miss communication between brain and body
Title: Re: POIS Theory Master List
Post by: Muon on April 23, 2024, 03:37:11 AM
Quote from: Ani1946 on April 23, 2024, 02:43:50 AM
I received betamethasone injection for dermatitis three days ago and today it cleared my brain fog, fatigue and most surprisingly PE. Also i don't feel pois on this injection like i can cum 3-4 times with no symptoms (not even 1%).
Title: Re: POIS Theory Master List
Post by: Muon on April 24, 2024, 04:09:47 AM
I will put this here. Apparently the brain has a microbiome. https://youtube.com/watch?v=mZPQ0bgqoq8
Title: Re: POIS Theory Master List
Post by: Muon on May 07, 2024, 05:59:47 PM
Quote from: IronFeather on March 27, 2021, 08:54:18 AM
7. My POIS theories
My sudden bursts of tachycardia, the inability to regulate my body temperature properly, the lack of appetite that has nothing to do with any issue in my digestive system, the feeling of nausea exactly where the vagus nerve is located under the sternum, my inability to apply pressure to that spot without POIS symptoms appearing... it all seems to fit with some kind of malfunction of the nervous system in general and/or the vagus nerve in particular. I first started thinking of the vagus nerve when I tried to train core strenght using the plank position and got sick, because it implies a lot of muscle tension in that point, same as resting my body weight on it when laying down in bed reading a book had made me sick too. Recently I've tried diaphragmatic breathing when I'm sick with POIS and it seems to reduce the symptoms, which would fit in this theory, since it stimulates the vagus nerve.

Also, the feeling of tension in the diaphragm that I always get before a POIS episode starts could suggest the nerves there being affected. It is a symptom that has got worse with time, and sometimes it even happens when I start eating: my diaphragm and core muscles seem to contract when food enters my stomach, but it goes away if I keep eating.
Quote from: IronFeather on August 04, 2021, 08:27:58 AM
I wanted to share something that has happened to me this week, and that in my opinion confirms my intuition that something is wrong with my vagus nerve and vagal tone in general, especially since my worsening last year with the bleach.

I'm moving house right now, going back for a year to where I was born, before starting my PhD. It has been a complete mess, with people who had promised to help cancelling at the last minute, so me and my mother were left alone with the prospect of moving dozens of very heavy boxes, shelves, tables, all my gym equipment with weights and a treadmill... Considering my exercise intolerance, I was sure I was going to be extremely sick for days after this. I had got sick with a fever before from just trying to do a couple of push-ups!

Well, for the last three days I've been running up and down the stairs with heavy boxes that I could barely lift, and carrying furniture around. Zero symptoms so far, quite the opposite, I actually feel good! After thinking it over and over, the only explanation I can find is this: I've been talking the whole time while I did all these things. And talking stimulates the vagus nerve! I believe my exercise intolerance is due to my vagus nerve not working properly, so that it's unable to control inflammation.
Title: Re: POIS Theory Master List
Post by: Muon on May 08, 2024, 10:10:59 AM
Quote from: Muon on May 06, 2024, 08:02:29 AM
I suspect that in my case brainstem function needs to be measured upon physical exertion and/or (post) sexual arousal/orgasm.
Quote from: ThuNd3rZ on April 01, 2024, 02:01:34 AM
If i had to guess brain stem has some degenerative changes that makes it super vulnerable and then when you pour neuroinflammation on top of it you can get some nasty symptoms. It might be that we are more susceptable and or lived a life of chronic stress that lead to the brain degeneration.
Title: Re: POIS Theory Master List
Post by: Muon on May 08, 2024, 03:59:25 PM
POIS relief by sleep/naps is common knowledge in the community for years. Often overlooked but can be helpful pinpointing the mechanism in research. Nanna1 has posted graphs about sleep (https://poiscenter.com/forums/index.php?topic=3456.msg39817#msg39817) #connectthedots

Quote from: AnchorMan10 on May 06, 2024, 11:29:12 PM
I'm always relieved, however, the very next day. I wake up, and I can tell immediately I'm back to normal. All symptoms gone. This also works if I take a nap the next day after O-ing. Two sleeps after O, I'm always back.

Does anyone else experience this? It's probably also important to note that I'm Vitamin D deficient. I used to take supplements daily with that, and I definitely did see an improvement, but I've just been bad with taking them every day now.
Title: Re: POIS Theory Master List
Post by: Muon on May 09, 2024, 12:04:39 PM
Quote from: stripe on April 28, 2024, 04:37:13 PM
In my opinion, this problem is related to the liver. The thing that globally affects well-being is insulin sensitivity, which can be improved with a diet for diabetics and aerobic exercise.

The second thing that strongly affects the condition is the limitation of fructose in the diet. I can't give exact numbers, I think it's an individual thing.
Title: Re: POIS Theory Master List
Post by: Muon on May 10, 2024, 11:09:27 AM
Found: the dial in the brain that controls the immune system (https://www.nature.com/articles/d41586-024-01259-2)

 A body–brain circuit that regulates body inflammatory responses (https://www.nature.com/articles/s41586-024-07469-y)

(https://media.nature.com/lw767/magazine-assets/d41586-024-01259-2/d41586-024-01259-2_27034296.jpg?as=webp)
A population of neurons in the brain stem, the stalk-like structure that connects the bulk of the brain to the spinal cord, acts as the master dial for the immune system.

Further experiments revealed two discrete groups of neurons in the vagus nerve: one that responds to pro-inflammatory immune molecules and another that responds to anti-inflammatory molecules

Desensitization succes in some individuals might just have been communication between semen content and the vagus nerve.
Title: Re: POIS Theory Master List
Post by: Muon on May 11, 2024, 08:47:35 AM
https://www.reddit.com/r/POIS/comments/1cpeaxy/my_journey_to_overcoming_pois_a_personal_research/
Quote
Successful Treatment:The link between varicocele and my symptoms led to a varicocelectomy, which has successfully resolved my POIS symptoms for several months now.
Quote
Similarities to Varicocele:Upon further evaluation and testing, I was diagnosed with varicocele, which presented an interesting parallel to the actions of doxycycline.

Both involve:

Increased MMP Activity: Varicocele can lead to higher MMP levels, which cause inflammation and tissue damage, similar to the inflammation mitigated by doxycycline.

Oxidative Stress: Varicocele can induce oxidative stress that damages cellular structures, including mitochondria. Doxycycline’s ability to reduce oxidative stress might explain why it temporarily alleviated my POIS symptoms.

Systemic Inflammation: The systemic inflammation caused by varicocele, driven by oxidative stress and elevated MMPs, closely mirrors the systemic effects that doxycycline helps to control.
Title: Re: POIS Theory Master List
Post by: Muon on May 15, 2024, 03:34:31 AM
Quote from: Crying24/7 on May 15, 2024, 02:43:49 AM
it's latent Hsv virus bro, I'm positive for hsv1 and ghsv2 ,
even Aciclovir helps in daily brainfog that I get from morning erection, Also monolaurin helps immensely
Title: Re: POIS Theory Master List
Post by: Muon on May 15, 2024, 03:38:02 PM
Quote from: Muon on March 05, 2024, 01:54:30 PM
I get the impression that the nervous system is hypersensitive, weak and easily overloaded.

POIS: A brief explanation:
https://www.reddit.com/r/POIS/comments/1csv0nu/pois_a_brief_explanation/

Quote
After some years I discovered that my symptoms were the result of a dysregulated nervous system. To put it simply, the difference between a person that struggles with POIS and a normal person is down to the sensitivity of their nervous system. A sensitive nervous system could be the result of years of self-stimulation, years of stress, years of trauma, or just genetic. The more the nervous system is over-stimulated by these events, the more sensitive your nervous system becomes.

(https://preview.redd.it/pois-a-brief-explanation-v0-wlanmbf8fn0d1.jpg?width=2048&format=pjpg&auto=webp&s=57bc9fe162fcddc8b8ef545d1fec0296510d5268)
Title: Re: POIS Theory Master List
Post by: Muon on May 21, 2024, 01:44:45 AM
I have seen comments of patients saying they feel like their (nervous) system ran out of juice with regards to POIS, exercise or even sleep deprivation.
Title: Re: POIS Theory Master List
Post by: Muon on May 21, 2024, 01:53:27 AM
People with thermal hypersensitivity might have abnormal nerve conduction velocities for certain types of nerve fibers.
Title: Re: POIS Theory Master List
Post by: Muon on May 23, 2024, 09:40:38 AM
Every human testicle contained microplastics in a new study (https://www.popsci.com/science/microplastics-testicles/)
Title: Re: POIS Theory Master List
Post by: Muon on June 03, 2024, 05:09:32 AM
Dr. Matt Curley June 3, 2024 (https://x.com/scubatropin/status/1797507463987781743):

"They keep saying that the "manifestations are elusive" that's a crock! Its a class 6 allergy to a protein found in semen where the body is convinced it's an invading virus. Since the prostate continues to produce this protein and it's an ongoing war with the immune system."

https://www.cureus.com/articles/245945-post-orgasmic-illness-syndrome-a-case-report#!/

Dr. Curley:

The REALITY is - Niacinamide may potentially worsen the condition. While I realize that a large number of men may try this method, I would warn them to be wary as Niacin related products can actually increase histamine.

Muon:

I have seen someone who developed POIS after high dose Niacin. There is a group of patients which time the niacin flush with orgasm for relief. PGD2 and 5-HT release (platelets) are involved in niacin flush. Low 5-HT is believed by some to be involved due to premature ejaculation

Dr. Curley:

I've been aware of the "Niacin" effect since 04. It has to do with four prostaglandins being released as a result of langerhans cells being triggered (fooled) into thinking that there is an infection present. As a result, the EJ immune system trigger is blunted.
Title: Re: POIS Theory Master List
Post by: Muon on June 03, 2024, 09:47:32 PM
Rapamycin (https://poiscenter.com/forums/index.php?topic=4545.msg48763#msg48763)
Title: Re: POIS Theory Master List
Post by: Muon on June 08, 2024, 01:39:50 PM
Two case reports (3 patients in total) of "succesfully" treated POIS patients by Omalizumab. #64 en #74 in POIS paper thread.

https://en.wikipedia.org/wiki/Omalizumab#Mechanism_of_action

Lemal. 2019. Omalizumab Therapy for Mast Cell-Mediator Symptoms in Patients with ISM, CM, MMAS, and MCAS (https://pubmed.ncbi.nlm.nih.gov/30954641/)

Chang. 2006. Anti-IgE as a mast cell–stabilizing therapeutic agent (https://www.jacionline.org/article/S0091-6749(06)00856-6/fulltext)

(https://www.jacionline.org/cms/attachment/3eea4064-c5a4-4a4a-b57b-c96f3fe26d89/gr2.gif)

Fig 2 Activated mast cells release and secrete 3 groups of mediators responsible for immediate-phase and delayed-phase reactions. VEGF, Vascular endothelial growth factor; FGF2, fibroblast growth factor 2; LT, leukotriene; PG, prostaglandin.

(https://www.jacionline.org/cms/attachment/f3c73568-012e-4b7a-8ae5-a60586851d8d/gr4.jpg)

Fig 4 Potential target sites for mast cell–stabilizing agents. A, The Fc?RI-initiated stimulatory signal-transducing pathway, the Fc?RIIB-initiated inhibitory signal-transducing pathway, and the mechanism by which the latter pathway inhibits the former pathway. B, The mast cell–stabilizing effects can be classified into those that reduce sensitivity and those that reduce the potency of the mast cell. SHIP, Src homology 2 domain–containing inositol 5-phosphatase; ITIM, immunoreceptor tyrosine–based inhibitory motif; ITAM, immunoreceptor tyrosine–based activating motif; PLC?, phospholipase C?; IP3, inositol-1,4,5-triphosphate; DAG, diacylglycerol; PKC, protein kinase C.

(https://www.jacionline.org/cms/attachment/ced60213-40f1-447f-820a-55c91c51f615/gr5.gif)

Fig 5 Multiple proved and potential pharmacologic and immunologic effects of anti-IgE. Therapeutic anti-IgE binds to (1) IgE and (2) membrane-bound IgE+ B lymphoblasts and memory cells, which each leads to a series of subsequent or indirect effects.

Regarding figure 4, I had posted something about SHIP in the MCAS thread:

Quote from: Muon on February 25, 2023, 02:45:23 PM
Multistep IgE Mast Cell Desensitization Is a Dose- and Time-Dependent Process Partially Regulated by SHIP-1 (https://journals.aai.org/jimmunol/article/doi/10.4049/jimmunol.2100485/238977/Multistep-IgE-Mast-Cell-Desensitization-Is-a-Dose)

 Kaempferol suppresses the activation of mast cells by modulating the expression of Fc?RI and SHIP1 (https://www.biorxiv.org/content/10.1101/2023.02.20.529186v1.abstract)
Title: Re: POIS Theory Master List
Post by: Muon on June 09, 2024, 09:04:03 AM
https://www.reddit.com/r/POIS/comments/1dbr187/pois_has_given_me_an_allergic_reaction_in_my/
Quote
For some reason it’s caused an allergic reaction in my esophagus and acid reflux and it hasn’t gone away after 4 months.
Title: Re: POIS Theory Master List
Post by: Muon on June 21, 2024, 02:37:37 AM
Measuring IgG4/IgE pre and post hyposensitization therapy in POIS patients to rule out immunoglobulin class switching when treatment is (partial) successful. More ratio's could be measured:

https://en.wikipedia.org/wiki/Immunoglobulin_class_switching
Title: Re: POIS Theory Master List
Post by: Muon on June 21, 2024, 02:57:20 AM
The point of measuring a large amount of different cytokines is that certain sets of abnormal cytokine levels may point towards certain cells as source. It is difficult to determine the type of cells being involved when you only measure a small selection of cytokines.
Title: Re: POIS Theory Master List
Post by: StressPOIS on June 22, 2024, 12:28:55 AM
Got a straightening of lumbar spine in my X-RAY. yet to consult the doctor. Noticed @hopeoneday and perhaps @sisphyus had the dame thing. Not optimistic because they haven't found their cure yet. I don't know if it's the symptom or the cause. Maybe the inflammation is getting in my spine or the spine is causing it.
Title: Re: POIS Theory Master List
Post by: Muon on July 04, 2024, 04:09:35 PM
Periodic changes in serum testosterone levels after ejaculation in men
https://pubmed.ncbi.nlm.nih.gov/12506329/
Quote
The purpose of this study was to determine the changes in sex hormone level in men after ejaculation. The serum testosterone concentrations of 28 male volunteers were investigated daily during abstinence period after ejaculation. We found that fluctuations of testosterone levels from day 2 to day 5 of abstinence were minimal. On day 7 of abstinence, a peak of serum testosterone appeared, reaching 145.7% of the baseline (P<0.01). After the peak, no regular fluctuation was observed. Ejaculation was the premise and beginning of the 7 days' periodic phenomenon. If there was no ejaculation, there was no periodical changes in serum testosterone level. These results indicate that the periodic change in serum testosterone level is caused by ejaculation.

What is the periodic change of T levels in POIS after ejaculation?
Title: Re: POIS Theory Master List
Post by: Muon on July 11, 2024, 03:49:28 AM
https://en.wikipedia.org/wiki/Long-term_potentiation#Properties

Quote
In neuroscience, long-term potentiation (LTP) is a persistent strengthening of synapses based on recent patterns of activity. These are patterns of synaptic activity that produce a long-lasting increase in signal transmission between two neurons.[2] The opposite of LTP is long-term depression, which produces a long-lasting decrease in synaptic strength

Quote
Associativity refers to the observation that when weak stimulation of a single pathway is insufficient for the induction of LTP, simultaneous strong stimulation of another pathway will induce LTP at both pathways

Quote
LTP is persistent, lasting from several minutes to many months, and it is this persistence that separates LTP from other forms of synaptic plasticity
Title: Re: POIS Theory Master List
Post by: Muon on July 11, 2024, 05:00:11 AM
Do we need more sensory testing in POIS patients?
https://poiscenter.com/forums/index.php?topic=4213.msg45055#msg45055
Title: Re: POIS Theory Master List
Post by: Muon on July 12, 2024, 04:02:53 PM
Histamine levels drop in systemic circulation post ejaculation for healthy male humans.
https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1439-0272.2011.01222.x

There is only one location in the brain that contains histamine releasing neurons:
tuberomammillary nucleus
https://www.sciencedirect.com/science/article/abs/pii/S0301008200000393

(https://i.pinimg.com/originals/b2/65/46/b26546e57b878dda1fcc04bec793683e.png)

Mast cells in brain

Mast Cells in Gut and Brain and Their Potential Role as an Emerging Therapeutic Target for Neural Diseases (https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2019.00345/full)

Quote
In small quantity, MCs are also present in the brain. Here, they are located in area postrema, parenchyma of thalamus and hypothalamus, leptomeninges, pineal organ, infundibulum, choroid plexus, and in dura mater of the spinal cord.

Area Postrema

(https://i.pinimg.com/originals/72/b2/4a/72b24ad439c7c69b5db6688c7d9b70de.png)

Leptomeninges

(https://i.pinimg.com/736x/e4/0f/24/e40f245ab566a4aadf9f18547961e033.jpg)

Pineal Gland and Choroid Plexus

(https://healthjade.com/wp-content/uploads/2017/09/pineal-gland-2.jpg)

Infundibulum

(https://thumbor.kenhub.com/Kra63SG-W38UDjQ_wSlCSYWudlY=/fit-in/940x940/filters:fill(FFFFFF,true):watermark(/images/watermark_only.png,0,0,0):watermark(/images/logo_url.png,-10,-10,0):format(jpeg)/images/anatomy_term/recessus-infundibuli/3VWAIC5B1XUWc252T2I7Uw_Recessus_infundibuli_m01.png)

Dura Mater Spinal Cord

(https://i.pinimg.com/originals/ad/cb/da/adcbda5ea9d77c75bee6768d4b7116ed.jpg)

parenchyma of thalamus and hypothalamus

Where is this?
Title: Re: POIS Theory Master List
Post by: demografx on July 12, 2024, 10:18:41 PM
Muon, great looking graphic.
Title: Re: POIS Theory Master List
Post by: Muon on July 14, 2024, 11:02:10 AM
Quote from: lycopoulos on February 02, 2020, 06:18:44 PM
Anyone think there's hope in this reasearch?

Trending News: Interleukin-24 Found as Catalyst of Pro-Inflammatory Autoimmune Disorders
https://www.pharmacytimes.com/news/trending-news-interleukin-24-found-as-catalyst-of-pro-inflammatory-autoimmune-disorders

It essentially descibes a potential new treatment new treatment that targets a specific symptom may have a positive impact for patients with schizophrenia. If POIS really is a pro-inflammatory disorder that causes all the psychiatriachal symptoms, this can potentially be beneficial for POIS attacks.

Let me know your thoughts!
Title: Re: POIS Theory Master List
Post by: Muon on July 14, 2024, 05:01:17 PM
Komisaruk's cancelled Heart Rate/Heart Rate Variability Study should get a second chance in my opinion.
Title: Re: POIS Theory Master List
Post by: Muon on July 15, 2024, 04:15:36 AM
Brainstem Dbh+ neurons control allergen-induced airway hyperreactivity (https://www.nature.com/articles/s41586-024-07608-5) (Su, Yujuan, et al. 2024)

Quote
Here we mapped a full allergen circuit from the lung to the brainstem and back to the lung. Delivery of noradrenaline antagonists to the NA blunted hyperreactivity, suggesting noradrenaline as the transmitter between Dbh+ nTS and NA. Together, these findings provide molecular, anatomical and functional definitions of key nodes of a canonical allergen response circuit. This knowledge informs how neural modulation could be used to control allergen-induced airway hyperreactivity.
Title: Re: POIS Theory Master List
Post by: Muon on July 15, 2024, 01:18:41 PM
Quote from female:
Quote from: Muon on February 07, 2023, 12:47:20 PM
If I really reflect, I can pinpoint when the symptoms got wayyyy worse to the same time when I started experiencing my POTS symptoms; this being after bad emotional trauma from an abusive relationship. I'm not sure if there is a link here between prolonged trauma and autonomic nervous system/dysregulation?

Changes in Autonomic Nervous System Activity are Associated with Changes in Sexual Function in Women with a History of Childhood Sexual Abuse (https://academic.oup.com/jsm/article-abstract/12/7/1545/6966809)
Title: Re: POIS Theory Master List
Post by: Muon on July 15, 2024, 11:48:48 PM
Quote from: largooo on July 15, 2024, 10:38:55 PM
some poiser have low or high testosterone -> testicular glands
(and some with low testosterone seems to have  some results  reducing POIS symtoms with testosterone replacement therapy.)

some poiser have low or high cortisol -> adrenal glands (this is my case)

some poiser have low or high t3 / t4 -> thyroid glands ( Iwillbeatthis's and marrtintintin's case)
Iwillbeatthis seems to have some result  reducing POIS symtoms treating  thyroid

but what do all these glands have in common ?
answer : hypothalamus

hypothalamus gives orders to other glands with -> acth, tsh, gh, etc ...
then the differents glands produce testosterone, thyroid hormones, cortisol, etc ...

so all those hormonal problems (that seem common to a lot of poiser and maybe the origin of POIS) could come from a specific gland but maybe our gland is ok and the problem could come from the hypothalamus on a higher level or maybe both.
thats why sometimes treat the gland gives some result reducing POIS symptoms but not always 100%

there could be many reason why your glands or hypothalamus would be defective but the main reason would be chronic/traumatic stress (a lot of poiser seems sensitiv to stress) or intoxication that tires or disrupts the glands.

but before focus on why we need to know which.

so for any new poiser my suggestion would be to do a blood test to check all this hormones before and after an orgasm to identify which hormones/ glands seems to be defective.
blood test : acth, tsh, gh, somatomedins, prl, fsh, lh, msh, oxytocin, adh, epinephrine, norepinephrine, cortisol, corticosterone, t3, t4, inhibin, testosterone,

note that as i tried to explain in my case (https://poiscenter.com/forums/index.php?topic=4556.msg48987#msg48987)
there could be many reasons why some of us could still have normal level for a hormone.
that's why doing a blood test after an orgasm even if it would be such a pain could be really helpfull to see clearer.
since an orgasm seems to break everything, a blood test after orgasm could  reveal more thing.

(https://www.superprof.fr/ressources/wp-content/uploads/2018/03/word-image-49-2048x1536.jpeg)
Title: Re: POIS Theory Master List
Post by: Muon on July 17, 2024, 05:47:16 AM
Did it start converting to Estrogen or is it some kind of CNS tolerance?
Quote from: Muon on June 12, 2023, 04:03:30 PM
https://www.reddit.com/r/POIS/comments/147v8ps/woman_with_pois_and_havent_posted_in_a_long_time/

Heather01111:

I haven't posted in a long time. I am a woman with POIS. I thought I had found my fix for this which was testosterone supplements. It did help for a few months but then it stopped. I was so happy and then so depressed about it that I kind of gave up hope. My body started to just convert the testosterone into estrogen apparently and it quit working. What I have found though is if I don't do the testosterone cream everyday and I only use it after sex along with an oxytocin nasal spray my headaches/train wreck feeling only lasts for about a day or 2 instead of 2 weeks. I am still searching on the cure as my sex life still sucks and somebody should start a gofundme page for my poor husband as he has to deal with me. This is such a hard thing to have. I try to stay optimistic, but if I let mywelf go there I just feel broken as a woman.
Title: Re: POIS Theory Master List
Post by: Muon on August 08, 2024, 03:14:29 AM
Does low vitamin D predict a response to steroids or COX inhibitors?
Title: Re: POIS Theory Master List
Post by: Muon on August 14, 2024, 02:14:06 AM
Dopamine and serotonin dysregulation:
https://www.reddit.com/r/POIS/comments/1ern1tm/pois_is_dopamine_and_serotonin_dysregulation/
Title: Re: POIS Theory Master List
Post by: Hopeoneday on August 14, 2024, 08:25:56 AM
Yes, neurotransmiters regulate body functions, buuut the katch
"16" with this theory is that it should be
at least 500 milions of poisers on earth wright now.

But if something is disturbing receptors(autoimune..etc) in poisers,
that is another story.
Title: Re: POIS Theory Master List
Post by: Muon on August 23, 2024, 03:02:47 PM
https://www.reddit.com/r/POIS/comments/1ezk7lg/pois_starting_after_30/
Quote
Interested in hearing from guys who have “secondary” POIS that started in your 30s or 40s. What are your theories as to what triggered it? What changed if anything?

I did not have POIS in any shape or form for the majority of my life and then seemingly spontaneously about 7 years ago in my late 30s a switch flipped and nothing was ever the same. I thought I was dying at first lol.

I do have a theory that my lifestyle in my 30s triggered the condition, particularly my enthusiastic use of a certain powdery white substance. I think I caused some sort of brain chemistry imbalance that set off a chain reaction. A few one offs aside, the lifestyle is well behind me, but I have not healed. It would be great if the injury was not permanent, but who knows.

https://www.reddit.com/r/POIS/comments/1ezk7lg/comment/ljl7k0o/
Quote
In my case, however, I think it is somehow genetics. My family has a history mental disorders. Depression, anxiety, psychosis etc.
Title: Re: POIS Theory Master List
Post by: Muon on October 04, 2024, 01:10:50 PM
Do we need fMRI studies for POIS, like these?
https://www.mdpi.com/1648-9144/60/8/1370
https://www.mdpi.com/2076-3425/14/5/450
Title: Re: POIS Theory Master List
Post by: demografx on October 04, 2024, 01:36:53 PM
Quote from: Muon on October 04, 2024, 01:10:50 PM
Do we need fMRI studies for POIS, like these?
https://www.mdpi.com/1648-9144/60/8/1370
https://www.mdpi.com/2076-3425/14/5/450


Sure, Muon, got $50,000+++? ;D


The cost of an fMRI study - - NOT including professional administrators, science writers, lab workers, medical analysts, etc. - - can vary significantly depending on the location and institution. At the University of Michigan, the scan rate is $561 per hour, with a recommendation to budget $600 per hour for grant proposals. Yale School of Medicine charges $696 per hour for their Siemens 3T scanners, with a typical 1.5-hour session costing $1,044. Prices can also differ by state, with costs ranging from $274 in Arkansas to $343 in California.
Title: Re: POIS Theory Master List
Post by: Muon on October 27, 2024, 02:01:43 PM
https://www.reddit.com/r/POIS/comments/1gb3usl/sexmasturbating_causing_reactivation/

"Every time I have sex or masturbate, my EBV reactivates. I get exhausted for the next couple days, and get red spots on the roof of my mouth and swollen tonsils with pus on them.

If I have sex and/or masturbate multiple times and get too fatigued, my ulcerative colitis will flare until I abstain from sex or masturbating for at least a few days to a week. Then the colitis and EBV will both go back into remission.

It's also suspected that my ulcerative colitis is actually EBV Colitis that mimicks ulcerative colitis."
Title: Re: POIS Theory Master List
Post by: Muon on November 08, 2024, 08:27:34 AM
Sexual activity poll on CFS reddit:
https://www.reddit.com/r/cfs/comments/1ggmu29/do_you_have_triggers_related_to_sexual_activity/

Same poll on MCAS reddit:
https://www.reddit.com/r/MCAS/comments/1ggl1xq/do_you_have_triggers_related_to_sexual_activity/
Title: Re: POIS Theory Master List
Post by: Muon on November 10, 2024, 06:16:55 AM
https://www.reddit.com/r/POIS/comments/1gmfh78/comment/lwe6ke1/

Quote
Personally I believe this is all driven by the parasympathetic nervous system. Most of the people here fit the criteria of acetylcholine dominance. There are a few things you can do, but there is no magic pill. So your sympathetic system is asleep and your stuck in this dark state. The only way out is to lower choline. Choline manufactures acetylcholine, when acetylcholine is high dopamine is low. there is an inverse relationship to the two. Tonic water has quinine which lowers acetylcholine. Search reddit, loads of ideas on this. One way to tell is if your breath rate, is low like 8 breaths per minute. Normal is around 14 breaths per minute . Is your blood pressure low? All of these things show what's going on with the autonomic system.

https://poiscenter.com/forums/index.php?topic=3591.0
Title: Re: POIS Theory Master List
Post by: Muon on November 10, 2024, 06:50:08 AM
Quote from: Muon on November 09, 2024, 01:19:24 PM
An extension of the previous post:

No_Age1208:

EDIT 2: My hormones are all normal, which... fun. So wish that could've been a solution.

Good question from POIS patient:

Pois_sufferer:

So r u female, how do you react to periods ? Curious to know about it, as with all of us slight hormonal flush do mess with immune response that leads latent virus to Reactivation.

No_Age1208:

Definitely have a reaction to my periods, (flushing, joint pain) but not as severe as the kind I get to orgasms.
Title: Re: POIS Theory Master List
Post by: Jan on November 12, 2024, 09:18:48 AM
Hi fellow patients,

Dr. De Boer has retired. He treated several patients with POIS and was also involved in research. He is listed on the "List of Doctors Who Know about POIS and are seeing POIS patients." I visited him as well and was impressed by his personal commitment. I sent him a thank-you message. Since he was involved with multiple POIS patients and research, perhaps more people could send him a message?

dr.lj.deboer at dbmgz.nl

I suspect he would appreciate this.
Title: Re: POIS Theory Master List
Post by: demografx on November 12, 2024, 02:13:44 PM
Quote from: Jan on November 12, 2024, 09:18:48 AM

Hi fellow patients,

Dr. De Boer has retired. He treated several patients with POIS and was also involved in research. He is listed on the "List of Doctors Who Know about POIS and are seeing POIS patients." I visited him as well and was impressed by his personal commitment. I sent him a thank-you message. Since he was involved with multiple POIS patients and research, perhaps more people could send him a message?

dr.lj.deboer at dbmgz.nl

I suspect he would appreciate this.


Thanks, Jan!
Title: Re: POIS Theory Master List
Post by: Muon on February 21, 2025, 10:02:39 AM
Patient thinks his POIS stems from a hypersensitive nervous system:
Quote from: Muon on February 21, 2025, 09:56:57 AM
21 February 2025 from channel Limbic Recovery: "How I recovered from POIS after years of struggle (Brain retraining saved me)"
https://youtu.be/qXiMCRlKiTo
Quote from: Muon on March 05, 2024, 01:54:30 PM
I get the impression that the nervous system is hypersensitive, weak and easily overloaded. Eating a meal right after a shower isn't a good idea. The body took a hit during shower and digestion burdens a similar system. Though, there is some slightly increased (nervous system?) resistance against certain triggers like sexual arousal since the last couple of months.