My POIS might be caused by an enzyme called PDE4

[yesyesyes]

Hi all, I'm suffering from POIS since age 13 (2001). I realized it's orgasm that makes me feel bad when I went celibate in 2013 for a few months and I was feeling happier and healthier with every passing month!

Since I've developed a too high libido (T and DHT are both too high due to my Grave's disease) so it's hard to avoid Os. I've tried aspirin and other NSAIDs (sp?) but they caused me to develop ulcers.

Recently I've tried taking Drotaverine, and OMG! It's the first thing that makes me feel much better after O. I take several doses for a few days after my O as a single dose works for a few hours only.  Antihistamines, vitamins, any herbs I've tried so far (and like most of you I've tried tons!) don't do anything at all for me. I'm happy that it lets me live with less of my POIS blues.

According to wiki it is "structurally related to papaverine, is a selective inhibitor of phosphodiesterase 4 (PDE4), and has no anticholinergic effects"

Please any scientist/doctor/reseracher reading this, look into inhibiting PDE4! Can anyone explain how orgasm may trigger something to do with PDE4? I don't know why inhibiting PDE4 makes me feel less blue after sex, but it does! And I don't even get what PDE4 is at all.

Seems like my stomach takes to Drotaveine better, is it ulcer-proof? I don't know about others here but I also have symptoms of elevated serotonin so I will also try some Cyproheptadine as a cure for my POIS-related cramps (SJW and seretogenic things are toxic to me, apparently Drotaveine might also boost serotonin, so I'd rather be safe).

I've actually developed all my other autoimmune/allergy issues after my POIS - thyroiditis, Grave's, gluten intolerance, yeast, fur, mold and other allergies etc. POIS certainly messes your immune system up, I was a perfectly healthy child before becoming sexually active.

Has anyone tried Drotaverine or Cyproheptadine for POIS?

[demografx]

yesyesyes, welcome to the forum!

[Mushnikk]

Interesting stuff!

What pointed you or your doctor (what speciality?) to PDE4 inhibitors and Drotaverine in particular? Were you taking it for another condition and noticed the effects by chance?

Do you take it only after O or also before?

What "herbs" did you try? Quercetin? Curcumin? Any other anti-inflammatory medications?

What were your POIS symptoms?

Interesting that other auto-immune conditions followed POIS in your case, I assumed it the other way around.

[yesyesyes]

^I don't know what really. Maybe because I'm done with NSAIDs dangerous side effects (ulcer). It's OTC and inexpensive.
People here usually take it for stomach or menstrual cramps.

Yes, I've tried SAMe (had serotonin syndrome from it), Quercetin, Curcumin, Lithium Othoratum, SJW (bad! makes me angry/anxious and causes serotonin syndrome), countles ADs (again, serotonin syndrome), various herbs.

My POIS symptoms are mainly related to my stomach and mind:

- severe depression/anxiety without any reason
- brain fog
- inability to feel any positive emotion
- cold hands/feet
- chest pains
- stomach cramps/inflammation-like pain in my stomach
- IBS/Chron's-like symptoms after each O (I call it my post-sex stomach scratching)
- irritability/hating loud noises
- watery or dry eyes

I have brain fog to a much much lesser degree when I ingest gluten (or it could be the yeast in bread, I tested negative for Celiac). Anyway, I went to my old personality and health when I went Gluten/Yeast + Sex-free back in 2013. Just Gluten/yeast are not enough, that's like just 10% more normality. The other 90% are achieved with avoiding Os for months, which is currently not possible.
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Everyone has the PDE4 enzyme in their DNA. It's pro-inflammatory and somehow orgasm triggers more PDE4 release or activation in me or sth like that, causing the POIS/inflammatory symptoms above. Abnormal PDE4 is found in people with bipolar disorder and schizophrenia. I display similar behaviour like avoiding socializing ever since I discovered masturbation/sex. Went completely symptom-free when I was celibate (no O for 5 or 6 months).

The only negative effect of abstination was that somehow my immune system was reacting to everything at one time. I had anaphylactic shock from eating mayonaise and raw peppers and exercising in the same day. Nowadays abstination causes my prostate to swell without frequent release due to me having too high DHT (and high T) due to being hyperthyroid...and nocturnal emissions lol. I was hypo when I abstained 7 years ago and had no such problems.

And 5htp and similar have made my Pois symptoms worse, not better. I pray all that serotonin didn't damage my heart as now even a single dose of a SJW causes me chest pain, hot flashes, and extreme irritability. I could tolerate it before.

[Labyrinth]

Hi there bro.
I was interested in reading your post cause it is actually reflecting all aspects of my illness
I get serotonin syndrome from SJW. Lithium and  antidepresants , 5htp

Symptoms aggrvated by over orgasming as you mentioned

What helped me so far curcumin. Taurine. L theanine. Passion flower

What are the things that helped you 

Appreciate your post
Rhanks

[yesyesyes]

^thanks man!
Curcumin doesn't do much for me.
L-carnitine, CoQ10 and especially Drotaverine  (it's called No-Spa here) help.

[Mushnikk]

^thanks man!
Curcumin doesn't do much for me.
L-carnitine, CoQ10 and especially Drotaverine  (it's called No-Spa here) help.

where do you live if I may ask?

[Muon]

Biological consequence of PDE4 inhibition vs cell type, Table 1:

PDE4 inhibitors: current status

Drotaverine decreases uptake of calcium in T-cells. Uptake of Ca is needed for cytokine release. Also interesting that it inhibits release of neuropeptides from sensory nerves.

Drotaverine also seem to inhibit LPS induced TNFα release. Page 64

A guy here used LDN: https://poiscenter.com/forums/index.php?topic=3221.0
Which is a TLR4 blocker. LPS binds to TLR4. LPS are products (toxins) from bacteria.

The only negative effect of abstination was that somehow my immune system was reacting to everything at one time. I had anaphylactic shock from eating mayonaise and raw peppers and exercising in the same day.

Sounds like MCAS to me.

[demografx]

Posted by charliem @ https://www.thenakedscientists.com/forum/index.php?topic=6576.new;topicseen#new

Re: Post Orgasmic Illness Syndrome (POIS)
« Reply #20179 on: Today at 19:09:25 »

Hi all! On page 165 here a poster has mentioned PDE4 might be involved in POIS: https://www.thenakedscientists.com/forum/index.php?topic=6576.msg224516#msg224516

11 years after that post I am taking a PDE4 blocker (Drotaverine) and it makes my POIS symptoms (brain fog, stomach inflammation, fatigue, depression) more bearable. It's the first thing that has an effect on me! So far nothing else has helped me. Please, look PDE4 up and I hope sciences start to investigate this link.

Blessings to all!

[yesyesyes]

^Oh that's actually me! Can't wait to share it everywhere I can as it might help someone else. 

[drop247]

Caffeine inhibits phosphodiesterase. It does seem to help my POIS. Though it's non-selective so it inhibits all phosphodiesterase not just PDE4 and is said to be somewhat weak.

[Daysleeper]

Are any of these drugs over the counter in the US? A lot of you have similar symptoms to me, but I don't know how to gain access to these drugs and try them.

[Labyrinth]

Cyproheptadine reduce srotonergic excitotoxicity. But can give some depression

[berlin1984]

PDE4 is also mentioned by @nanna1 here:

  I understand that some have had bad experiences with caffeine overdosing. In many cases, a bad experience is enough to avoid future experiences. I understand that reasoning. Please listen to your body!

  But for those who are experimenting with phosphodiesterase inhibitors, caffeine has the best safety reputation and is the most effective phosphodiesterase (PDE) inhibitor available. Caffeine is also broad spectrum, meaning it inhibits multiple PDEs (PDE1, PDE3, PDE4, PDE5). It has low financial cost, high bioavailability and is readily available from healthy food sources.

And here: https://poiscenter.com/forums/index.php?topic=2502.msg23238;topicseen#msg23238

[Muon]

Effects on inflammatory cells 2nd page:

Recent Advances in PDE4 Inhibitors as Immunoregulators and Anti-Inflammatory Drugs

It might work as an anti-inflammatory drug in your case. Your anaphalactic shock and allergies may indicate mast cell, eosinophil and/or basophil involvement. Look under the header of these cells, one or more of these inflammatory molecules which are supressed by PDE4 inhibitors may be elevated.

Hmmm PDE4 can be of interest for my own case. It inhibits IL-8 from neutrophils and IFN-g production from Th1 cells. Also inhibits IL-13 production in multiple cell types which is able to induce IgG4 from B cells.

[Muon]

Some talk about PDE here:
Atopic dermatitis: a defect of intracellular secondary messenger systems?

H1 and H2 activation ---> Increased PDE activity