I was recently informed that there are still POIS papers discussing POIS as a semen allergy. So I wanted to comment about This. The paper (
Stafie and Stafie, 2019) ruled out mastocytosis but then presented the hypothesis that POIS might be an autoimmune semen allergy. The paper of Stafie (2019) is very similar to
Waldinger, et al. (2011) and Kim,
et al. (2018)(
Intralymphatic Immunotherapy With Autologous Semen in a Korean Man With Post-Orgasmic Illness Syndrome). The papers Waldinger (2011), Kim (2018) and Stafie (2019) all found elevated IgE in semen and produced positive skin prick test. But none of them was able to find an antigen associated with IgE, and they also did not have a healthy control group to compare their results to. In other words,
they did not establish a cause and effect relationship between semen allergy and POIS. Then Attia,
et al. (2013) published the paper
Post-orgasmic illness syndrome: a case report (version 1; peer review: 3 approved with reservations, 1 not approved) which was reviewed by several famous POIS researchers, including 3.Goldmeier and 4.Waldinger.
Abdalla Attia correctly argues that it is not possible for POIS to be caused by an allergy because the immune system would attack any part of reproductive system producing protein antigen (including sperm). Below is a direct quote from Attia's response to Waldinger's review of the paper:
"In regards to testing for allergic reactions, we would like to ask whether you think that the skin prick test is reliable as a diagnostic test for allergy. Is it valid to conclude that POIS patients are allergic to their own semen on the basis of this test and suggest that this is the cause of POIS? We would suggest that skin prick tests can lead to many false positive and negative results. As andrologists we know (and there is a body of evidence for this), that semen is regarded as foreign by the body and the immune system. Immune tolerance to semen is not present. Semen is separated from the immune system by a very competent blood-testis barrier that is formed by the highly efficient Sertoli-Sertoli cell junctional complex. We would suggest that this is not a "hypothetical membrane". In certain known pathological conditions this barrier may be broken. If this occurs, auto-antibodies can form against semen. Thus, if a subject's own semen is then injected intradermally, a reaction may take place as it is recognized as a foreign antigen. We would suggest that many people would get a positive reaction on the basis of such a prick test even though they do not suffer from POIS. If allergy to the patient's own semen is a suspected cause of POIS, it will be necessary to measure serum and seminal plasma anti-sperm antibodies; IgA, IgG and IgM, to conduct immuno bead and MAR testing and to report on the patient's seminogram changes. This might also suggest that POIS patients would be mostly infertile due to formation of anti sperm antibodies.
Given these concerns regarding prick testing, we do not believe that the cause of POIS is allergy to one's own semen and also have doubts about the use of hyposensitization as a possible treatment." -
Post-orgasmic illness syndrome: a case report (Attia, et al., 2013) (reply to reviewer 4)
After the Attia (2013) paper, Jiang,
et. al. (2015) published "
Postorgasmic illness syndrome (POIS) in a Chinese man: no proof for IgE-mediated allergy to semen", which is the most important POIS paper that I know of because
this is the first POIS study to use a control group. Jiang (2015) showed that healthy (non-POIS) males also have semen IgE and positive skin prick allergy test. This validated Attia's (2011) reply to Waldinger, namely that
semen allergy is a common and separate disease from POIS. People need to know that you can have more that one disease, and one disease does not necessarily cause another.
After Attia,
et al. (2013) and Jiang,
et al. (2015), Waldinger revised his original hypothesis to exclude Type I IgE allergy from his description of POIS (Waldinger, 2016):
"POIS is not associated with increased total serum IgE concentrations." -Post orgasmic illness syndrome (MD Waldinger, 2016) Finally, the study
"Immunophenotypical Characterization of a Brazilian POIS (Post-Orgasmic Illness Syndrome) Patient: Adding More Pieces to Puzzle" by Amicis
et al. (2019)
used a control group to show that men with POIS and men without POIS have similar clinical reations to dilute semen skin prick test and subcutaneous semen injections. The POIS patient did not have elevated semen IgE, but two of the non-POIS healthy controls did have elevated semen IgE. So
semen allergy was shown to be a separate disease from POIS. Also,
both Amicis et al. (2019) and Kim et al. (2018) showed that hypodesensitization therapy (autologous semen injections) failed to produce lasting reductions of POIS symptoms. Amicis
et al. (2019) did find elevated IgG in the semen of the POIS patient. And medical test from POISers on this forum
do not confirm any correlation between POIS and semen allergy:
MCAS and mastocytosis test
--8 of us show normal trypase (mast cell activation syndrome) levels (itsmel, BluesBrother, nanna1, Vandemolen, Muon, Muon's brother, jakov, Simon66).
--11 of us show normal IgE (allergy) levels (BlueBrother, aswinpras06, certainlypois2, Vandemolen, kurtosis, rjmlr, Yin POIS Study, jakov, Depreux POIS study, kingfisher, Arata POIS study)
--3 of us show normal histamine levels (nanna1 tested histamine, itsmel and Muon tested histamine and N-methyl-histamine).
--1 of us show low histamine levels (Simon66, tested histamine and N-methyl-histamine)
--1 of us show normal PGD2 levels (muon).
--1 of us test negative for mastocytosis (Stafie POIS study)
Autoimmunity test
--5 of us have normal autoimmune panel test (nanna1, quotz, Vandemolen, muon, Arata POIS study).
--1 of us show possible autoimmunity (Iwillbeatthis), correlated with positive EBV (HHV-4) infection
--1 of us show normal/negative autoimmune antibody test for onconeural antibodies, insulin, peripheral NMDA-receptor, adrenal-cortex, potassium channel, glutamic acid decarboxylase (Muon's brother)
Inflammation
--4 show normal C reactive protein (CRP) (kingfisher, certainlypois2, BluesBrother, Simon66)
--3 show normal ESR (Simon66, nanna1, certainlypois2)
--1 complement system activity (C3a, C4) normal (BluesBrother)
I think that the semen allergy hypothesis has been thoroughly studied and discredited. I suspect that
men (both POISers and non-POISers) with elevated immunoglobins (IgE or IgG) in their semen have sexually transmitted diseases. Some infections like CMV and HPV can be transferred through non-sexual contact, fluid exchange or from mother to child at childbirth. This is my personal hypothesis: viruses and bacteria that enter the seminal fluid can also stimulate immune cells to produce IgE/IgG antibodies against those pathogens so that they do not infect the female or kill the sperm. Injecting those viruses or bacteria (and their IgE/IgG antibodies) back into the body is probably not a good idea. I hope this helps.