Case of post-orgasmic illness syndrome associated with
Teppei Takeshima, Shinnosuke Kuroda and Yasushi Yumura
Department of Urology, Reproduction Center, Yokohama City University Medical Center, Yokohama, Japan
Abbreviations & Acronyms
AMS = aging male symptom
hCG = human chorionic
NSAIDs = nonsteroidal anti-
POIS = post-orgasmic illness
QOL = quality of life
SHIM = sexual health
inventory for men
SPT = skin pick test
TRT = testosterone
Takeshima M.D., Ph.D.,
Department of Urology,
Reproduction Center, Yokohama
City University Medical Center,
4-57 Urafune-cho, Minami-ku,
Yokohama, Kanagawa 232-
0024, Japan. Email:
How to cite this article:
Takeshima T, Kuroda S,
Yumura Y. Case of post-
orgasmic illness syndrome
associated with hypogonadism.
IJU Case Rep. 2020;
This is an open access article
under the terms of the Creative
Commons Attribution License,
which permits use, distribution
and reproduction in any
medium, provided the original
work is properly cited.
Received 8 April 2020; accepted
2 June 2020.
Introduction: Post-orgasmic illness syndrome is a rare condition that occurs after
ejaculation and persists for 2–7 days and is characterized by ﬂu-like symptoms, which
can signiﬁcantly reduce quality of life.
Case presentation: A 21-year-old unmarried man was referred to our hospital due to
ﬂu-like symptoms that developed after ejaculation by masturbation and persisted for
about 2 days. The patient’s free testosterone level was slightly lower than normal.
Nonsteroidal anti-inﬂammatory drugs were initially administered and helped relieve
headache and muscle pain. Thereafter, the patient was able to ejaculate three times a
week. In addition, after administering testosterone enanthate once or twice a month, his
general fatigue signiﬁcantly improved, and he could ejaculate every day.
Conclusion: The pathophysiology of post-orgasmic illness syndrome has not been fully
elucidated. The treatments for this condition must be accurately selected according to
Key words: ejaculatory disorder, hypogonadism, post-orgasmic illness syndrome,
testosterone replacement therapy.
POIS is a rare condition that occurs after ejaculation and persists for 2–7 days and is charac-
terized by ﬂu-like symptoms. We experienced a case of POIS associated with hypogonadism.
We had successfully treated symptoms of POIS with administration of NSAIDs followed by
POIS is a rare condition that occurs after ejaculation and persists for 2–7 days and is charac-
terized by ﬂu-like symptoms.
In 2001, Waldinger and Schweitzer ﬁrst reported about POIS,
and proposed ﬁve preliminary diagnostic criteria for POIS, as shown in Table 1.
toms of POIS were classiﬁed into seven clusters, which can impair a patient’s motivation to
ejaculate and QOL. However, the actual pathophysiologies of POIS have not been fully eluci-
dated; therefore, effective treatments have not been established thus far. They also have
reported about two patients treated with subcutaneous immunotherapy with autologous semen,
which decreased the symptoms.
However, randomized controlled trials of immunotherapy
have not been performed; thus, the efﬁcacy of this treatment has not been validated. By con-
trast, Ashby et al. have hypothesized that the production of inﬂammatory cytokines is the
mechanism associated with POIS and that the administration of NSAIDs is effective.
we report a case of POIS associated with hypogonadism that was successfully treated with
TRT combined with NSAIDs.
A 21-year-old unmarried man was referred to the men’s health clinic of our hospital due to
ﬂu-like symptoms that developed after ejaculation by masturbation and that persisted for
about 2 days. He had his ﬁrst masturbation with hand thrust at the age of 19 years. Since
then, he experienced general fatigue, chills, headache, nasal congestion, and muscle pain
©2020 The Authors. IJU Case Reports published by John Wiley & Sons Australia, Ltd on behalf of the Japanese Urological Association 1
IJU Case Reports (2020) doi: 10.1002/iju5.12184
almost every after ejaculation. The symptoms lasted for about
2 days and spontaneously disappeared. Moreover, the fre-
quency of his morning erection signiﬁcantly decreased. The
patient’s symptoms met the POIS criteria; therefore, he was
diagnosed with POIS.
The growth of his pubic hair and penis was normal (each
with a Tanner’s grade of 5). On physical examination, his
testicular volume was a little atrophic on the left side
His total testosterone level (4.75 ng/mL), gonadotropic
level (luteinizing hormone: 3.5 mIU/mL and follicle stimulat-
ing hormone: 8.7 mIU/mL) was normal, and free testosterone
level (10.3 pg/mL) was mildly low.
The patient’s AMS score was 45 (psychological: 10,
somatic: 19, and sexual: 16), and his SHIM score was 3.
Antihistamine drugs were administered for allergic symp-
toms. However, the treatment was not effective. For headache
and muscle pain, celecoxib 200 mg, which is an NSAID, was
administered daily just after ejaculation. Immediately after the
intake of the drug, headache and muscle pain were relieved,
and the patient was able to ejaculate 3 days per week. How-
ever, general fatigue did not improve.
Thereafter, in addition to NSAIDs, 250 mg of testosterone
enanthate was administered as a TRT every 2 weeks because
the patient’s serum free testosterone level was lower than
70% of the average value in young adult men.
fatigue signiﬁcantly improved, and morning erection has been
achieved every day. Therefore, he can ejaculate everyday by
masturbation. The patient’s AMS score decreased to 21 and
SHIM score increased to 7. The interval of drug administra-
tion was changed from 2 to 4 weeks. However, no recurrence
of symptoms was observed.
TRT was switched to testosterone ointment (Glowmin®;
Daito Pharma, Tokyo, Japan), and his symptoms continually
POIS is a rare condition that occurs after ejaculation and per-
sists for 2–7 days and is characterized by ﬂu-like symptoms.
Waldinger et al. have proposed ﬁve preliminary diagnostic
criteria for POIS, as shown in Table 1.
POIS is classiﬁed in
two types: primary type (from the ﬁrst ejaculation during
puberty or adolescence) and secondary type (from ejaculation
later in life).
POIS develops within 30 min after ejaculation
in 87% of men and persists for an average of 4.6 2.8 days.
Moreover, the average frequency of sexual intercourse in
73% of patients is 1.04 1.00 times per week, and 17.8%
engage in sexual intercourse once in 2–6 months. However,
6.7% of patients abstain from intercourse.
syndrome can be a psychological burden on patients, which
can lead to decreased ejaculation frequency, avoidance of
sexual activities and romantic relationships, schedule prob-
lems, and struggles in preventing eroticism.
could signiﬁcantly reduce a patient’s QOL.
However, the pathophysiology of POIS has not been
fully elucidated. Waldinger et al. hypothesized that POIS is
an autoimmune or allergic disorder caused by an inﬂamma-
tory response of the urethral mucosal epithelium to antigens
in a patient’s own seminal ﬂuid. A total of 33 patients
with POIS underwent SPT; 88% had a positive reaction to
their own semen.
Two patients had hyposensitization ther-
apy with autologous semen, and both were successfully
treated, with 60% and 90% improvement in POIS com-
plaints at 31 and 15 months.
However, the efﬁcacy of this
therapy was not assessed in a randomized placebo-con-
trolled study. Alternatively, Ashby and Goldmeier hypothe-
sized that POIS is caused by a disorder in the cytokine
and neuroendocrine response.
In this study, the administra-
tion of NSAIDs (diclofenac) was effective in alleviating
symptoms (up to 80% improvement), and the patient expe-
rienced increased sexual frequency from 2 to 4 times a
In our case, the patient’s non-speciﬁc IgE level
did not increase, as previously reported,
and SPT was not
performed. Alternatively, NSAID was administered and had
a partial efﬁcacy.
Most studies about the physiological involvement of
testosterone in an ejaculatory disorder used animal-based
and human-based studies of the relationship
between serum testosterone level and ejaculatory function
are extremely limited. Several studies have reported that
ejaculatory disorders during sexual intercourse are associated
with decreased serum testosterone levels.
previous studies has shown that POIS is associated with
In our case, though decline of his free testos-
terone level was modest, POIS associated with hypogo-
nadism was suspected. Because the patient in our case was
not married and did not have any desire to have babies, he
chose TRT once or twice a month though we proposed self-
injection of hCG to avoid possible testicular atrophy due to
the negative feedback of gonadotropin. TRT was markedly
effective. After switching the treatment to testosterone ointment,
his symptoms continually improved. Bolanos and Morgentaler
also reported a case of POIS associated with hypogonadism,
which was successfully treated with administration of hCG.
Herein, we report a case of POIS associated with hypogo-
nadism, which was different from allergy-associated condition,
thereby treatments must be accurately selected according to
Table 1 Five preliminary diagnostic criteria for POIS
1≥1 of the following symptoms: sensation of ﬂu-like state,
extreme fatigue or exhaustion, weakness of musculature,
experiences of feverishness or perspiration, mood
disturbances and/or irritability, memory difﬁculties,
concentration problems, incoherent speech, congestion of
nose, or watery nose, itchy eyes
2 All symptoms occur immediately (e.g. seconds), soon (e.g.
minutes), or within a few hours after ejaculation that is
initiated by coitus and/or masturbation and/or spontaneously
(e.g. during sleep)
3 Symptoms occur always or nearly always (i.e. >90% of
4 Most of these symptoms last for 27 days
5 Symptoms disappear spontaneously
2©2020 The Authors. IJU Case Reports published by John Wiley & Sons Australia, Ltd on behalf of the Japanese Urological Association
T TAKESHIMA ET AL.
The authors thank Dr Takeshi Tomoda for initial examina-
tions of this case.
Conﬂict of interest
The authors declare no conﬂict of interest.
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©2020 The Authors. IJU Case Reports published by John Wiley & Sons Australia, Ltd on behalf of the Japanese Urological Association 3
Case of POIS associated with hypogonadism