Background Peri orgasmic dysfunctions are very rare and little information exists on their diagnosis and treatment. One of these conditions is post-orgasmic illness syndrome (POIS), manifesting by a debilitating cluster of symptoms affecting men within seconds, minutes, or hours after ejaculation. The aim of this article is to do a thorough literature review about POIS, in order to elucidate the pathophysiology, the diagnosis and the management of this rare disease. Results Updated literature review on Pubmed was done, using the following terms: "orgasm illness", "post-orgasmic" and "postorgasmic illness syndrome". The references of the 17 identified publications were also reviewed for additional 8 relevant articles that were all included in the results. POIS has 5 preliminary diagnostic criteria and criterion 1 has 7 described clusters. Pathophysiological hypotheses include: immunological phenomenon (most relevant), opioid-like withdrawal, neuroendocrine response, transient deregulation of the autonomic nervous system, hypersensitivity and disordered cytokines. Differential diagnoses include: chronic prostatitis, orgasmolepsy, benign orgasmic cephalgia, sneezing and rhinorrhea, postcoital dysphoria, post-coital asthma and rhinitis. Patients have been symptomatically treated with antihistamines, non-steroidal anti-inflammatory drugs, selective serotonin reuptake inhibitors, and benzodiazepines. A trial of hyposensitization therapy with autologous semen was successful. Conclusion POIS is a rare condition that is underdiagnosed, most probably because of its unclear pathophysiology leading to a lack of treatment options. Further studies are warranted to investigate the prevalence, pathophysiology, and management of this debilitating condition. Keywords: Post orgasmic illness syndrome (POIS), Pathophysiology, Symptoms and complaints, Differential diagnoses, Work up, Management
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