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SAN ANTONIO -- Numerous studies and clinical evaluations have yet to uncover the etiology of post-orgasmic illness syndrome (POIS), which almost exclusively affects "people with penises," sexual medicine specialists said here.

A rare, poorly understood condition, POIS is characterized by feelings of illness after orgasm. Fewer than 500 documented cases have been described in the medical literature, said Olivia Paulsen, a student at Idaho College of Osteopathic Medicine in Meridian, at the American Urological Association annual meeting. The presentation served as an introduction to a POIS registry.

"We created an international registry to get a better understanding of the lived experiences of people with POIS," said Paulsen. "A survey will be distributed among several online platforms but mostly the , which is the largest POIS support group to date. On top of a multiple-choice questionnaire, we will include a free text response for [patients] to include anything they feel like was not well-represented in the survey."

Aside from demographics, investigators hope to collect information on diagnostic status and criteria, medical history, and the condition's personal impact (mental health, relationships, knowledge of POIS), she added. Notably, the survey will seek to elicit information about anatomy. Cases to date have almost exclusively involved individuals with penises.

"Anatomy is important because we want to see whether it's prevalent in people with vulvas and vaginas," said Paulsen. "There is no research on that."

The survey and free text responses will remain anonymous. Initially, the registry will be centered at the POISCenter, but during a second phase of development, the questionnaire will be expanded and additional sites will join.

POIS is classified as primary -- after a first orgasm in life -- or secondary, occurring at some other point in life. Symptoms begin immediately after or within hours of ejaculation by any means -- coitus, masturbation, or spontaneous, such as during sleep, said Paulsen. The illness may persist for as long as 7 days before resolving spontaneously.

Symptoms usually occur in one or more of seven clusters, originally described by Dutch sexual medicine specialist :

• General (fatigue, exhaustion, confusion, word-finding difficulties)
• Flu-like
• Head
• Eyes
• Nose
• Throat
• Muscle

Some patients have symptoms that overlap the cluster groups, said Paulsen. Symptoms occur always or almost always (>90% of the time) after an ejaculatory event.

Authors of a of 34 published studies about POIS stated that the etiology remains unclear and knowledge about the etiology and treatment continues to evolve.

Several etiologies have been proposed for POIS, but none has been proven. The best data exist to support an for the disorder. Waldinger and colleagues investigated hyposensitization in 33 men with POIS. Skin-prick tests with the men's own semen proved positive in 29 cases, with POIS symptom onset within 30 minutes of ejaculation in most cases.

In a , two men with positive skin-prick tests received a series of subcutaneous injections of autologous semen. The treatment was associated with significant improvement in POIS symptoms. One man with a history of premature ejaculation had improvement in latency from 20 seconds at baseline to 10 minutes after 3 years, which the investigators could not explain.

In response to a question from the audience, Paulsen said treatment for POIS has spanned a broad gamut, including nonsteroidal anti-inflammatory drugs, silodosin, and gabapentin.

"Most of these treatments are only mildly effective," she said. "There has been a lot of trial and error."

An unidentified member of the audience said one of his patients had good results with prednisone premedication before sex. Another said one of his patients reported substantial symptom improvement with MDMA.

"Registries are a great way to try to figure it out," he added, "but again, it's going to come down to characterizing the effects, which are so variable from one patient to the next. Classifying what kind of POIS you have is going to be really important for what treatments to use for those guys."

A couple of speakers said more recent studies have raised doubts about the immunologic etiology. One urologist said one of his own patients tried autologous semen injections for several months with no noticeable effect on POIS symptoms.

Following her presentation, Paulsen told MedPage Today that most patients with POIS have a psychological evaluation at some point, and no consistent evidence of a psychological component has resulted.

Rachel Rubin, MD, a sexual medicine specialist in Washington, D.C., also noted that she sees "lots of these patients and we can't find any [psychological component]. It's very biological. It is just so chemical. When they're not ejaculating, they're fine, and after ejaculation, it completely changes things."

Lack of recognition and awareness have hindered progress toward a better understanding of POIS, she added.

"A guy once came to me because his girlfriend was like, 'This isn't normal,'" said Rubin. "He had no idea that it wasn't normal because it was all he ever knew. She started researching it and found POIS because of Dr. Waldinger's work and then [they] were able to find me."

"The few of us that do this work play with it to try to find what helps," she said. "Many find antihistamines very helpful, which is sort of that immunology piece. We find opioids very helpful, which is very strange. We find some serotonin modulators very helpful. It's really a fascinating medical mystery."

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