Hello all, I’m currently in my final year of medical school in Spain and deal with PSSD myself. I’d like to present a hypothesis that I believe explains this disorder logically.
My view is that PSSD primarily stems from peripheral nerve damage in susceptible individuals. SSRIs elevate serotonin levels globally, not just centrally, with a significant impact on the enteric nervous system, which holds the bulk of the body’s serotonin. In those who are predisposed, this surplus can cause stress and harm to small peripheral fibers (Aδ and C). Axonal injury leads to the release of proteins into the adjacent tissue. Resident macrophages might then ingest these proteins and display them to lymphocytes, potentially sparking autoantibody production. These antibodies circulate and can access the dorsal root ganglia and peripheral nerves—areas vulnerable due to permeable barriers—subsequently targeting small fibers across the entire body.
Notably, the most susceptible and exposed fibers are the unmyelinated C fibers and the lightly myelinated Aδ fibers. Their role is to convey thermal and basic tactile information. The primary symptom described in PSSD—diminished temperature awareness and rough touch sensitivity in the genitals—aligns perfectly with this. This connection is remarkable, as it corresponds exactly to the fiber types impacted by small fiber neuropathy.
This framework accounts for the core clinical signs: genital numbness, erectile and ejaculatory issues, decreased lubrication, poor blood flow to the penis, and potentially testicular atrophy or fibrosis resulting from long-term low perfusion and autonomic dysfunction. I see this as the fundamental process connecting all the dots.
Instances where symptoms appear after just a couple of doses might involve an immediate receptor disturbance. While usually temporary, in certain patients, this fails to resolve and evolves into the chronic state I’ve outlined.
While other elements like widespread epigenetic modifications or central neurotransmitter shifts might play a role, I suspect they are secondary to the immune-driven peripheral injury.
To provide perspective: small fiber neuropathy occurs in only about 0.01–0.05% of the general public. Conversely, roughly 50% of PSSD patients who undergo skin biopsies exhibit low small fiber density. Given that biopsies are specific but lack high sensitivity, the actual rate could be even greater.
To conclude, I propose that PSSD begins as an acute functional glitch, progresses to peripheral axonal damage, and turns into an immune-mediated neuropathy in vulnerable people. In my opinion, this is the primary mechanism and the one that best explains my own symptoms.