What is the diagnosis and treatment for a young male with complete loss of penile sensation, severe erectile dysfunction, secondary hypogonadism, and severe gut dysbiosis, with normal vascular studies and no history of diabetes or pelvic trauma?

Complete Penile Sensory Loss in a Young Non-Diabetic Male

Differential Diagnosis

The most likely diagnosis is pudendal nerve entrapment or pudendal neuropathy, given the complete sensory loss, absence of vascular pathology, and associated erectile dysfunction without pain. 1, 2

The differential diagnosis for complete penile sensory loss in a young non-diabetic male includes:

• Pudendal nerve entrapment/compression at the inferior pubic ramus canal or Alcock's canal—this is the primary consideration given complete sensory loss with normal vascular studies and absence of diabetes 1, 2
• Traumatic pudendal neuropathy from occult pelvic trauma, even without recalled injury 1
• Large fiber peripheral neuropathy affecting the dorsal penile nerve (branch of pudendal nerve), though less likely given normal HbA1c 3
• Small fiber neuropathy is less likely as this typically presents with burning/dysesthesia rather than complete anesthesia 3
• Central neurological lesions affecting sacral segments S2-S4, though this would typically present with other neurological deficits 3
• Severe hypogonadism-related neuropathy, though this is an uncommon cause of isolated penile sensory loss 3, 4

Specific Diagnostic Testing Indicated

The following specialized neurological tests should be performed to evaluate pudendal/penile neuropathy:

• Pudendal nerve terminal motor latency (PNTML) testing to assess pudendal nerve conduction 3
• Dorsal penile nerve somatosensory evoked potentials (SSEPs) to evaluate sensory pathway integrity from penis to cortex 3
• Bulbocavernosus reflex testing to assess sacral reflex arc function 3
• Dorsal sensory nerve conduction studies of the penis to measure amplitude and latency 3
• Penile sympathetic skin response (SSR) amplitude and latency measurements 3
• Quantitative sensory testing (QST) of the penile skin to objectively document sensory thresholds 3
• MRI of the pelvis to evaluate for pudendal nerve entrapment at known compression sites (Alcock's canal, inferior pubic ramus) 1, 2

The absence of diabetes (HbA1c 5.4%) makes diabetic neuropathy unlikely, but these specialized tests will differentiate between large fiber neuropathy, small fiber neuropathy, and focal nerve entrapment 3.

Type of Neuropathy: Large Fiber vs Small Fiber vs Entrapment

This presentation is most consistent with pudendal nerve entrapment or large fiber neuropathy affecting the dorsal penile nerve, rather than small fiber neuropathy. 1, 2

Key distinguishing features:

• Complete loss of touch, pressure, and temperature sensation indicates involvement of both large (touch/pressure) and small (temperature) fibers, suggesting a complete nerve lesion rather than selective small fiber neuropathy 3, 1
• Absence of burning pain or dysesthesia argues against isolated small fiber neuropathy, which typically presents with positive sensory symptoms 3
• Associated erectile dysfunction and absent morning erections strongly suggest pudendal nerve involvement, as the pudendal nerve carries both sensory and autonomic fibers critical for erection 1, 2
• Pudendal nerve entrapment at the inferior pubic ramus canal can cause complete sensory loss, erectile dysfunction, and ejaculatory dysfunction without pain in some cases 1, 2

The "lost penis syndrome" described in the literature typically involves loss of sensation during intercourse but not complete baseline anesthesia, making this a more severe presentation 5.

Prognosis and Recovery Potential

Recovery is possible with appropriate intervention, particularly if pudendal nerve entrapment is identified and surgically decompressed. 1, 2

Evidence for recovery:

• Pudendal nerve decompression surgery resulted in complete recovery of erogenous sensation in 83% (5/6) of men with loss of penile sensation after trauma, with partial relief in the remaining 17% 1
• Restoration of erectile function occurred in 67% (2/3) of men with erectile dysfunction who underwent pudendal nerve neurolysis 1
• One case report documented complete return of genital sensation and erections after pudendal nerve decompression in a patient with penile numbness and erectile dysfunction from pudendal nerve entrapment 2
• Mean follow-up of 57 weeks (range 28-85 weeks) showed sustained improvement after surgical decompression 1

However, prolonged denervation (18 months in this case) may reduce recovery potential due to irreversible nerve damage and corporal smooth muscle degeneration 1, 4. The absence of improvement over 18 months despite various ED treatments suggests either severe nerve damage or an unaddressed structural compression 1, 2.

Treatment Options for Confirmed Penile Sensory Neuropathy

If pudendal nerve entrapment is confirmed, surgical neurolysis of the dorsal nerve to the penis at the inferior pubic ramus canal is the definitive treatment. 1, 2

Surgical Treatment

• Pudendal nerve decompression/neurolysis at the site of entrapment (typically Alcock's canal or inferior pubic ramus) is the primary treatment for confirmed pudendal nerve entrapment 1, 2
• Bilateral surgery was performed in 71% of cases in one series, suggesting bilateral involvement is common 1
• Success rates: 83% complete recovery of sensation, 67% restoration of erectile function 1

Medical Management

• Testosterone replacement therapy should be optimized given the secondary hypogonadism (low LH/FSH with low-normal free testosterone), as testosterone has direct effects on erectile tissue and may support nerve recovery 3, 4
• PDE5 inhibitors (sildenafil, tadalafil, vardenafil) should be continued as first-line therapy for erectile dysfunction, though efficacy may be limited with severe neuropathy 3, 6
• Combination therapy with testosterone and PDE5 inhibitors may be more effective than either alone in hypogonadal men with ED 4
• Intracavernosal alprostadil (prostaglandin E1) may be considered if oral PDE5 inhibitors fail, as it works through a different pathway (cAMP vs cGMP) 4

Adjunctive Treatments

• Psychosexual counseling should be offered to address performance anxiety and relationship issues, even when organic pathology is present 6
• Treatment of gut dysbiosis with probiotics and dietary modification, though evidence linking gut dysbiosis to peripheral neuropathy is limited 3

Important caveat: The EAU guidelines state that surgical management for sexual dysfunction should generally be considered experimental outside of established indications, but pudendal nerve decompression for documented nerve entrapment is a recognized neurosurgical procedure 3, 1.

Gut Dysbiosis and Hypogonadism as Causes of Peripheral Neuropathy

Neither severe gut dysbiosis nor secondary hypogonadism are established causes of isolated peripheral sensory neuropathy affecting the penis. 3

Gut Dysbiosis

• No direct evidence links gut dysbiosis to peripheral sensory neuropathy in the absence of systemic disease 3
• Gut dysbiosis may contribute to systemic inflammation and metabolic dysfunction, but this would typically manifest as generalized neuropathy rather than isolated penile sensory loss 3
• The patient's normal HbA1c (5.4%) argues against metabolic causes of neuropathy 3

Secondary Hypogonadism

• Hypogonadism primarily affects libido and erectile function through reduced nitric oxide synthase activity and corporal smooth muscle degeneration, not through direct effects on sensory nerves 3, 4
• The patient's testosterone levels (total testosterone normal, free testosterone low-normal) are unlikely to cause complete sensory loss 3
• Hypogonadism may impair nerve recovery and worsen erectile dysfunction, but is not a primary cause of sensory neuropathy 4
• The fluctuating prolactin levels (8.5 → 15.5 → 11.5 ng/mL) suggest possible secondary hypogonadism from hypothalamic-pituitary dysfunction, which should be further evaluated with repeat morning testosterone and consideration of MRI pituitary if prolactin remains elevated 3

Critical Next Steps

Immediate referral to a neurologist or peripheral nerve surgeon with expertise in pudendal nerve disorders is essential for specialized neurophysiological testing and consideration of surgical decompression. 1, 2

The combination of complete sensory loss, normal vascular studies, absence of diabetes, and failure to improve over 18 months strongly suggests a structural nerve lesion requiring surgical intervention rather than medical management alone 1, 2.