Sleep-related painful erections treated with sodium oxybate

Abstract

A 39-year-old male with a medical history significant for migraine, psoriatic arthritis, postural orthostatic tachycardia syndrome, vitamin D deficiency, and hypoglycemia presented with a 2-year history of sleep-related painful erections. Because the reported prevalence is low, there is limited understanding of the possible etiologies of the disorder and few published clinical data on treatment algorithms. Thus, he had tried multiple therapies. Baclofen was effective but not tolerated. Pelvic physiotherapy and tadalafil were ineffective. Imipramine, clonazepam, vitamin B, iron, and selenium provided minimal benefit. Opiates were initially effective but lost efficacy after 2–3 weeks. Finally, he was started on sodium oxybate after fully counseling the patient on the potential side effects of the treatment and consenting the patient for off-label use. This has effectively treated his sleep-related painful erections. Sodium oxybate is a novel therapy for and a possible new treatment for this rare and challenging disorder that merits further study.

Citation:

Chaudhary HS, Zeidman E, Punjani N, Tashman Y. Sleep-related painful erections treated with sodium oxybate. J Clin Sleep Med. 2024;20(7):1209–1211.

INTRODUCTION

Sleep-related painful erection (SRPE) is a rare parasomnia characterized by painful penile erection associated with rapid eye movement sleep that often wakes the patient several times a night. Normal, painless erections continue to occur outside of this context.¹ Forty-four cases of SRPE have been reported in the literature, and no randomized controlled trials are available. Pathophysiology and appropriate treatments are unclear due to sparse evidence. Possible etiologies of SRPE include neurologic dysfunction at the level of the ischiocavernosus and bulbocavernosus muscles peripherally or centrally in the hypothalamus, an association with untreated obstructive sleep apnea, or a sequela of autonomic dysfunction.² The only consistent diagnostic abnormality on diagnostic polysomnography is a fragmented pattern of sleep manifested by poor sleep efficiency, reduced total sleep time, and increased wake after sleep onset.³ Diagnostics otherwise previously suggested in the literature include a combination of nocturnal penile tumescence coupled with simultaneous polysomnography and electromyography of the pelvic floor muscles, as well as blood gas from corpus cavernosa aspirate during SRPE and functional brain magnetic resonance imaging. These would likely be helpful given they evaluate several of the potential factors that may be involved in SRPE, such as hypertonia of the pelvic floor muscles, relation to other sleep abnormalities, or structural brain abnormalities such as compression of the lateral preoptic area. However, the feasibility of this testing is unfortunately limited by cost and its invasive nature.⁴

Currently, there is no single known effective treatment, which poses a significant challenge to successful management of these patients. There are reports of symptomatic improvement from treatment of concomitant sleep apnea or pelvic physiotherapy. Benzodiazepines, opiates, and antidepressants have not been shown to have a lasting or stable effect. Low-dose phosphodiesterase-5 inhibitors such as tadalafil were sometimes effective. The antipsychotic clozapine also showed some success but is also associated with significant side effects such as agranulocytosis and myocarditis. Some response to baclofen was observed in most patients; in a meta-analysis, out of 17 patients in whom baclofen was trialed, 6 achieved full, lasting resolution of symptoms, another 10 reported partial relief, and only 1 reported no effect.^1,4 In this case of SRPE, multiple previously studied treatments suggested in the literature were tried and ultimately failed. However, treatment with sodium oxybate has provided effective and sustained benefit since April 2022.

REPORT OF CASE

Our patient is a 39-year-old male with medical comorbidities significant for migraine headaches, psoriatic arthritis, postural orthostatic tachycardia syndrome, vitamin D deficiency, and hypoglycemia who presented to our practice in 2020 for SRPE.

He had a history of painful nocturnal erections starting in 2018 during sleep and occurring between midnight and 6 AM. The frequency was once every 20 minutes, contributing to poor sleep and daytime tiredness. The duration of the erection could last hours, although episodes were never greater than 4 hours nor did they require emergency priapism intervention. The pain would be alleviated by walking or masturbation. While he was awake his erections were painless. He was not taking testosterone or sexual stimulants. There had been no abdominopelvic surgery or recent trauma. Baseline erectile function was normal.

In 2019, he was evaluated by urology and was prescribed baclofen at doses up to 30 mg daily. This decreased the frequency of the episodes from 15–20 to 1–6 times per night. However, he became excessively somnolent, struggling to drive, focus, and concentrate. He would have to stand during work meetings to prevent himself from falling asleep. Due to these disabling side effects, he was unable to tolerate the medication and discontinued this treatment in October 2020.

He was compliant with pelvic physiotherapy for 6 months, but this did not alleviate his symptoms. Starting in March 2020, he was prescribed imipramine initially at 10 mg, titrated up to 80 mg daily, and begun on 0.25 mg of clonazepam nightly. The combination helped him return to sleep, but he was still experiencing SRPE. In September 2020, 2.5 to 5 mg of tadalafil nightly was additionally trialed without relief. Cinitapride was considered, but the patient was unable to attain this in the United States.

Events were characterized based on the patient’s report. Actigraphy was not performed given there was not any clinical suspicion for a circadian rhythm disorder, and the study would not have otherwise been helpful in the diagnosis of SRPE. Polysomnography was not performed given that nocturnal penile tumescence testing is not offered during in-laboratory sleep studies at our center. A Watchpat home sleep study was performed, predominantly to evaluate for obstructive sleep apnea. Apneas and hypopneas occurred 4.6 times per hour, and the number of respiratory disturbance events were estimated at 1.2 per hour. The mean oxygen saturation was 95% and the lowest oxygen saturation was 93%. The study was scored using the 3% criteria for hypopneas. Overall, there was no evidence of clinically significant sleep-disordered breathing. Magnetic resonance imaging of the brain and cervical, thoracic, and lumbar spine was also performed and did not show significant abnormalities.

In April 2021, he was involved in a motor vehicle accident, wherein he sustained an L5 compression fracture and an avulsion fracture of the second metacarpal base. He required L4 through S1 percutaneous spinal instrumentation and fixation. Postoperatively, he was prescribed 5 mg of oxycodone. Interestingly, it was effective in treating his SRPE for 5 hours each night. Subsequently, in May 2021, he was prescribed extended-release 10-mg morphine sulfate for an 8-hour duration of action and an imipramine and clonazepam taper was planned. The morphine was effective for 1–2 weeks, but the painful erections returned. He restarted his imipramine at 50 mg daily and clonazepam at 0.25 mg daily due to the recurrent symptoms. The patient also tried vitamin B, iron, and selenium supplementation, which did not provide any relief.

In April 2022, the patient was started on sodium oxybate. Daily clonazepam at 0.25 mg was discontinued due to the risk of respiratory depression but imipramine at 50 mg daily was continued. With an initial dose of 2.25 g of sodium oxybate twice nightly he would continue to wake up after about 4 hours with SRPE. Increasing sodium oxybate to 2.75 g twice nightly effectively treated the SRPE. Initially, the therapy was complicated by new onset of severe depression and anxiety, but these psychiatric manifestations resolved within 2 weeks after initiation of therapy.

As of April 2022, he is taking 2.75 g of sodium oxybate at bedtime followed by a second dose 4 hours later. On this regimen, he can successfully sleep an average of 7.5 hours per night. He does experience the SRPE if he takes the second dose of sodium oxybate more than 4 hours later or if he sleeps more than 7.5 hours. Alternative dosing has subsequently included 3 g of sodium oxybate at bedtime, 3 g 3.5 hours later, and the final 3 g at the 7th hour, promoting 9.5 hours of sleep. The patient reported being very satisfied with the treatment, having had significant improvement in his quality of life with resolution of the prior daytime sleepiness and no symptoms of sexual dysfunction.

DISCUSSION

SRPE is a rare disorder without generally accepted consensus on its pathophysiology or treatment. It is thought that sleep-related erections are in large part modulated by gamma-aminobutyric acid (GABA)–related systems. Hypotheses include elevated androgens, autonomic dysfunction, psychosomiasis, and obstructive sleep apnea. Treatment trials have included antidepressants, clozapine, antiepileptics, cinitapride, benzodiazepines, antiandrogens, beta blockers, phosphodiesterase-5 inhibitors, baclofen, biperiden, finasteride, terbutaline, and digoxin.⁴

In our patient, baclofen showed partial efficacy, which supports what has been previously reported in the literature but was not tolerated due to excessive daytime sleepiness and dysfunction. Similarly, clonazepam and imipramine together also provided partial benefit but resulted in unacceptable somnolence. Opiates provided only temporary relief and may be associated with issues of long-term dependence. Ineffective therapies included pelvic physiotherapy, tadalafil, vitamin B, iron, and selenium (Table 1). However, at an appropriate dose of sodium oxybate the patient’s symptoms were successfully treated.

Table 1.

Summary of treatments considered or trialed in our patient.

Treatment	Dose	Result
Baclofen	30 mg daily	Effective, decreasing episodes from 15–20 to 1–6 nightly, but caused excess somnolence
Pelvic physiotherapy	Consistently for 6 months	Ineffective
Imipramine	80 mg daily	Helped return to sleep, but still symptoms to some degree
Clonazepam	0.25 mg nightly	Helped return to sleep, but still symptoms to some degree
Tadalafil	5 mg nightly	Ineffective
Cinitapride	—	Unable to attain in the United States
Oxycodone	5 mg daily	Treated for 5 hours per night, but only took temporarily for postoperative pain
Morphine sulfate extended release	10 mg daily	Effective for 1–2 weeks, then symptoms returned
Vitamin B	Self-trialed, unclear dose	Ineffective
Iron	Self-trialed, unclear dose	Ineffective
Selenium	Self-trialed, unclear dose	Ineffective
Sodium oxybate	2.75 g twice nightly up to 3 g three times nightly	Effectively treated, allowing him to sleep 7.5 to 9 hours without symptoms

On review of the available literature, there have been no prior reports of using sodium oxybate in treatment of SRPE. This highlights the possibility of another treatment option that should be further studied. This agent is a γ-hydroxybutyrate and GABA-β receptor agonist currently approved for treatment of narcolepsy and idiopathic hypersomnia. The exact mechanism of action is unknown in SRPE. We hypothesize that sodium oxybate may have a mechanism of action similar to that of baclofen, which is one of the more studied therapies in the literature. Baclofen binds to GABA-β receptor and inhibits the release of glutamate and aspartate. Suppression of glutamate release results in the relaxation of the ischiocavernosus and bulbospongiosus muscles, which are involved in penile erections.³ Andersen and Tufik have also studied the inhibitory effect of GABA system on frequency of sleep-related erections in an animal model and noted that administration of GABA-ergic compounds inhibited cocaine-induced penile erection in male sleep-deprived rats, which suggests that GABA may have an inhibitory effect on erection.⁵

In summary, a 39-year-old male presented with symptoms of SRPE, the treatment of which is not well-established due to the rarity of the condition and the paucity of literature. Several therapies were tried, including many of those previously studied, without success. Ultimately, an appropriate dose of sodium oxybate successfully treated his SRPE. Further studies should include the study of both the efficacy of this drug for SRPE as well as potential mechanisms of action.

DISCLOSURE STATEMENT

All authors have seen and approved the manuscript. Work for this study was performed at the Mayo Clinic in Arizona. The authors report no conflicts of interest.

ABBREVIATIONS

GABA

gamma-aminobutyric acid

SRPE

sleep-related painful erections