Sleep-related painful erections Pathophysiology and management of a rare disease
to more than 5 years. In these 27 patients, three discontinued the medication due to side effects. A symptom relapse often occurred upon cessation of the medication. Anti-androgens Anti-androgens block androgen receptors thus inhibiting the effect of testosterone. These medications have been used successfully to manage patients with stuttering priapism by causing a hypogonadal state and inhibiting penile erection (erotic and sleep-related). Side effects of these medications are often intolerable and include erectile dysfunction, loss of libido, reduction in muscle mass, cognitive impairment, and cardiovascular disease [19]. Cyproterone acetate [5, 18, 20] has been used in 26 patients, 17 reported no improvement in their symptoms. Four patients have reported a partial response and four patients reported full remission of their symptoms. The final patient reported an improvement when using cyproterone acetate and baclofen in combination. Sixteen of these 26 patients reported significant side effects including erectile dysfunction, tiredness, and hot flushes. Bicalutamide has also been used in one patient unsuccessfully. "Oral baclofen appears to be the most effective treatment currently available." Adrenergic receptor agonists and antagonists Adrenergic receptor agonists and antagonists have been used in the treatment of SRPE. α-adrenergic agonists have an inhibitory effect on cavernosal smooth muscles and inhibit penile erection [21]. The α-agonist, etilefrine has been used successfully in the context of stuttering priapism in men with sickle cell disease [22]. Based on the aforementioned, β-adrenergic hyperactivity that was seen in men with SRPE, β-blockers have also been used [23]. β-blockers also have a direct effect on testicular Leydig cells and can lower serum testosterone, which can affect penile erection [24]. The α-agonist, pseudoephedrine has been used in 19 men, resulting in an improvement in symptoms in six patients and having no effect in the remaining 13 patients [18]. Four of the men reported side effects in the form of palpitations and hypertension. β-blockers have been used in five patients with SRPE and have been found to have a temporary positive effect in one of these patients [8, 17, 23]. One of the patients did report an improvement when used alongside bromazepam. Phosphodiesterase-5 inhibitors (PDE5i) PDE5i are commonly used for the treatment of erectile dysfunction [25]. PDE5 is an enzyme that is responsible for the inhibition of cyclic guanosine monophosphate (cGMP). Therefore, inhibition of PDE5 increases intracavernosal cyclic GMP
preventing detumescence of the penis. PDE5i also appear to have a paradoxical effect in reducing prolonged erections in men with stuttering priapism when used in low doses [26]. Based on this, PDE5i have been used in the management of SRPE. Overall, PDE5i are well tolerated with mostly mild and short lived side effects, including headache, flushing, nasal congestion, and gastroesophageal reflux symptoms. PDE5i have been used in eight patients with SRPE. One patient reported full remission of symptoms, two patients have reported a partial improvement in symptoms, and the remaining men reported no response [5, 18]. Antidepressants, antipsychotics, antiepileptics and benzodiazepines Antidepressants, antipsychotics, antiepileptics and benzodiazepines have also been used in men with SRPE in variable success. Notably, clonazepam is a REM-sleep suppressant and has been used successfully to treat other REM-sleep parasomnias.
Increased androgens Physiological sleep-related erections are androgen dependent [9]. It is therefore postulated that increased androgens may be responsible for increased SRPE. However, the three largest case series have failed to show an association with increased testosterone levels and SRPE. Furthermore, the use of anti-androgens as a treatment has been found to be ineffective [3,6,7]. Alterations in autonomic function Penile erection is regulated autonomic control. Acetylcholine under parasympathetic control initiates a cascade that results in vasodilation, veno-occlusion, and penile erection. Contraction of the smooth muscle (and therefore, detumescence) occurs under sympathetic control [3]. There is no direct test for measuring penile autonomic function. A reduction in cardiac vagal activity and increased accelerations of the heart rate was found in men with SRPE when compared to controls [5]. These findings may suggest an alteration in autonomic function in men with SRPE. Despite this, β-adrenergic blockers do not appear to be helpful in the management of SRPE [2]. Compression of the Lateral Preoptic area (LPOA) Bilateral lesions in the LPOA eliminate sleep-related erections, whilst awake erections remain intact [10]. Szucs et al, found compression at the lateral hypothalamic border (area corresponding to the LPOA) in a patient with SRPE. Of those patients that also underwent a brain MRI, no others were found to have an abnormality in this area [11]. Psychological factors There is some evidence that SRPE fully resolved with improvement in marital issues and anxiety. However, it is impossible to draw firm conclusions regarding cause or effect. Poor sleep is a risk factor for mental illness and marital issues. It would therefore seem reasonable that an improvement in symptoms could increase sleep quality, thus improve mental wellbeing and strengthen a marriage [2, 12]. Interestingly, sleep fragmentation as seen in men with SRPE has been found to increase the sensitivity to pain. This could create a vicious circle of increased sleep fragmentation leading to increased pain [13]. Investigations Multiple investigations have been used to better understand the cause of SRPE. As demonstrated above, it is unclear which investigations are helpful. At present, there is no structured approach to the diagnostics. SRPE is a clinical diagnosis based predominantly on the history provided from the patient. A good history is often enough to start the patient on oral medications as described later in this article.
Mr. Mark Johnson Urology trainee, Yorkshire and Humber deanery (GB)
Co-author: Prof. David Ralph FRCS (Urol), University College London Hospital (GB)
Sleep-related painful erections (SPRE) is a parasomnia typified by painful erections occurring during rapid-eye-movement (REM) sleep that differ from painless erotic erections. Parasomnias are defined as undesirable experiences or physical phenomena whilst during sleep, falling asleep or waking up [1]. Men with SRPE can experience pain with each REM cycle causing them to wake and leading to sleep fragmentation and daytime fatigue. Other causes of penile pain, such as phimosis or Peyronie’s disease, can co-exist with SRPE. However, these clearly have different pathology and do not explain SRPE [2]. SRPE is a rare condition not currently recognised in international urological guidelines. This can lead to an incorrect or a delay in diagnosis. The literature for SRPE is limited to retrospective case series and case reports, leading to a high-level bias, and contradiction. The aim of this review is to discuss the pathophysiology, diagnostic tests, and treatment options currently available. Pathophysiology The pathophysiology of SRPE is undefined. The available evidence is summarised below. Penile compartment syndrome Normal/physiological penile erections are an ischemic event resulting from veno-occlusion of the corpus cavernosa of the penis, which resolves with detumescence [3]. Persistence (> 4 hours in duration) of a penile erection results in a compartment syndrome of the corpus cavernosum and is defined as ischemic priapism. This results in time-dependent histological changes in the tissue from ischemia, to infarction and fibrosis. Stuttering priapism is a sub-type of ischemic priapism typified by recurrent minor episodes of painful priapism often at night or in the early morning. This condition most commonly affects men with sickle cell disease, however can be idiopathic. There are obvious similarities in the clinical features between stuttering priapism and SRPE. However, men with SRPE often have significantly more episodes of painful erection each night and detumescence usually occurs very shortly after waking [4]. A comparison of penile blood gas analysis would be helpful in defining the similarities and differences between these two conditions. Hypertonicity of the pelvic floor Contraction of the pelvic floor muscles occurs normally during the rigid phase of penile erection [3]. Hypertrophy and contraction of these muscles could result in pain that radiates to the penis during sleep-related erections. This may explain why men with SRPE report pain in different locations (e.g. penis, perineum, scrotum, and lower abdomen) [5]. Hypertrophy of the pelvic floor has been noted in two patients on Doppler ultrasound [6] and increased muscle tone has been noted on electromyography [5]. However, the pelvic floor would contract during erotic erections which are pain-free in men with SRPE. Obstructive sleep apnoea (OSA) OSA is known to alter autonomic and hormonal pathways and is already implicated in other urological conditions such as nocturnal polyuria [7]. There are two cases in the literature of successful treatment of SRPE with continuous positive airway pressure [8]. In contrast, there are only five cases in the literature of men with SRPE and OSA [2] and in a larger series, the Apnoea-hyponea index was normal in all eight patients that underwent polysomnography [4], making the association between OSA and SRPE less likely.
It was found to be effective in five patients. Amitriptyline is the most commonly used
antidepressant medication in this context and has been helpful in four men and had no improvement in four other men. Unfortunately, these psychotropic medications are often poorly tolerated and should be avoided in the long term [2, 27, 28]. Surgical management Surgical management with implantation of a penile prosthesis has also been used in two patients. This results in destruction of the tissue of the corpus cavernosa which prevents any subsequent spontaneous erections. Unfortunately, the two patients that underwent surgery continued to have symptoms [18]. This suggests that the pain does not originate from the penis and is likely to be a referred pain from elsewhere. Conclusion SRPE is a rare parasomnia the results in penile pain that wakes the patient up following each REM sleep cycle. Poor sleep is often the primary complaint and can have a significant physical and psychological toll on the patient. It is a clinical diagnosis and the pathophysiology is currently undefined. Investigations that are deemed appropriate are based on the patient history and examination findings. Oral baclofen appears to be the most effective treatment currently available. However, the symptoms often return upon cessation of baclofen. Given the rarity of this condition, collaborative research between multiple institutions is likely to be required to gain a better understanding of SRPE.
References can be requested from the corresponding authors.
The following investigations have previously been used and can be considered, based on the history
Monday 13 March 12:30 - 12:40 Thematic Session: Immediate and delayed management of priapism Yellow Area, Amber 3
and examination findings at the time of presentation: serum hormonal profile,
polysomnography/overnight oximetry, nocturnal penile tumescence, brain MRI, and pelvic floor electromyography. However, many of these tests are expensive and may not alter the management. Management Oral medications that aim to [1] abolish nocturnal erections through hormonal manipulation, [2] reduce sleep fragmentation or [3] suppress REM sleep, and/ or [4] relax the muscles of the pelvic floor have all been used to treat men with SRPE. The available evidence is summarised below. Baclofen Baclofen relaxes skeletal muscles by inhibiting the release of aspartate and glutamate. Baclofen is a GABA-b receptor agonist with actions in the spinal cord and brain. Based on animal data, Baclofen has been found to have inhibitory effect on penile erection [14]. It has also been used to treat pelvic floor hypertonicity (more commonly in women) as a pelvic floor muscle relaxant [15]. The combination of these two factors may explain its beneficial effect in men with SRPE. In the literature, Baclofen has been used in 27 patients [5, 16 - 18] across four case series and a case report. Seven of these patients have reported full remission of symptoms, 17 have reported partial improvement in symptoms, and 3 patients have reported no improvement. Follow-up protocol was variable across the studies and ranged from weeks
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