University of Groningen Pathologic erections Vreugdenhil, Sanne

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Pathologic erections

Vreugdenhil, Sanne

DOI:

10.33612/diss.95437816

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Publication date: 2019

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Vreugdenhil, S. (2019). Pathologic erections: historical, pathophysiological and clinical aspects. Rijksuniversiteit Groningen. https://doi.org/10.33612/diss.95437816

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series of 24 patients regarding diagnostics

and treatment options

CHAPTER 5

Sanne Vreugdenhil MD1_{, Alida Cornelia Weidenaar MD, PhD}1_, Igle Jan de Jong MD, PhD1_{, Mels Frank van Driel MD, PhD}1 1_{Department of Urology, University Medical Center Groningen,}

University of Groningen, Groningen, the Netherlands.

Sex Med. 2017 Dec;5(4):e237-e243. https://doi.org/10.1016/j.esxm.2017.09.001

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Abstract

Background Patients with sleep-related painful erections (SRPEs) suffer from deep penile pain during nocturnal erection, waking them up and disturbing their nights of sleep. This rare parasomnia is poorly recognized by general practitioners as well as urologists and sexologists. Aim To gain more insight in respect of diagnostics and therapeutic options.

Methods Data from a series of 24 consecutive patients, who presented with SRPEs at the outpatient clinic from 1996 to 2015, were retrospectively analyzed. Additional questionnaires were sent to complement data and to get information about follow-up. Long term treatment efficacy of baclofen was assessed using the Wilcoxon Signed Rank test.

Outcome SRPEs proved neither to be associated with urological, surgical or psychiatric history nor with serum testosterone levels. The mean doctors’ delay was 3,5 years. Fourteen of the 24 patients were treated with baclofen (10-75 mg). In 11 of them complete remission was observed within a few weeks. Two of the 3 remaining patients noticed a slight improvement of SPRE symptoms and only one patient experienced no effect at all. After an average follow-up of 4.5 years, only 41.6% of the patients that had used baclofen were satisfied with regard to their SRPEs. The others (58.4%) were dissatisfied, mostly due to relapse of symptoms after the discontinuation of baclofen. Other treatment forms were applied sporadically with strongly varying results.

Clinical implications This overview of SRPE contributes to a better clinical understanding and recognition of the phenomenon and provides new, more constructed advice about therapeutic implications, especially concerning the use of baclofen.

Strengths & limitations This study provides a systematic overview of a relatively large series of SRPE patients, which provides a substantiated treatment advice. However, treatment efficacy was mainly based on the patients’ subjective perception and it was not possible to compare the results of baclofen with other forms of pharmacological treatment, since these alternative drugs were only applied sporadically. Nevertheless this study is directional for future research.

Conclusion This study confirmed a high doctors’ delay in SRPE patients. There was no association between SRPEs and comorbidity and total serum testosterone levels. Treatment with baclofen proved to be successful and safe on the short-term. Long-term feasibility needs further investigation.

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Introduction

Patients with sleep-related painful erections (SRPEs) experience episodes of penile pain during nocturnal erections, frequently waking up the person concerned. The SRPEs occur during rapid eye movement (REM) sleep. Erections related to sexual activities, however, are not painful and normal in terms of duration and rigidity and generally no penile anatomic abnormalities are found during physical examination. Obviously Peyronie’s disease and phimosis may be present in some patients but they seldom explain the typical clinical presentation of SRPEs.[1]

The intensity of pain and duration of the associated sleep defi cit commonly increase during the second part of the night when REM sleep episodes become longer and more frequent.[2] The underlying pathophysiological mechanism and predisposing factors with regard to SRPEs are not yet known. Treatment is still in an expert-based opinion phase and there is no consensus about how to treat this parasomnia. Additionally, there is a lack of information about long-term follow-up. By documenting the symptomatology, diagnostic measurements and treatment outcomes of our SRPE patients we aimed to gain a better understanding of the pathophysiology and to create a more substantiated advice about diagnostics and therapeutic implications of SRPEs.

Methods

Study population

In this retrospective descriptive study, we collected data from all patients who presented with SRPE complaints at our outpatient clinic between 1996 and July 2015. Two patients included in this study were previously described.[2] Patients who also suff ered from painful erotic erections or anatomical abnormalities e.g. Peyronie’s disease and phimosis were excluded. Two patients, who developed Peyronie’s disease a couple of years after the onset of SRPE and patients suff ering from daytime painful non-erotic erections during follow up, were not excluded. Information about demographics, symptomatology, psychosocial factors, fi ndings on physical examination and diagnostics were extracted from the patients’ medical fi les.

Special attention was paid to the applied treatment modalities and their eff ectiveness, as well as their adverse event profi le. Questionnaires (see Appendix) about the subjective perception of short- and long-term results were send to all patients. Classifi cation of treatments was based on their answers: 0 = no eff ect, 1 = partial remission and 2 = full remission. Satisfaction concerning the achieved eff ect was classifi ed into three categories; 0 = dissatisfi ed, 1 = moderately satisfi ed and 2 = satisfi ed.

Analysis

Data were analyzed using IBM SPSS Statistics Data Editor version 23. The primary endpoints of treatment effi cacy on the short term (fi rst three months of treatment) were change in frequency and duration of the SRPEs as reported by the patient. Frequency was divided into six categories (0 = no SRPE, 1 = 0-1, 2 = 1-2, 3 = 2-3, 4 = 3-4, 5 = 4-5, 6 = more than 5 times per night). Duration was classifi ed into fi ve categories (0 = no SRPE, 1 = 1-15minutes, 2 = 16- 30 minutes, 3 = 31-60 minutes, 4 = more than 61 minutes). Diff erences between the average frequency and duration of SRPEs

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of the patients treated with baclofen before and (years) after treatment was estimated using the Wilcoxon Signed Rank test. All tests were two-tailed and a significant difference was defined as a p-value ≤ 0.05. Effect size was interpreted according to Cohen. The baclofen group alone was big enough to be assessed in this manner. Participants who quit treatment prematurely due to side effects or for other reasons still contributed to the average outcomes. Data of patients who did not return the questionnaire were disregarded for follow-up analysis.

Results

Demographics

We included 24 patients with a median age of 53 (38-74) at the onset of SRPEs. Twenty-two answered the questionnaires. All men were heterosexual and most of them married for a longer period of time. Two were in a divorce during the onset of SRPEs, two were single and one man had recently become a widower. Table 1 summarizes the medical or psychiatric history including urogenital, abdominal- or spine surgery, chronic- and psychiatric disease and urological illness.

Symptomatology

The median (range) time between the onset of SRPEs and the first consultation of a urologist was 2,5 years (0.5-20 years). The median frequency of nocturnal awakenings as result of a painful erection was three times a night (range 1-10), and the erection persisted <15 minutes in 45% of the patients. In 37% the duration was shorter than 60 minutes and in four (18%) the SRPEs persisted up to one hour. The pain was often described as stabbing, aching and/or pressing. Twelve of the 24 patients reported radiation to one or more adjacent areas (Table 2).

After waking up from an SRPE, several maneuvers were applied to achieve detumescence (Figure 1). Urinating and walking around proved to be the most effective; respectively in 54 and 50% of the 22 patients. There were varying experiences concerning the effect of alcohol and eating before bedtime. However, all men reported that staying in bed maintained or even worsened the erection. One patient explicitly mentioned that marital issues and related stress were strongly influencing his complaints. After the divorce, he said, his SRPEs had disappeared spontaneously. One more patient noticed a relation between stress levels due to his work and the severity of his complaints.

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67 Table 1. Patient characteristics. Overview of medical history with special attention to surgical, urologic and psychiatric history.

COPD = chronic obstructive pulmonary disease; M. = Morbus; OSAS = obstructive sleep apnea syndrome; CPAP = continues positive airway pressure; LUTS = lower urinary tract symptoms; TUR= transurethral resection

Over eighty percent reported sexual satisfaction to be unchanged since start of the symptoms. SRPEs appeared not to impair erectile function. However, sex drive decreased in 8 out of the 24 men (33%). All patients complained about sleep deprivation and for nearly all of them this was the main reason why they had consulted a physician. Daytime sleepiness and fatigue was reported by 78.8%. In 25% (n=6) daytime fatigue had forced them to partial or complete work absenteeism. General history Cardiovascular disease Diabetes Mellitus II Pulmonary disease Prolactinoma Multiple Sclerosis Epilepsy M. Bechterew Hypothyroidism M. Steinert OSAS Chronic- fatigue syndrome 6 3 3 1 1 1 1 1 1 1 1 hypertension 2x, supraventricular tachycardias 2x, atrial fibrillation2x asthma 1x, COPD 1x, emphysema 1x

treated with CPAP

Operations Abdominal Urogenital Spine 6 3 2

appendectomy 3x, inguinal hernia correction 2x, epigastric hernia correction 1x

scrotal surgery 2x, TUR-prostate 1x herniated nucleus pulposus operation 2x

Urologic history LUTS Premature ejaculation Varicocele Post-vasectomy syndrome Priapism 5 1 1 1 1

for which treatment with α-blocker 3x, together with anticholinergic 1x + pelvic physiotherapy 1x, with TUR-prostate 1x surgery needed

surgery needed

1x drainage + injection of phenylephrine

Psychiatric history

Mood disorder 2 depression 2x, 1x together with anxiety disorder

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Table 2. Pain radiation (n=12)

*_{= patient also experienced painful non-erection erections during daytime} †_{=patient also experienced lower urinary tract symptoms (LUTS)}

Figure 1. Maneuvers performed by the patients to achieve detumescence.

Patient (Hemi)scrotum Groins Perineum Glans _penis Lower _abdomen

1*† _x _x _x 2 x 3 x x 4 x 5*† _x _x 6*† _x 7 x 8*† _x 9 x 10 x 11* x x x 12† _x _x Total 7 2 4 4 2 0 10 20 30 40 50 60 urinating walk

around "think theerection away"

bending

the knees ejaculationbefore bedtime cooling Pe rce nt ag e of SR PE pat ie nt s ( n=22)

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69 Diagnostics

In 22 out of the 24 patients, serum testosterone levels were measured in the morning in between 9- 10am. The mean (±SD) serum testosterone level was 16.4 nmol/l (±5.07). Six had a level below 14 nmol/l. The patient with a level of 5.6 nmol/l had a history of prolactinoma. None of the patients had a testosterone level above the upper limit.

To visualize the duration and intensity of the SRPEs, in 15 out of 24 patients nocturnal penile tumescence and rigidity (NPT-R) measurements were performed. In two patients NPT-R was combined with a polysomnography (PSG). According to the age-related criteria formulated by Burris et al. NPT-R measurements were aberrant in 7 of these 15 patients and showed prolonged episodes with erection.[3] One patient could not fi nish the NPT-R measurement due to pain and the other seven showed a normal pattern. One of the two patients in whom PSG was performed showed typical characteristics: an increased percentage of REM sleep (25%) and all REM episodes accompanied by erection and subsequent awakening, resulting in sleep fragmentation and reduced sleep effi ciency of 73%. Simultaneously performed electromyography (EMG) of the pelvic fl oor muscles showed irregular increase of muscle tonus during REM-sleep episodes. In the other patient, PSG showed no abnormalities.

In eight men a Doppler ultrasound of the cavernosal arteries was made, which showed an increased rest fl ow in three of them, 0.26, 0.28 and 0.37 m/s respectively. The others showed normal values.

Treatment and follow-up

Before the initial visit to our outpatient clinic a wide variety of drugs had been tried by patients prescribed by several specialists, including benzodiazepins (clonazepam, nitrazepam and oxazepam), opiates (tramadol, oxycontin), anti-epileptics (carbamazepine, pregabaline), antidepressants (mirtazapine, paroxetine, venlafaxine and amitriptyline), antihypertensives (β-blockers and clonidine) and β-agonists (terbutaline). Except for amitriptyline, none of these medications was eff ective (enough) and/or had caused too much disabling side eff ects. After fi rst consultation at our clinic four out of the 24 patients refrained from further treatment. After extensive counseling with regard of the off -label use 18 out of the remaining 20 patients were willing to try a pharmacological treatment, with or without non- pharmacological interventions as pelvic physiotherapy and/or sexological counseling. Two patients received only non-pharmacological treatment. Table 3 summarizes the data on the applied treatment per patient, its short-term eff ect and reported side eff ects. In 22 out of 24 patients, data were available on the long-term results of the treatment after a median (range) follow-up of 5.0 years (0.5-17.0).

Baclofen

Of the 18 patients receiving pharmacological treatment 14 were treated with baclofen (Lioresal®) starting with a dose of 10mg ante noctum. Depending on the (side) eff ects the patient was advised to increment the dose, initially up to a maximum of 40mg. However, two men required a dosage of respectively 75mg and 80mg before adequate improvement was noticed. Five out

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of the 14 patients treated with baclofen (35.7%) experienced completeremission of symptoms after a few weeks, eight (57.1%) noticed partial improvement and in one (7.1%) baclofen was not effective at all. Generally, baclofen was well tolerated. Two patients used baclofen combined with cyproteronacetate (50mg).

Table 3. Treatment. Overview applied treatment per patient with short- and long-term results (0=unaltered, 1=partial remission and 2=full remission) and reported side effects.

41 Baclofen 20mg 1 none 44 Baclofen 10mg 2 none 55 Baclofen 30 mg 1 weight gain 66 Baclofen 20mg 1 debilitating headache 69 Baclofen 30mg 1 none

53 Baclofen 10mg + Cyproteronacetate 50mg 1 loss of sexdrive 71 Baclofen 20mg + Cyproteronacetate 50mg 2 none 58 Baclofen 75mg

Cyproteronacetate 20mg 2 0 none loss of sexdrive, erectile dysfunction 40 Baclofen 20-30mg Cyproteronacetate 50mg Amitriptyline Pelvic physiotherapy 1 0 0 0

myalgia with 30mg, none with 20mg none

delusions, suicidal thoughts none 43 Baclofen 30mg Cyproteronacetaat 10 mg+ Amitriptyline20mg Cyproteronacetaat 30mg 0 0 0 mild drowsiness

loss of sexdrive, erectile dysfunction itching around genitals

47 Baclofen 30mg Cyproteronacetaat 10mg Amitriptyline Carbamazepine Pelvic physiotherapy 2 0 1 0 0 none fever?

drowsiness, mood swings none none 62 Baclofen 80mg Cyproteronacetaat 50mg Amitriptyline 30mg Tadalafil 5mg 1 0 1 0 none none none more erections 53 Baclofen 30 mg

Carbamazepine 100mg 1 1 mild fatigue/lethargy (in morning) none 53 Tadalafil 5mg

Baclofen 10 mg ? 2 none mild headache (sometimes) 47 Amitriptyline

Pelvic physiotherapy 0 2 none none 65 Tadalafil 5mg + Pelvic physiotherapy 2 none 58 Tadalafil 5mg 2 none

47 Sexologist 1 none

49 Sexologist+ venlafaxine 1 none 74 Sexologist + Pelvic physiotherapy 2 none

38 - 0 -

41 - 1 -

50 - 2 -

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In 12 of the 14 patients long-term information was available. We looked at results of baclofen on frequency and duration of the SRPEs after a mean follow-up of 4.5 years (±3.25). (Figure 2). The Wilcoxon Signed Rank test showed a statistical signifi cant decrease of mean SRPE frequency in the whole series of patients treated with baclofen (p= 0.026), with a medium eff ect size (Z= -2.232, r = -0.43). The same was assessed for SRPE duration. The mean SRPE duration of the whole series of patients using baclofen had decreased signifi cantly (p= 0.038), with again a medium eff ect size (Z= -2.070, r=-0.43).

Four patients (33.3%) were completely free of symptoms, of whom two were still using baclofen. Two (16.7%) experienced a partial remission about which one was completely satisfi ed, in contrast to the other. In six (50%) SRPEs fully relapsed after discontinuation of baclofen. Only three patients were successfully using baclofen after respectively 0.5, 4.5 and 1 year(s) in the absence of any signifi cant side eff ects (Figure 2).

Figure 2. Long-term treatment results of baclofen. Median and interquartile range of SRPE frequency and duration before treatment compared with SRPE frequency and duration after long-term follow-up in patients treated with baclofen. SRPE 1⁄4 sleep-related painful erection.

Before treatmentAfter treatment 0 1 2 3 4 5 6 SRPE frequency

Long-term treatment results of baclofen

Before treatmentAfter treatment 0 1 2 3 4 5 SRPE duration

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Other treatment modalities

Other pharmacological treatments included cyproteronacetate (Androcur®), an antiandrogen; tadalafil (Cialis®), a phosphodiesterase type 5 inhibitor (PDE-5-inhibitor); and amitriptyline (Sarotex®), a tricyclic antidepressant (TCA).

Cyproteronacetate was used by 7 patients, dosages varying from 10-50mg, and was only efficacious in one, who used 50mg cyproteronacetate combined with baclofen 20mg. The remaining patients reported no relieving effect whatsoever. Moreover, the drug caused debilitating side effects including loss of sex drive and impaired sex-related erections. Tadalafil 5mg once a day was used in four patients and two of them experienced full remission (one also had pelvic floor physiotherapy). This beneficial effect on the short-term sustained on the long-term, but to a lesser extent after respectively five years and six months of treatment. The other two patients experienced either no improvement or even aggravation of symptoms.

Amitriptyline was prescribed to five patients, of whom one used it combined with cyproteronacetate and the other four used it as monotherapy. Two of these five reported partial remission, but the other three (amongst whom was the one patient using combination therapy) experienced no remission whatsoever. Furthermore, three mentioned disabling side effects including drowsiness and mood disorders.

Five patients were referred to a pelvic floor physiotherapist. In two of them the therapy was combined with either tadalafil 5mg or sexological counseling. In the remaining three pelvic floor physiotherapies were used as a last resort treatment option after several previously disappointing experiences with drugs. Two patients experienced not any remission of symptoms. The other three reported full symptom remissions on the short term, amongst whom one received simultaneous sexological counseling, one used tadalafil at the same time and one tried pelvic floor physiotherapy as a monotherapy.

Of the four patients using no treatment in any form, one was completely free of symptoms, one experienced partial remission, one suffered from SRPEs unabatedly and in one data on this subject were not available.

Discussion

To our knowledge this series is the largest study describing patients with SRPEs with a relatively long follow-up. Data show heterogenicity with regard to age of onset (38-74 years) and medical background. The symptomatology of SRPEs, however, appears to be remarkably similar in all patients. In the majority the SRPEs do not negatively affect their sex life. However, they cause significant sleep deprivation and a vast majority (79%) suffers from fatigue with big implications on daily life. We found no association between SRPEs and comorbidity.

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Initially almost all patients treated with baclofen (10-75mg) reported a substantial relief of symptoms. However, on the long-term only 41.6% of the baclofen users was satisfi ed about treatment results, mostly due to relapse of symptoms after discontinuation.

A variety of other drugs were used with variable results. More frequently used medicines, including amitriptyline (n=5) and cyproteronacetate (n=7), were discontinued at an early stage because of debilitating side eff ects. Moreover, in our patients cyproteronacetate had little or no eff ect on SRPEs. This is remarkable while sleep related erections (SREs) are more androgen dependent than erections related to sexual activities.[4-6] Other pharmacological treatment forms were used in only a small number of patients which makes it impossible to draw any conclusions.

Baclofen is a muscle relaxant with spinal and central point of action. Rourke et al. fi rst reported on the use of oral nightly baclofen 40 mg in the management of recurrent priapism in patients with neurological lesions.[7] On spinal level baclofen inhibits mono- and polysynaptic refl ex transmission in the aff erent terminal nerves. Theoretically, the effi cacy of baclofen in patients with SRPEs may also be based on relaxation of the ischiocavernous-, bulbospongious- and other pelvic fl oor muscles. This probably proceeds through stimulation of gamma aminobutyric acid(GABA)-β-receptors, impeding the release of glutamic and aspartic acid. Stimulation of the GABA-ergic system has an inhibitory eff ect on the frequency of nocturnal erections.[8,9] Some of our observations suggest that SRPEs can be related to hypertonia of the pelvic fl oor muscles. These include the radiation of the penile pain to adjacent areas, the high concomitant occurrence of lower urinary tract symptoms (LUTS), the relationship with psychological stress and the alternating increased pelvic fl oor muscle tone during REM-sleep. In addition, we found positive long-term treatment results of pelvic fl oor physiotherapy in three out of fi ve patients.

There are some similarities in SRPE patients and in those with so-called stuttering priapism (also mentioned intermittent or recurrent priapism). The European guideline states that the etiology of stuttering priapism is similar to that of ischemic priapism, sickle cell disease being the most common cause.[10] According to the UK guidelines stuttering priapism is often either self-limiting or resolves following oral medication or conservative therapeutic maneuvers that patients themselves develop e.g. waking up, going up and down stairs or exercising.[11] In fact, the UK guidelines consider patients with stuttering priapism as a group with no obvious underlying risk factors who often present with self-limiting SRPEs, in other words, also with erections lasting shorter than one hour. In contrary to the European guidelines those out of the UK do not confi rm that in case of stuttering priapism a period of erection of at least 4 hours is obligate.

Our results show a couple of diff erences between stuttering priapism and SRPEs. None of the SRPE patients suff ered from a hematological disease, which is the most common cause of stuttering priapism. Moreover, the duration of the last nocturnal erection in patients with stuttering priapism often persists during three to four hours and in one third of all cases ends with ischemic priapism requiring emergent intervention.[6] In contrary, the duration of SRPEs after awakening is often less than one hour and even limited to <15 minutes in a large amount of patients. Moreover, none of the patients with SRPE needed intervention other than cooling, micturition, walking around or simply “thinking the erection away”. Although we describe fi ve patients who developed painful non-sex-related erections during daytime, we could not diagnose stuttering priapism, while

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these erections disappeared within four hours. Moreover, in SRPEs there is a complete erection, while in stuttering priapism the erection is limited to the cavernous bodies.

This study concerned a retrospective analysis of a limited population. For this reason, the results were mostly descriptively assessed. Furthermore, it was not possible to compare the effect of all different treatment forms applied in our patient population, while several drugs had already been applied before they visited our outpatient clinic and groups were too small. The interpretation of treatment results was strongly dependent on the patients’ subjective perceptions.

However, compared to previous studies the systematic overview of symptomatology and impact of this parasomnia in daily life comprised a relatively large number of patients. In addition, this study provides a direction for future research, especially with regard of the role of the pelvic floor muscles.

Conclusions

SPRE is a poorly recognized parasomnia which is difficult to objectify and has debilitating consequences for daily life. However, sex life is not impaired in the majority of patients. Although the aetiology and pathophysiology of SRPEs is not yet clarified, our results suggest involvement of hypertonic pelvic floor muscles. According to our overview of the clinical presentation of SRPE, we believe that it differs substantially from stuttering priapism. Ideally diagnostics would standardly include NPT-R measurement with simultaneous PSG and EMG, but in practice this is very difficult to realize. Moreover, it would be interesting to aspirate blood out of the cavernous body during an SRPE to exclude ischemia.

The results of this study suggest that relief of SRPEs and consequent improvement of sleep architecture might best be achieved by baclofen, rather than other treatment modalities. However, pelvic physiotherapy showed promising results in 3 out of 5 patients and its role in the treatment of SRPE needs to be furthers assessed.

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References

Ferre A, Vila J, Jurado MJ, Arcalis N, Camps J, Cambrodi R, Romero O. Sleep-related painful erections associated with obstructive sleep apnea syndrome. Arch Sex Behav 2012;41(4):1059-63.

van Driel MF, Beck JJ, Elzevier HW, van der Hoeven JH, Nijman JM. The treatment of sleep-related painful erections. J Sex Med 2008;5(4):909-18.

Burris AS, Banks SM, Sherins RJ. Quantitative assessment of nocturnal penile tumescence and rigidity in normal men using a home monitor. J Androl 1989;10(6):492-7.

Giuliano F, Rampin O. Neural control of erection. Physiol Behav 2004 Nov 15;83(2):189- 201.

Montorsi F, Oettel M. Testosterone and sleep-related erections: an overview. J Sex Med 2005 Nov;2(6):771-84. Hoeh MP, Levine LA. Management of Recurrent Ischemic Priapism 2014: A Complex Condition with Devastating Consequences. Sex Med Rev 2015(3):24-35.

Rourke KF, Fischler AH, Jordan GH. Treatment of recurrent idiopathic priapism with oral baclofen. J Urol 2002;168(6):2552.

Gulia KK, Mallick HN, Kumar VM. Sleep-related penile erections do not occur in rats during carbachol-induced rapid eye movement sleep. Behav Brain Res 2004;154(2):585-7.

Andersen ML, Tufi k S. Inhibitory eff ect of GABAergic drugs in cocaine-induced genital refl exes in paradoxical sleep-deprived male rats. Pharmacol Biochem Behav 2004 Jun;78(2):301-7.

Salonia A, Eardley I, Giuliano F, Hatzichristou D, Moncada I, Vardi Y, et al. European Association of Urology guidelines on priapism. Eur Urol 2014 Feb;65(2):480-9.

Muneer A, Ralph D. Guideline of guidelines: priapism. BJU Int 2017 Feb;119(2):204-8.

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Supplemental material - Questionnaire Sleep Related Painful Erections (SRPE)

Patient characteristics and symptomatology during the ﬁ rst consultation at the outdoor clinic Urology at the University Medical Centre Groningen

Age: ... years Nationality: ...

1. For how long did the complaints exist already before you went to see the general practitioner? o 0 - 0,5 years o 0,5 - 1 years o 1 - 2 years o 2 - 5 years o 5 - 10 years o > 10 years

2. What was your marital status at the time? o married since...years

o single

o in a relationship; living together o long distance relationship o (recently) divorced o widower

o otherwise, namely... 3. What is your sexual orientation? o Heterosexual

o Homosexual o Bisexual

4. How many times did you wake up due to a painful erection per night? o 1 - 2 timesper night

o 2 - 3 timesper night o 3 - 4 times per night o 4 - 5 times per night o > 5 times per night o I never woke up

5. For how long persisted the erection after waking up? o 0 - 15 minutes

o 15 - 30 minutes o 30 - 60 minutes o > 60 minutes

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6. What did you do to make the erection go away?

Please tick the boxes of these below mentioned measures that did or did not help you.

yes no never tried

- stand up and walk aroud - try to “think the erection away” - micturition

- achieve ejaculation by masturbation - cooling (ice packs/cold shower) - pull up the knees

- physical exercise

- have intercourse before sleep - otherwise, namely

... ... 7. Which measure worsened the SRPEs ?

yes no I don’t know

- lay flat on the back - masturbation

- have intercourse before sleep - type of food/drinks

- if yes, which?... - physical exercise

- otherwise, namely... 8. How would you describe the pain sensation?

o burning o stabbing o nagging o stinging

o otherwise, namely: ... 9. Where was the pain localised during an SRPE? (More answers possible)

o inside the penis o at the glans penis o scrotal/testical o inguinal o perineal/anal o otherwise, namely ... o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o

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Quality and function of erotic erections (e.g. during intercourse, masturbation, sexual fantasies or other sex-related activities)

10. Are/were your erotic erections painful as well? o never

o sometimes o always

11. Did you also experience non-sex-related painful erections during daytime? o yes, sometimes

o yes, regularly o yes, allthetime o never

12. How would you describe your erectile function compared to the time before the onset of SRPEs?

o Exactly the same as before

o The erotic erection is less tumescent, but I’m perfectly able to penetrate and reach orgasm o The erotic erection is obviously less tumescent, I can no longer penetrate

o The erotic erection is completely disturbed/absent o The erotic erection seems more tumescent as before

13. How was your satisfaction about your sexlife before the onset of SRPEs? o very satisfi ed

o fairly satisfi ed

o about equally satisfi ed and dissatisfi ed o fairly dissatisfi ed

o very dissatisfi ed

14. How was your satisfaction about your sexlife during the time you suff ered from SRPEs? o very satisfi ed

o fairly satisfi ed

o about equally satisfi ed and dissatisfi ed o fairly dissatisfi ed

o very dissatisfi ed

15. Did your libido/sexdrive change during the onset of SRPEs? o as much sexdrive

o reduced sexdrive o increased sexdrive

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Impact on daily life

16. It is known that patients with SRPEs suffer from interrupted sleep as a consequence of frequent awakenings due to painful nocturnal erections. To what extent did you experience daytime fatigue as a result of your complaints?

o I did not experience daytime fatigue o I was moderately fatigued during daytime o I was severly fatigued during daytime

17. To what extent did you experience limitations in daily life due to SRPEs? o I could perform my activities without any limitations

o I experienced limitations, but was able to continue to do my activities o I had to call in sick partially

o I had to call in sick completely

18. Do you have any additional comments on the consequences of SRPEs on you daily life? ... ... ... ... Treatment and treatment efficacy

19. Have you been treated for your SRPEs? o Yes, I’m still receiving treatment

o Yes, but meanwhile I quit/finished thetreatment for...weeks/months/years o No, I have never been treated at my own request

o No, I have never been treated

20. Which treatment form did you receive? (more answers possible) o Pelvic floor physiotherapy

o Consultation psychologist/sexologist o Baclofen (=Lioresal®) - dosage:...

o Cyproteronacetate (=Androcur®) - dosage:... o Amitriptyline (=Sarotex®) - dosage:... o Tadalafil (=Cialis®) - dosage:... o Clonazepam (=Rivotril®) - dosage... o Tamsulosine (=Omnic®) - dosage...

o Combination of above mentioned treatmentforms namely:...

o Otherwise, namely:

... ...

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21. If applicable, how eff ective was every treatment form you received?

Full remission Partial/Temporarily Inadequate None

- Pelvic fl oor physiotherapist - psychologist/sexologist - Baclofen (=Lioresal®) - Cyproteronacetate (= Androcur®) - Amitriptyline (=Sarotex®) - Tadalafi l (= Cialis®) - Clonazepam (=Rivotril®) - Tamsulosine (= Omnic®) - Combination (see question 20)

- Otherwise, namely (see question 20)

Optional explanation: ... ... ... 22. Did you experience side eff ects? If yes, to what extent?

o I did not use any drugs (continue to question23)

o I did use drugs, but experienced no signifi cant side eff ects (continue to question23)

o I did use drugs and experienced some important side eff ects (see table)

Medication Side eff ect Description Discontinued because (yes/no) of side eff ect? (yes/no)

o Baclofen (... mg) o Cyproteronacetate(... mg) o Amitriptyline (... mg) o Tadalafi l (... mg) o Clonazepam (... mg) o Tamsulosine (... mg) o Otherwise, namely ... ... ... o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o

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23. Do you still receive any treatment for SRPEs? o No

o Yes, namely... Follow up

24. How are you now, considering your SRPEs?

o I’m completely free of symptoms, without receiving any treatment (go to question 26)

o I’m completely free of symptoms, while receiving above mentioned treatment (go to question 26)

o I experience SRPEs to a lesser extent without receiving any treatment and I am satisfied about it

o I experience SRPEs to a lesser extent without receiving any treatment, but I am dissatisfied about it

o I experience SRPEs to a lesser extent while receiving above mentioned treatment and I am satisfied about it

o I experience SRPEs to a lesser extentwhile receiving above mentioned treatment, but I am dissatisfied about it

o I still experience serious SRPEs without receiving any treatment, but I wish no further treatment, because ... ... o I still experience serious SRPEs without receiving any treatment and I would like to try

(another) treatment (form).

o I still experience serious SRPEs while receiving above mentioned treatment

25. How many times do you wake up due to a painful erection per night at this moment? o 1-2 times per night

o 2-3 times per night o 3-4 times per night o 4-5 times per night o >5 times per night o In ever wake up

26. How long does the SRPE persist after waking up at this moment? o 0-15 minutes

o 15-30 minutes o 30-60 minutes o >60 minutes

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27. Can you briefl y summarize below how your symptoms developed after your last visit at our outpatient clinic.

... ... ... ... ... ... ... ... ... ... ... ... 28. How do you envisage the future considering your SPRE complaints?

... ... ... ... ... ... ... ... 29. I want to receive a copy of the manuscript after ﬁ nishing the study

yes/no 30. Any comments? ... ... ... ... ... ... ... ... Thank you very much for you time!

S. Vreugdenhil M.F. van Driel

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