Glimpses into the molecular pathogenesis of Peyronie's disease.

Peyronie's disease (PD) is a fibroproliferative disease of the penis. Since little is known about the molecular pathogenesis of PD, we compared the biochemical make-up of PD plaques with normal tunica albuginea to clarify pathological processes in the scarred tissue. Protein and mRNA levels were measured in plaques and in unaffected pieces of the tunica albuginea. We investigated the presence of myofibroblasts, the deposition of collagens, and some key elements of Wnt and YAP1 signaling at protein level. The expression of 45 genes, all related to collagen homeostasis and extracellular matrix proteins, was quantified. In plaques, more myofibroblasts were present, and we observed an activation of Wnt signaling and YAP1 signaling. Increased levels of the collagens types I and III confirm the fibrotic nature of plaques. The mRNA ratio of collagen types III, IV, and VI to type I was increased. The expression of lysyl hydroxylase 3 was higher, whereas a decreased expression level was seen for fibronectin and cathepsin K. The biochemical composition of plaques was different from unaffected tunica albuginea: the relative and absolute abundance of various extracellular matrix proteins were changed, as well as the quality of collagen and the level of the collagen-degrading enzyme cathepsin K.

Sleep-Related Painful Erections Following Sexual Intercourse.

Sleep-related painful erections (SRPE) is a rare disorder characterized by recurrent painful nocturnal erections during REM sleep in the absence of pain during daytime erections. Approximately 35 cases of SRPE have been reported in the literature, none of them associated with preceding sexual intercourse. We add the report of a 40-year-old patient with a 6-year history of SRPE which only, but always, occurred after sexual intercourse with ejaculation in the evening before. As a result, the frequency of intercourse diminished, causing relationship problems. A non-pharmacological solution was found in shifting the time of sexual intercourse. The patient refused any proposed pharmacological treatment, because of "not wanting to be a patient at his age."

Sleep-related erections throughout the ages.

INTRODUCTION: The occurrence of sleep-related erections (SREs) has been known since antiquity. AIM: To highlight historical, theological, and sexual medicine-related aspects of SREs throughout the ages. METHODS: Review of old medical books on male sexual functioning and review of scientific medical and theological articles on SREs from about 1900 on. RESULTS: The cyclic character of SREs was first noted by German researchers in the forties of the 20th century. However, already before the beginning of the Christian era, one knew that men had erections and ejaculations during sleep. In the Middle Ages, SREs were generally considered to be rebellious manifestations of the male body, while it seemed to disobey its owner and showed up its perverted and sinful side. From the fifteenth to the end of the 17th century, severe erectile dysfunction (ED) was ground for divorce. The ecclesiastical court records show that if necessary, the members of the jury sat at the defendant's bedside at night to be able to judge any SREs occurring. Since the 17th century, SREs were considered to be part of masturbation, which could cause many ailments and diseases. Psychoanalyst Stekel acknowledged in 1920 that a morning erection, the last SRE, is a naturally occurring phenomenon in healthy men from infancy to old age. Today, some scientists assume that SREs protect the integrity of the penile cavernous bodies. CONCLUSIONS: Throughout the ages, philosophers, theologians, physicians, members of ecclesial law courts, psychoanalysts, psychiatrists, sexologists, physiologists, and urologists have shown interest in SREs. Obviously, the observations and testing of SREs have a long history, from antiquity to modern sleep labs, in men and in women, in newborns and old adults, by penis rings with sharp spikes to fancy strain gauge devices. Despite all these efforts, the mechanisms leading to SREs and its function are however not yet completely understood.

Sexual abuse history in GI illness, how do gastroenterologists deal with it?

INTRODUCTION: Data support an increased prevalence of sexual abuse (SA) among patients with gastrointestinal (GI) complaints. Sexual abuse causes multiple symptoms related to pelvic floor and stress mediated brain-gut dysfunctions. Treating these patients asks for a holistic approach, using centrally targeted interventions. However, gastroenterologists have never been surveyed regarding their practice patterns and constraints about inquiring into SA. AIM: To evaluate whether gastroenterologists address SA in their daily practice and to evaluate their knowledge regarding the implications of SA in GI illness. METHODS: A 42-item anonymous questionnaire was mailed to all 402 members of the Dutch Society of Gastroenterology (gastroenterologists and fellows in training). The questionnaire addressed SA and pelvic-floor-related complaints. MAIN OUTCOME MEASURES: The results of this survey. RESULTS: One hundred eighty-three of the 402 (45.2%) questionnaires were returned. Overall, 4.7% of the respondents asked their female patients regularly about SA; in males, this percentage was 0.6%. Before performing a colonoscopy, these percentages were even smaller (2.4% and 0.6%, respectively). When patients presented with specific complaints, such as chronic abdominal pain or fecal incontinence, 68% of the gastroenterologists asked females about SA and 29% of the males (P < 0.01). The majority of respondents stated it as rather important to receive more training on how to inquire about SA and its implications for treatment. CONCLUSION: Gastroenterologists do not routinely inquire about a history of SA and they rarely ask about it before performing colonoscopy. There is a need for training to acquire the skills and knowledge to deal with SA.

Long-term results of an individualized, multifaceted, and multidisciplinary therapeutic approach to provoked vestibulodynia.

INTRODUCTION: Although it is highly recommended to use a multifaceted approach to treat provoked vestibulodynia (PVD), the large majority of treatment studies on PVD used a one-dimensional approach. AIM: To evaluate the long-term treatment outcome of a multifaceted approach to vulvar pain, sexual functioning, sexually related personal distress, and relational sexual satisfaction in women with PVD. METHODS: Retrospective questionnaire survey 3-7 years after treatment. MAIN OUTCOME MEASURES: Sexual functioning, sexually related personal distress, and relational sexual satisfaction were measured using the Female Sexual Function Index (FSFI), the Female Sexual Distress Scale (FSDS), and the Dutch Relationship Questionnaire (NRV), respectively. An additional questionnaire assessed socio-demographic variables, intercourse resumption, and the level to which the women would recommend the treatment to other women with PVD. Post-treatment vulvar pain scores were obtained using a visual analog scale (VAS). Pretreatment scores were reported in retrospect on a separate VAS. RESULTS: The questionnaires were completed by 64 out of 70 women (91%). Mean follow-up was 5 years (range 3-7). Comparison of the mean pretreatment and post-treatment VAS scores showed a significant reduction in vulvar pain. Pain reduction was reported by 52 women (81%), whereas no change and pain increase were reported by 7 women (11%) and 5 women (8%), respectively. Post-treatment, 80% of the women had resumed intercourse. Only 5 women (8%) reported completely pain-free intercourse. Comparisons with age-related FSFI and FSDS Dutch norm data showed that scores for sexual functioning in the study group were significantly lower, while scores for sexually related personal distress were significantly higher. There were no significant differences in relational sexual satisfaction ratings between the study group and the NRV Dutch norm data. CONCLUSION: These retrospective data on long-term treatment outcome support the hypothesis that a multifaceted approach to PVD can lead to substantial improvements in vulvar pain and the resumption of intercourse.

How do continence nurses address sexual function and a history of sexual abuse in daily practice? Results of a pilot study.

INTRODUCTION: There is a strong association between urological complaints, sexual dysfunction, and history of sexual abuse (SA), and it is unknown whether urological continence nurses integrate this knowledge in their daily practice. AIM: To evaluate how, in their daily practice, Dutch urological continence nurses address sexual dysfunction and possible SA. METHODS: An anonymous 19-item questionnaire was distributed among all Dutch urinary continence nurses visiting their yearly congress. MAIN OUTCOME MEASURES: The survey results. RESULTS: The response rate was 48.9% (93/190). Of the respondents, 11.8% did not ask their female patients about sexual function; 37.6% asked only rarely; 44.1% asked often; and 6.5% always asked. Sexual functioning in males was not evaluated by the majority of the nurses (13.2% never, and 46.2% rarely). A minority of continence nurses asked males about sexual functioning (36.3% often and 4.3% always). Important reasons for not asking were insufficient knowledge of how to adequately ask males (38.9%) and females (47.8%) about sexual problems, and because nurses assumed the urologist had addressed this issue (48.1% asking males, 39.1% asking females). Younger nurses found it particularly difficult to raise sexual issues with both male and female patients (P=0.001 and P=0.003, respectively). Screening for sexual dysfunction was stated to be important by almost all nurses (65.2% "quite important," and 31.5% "very important"). Within their patient population, both male and female, 28% of the nurses never asked about SA and 49.5% asked only rarely. CONCLUSION: Dutch urological incontinence nurses acknowledge the importance of sexual problems in their patient population, but asking about this issue was not part of routine care. The main reasons for not asking, according to the nurses' responses, were that they had insufficient knowledge and that they assumed the urologist had already asked about sexual problems.

Prevalence of sexual abuse among patients seeking general urological care.

INTRODUCTION: Sexual abuse (SA) history can be found in the backgrounds of an important fraction of men (8-10%) and women (12-25%). Until now there are no data about this prevalence within a urological patient population. AIM: To establish the prevalence of SA among men and women visiting a urological outpatient clinic and to assess their opinion on screening for SA by urologists. METHODS: A questionnaire to identify SA was translated into Dutch, English, and Turkish, and was adjusted for use in men. These questionnaires were anonymously distributed among 1,016 adult patients attending the urological outpatient clinic. MAIN OUTCOME MEASURE: The self-reported prevalence of SA. Secondary outcome measures were data about the assailant, victim's age at the time of the abuse, if the abuse was disclosed to the urologist, if the urologist had asked for SA, and patient opinions on standard screening for SA in urological care. RESULTS: A total of 878 questionnaires were returned, giving a total response rate of 86.4% (878/1,016). Thirty-three patients refused to participate. This resulted in 845 filled-out questionnaires suited for analysis (845/1,016 = 83.2%). There were more male (75.7%) than female respondents (21.8%); 2.1% (13/624) and 13.0% (21/161) of the male and female respondents reported a history of SA, respectively. Almost 42% reported a stranger as assailant. In nearly 90%, the SA took place before adulthood: 56.2% in childhood and 31.2% in adolescence. Fifteen percent of the respondents with SA had it disclosed to their urologist. More than 70% of the abused respondents considered the idea to screen for SA in urological practice to be a good one. CONCLUSIONS: The prevalence of SA in patients seeking urological care in the Netherlands is 2.1% for men and 13.0% for women.

Surgery for an "acute erection angle," when counseling fails.

INTRODUCTION: During erection, the penis increases in volume, rigidity, and angle. Textbooks of urology and sexology provide only very limited information about erection angle dysfunction. In some men, this angle is too tight toward their belly, causing problems with intercourse. AIM: We reported two cases of an acute erection angle and reviewed pertinent literature. METHODS: Comprehensive literature review was performed using PubMed. We performed additional searches based on relevant books. RESULTS: There is very limited knowledge about erection angles and the "acute erection angle." Our cases show that simple and safe surgical techniques can yield adequate results. CONCLUSION: Counseling a couple with complaints of sexual inadequacy, which has resulted specifically from the increased erection angle, should be based on objective reassuring information about anatomical and physiological facts. In selected cases surgical intervention can yield adequate results.

Sexual experiences of men with incontinent partners.

INTRODUCTION: Several studies show that urinary incontinence (UI) impairs women's sexual functioning and sexual satisfaction. However, there is no scientific knowledge about the effects of UI on sexual functioning of the male partners. AIM: To analyze sexual functioning of the male partners of females with UI. METHODS: During a period of 2.5 years all new female patients and their partners (both groups aged 18 years and older), who presented at our outpatient clinic for urological evaluation, were asked for demographic characteristics, medical history, and referral indication including the main urological complaint. In addition they were asked to fill in the Golombok Rust Inventory of Sexual Satisfaction questionnaires about sexual functioning. MAIN OUTCOME MEASURES: Sexual function measured by the Golombok Rust Inventory of Sexual Satisfaction questionnaire. RESULTS: A total of 189 sexually active couples completed the questionnaires. Eighty-one (42.9%) of the women had UI as main urological complaint. Differences were found between women with UI and those without. Women with UI have a lower overall sexual function (P = 0.02), lower frequency of intercourse (P = 0.02), more problems with communication (P = 0.036), and more often show avoidable behavior with regard to sexual activity. (P = 0.002) Men with partners with UI showed a diminished overall sexual function (6.66 +/- 1.53) compared with men with women without UI (5.95 +/- 1.22, P = 0.001). Furthermore, comparisons of subscales also demonstrate a lower frequency of intercourse (5.62 +/- 2.00, 6.49 +/- 1.96), less satisfaction (8.08 +/- 2.79, 9.69 +/- 3.63), and more erectile problems (6.01 +/- 2.28, 6.87 +/- 3.23) in men with partners with UI. (P = 0.03, P = 0.001, P = 0.037) CONCLUSIONS: This study shows that female urinary incontinence correlates with their partners' overall sexual functioning and sexual satisfaction. In addition, significant differences were found with regard to the satisfaction with one's sex life between a woman with UI and her partner.

Prevalence of Peyronie and Ledderhose Diseases in a Series of 730 Patients with Dupuytren Disease.

BACKGROUND: Dupuytren, Peyronie, and Ledderhose diseases are related fibroproliferative disorders characterized by abnormalities in the connective tissue of the palm of the hand, the tunica albuginea of the penis, and the sole of the foot, respectively. Concomitant prevalence rates of these diseases have only been described in a few small populations. This article aims to report on a large population and to raise awareness in surgeons treating Dupuytren disease for concurring related fibroproliferative disorders. METHODS: Patients diagnosed as having Dupuytren disease were recruited from outpatient clinics in the northern part of the Netherlands from 2007 to 2016. Questionnaires concerning demographics, clinical characteristics, the coexistence of Ledderhose and/or Peyronie diseases, and other factors were filled in by the participants and by plastic surgeons. RESULTS: For 730 men with Dupuytren disease, the surgeons' reported prevalence rate of Peyronie disease was 7.8 percent and of Ledderhose disease was 16.1 percent. The participants themselves reported prevalence rates of 8.8 percent for Peyronie disease and of 22.0 percent for Ledderhose disease. CONCLUSIONS: In the Dupuytren patient cohort, the prevalence of Peyronie disease was lower than that described in the literature. The prevalence of Ledderhose disease corresponded with the rates from the literature. However, both were underreported by plastic surgeons, which calls for a rise in awareness, recognition, and referral to a urologist when the conditions are bothersome or symptomatic.

THIS ARTICLE HAS BEEN RETRACTED. Physical therapy for premature ejaculation, erectile dysfunction and chronic pelvic pain syndrome.

There is limited knowledge about the exact role of the pelvic floor in male sexual functioning. Pelvic floor muscle function might be involved in the enhancement of blood flow to the penis, and evidence suggests an active role for the ischio- and bulbocavernous muscles and other pelvic floor muscles in the initiation and maintenance of erection. Increased activity of pelvic floor muscles might also be preparatory to ejaculation. Studies have shown positive results after physical therapy for erectile dysfunction, premature ejaculation and chronic pelvic pain syndrome. However, the methodological quality of some of these studies is poor and further research validating specific physical therapies in the assessment and treatment of male sexual function is necessary. In this respect physical therapists have a potential role as integral members of healthcare teams involved in the improvement of male sexual health.

Ischemic priapism as a model of exhausted metabolism.

In vivo metabolic studies typically concern complex open systems. However, a closed system allows better assessment of the metabolic limits. Ischemic priapism (IP) constitutes a special model of the compartment syndrome that allows direct sampling from a relatively large blood compartment formed by the corpora cavernosa (CC). The purpose of our study was to measure metabolic changes and the accumulation of end products within the CC during IP. Blood gas and biochemical analyses of aspirates of the CC were analyzed over an 8-year period. Mean ± SD pH, pCO2 , pO2 , O2 -saturation, lactate, and glucose of the aspirated blood were determined with a point-of-care analyzer. Forty-seven initial samples from 21 patients had a pH of 6.91 ± 0.16, pCO2 of 15.3 ± 4.4 kPa, pO2 of 2.4 ± 2.0 kPa, and an O2 -saturation of 19 ± 24% indicating severe hypoxia with severe combined respiratory and metabolic acidosis. Glucose and lactate levels were 1.1 ± 1.5 and 14.6 ± 4.8 mmol/L, respectively. pH and pCO2 were inversely correlated (R2  = 0.86; P < 0.001), glucose and O2 -saturation were positively correlated (R2  = 0.83; P < 0.001), and glucose and lactate were inversely correlated (R2  = 0.72; P < 0.001). The positive correlation of CO2 and lactate (R2  = 0.69; P < 0.001) was similar to that observed in vitro, when blood was titrated with lactic acid. The observed combined acidosis underscores that IP behaves as a closed system where severe hypoxia and glycopenia coexist, indicating that virtually all energy reserves have been consumed.

The treatment of sleep-related painful erections.

INTRODUCTION: As specialists in male genital problems, urologists and sexologists will most likely to be involved in the treatment of males presenting with sleep-related painful erections (SRPEs). This means that this phenomenon needs to be recognized by urologists and sexologists, and that they should have knowledge of the current diagnostic and therapeutic approaches. Aim. To review the literature on SRPE and to find the best pharmacological treatment. Methods. Four personal clinical observations from two clinics and 29 other cases with SRPE found in PubMed were analyzed, especially regarding the results of pharmacological treatment. MAIN OUTCOME MEASURES: The results of pharmacological treatment. RESULTS: Many of the various treatments proved to be ineffective and only a few showed efficacy for a few weeks or months. The only effective drugs in the long term were baclofen, clonazepam, and clozapine. CONCLUSIONS: Until now, the phenomenon of SRPE is not well understood. The rarity of the published cases undoubtedly does not reflect the actual occurrence of SRPE. Controlled double-blind pharmacological trials are needed, and long-term follow-up including polysomnography coupled with nocturnal penile tumescence and rigidity monitoring may provide further information about SRPE.

[Erectile dysfunction from a urological perspective]. / Erectiele disfunctie in urologisch perspectief.

Erectile dysfunction is the continuous or recurring inability to get or to maintain an erection rigid enough for sexual activity. Non-urologists will often restrict themselves to counselling, lifestyle advice or the prescription of an erection pill. However, most erection pills are manufactured and traded illegally. The Dutch Institute for Rational Use of Medicine has repeatedly pleaded the case for over-the-counter trading, but the Dutch College of General Practitioners opposes this. It is the needs expressed by the patient and the appropriate expertise rather than the cause of the problem that determine referral. For some patients intracavernous self-injection with vasoactive substances may be an acceptable solution. Implantation of a penile prosthesis is currently carried out under stringent conditions at a limited number of healthcare centres. In the 2018 Dutch urological training programme, residents are able to apply for an internship in andrological urology and engage in the diagnosis and treatment of sexual dysfunction.

Verteporfin as a Medical Treatment in Peyronie's Disease.

INTRODUCTION: In Europe and the United States, verteporfin (Visudyne; VP) is registered and used in treating macular degeneration. Research showed that VP decreased expression of fibrotic genes in fibroblasts collected from nodules of patients suffering from Dupuytren's disease, plausibly by de-activating transcription in the Yes Activated Protein (YAP) pathway. AIM: To analyze the effect of VP on myofibroblasts cultured from Peyronie's disease (PD) plaques. METHODS: At surgery for PD we took biopsies from the plaques of 5 patients. By immunostaining, the presence of the pathologic myofibroblasts was determined. After culturing cells, VP was dispensed in starvation medium for 24 and 48 hours and messenger(m)RNA levels of COL1A1, ACTA2, COL5A1, EDA-FN, LOXL2, CCN2, SERPINH1, PLOD2, and YAP were quantified and compared with controls with real-time polymerase chain reaction. MAIN OUTCOME MEASURE: mRNA-levels of COL1A1, ACTA2, COL5A1, EDA-FN, LOXL2, CCN2, SERPINH1, PLOD2, and YAP. RESULTS: The pathologic phenotype of cells isolated from PD plaques was confirmed with baseline immunofluorescent stainings that showed considerable levels of α-smooth muscle actin, being a marker for the presence of myofibroblasts. The mRNA ratios of all the genes related to fibrosis (COL1A1, etc.) except YAP decreased significantly after treatment with VP within 24 and 48 hours. These results suggest inhibition of fibrosis in the YAP cascade, downstream of YAP. CONCLUSION: In our opinion, urologists must move the focus to disease before deformity, and the search for new oral or intralesional agents, well-tolerated and effective in both the acute and chronic phase of PD must continue. VP blocked the expression of genes related to fibrosis in the YAP cascade in myofibroblasts derived from PD plaque. Mohede DCJ, de Jong IJ, Bank RA, et al. Verteporfin as a medical treatment in Peyronie's disease. Sex Med 2018;6:302-308.

Physiology of Penile Erection-A Brief History of the Scientific Understanding up till the Eighties of the 20th Century.

INTRODUCTION: Understanding the physiology of penile erection is important for all who work in the field of sexual medicine. AIM: The aim of this study was to highlight and analyze historical aspects of the scientific understanding of penile erection. METHODS: (i) Review of the chapters on the physiology of erection out of the author's collection of books dealing with male sexual functioning published in the German, French, Dutch, and English language in between 1780 and 1940. (ii) Review of the topic "physiology of penile erection" of relevant chapters of C lassical writings on erectile dysfunction. A n annotated collection of original texts from three millennia, including the study of all relevant references mentioned in these books. MAIN OUTCOME MEASURE: The main outcome measure used for the study was the scientific understanding of the physiology of penile erection. RESULTS: In Antiquity, Galen considered penile erection as the result the accumulation of air. His ideas so dominated medieval medicine that nearly everyone then alive was a Galenist. The beginning of the Renaissance shows meaningful examples of experimental scientific work on the penis. Da Vinci correctly concluded that erections were caused by blood, and in the 18th century, Von Haller from Switzerland was the first who explained that erections were under the control of the nervous system. In the 19th century, a mindset that emphasized on experimentation determined a new direction, namely experimental physiology. Animal studies clarified that stimulation of the nervi erigentes-induced small muscle relaxation in the corpora cavernosa. Nearly all were published in the German language. That may be one of the reasons that the existence of the concept of smooth muscle relaxation remained controversial until the first World Congress on Impotence in 1984 in Paris. CONCLUSIONS: As the Renaissance's innovative research defined neural and vascular physiologic phenomena responsible for penile erection. The concepts from animal experimentations in Europe in the 19th century significantly contributed to the current understanding of penile erection. van Driel MF. Physiology of penile erection-a brief history of the scientific understanding up till the eighties of the 20th century. Sex Med 2015;3:343-351.

Male sexuality after cancer treatment--needs for information and support: testicular cancer compared to malignant lymphoma.

Testicular cancer (TC) as well as malignant lymphoma (ML), both have nowadays an excellent prognosis. However, both types of cancer may be diagnosed at young adulthood and patients may experience sexual concerns. In this article the need for information and support concerning sexuality will be explored, and the traumatic impact of cancer diagnosis with respect to this will be considered. A total of 264 patients with testicular cancer, median age 36 (S.D. 9.7) years, and 50 patients with malignant lymphoma, median age 42 (S.D. 11.7) years returned a questionnaire concerning sexual functioning; four items assessed the need for information or support concerning sexuality, at diagnosis and at follow-up. It appeared that more than half of the patients with testicular cancer reported a lack of information and support concerning sexuality during treatment; 67% of them still had a need for information at follow-up. These rates were significantly lower for patients with malignant lymphoma. Especially patients with testicular cancer who suffered sexual dysfunction reported extremely high needs for information and support. According to these findings it can be concluded that more attention should be paid to the doctor-patient communication with respect to sexual concerns in general, and especially where it concerns patients with testicular cancer.

Type B aortic dissection after the use of tadalafil.

A 63-year-old male patient with a type B aortic dissection after the use of tadalafil, a phosphodiesterase type 5 inhibitor, is presented. The possible role of a novel predisposing factor--sexual activity combined with tadalafil--is reviewed. This report and three other cases add a new dimension to the known predisposing factors such as chronic systemic hypertension, hereditary connective tissue diseases- and congenital aortic valve diseases. However, the precise role of phosphodiesterase type 5 inhibitors in the pathophysiology of aortic dissection remains unknown.