Restless Genital Syndrome (ReGS) Should Be Distinguished From Spontaneous Orgasms: A Case Report of Cannabis-Induced Spontaneous Orgasm.

A case is described of a 40-year-old woman with persistent spontaneous orgasms after use of cannabis and five hours of intense pounding sexual activity. She presented with severe anxiety, in particular suffering from restless genital syndrome (ReGS). However, she did not fulfill any of the five criteria of ReGS. It was concluded that her spontaneous orgasms were the result of the use of cannabis combined with the long duration of previous sexual activity. This finding is not only important for physicians, but also for highly exposed subjects such as those active in the sex industry.

Toward a More Evidence-Based Nosology and Nomenclature for Female Sexual Dysfunctions-Part II.

INTRODUCTION: Current Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) definitions of sexual dysfunction do not identify all sexual problems experienced clinically by women and are not necessarily applicable for biologic or biopsychosocial management of female sexual dysfunction. A unified nomenclature system enables clinicians, researchers, and regulatory agencies to use the same language and criteria for determining clinical end points, assessing research results, and managing patients. AIM: To develop nomenclature with classification systems for female sexual desire, arousal, and orgasm disorders with definitions pertinent to clinicians and researchers from multiple specialties who contribute to the field of sexual medicine. METHODS: Key national and international opinion leaders diverse in gender, geography, and areas of expertise met for 2 days to discuss and agree to definitions of female sexual desire, arousal, and orgasm disorders and persistent genital arousal disorder. The attendees consisted of 10 psychiatrists and psychologists; 12 health care providers in specialties such as gynecology, internal medicine, and sexual medicine; three basic scientists; and one sexuality educator, representing an array of societies working within the various areas of sexual function and dysfunction. MAIN OUTCOME MEASURE: A unified set of definitions was developed and accepted for use by the International Society for the Study of Women's Sexual Health (ISSWSH) and members of other stakeholder societies participating in the consensus meeting. RESULTS: Current DSM-5 definitions, in particular elimination of desire and arousal disorders as separate diagnoses and lack of definitions of other specific disorders, were adapted to create ISSWSH consensus nomenclature for distressing sexual dysfunctions. The ISSWSH definitions include hypoactive sexual desire disorder, female genital arousal disorder, persistent genital arousal disorder, female orgasmic disorder, pleasure dissociative orgasm disorder, and female orgasmic illness syndrome. CONCLUSION: Definitions for female sexual dysfunctions that reflect current science provide useful nomenclature for current and future management of women with sexual disorders and development of new therapies.

Interview with Oswalt Kolle (1928-2010): German sex education pioneer.

INTRODUCTION: Alfred Kinsey (1894-1956) was the first pioneer of scientific sexology after World War II with his surveys on human sexuality in the male (1948) and the female (1953), which underwent worldwide translations and also had a major impact in Europe. AIM: To clarify the role of the journalist Oswalt Kolle (1928-2010) as the promoter of sex education in Germany and Western Europe in the late 1960s. METHODS: The information is almost exclusively based on a live interview taken with the time witness Oswalt Kolle in February 2010. This scientific technique of oral history is well established in the field of history research today. RESULTS: Kolle has a strong family background in the medical field as his father was a well-known psychiatrist and his grandfather a prominent bacteriologist. Before starting an interest in sex education, Kolle was a successful journalist by interviewing celebrities but turned into one of the most important critics against the restricted views on sex in Germany and Western Europe in the 1960s. His books and films on sexuality were translated into at least 12 languages and were major blockbusters for at least a decade. CONCLUSIONS: Oswalt Kolle had more influence on the public awareness and practice of sexuality in Western Europe and especially Germany than any other single person in his time.

An update of the International Society of Sexual Medicine's guidelines for the diagnosis and treatment of premature ejaculation (PE).

INTRODUCTION: In 2009, the International Society for Sexual Medicine (ISSM) convened a select panel of experts to develop an evidence-based set of guidelines for patients suffering from lifelong premature ejaculation (PE). That document reviewed definitions, etiology, impact on the patient and partner, assessment, and pharmacological, psychological, and combined treatments. It concluded by recognizing the continually evolving nature of clinical research and recommended a subsequent guideline review and revision every fourth year. Consistent with that recommendation, the ISSM organized a second multidisciplinary panel of experts in April 2013, which met for 2 days in Bangalore, India. This manuscript updates the previous guidelines and reports on the recommendations of the panel of experts. AIM: The aim of this study was to develop clearly worded, practical, evidenced-based recommendations for the diagnosis and treatment of PE for family practice clinicians as well as sexual medicine experts. METHOD: A comprehensive literature review was performed. RESULTS: This article contains the report of the second ISSM PE Guidelines Committee. It offers a new unified definition of PE and updates the previous treatment recommendations. Brief assessment procedures are delineated, and validated diagnostic and treatment questionnaires are reviewed. Finally, the best practices treatment recommendations are presented to guide clinicians, both familiar and unfamiliar with PE, in facilitating treatment of their patients. CONCLUSION: Development of guidelines is an evolutionary process that continually reviews data and incorporates the best new research. We expect that ongoing research will lead to a more complete understanding of the pathophysiology as well as new efficacious and safe treatments for this sexual dysfunction. We again recommend that these guidelines be reevaluated and updated by the ISSM in 4 years.

An evidence-based unified definition of lifelong and acquired premature ejaculation: report of the second International Society for Sexual Medicine Ad Hoc Committee for the Definition of Premature Ejaculation.

INTRODUCTION: The International Society for Sexual Medicine (ISSM) Ad Hoc Committee for the Definition of Premature Ejaculation developed the first evidence-based definition for lifelong premature ejaculation (PE) in 2007 and concluded that there were insufficient published objective data at that time to develop a definition for acquired PE. AIM: The aim of this article is to review and critique the current literature and develop a contemporary, evidence-based definition for acquired PE and/or a unified definition for both lifelong and acquired PE. METHODS: In April 2013, the ISSM convened a second Ad Hoc Committee for the Definition of Premature Ejaculation in Bangalore, India. The same evidence-based systematic approach to literature search, retrieval, and evaluation used by the original committee was adopted. RESULTS: The committee unanimously agreed that men with lifelong and acquired PE appear to share the dimensions of short ejaculatory latency, reduced or absent perceived ejaculatory control, and the presence of negative personal consequences. Men with acquired PE are older, have higher incidences of erectile dysfunction, comorbid disease, and cardiovascular risk factors, and have a longer intravaginal ejaculation latency time (IELT) as compared with men with lifelong PE. A self-estimated or stopwatch IELT of 3 minutes was identified as a valid IELT cut-off for diagnosing acquired PE. On this basis, the committee agreed on a unified definition of both acquired and lifelong PE as a male sexual dysfunction characterized by (i) ejaculation that always or nearly always occurs prior to or within about 1 minute of vaginal penetration from the first sexual experience (lifelong PE) or a clinically significant and bothersome reduction in latency time, often to about 3 minutes or less (acquired PE); (ii) the inability to delay ejaculation on all or nearly all vaginal penetrations; and (iii) negative personal consequences, such as distress, bother, frustration, and/or the avoidance of sexual intimacy. CONCLUSION: The ISSM unified definition of lifelong and acquired PE represents the first evidence-based definition for these conditions. This definition will enable researchers to design methodologically rigorous studies to improve our understanding of acquired PE.

Foot orgasm syndrome: a case report in a woman.

INTRODUCTION: Spontaneous orgasm triggered from inside the foot has so far not been reported in medical literature. AIMS: The study aims to report orgasmic feelings in the left foot of a woman. METHODS: A woman presented with complaints of undesired orgasmic sensations originating in her left foot. In-depth interview, physical examination, sensory testing, magnetic resonance imaging (MRI-scan), electromyography (EMG), transcutaneous electrical nerve stimulation (TENS), and blockade of the left S1 dorsal root ganglion were performed. MAIN OUTCOME MEASURES: The main outcomes are description of this clinical syndrome, results of TENS application, and S1 dorsal root ganglion blockade. RESULTS: Subtle attenuation of sensory amplitudes of the left suralis, and the left medial and lateral plantar nerve tracts was found at EMG. MRI-scan disclosed no foot abnormalities. TENS at the left metatarso-phalangeal joint-III of the left foot elicited an instant orgasmic sensation that radiated from plantar toward the vagina. TENS applied to the left side of the vagina elicited an orgasm that radiated to the left foot. Diagnostic blockade of the left S1 dorsal root ganglion with 0.8 mL bupivacaine 0.25 mg attenuated the frequency and intensity of orgasmic sensation in the left foot with 50% and 80%, respectively. Additional therapeutic blockade of the same ganglion with 0.8 mL bupivacaine 0.50 mg combined with pulsed radiofrequency treatment resulted in a complete disappearance of the foot-induced orgasmic sensations. CONCLUSION: Foot orgasm syndrome (FOS) is descibed in a woman. Blockade of the left S1 dorsal root ganglion alleviated FOS. It is hypothesized that FOS, occurring 1.5 years after an intensive care emergency, was caused by partial nerve regeneration (axonotmesis), after which afferent (C-fiber) information from a small reinnervated skin area of the left foot and afferent somatic and autonomous (visceral) information from the vagina on at least S1 spinal level is misinterpreted by the brain as being solely information originating from the vagina.

Hyposensitization therapy with autologous semen in two Dutch caucasian males: beneficial effects in Postorgasmic Illness Syndrome (POIS; Part 2).

INTRODUCTION: Postorgasmic illness syndrome (POIS) is a post-ejaculatory complex of local and/or systemic symptoms that nearly always occurs within seconds, minutes, or hours post-masturbation, coitus, or spontaneous ejaculation. Recent data suggest an autoimmunogenic/allergic underlying mechanism. AIM: To treat males with POIS by hyposensitization with their own semen (autologous semen). METHODS: Two males suffering from POIS, of which one male with coincidental lifelong premature ejaculation (PE) were investigated. Based on their local and systemic symptoms including a positive dermatologic reaction after skin-prick testing with autologous semen, auto-allergy to semen was likely an underlying mechanism. A hyposensitization program was initiated, including multiple subcutaneous (SC) injections with autologous semen, initially at 2 weeks intervals in the first year and gradually at 4 weeks intervals in the second and third year. From initial semen dilutions of 1 on 40,000 and 1 on 20,000, the titers were gradually increased to 1 on 20 and 1 to 280, respectively. MAIN OUTCOME MEASURES: Evaluation with a dedicated questionnaire about severity of POIS symptoms and specialized interviews on self-perceived intravaginal ejaculation latency times (IELT) before and during the desensitization program. RESULTS: POIS was confirmed in both subjects, PE was confirmed in one male, and skin-prick tests with autologous semen in both subjects were positive. During the program, gradual reduction of complaints resulted in 60% and 90% amelioration of POIS complaints at 31 and 15 months, respectively, which coincided in one male with a delay of the IELT from 20 seconds at baseline to 10 minutes after 3 years of treatment. The cause of this association with IELT is unknown and remains to be elucidated. CONCLUSIONS: Two males with POIS were successfully treated by hyposensitization with autologous semen, which supports an immunogenic/allergic etiology and underscores the clinical implication for immunological sexual medicine.

Postorgasmic Illness Syndrome (POIS) in 45 Dutch caucasian males: clinical characteristics and evidence for an immunogenic pathogenesis (Part 1).

INTRODUCTION: Postorgasmic illness syndrome (POIS) is a combination of local allergic symptoms and transient flu-like illness. In this study, the investigators propose five preliminary criteria to establish the diagnosis. AIM: To describe the clinical details in 45 males being suspected of having POIS and to test an immunogenic hypothesis as the underlying mechanism of their presentations. METHODS: Forty-five males were studied according to standardized protocol, including neuropsychiatric and medical sexological evaluations; their complaints were categorized using their own words, and their self-perceived intravaginal ejaculation latency time (IELT). Skin-prick testing with autologous diluted semen in 33 men were also performed. MAIN OUTCOME MEASURES: Clinical features of POIS including self-perceived IELTs and the results of skin-prick testing with autologous diluted seminal fluid. RESULTS: Of the 45 included men, 33 subjects consented with skin-prick testing. Of them, 29 (88%) men had a positive skin-prick test with their own (autologous) semen, and four had a negative test. In 87% of men, POIS symptoms started within 30 minutes after ejaculation. Complaints of POIS were categorized in seven clusters of symptoms, e.g., general, flu-like, head, eyes, nose, throat, and muscles. Local allergic reactions of eyes and nose were reported in 44% and 33% of subjects, a flu-like syndrome in 78% of subjects, exhaustion and concentration difficulties in 80% and 87% of subjects. Of all subjects, 58% had an atopic constitution. Lifelong premature ejaculation, defined as self-perceived IELT < 1 minute, was reported in 25 (56%) of subjects. CONCLUSIONS: The combination of allergic and systemic flu-like reactions post-ejaculation together with a positive skin-prick test in the majority of males underscores the hypothesis of an "immunogenic" etiology of POIS, e.g., that POIS is caused by Type-1 and Type-IV allergy to the males' own semen, as soon it is triggered by ejaculation.

Chronic paroxetine treatment does not affect sexual behavior in hormonally sub-primed female rats despite 5-HT1(A) receptor desensitization.

INTRODUCTION: Selective serotonin reuptake inhibitors (SSRIs) cause sexual dysfunctions in humans. However, because SSRIs are used to treat depression, it is unclear whether the problems are caused by the drug, by the depression itself, or an interaction between both. AIM: The present study investigated the effects of chronic paroxetine treatment on sexual behavior in female rats. Furthermore, we tested whether 5-hydroxytryptamine (5-HT)1(A) receptors were desensitized in these females. METHODS: Ovariectomized female rats, either sub-primed with estradiol or fully primed with estradiol and progesterone, were tested in a paced mating test. Proceptive (darting and hopping), receptive (lordosis), and paced mating-related (percentages of exits and contact-return latencies) behaviors were quantified during the course of 56 days of chronic paroxetine treatment (10 mg/kg and 20 mg/kg per day). The 5-HT1(A) /5-HT7 receptor agonist (±)-8-hydroxy-2-(dipropylamino)tetralin hydrobromide ((±)8-OH-DPAT) alone and in combination with the selective 5-HT1(A) receptor antagonist WAY-100635 was administered to study putative 5-HT1(A) desensitization in the same females. MAIN OUTCOME MEASURES: Proceptive, receptive, and paced mating behaviors were quantified. RESULTS: Acute and chronic paroxetine treatment did not change proceptive and receptive behaviors in both sub-primed and fully primed female rats. In all groups, (±)8-OH-DPAT showed a clear dose-dependent inhibition of sexual behaviors in vehicle-treated females and a right-shifted dose-response effect in the paroxetine-treated rats. WAY-100635 attenuated the inhibiting effect of the 5-HT1(A) receptor agonist in all females. These data suggest 5-HT1(A) receptor desensitization after chronic paroxetine treatment. CONCLUSIONS: Chronic paroxetine treatment does not cause sexual side effects in sub- or fully hormonally primed female rats. Furthermore, chronic treatment causes adaptive changes in the serotonin system such as desensitization of 5-HT1(A) receptors, which may counteract the inhibiting effects of increased extracellular serotonin levels in the chronic paroxetine-treated rats.

Combination of testosterone and vardenafil increases female sexual functioning in sub-primed rats.

INTRODUCTION: Hypoactive sexual desire disorder (HSDD) is a common problem in women and may have a negative impact on quality of life. A recent clinical study shows an increase in sexual drive of HSDD women after cotreatment of testosterone and vardenafil (phosphodiesterase type 5 inhibitor). AIM: In this study, we investigated the effect of testosterone and vardenafil on sexual activity in female rats. MAIN OUTCOME MEASURES: Proceptive (darts and hops), receptive (lordosis), and paced-mating (percentages after exits and contact-return latencies) behaviors were quantified. METHODS: Ovariectomized female rats, sub-primed with only estradiol and fully primed with estradiol and progesterone, were tested in a paced-mating sex test and sexual behaviors were quantified. The sub-primed rats are thought to model HSDD. The effect of testosterone (100 and 300 µg, subcutaneous [SC]) and vardenafil (10 mg/kg, per os [PO]) alone and testosterone (300 µg, SC) in combination with vardenafil (3 and 10 mg/kg, PO) were tested. We also studied the effects of testosterone (300 µg, SC) + intracerebroventricular (ICV) injections of vardenafil (25 and 50 µg) on sexual activity. RESULTS: No effect of testosterone and vardenafil alone was found, but cotreatment of testosterone and vardenafil (PO) caused a significant increase in proceptive and receptive behavior in the sub-primed female rats. Testosterone and vardenafil did not affect fully primed females. ICV administration of vardenafil combined with systemic testosterone, on the other hand, had no effect on sexual activity in both sub-primed and fully primed female rats. CONCLUSIONS: We conclude that cotreatment of subcutaneous testosterone and oral vardenafil increase sexual activity in sub-primed female rats. Our data supports the human finding that combination treatment of testosterone and vardenafil could be used as a new treatment for women with HSDD.

A new female rat animal model for hypoactive sexual desire disorder; behavioral and pharmacological evidence.

INTRODUCTION: Female sexual dysfunction (FSD) affects 33-48% of women. Female rats with low sexual activity might model FSD. AIM: In this study, we have investigated whether in a population of normal female rats, subpopulations of rats exist with different levels of sexual behavior. METHODS: Sexually experienced, intact, estradiol-primed female rats were placed in an empty compartment adjacent to a compartment with a male. The females were allowed, during 30 minutes, to switch between the compartments via a hole through which only the females could pass (paced mating). Next, we investigated the acute effects on female sexual behavior of apomorphine, a D(1) - and D(2) -type dopamine receptor agonist, (+/-)-8-hydroxy-2-(dipropylamino)tetralin hydrobromide (± 8-OH-DPAT), a 5-HT1A receptor agonist, and paroxetine, a selective serotonin reuptake inhibitor. MAIN OUTCOME MEASURES: Time spent in compartments, proceptive behaviors, contact-return latencies, and percentages of exits were quantified. RESULTS: Based on their behavior in the paced mating sex test, estradiol-primed, intact female rats can be divided into three groups: those that mostly avoid the male, a large middle group, and those that mostly approach the male. The avoiders also showed significantly less proceptive behavior than the male approachers. The sexual behavior of the females was relatively stable over time, suggesting the existence of different endophenotypes in female rats. Apomorphine and ± 8-OH-DPAT had an inhibiting effect on sexual behavior, but only females dosed with apomorphine showed a different response in avoiders and approachers, more inhibiting effect in avoiders than approachers. Paroxetine had no effect on proceptive behavior. DISCUSSION: The stable, male-avoiding behavior of some females might correspond to the characteristics of women with FSD. Therefore, these avoiders are a promising new model for FSD, specifically for sexual desire and/or arousal disorders. Furthermore, the apomorphine data suggest that differences in the dopamine system may (partly) underlie the differences in sexual behaviors between avoiders and approachers.

Stronger evidence for small fiber sensory neuropathy in restless genital syndrome: two case reports in males.

INTRODUCTION: Restless genital syndrome (ReGS) is characterized by unwanted, unpleasant genital sensations, restless legs, and/or overactive bladder, as well as neuropathy of the dorsal nerve of the clitoris. So far, ReGS has only been reported in females. AIM: To report the occurrence of ReGS in two males. METHODS: Two males with unwanted genital sensations presented in our clinic. In-depth interview, routine and hormonal investigations, electro-encephalography, magnetic resonance imaging of brain and pelvis, manual examination of the pubic bone, and sensory testing of genital dermatomes were performed. In both males, conventional transcutaneous electrical nerve stimulation was applied bilaterally at the pudendal dermatome. MAIN OUTCOME MEASURES: Oral report, questionnaire on frequency and intensity of restless genital feelings, restless legs, overactive bladder, and satisfaction with the transcutaneous electrical nerve stimulation (TENS) treatment. RESULTS: ReGS in a 74-year-old male manifested as unpleasant genital sensations of being on the edge of an orgasm with overactive bladder, in the absence of erection and ejaculation. Genital sensory testing elicited bilateral points of static mechanical hyperesthesia in the pudendal dermatome. Manual examination of the dorsal nerve of the penis (DNP) elicited the genital sensations. TENS application resulted in a 90% reduction of genital sensations and complaints of overactive bladder syndrome (OAB). ReGS in a 38-year-old male manifested as unwanted and unpleasant spontaneous ejaculations and complaints of OAB. Genital sensory testing elicited bilateral points of static mechanical hyperesthesia in the pudendal dermatome. Manual examination of the DNP elicited the genital sensations. TENS application had no effect on genital complaints and complaints of OAB. CONCLUSIONS: ReGS is not a typical female disorder as it also affects males. This notion and the finding of typical sensory abnormalities of the genital end branches of the pudendal nerve in males and females--as previously reported--provides strong evidence for Small Fiber Sensory Neuropathy as a common cause of ReGS.

The serotonin transporter plays an important role in male sexual behavior: a study in serotonin transporter knockout rats.

INTRODUCTION: Serotonin (5-HT) is an important neurotransmitter for sexual behaviors. Heterozygous (+/-) serotonin transporter (SERT) rats and SERT knockout rats (-/-) have serotonergic disturbances with significant elevations of basal extracellular 5-HT levels. AIM: To investigate the putative role of the SERT in male sexual behavior. METHODS: After extensive sexual training, the effects of the 5-HT(1A/7) receptor agonist ± 8-OH-DPAT, the 5-HT(1A) receptor antagonist WAY100 635 and a combination of both on sexual behaviors of SERT(-/-) and SERT(+/-) knockout and wildtype (SERT(+/+) ) male Wistar rats were examined. MAIN OUTCOME MEASURES: Male rat sexual behaviors of mounts, intromissions, and ejaculations. RESULTS: SERT(-/-) had lower basal ejaculation frequencies than SERT(+/-) and SERT(+/+) animals. ± 8-OH-DPAT enhanced sexual performance in all three genotypes to the same extent. WAY100635 dose-dependently inhibited sexual behavior in all three genotypes with significant dose to genotype interactions. WAY100635 exerted the strongest effects in SERT(-/-) animals. The combination of a dose range of ± 8-OH-DPAT and a selected dose of WAY100635 revealed only partial antagonism by ± 8-OH-DPAT of the sexual inhibitory effects of WAY100635. CONCLUSIONS: Absence of the serotonin transporter reduces basal ejaculatory performance in male rats. Pharmacological experiments suggest that separate pools of 5-HT(1A) receptors regulate different aspects of sexual performance in male rats. 5-HT(7) receptors may play a minor role in the partial recovery of sexual behavior after combination of ± 8-OH-DPAT and WAY100635. The SERT(-/-) rat may be a model for chronic SSRI treatment, delayed ejaculation, anorgasmia, and/or low libido.

Successful transcutaneous electrical nerve stimulation in two women with restless genital syndrome: the role of adelta- and C-nerve fibers.

INTRODUCTION: Currently, efficacious treatment of restless genital syndrome (ReGS) is not available. AIM: This study aimed to report the results of transcutaneous electrical nerve stimulation (TENS) for ReGS, being a combination of genital dysesthesias, imminent and/or spontaneous orgasms, and/or restless legs, and/or overactive bladder. METHODS: Two women with ReGS were referred to our clinic. In-depth interview, routine and hormonal investigations, electroencephalography, magnetic resonance imaging (MRI) of the brain and pelvis, manual examination of the ramus inferior of the pubic bone, and sensory testing of genital dermatomes were performed. Conventional TENS (frequency: 110 Hz; pulse width: 80 milliseconds) was applied bilaterally at the region of the pudendal dermatome in which immediate reduction of genital sensations occurred. Patients were instructed for self-application of TENS each day for 2 months. MAIN OUTCOME MEASURES: Oral report, questionnaires on frequency of imminent and/or spontaneous orgasms, combined with questions on intensity of restless genital feelings, restless leg syndrome (RLS), overactive bladder syndrome (OAB), and satisfaction with TENS treatment. RESULTS: ReGS in a 56-year-old woman manifested as multiple spontaneous orgasms, RLS, and OAB. TENS applied to the sacral region resulted in immediate reduction of complaints and a 90% reduction of spontaneous orgasms, RLS, and OAB in 2 months. ReGS in a 61-year-old woman manifested as a continuous restless genital feeling, imminent orgasms, and OAB. TENS applied to the pubic bone resulted in a complete disappearance of restlessness in the genital area as well as OAB complaints in 2 months. Both women reported to be very satisfied and did not want to stop TENS treatment. CONCLUSIONS: Conventional TENS treatment is a promising therapy for ReGS, but further controlled research is warranted. Preorgasmic and orgasmic genital sensations in ReGS are transmitted by Adelta and C fibers and are inhibited by Abeta fibers. A neurological hypothesis on the pathophysiology of ReGS encompassing its clinical symptomatology, TENS, and drug treatment is put forward.

Disorders of orgasm and ejaculation in men.

INTRODUCTION: Ejaculatory/orgasmic disorders are common male sexual dysfunctions, and include premature ejaculation (PE), inhibited ejaculation, anejaculation, retrograde ejaculation, and anorgasmia. AIM: To provide recommendations and guidelines concerning current state-of-the-art knowledge for management of ejaculation/orgasmic disorders in men. METHODS: An international consultation in collaboration with the major urology and sexual medicine associations assembled over 200 multidisciplinary experts from 60 countries into 25 committees. Committee members established specific objectives and scopes for various male and female sexual medicine topics. The recommendations concerning state-of-the-art knowledge of disorders of orgasm and ejaculation represent the opinion of seven experts from seven countries developed in a process over a 2-year period. MAIN OUTCOME MEASURE: Expert opinion was based on grading of evidence-based medical literature, widespread internal committee discussion, public presentation and debate. RESULTS: Premature ejaculation management is largely dependent upon etiology. Lifelong PE is best managed with PE pharmacotherapy (selective serotonin re-uptake inhibitor [SSRI] and/or topical anesthetics). The management of acquired PE is etiology specific and may include erectile dysfunction (ED) pharmacotherapy in men with comorbid ED. Behavioral therapy is indicated when psychogenic or relationship factors are present and is often best combined with PE pharmacotherapy in an integrated treatment program. Retrograde ejaculation is managed by education, patient reassurance, pharmacotherapy, or bladder neck reconstruction. Delayed ejaculation, anejaculation, and/or anorgasmia may have a biogenic and/or psychogenic atiology. Men with age-related penile hypoanesthesia should be educated, reassured, and instructed in revised sexual techniques which maximize arousal. CONCLUSIONS: Additional research is required to further the understanding of the disorders of ejaculation and orgasm.

Restless genital syndrome before and after clitoridectomy for spontaneous orgasms: a case report.

INTRODUCTION: Females despairing of restless genital syndrome (ReGS) may request clitoridectomy for treatment of unwanted genital sensations. Aim. The aim of this study was to report persistence of ReGS despite clitoridectomy. METHODS: Following a clitoridectomy for spontaneous orgasms, a 77-year-old woman was referred to our clinic for persistent unwanted genital sensations and feelings of imminent orgasm. An in-depth interview, routine and hormonal investigations, electroencephalography (EEG) and magnetic resonance imaging (MRI) of the brain and pelvis were performed. The localizations of genital sensations were investigated by manual examination of the ramus inferior of the pubic bone (RIPB) and by sensory testing of the skin of the genital area with a cotton swab. MAIN OUTCOME MEASURES: The main outcome measures included sensitivity of dorsal nerve of the clitoris in RIPB and MRI-pelvis. RESULTS: Genital dysesthesias, paresthesias, intolerance (allodynia) for tight clothes, aggravation of symptoms during sitting, restless legs, and overactive bladder were diagnosed. Laboratory assessments, and EEG and MRI of the brain were in agreement with aging, but all results were within the normal range. MRI of the pelvis disclosed varices of the uterus and of the left ovarian vein, and a visible scar in the region of the clitoris. Sensory testing of the genital area showed various points of static mechanical hyperesthesia at the left dermatome of the pudendal nerve. Manual examination of the RIPB also elicited the genital sensations at the left side of the vagina at about the 3 o'clock position. CONCLUSIONS: This patient fulfilled all clinical criteria of ReGS that is believed to be caused by neuropathy of the left pudendal nerve. Clitoridectomy abolished spontaneous orgasms for a great part but not completely, and it did not diminish the typical dysesthesias, paresthesias, and feelings of imminent orgasms that typically belong to ReGS. Clitoridectomy is no optional treatment of ReGS. There is a need for publications of ReGS in general medical journals.

Persistent genital arousal disorder in 18 Dutch women: Part II. A syndrome clustered with restless legs and overactive bladder.

INTRODUCTION: A systematic study in women with persistent genital arousal disorder (PGAD) is urgently needed to develop its clinical management. AIM: To investigate the features, possible causes, and treatment of PGAD. METHODS: Eighteen women who fulfilled the five criteria for PGAD were included in the study. In-depth interviews were combined with laboratory and imaging studies as reported in Part I of the study. Clinical responses were observed with drugs exerting activity against a number of different neuro-regulatory mechanisms. MAIN OUTCOME MEASURES: Detailed descriptions and clustering of some well established clinical syndromes. RESULTS: The majority of women experienced PGAD during early menopause without pre-existing psychiatric disorders and laboratory abnormalities. Most women had difficulties in describing the quality of the genital sensations. These were described in various terms and were diagnosed as dysesthesias and paresthesias. Their intensity was most severe during sitting. A few women reported PGAD during pregnancy and premenstrual. The majority of women also reported preexistent or coexistent restless legs syndrome (RLS) and overactive bladder syndrome (OBS). These strongly associated morbidities point into the direction of a clinical cluster, which harbors PGAD or PGAD plus these typical other disorders. Notably, as in RLS and OBS, it appeared that daily treatment with clonazepam 0.5-1.5 mg was effective in 56% of PGAD women. Also, oxazepam 10 mg and tramadol 50 mg elicited PGAD-reducing effect. CONCLUSIONS: PGAD seems to belong to a highly associated disease cluster including morbidities, which share an imperative urge to suppress dysesthesias and paresthesias by firm manipulative actions. PGAD--or as proposed by our group, restless genital syndrome (RGS) in the context of its strong association with restless legs--is probably the expression of a nonsexually driven hyperexcitability of the genitals and subsequent attempts to overcome it by genital manipulations.

A five-nation survey to assess the distribution of the intravaginal ejaculatory latency time among the general male population.

INTRODUCTION: The duration of the intravaginal ejaculation latency time (IELT) may give rise to subjective complaints of premature ejaculation (PE) and is usually determined by self-assessment or by stopwatch. AIM: The aim of this study was to investigate the IELT distribution in the general male population and the accuracy of IELT assessment by using a blinded timer device instead of a stopwatch, thereby minimizing possible interference with the spontaneous and natural way of having intercourse. METHODS: The IELT was measured with a timer device during 4 weeks in a nonselected sample of 474 men from The Netherlands, Spain, United Kingdom, Turkey, and the United States. Questionnaires were administered before and after the 4-week IELT assessments. MAIN OUTCOME MEASURES: IELT; erectile function dysfunction score of International Index of Erectile Dysfunction (IIEF). RESULTS: The IELT had a positively skewed distribution, with a geometric mean of 5.7 minutes and a median of 6.0 minutes (range: 0.1-52.1 minutes). Men from Turkey had the shortest median IELT (4.4 minutes). Men from the United Kingdom had the longest IELT (10.0 minutes). Circumcision and condom use had no significant impact on the median IELT. Subjects who were discontent with their latency time had slightly lower median IELT values of 5.2 minutes than the median of the population. CONCLUSION: The IELT distribution, measured with a blinded timer device, is very similar to the IELT distribution of our previous population survey which utilized a stopwatch. In the general male population, complaints of discontent with self-perceived latency had a slightly lower median IELT value than the median of the overall population.

New insights into restless genital syndrome: static mechanical hyperesthesia and neuropathy of the nervus dorsalis clitoridis.

INTRODUCTION: Systematic study of dysesthetic and paresthetic regions contributing to persistent genital arousal in women with restless genital syndrome (ReGS) is needed for its clinical management. AIM: To investigate distinct localizations of ReGS. METHODS: Twenty-three women, fulfilling all five criteria of persistent genital arousal disorder were included into the study. In-depth interviews, routine and hormonal investigations, electroencephalographs, and magnetic resonance imaging (MRI) of brain and pelvis were performed in all women. The localizations of genital sensations were investigated by physical examination of the ramus inferior of the pubic bone (RIPB) and by sensory testing of the skin of the genital area with a cotton swab (genital tactile mapping test or GTM test). MAIN OUTCOME MEASURES: Sensitivity of RIPB, GTM test. RESULTS: Of 23 women included in the study, 18(78%), 16(69%), and 12(52%) reported restless legs syndrome, overactive bladder syndrome, and urethra hypersensitivity. Intolerance of tight clothes and underwear (allodynia or hyperpathia) was reported by 19 (83%) women. All women were diagnosed with ReGS. Sitting aggravated ReGS in 20(87%) women. In all women, MRI showed pelvic varices of different degree in the vagina (91%), labia minora and/or majora (35%), and uterus (30%). Finger touch investigation of the dorsal nerve of the clitoris (DNC) along the RIPB provoked ReGS in all women. Sensory testing showed unilateral and bilateral static mechanical Hyperesthesia on various trigger points in the dermatome of the pudendal nerve, particularly in the part innervated by DNC, including pelvic bone. In three women, sensory testing induced an uninhibited orgasm during physical examination. CONCLUSIONS: ReGS is highly associated with pelvic varices and with sensory neuropathy of the pudendal nerve and DNC, whose symptoms are suggestive for small fiber neuropathy (SFN). Physical examination for static mechanical Hyperesthesia is a diagnostic test for ReGS and is recommended for all individuals with complaints of persistent restless genital arousal in absence of sexual desire.

Serotonin transporter promoter region (5-HTTLPR) polymorphism is associated with the intravaginal ejaculation latency time in Dutch men with lifelong premature ejaculation.

INTRODUCTION: Lifelong premature ejaculation (LPE) is characterized by persistent intravaginal ejaculation latency times (IELTs) of less than 1 minute, and has been postulated as a neurobiological dysfunction with genetic vulnerability for the short IELTs, related to disturbances of central serotonin (5-hydroxytryptamine [5-HT]) neurotransmission and 5-HT receptor functioning. AIM: To investigate the relationship between 5-HT transporter gene-linked polymorphism (5-HTTLPR) and short IELTs in men with lifelong PE. METHODS: A prospective study was conducted in 89 Dutch Caucasian men with lifelong PE. IELT during coitus was assessed by stopwatch over a 1-month period. Controls consisted of 92 Dutch Caucasian men. All men with LPE were genotyped for a 5-HTT-promoter polymorphism. Allele frequencies and genotypes of short (S) and long (L) variants of 5-HTTLPR polymorphism were compared between patients and controls. Association between LL, SL, and SS genotypes, and the natural logarithm of the IELT in men with LPE was investigated. MAIN OUTCOME MEASURES: IELT measured by stopwatch, 5-HTTLPR polymorphism. RESULTS: In men with lifelong PE, the geometric mean, median, and natural mean IELTs were 21, 26, and 32 seconds, respectively. There were no significant differences in the 5-HTT polymorphism alleles and genotypes between 89 Dutch Caucasian men with LPE (S 47%, L 53%/LL 29%, SL 48%, SS 22%) and 92 Dutch Caucasian controls (S 48%, L 52%/LL 29%, SL 45%, SS 26%). In men with lifelong PE there was a statistically significant difference between LL, SL, and SS genotypes in their geometric mean IELT (P < or = 0.027); the LL genotypes had significantly shorter IELTs than the SS and SL genotypes. CONCLUSIONS: The 5-HTTLPR polymorphism is associated with significant effects on the latency to ejaculate in men with lifelong PE. Men with SS and SL genotypes have 100% and 90% longer ejaculation time, respectively than men with LL genotypes.