Papers by Marcel Waldinger
Pharmacology Biochemistry and Behavior, 2014
Antidepressant-induced sexual dysfunction adversely affects the quality of life of antidepressant... more Antidepressant-induced sexual dysfunction adversely affects the quality of life of antidepressant users and reduces compliance with treatment. Animal models provide an instructive approach for examining potential sexual side effects of novel drugs. This review discusses the stability and reproducibility of our standardized test procedure that assesses the acute, subchronic and chronic effects of psychoactive compounds in a 30 minute mating test. In addition, we present an overview of the effects of several different (putative) antidepressants on male rat sexual behavior, as tested in our standardized test procedure. By comparing the effects of these mechanistically distinct antidepressants (paroxetine, venlafaxine, bupropion, buspirone, DOV 216,303 and S32006), this review discusses the putative mechanism underlying sexual side effects of antidepressants and their normalization. This review shows that sexual behavior is mainly inhibited by antidepressants that increase serotonin neurotransmission via blockade of serotonin transporters, while those that mainly increase the levels of dopamine and noradrenaline are devoid of sexual side effects. Those sexual disturbances cannot be normalized by simultaneously increasing noradrenaline neurotransmission, but are normalized by increasing both noradrenaline and dopamine neurotransmission. Therefore, it is hypothesized that the sexual side effects of selective serotonin reuptake inhibitors may be mediated by their inhibitory effects on dopamine signaling in sex brain circuits. Clinical development of novel antidepressants should therefore focus on compounds that simultaneously increase both serotonin and dopamine signaling.
Psychopharmacology, 2005
Rationale: Chronic treatment with selective serotonin reuptake inhibitors (SSRIs) can delay ejacu... more Rationale: Chronic treatment with selective serotonin reuptake inhibitors (SSRIs) can delay ejaculation in humans, but the extent of this effect differs between SSRIs. The involvement of 5-HT 1A receptors is likely, since 5-HT 1A receptor agonists accelerate ejaculation and chronic SSRI treatment is thought to desensitize 5-HT 1A receptors. Objectives: This study was conducted to examine the effects of chronic pretreatment with the SSRIs fluvoxamine and paroxetine on the facilitation of ejaculation induced by the 5-HT 1A receptor agonist 8-OH-DPAT. Methods: Sexually experienced Wistar rats with normal ejaculatory behavior were treated for 22 days with vehicle, fluvoxamine (30 mg/kg/day), or paroxetine (10 or 20 mg/kg/day, p.o.). On day 22, rats received a challenge with saline or 8-OH-DPAT (0.4 mg/kg, s.c.). Sexual behavior was tested on days 1, 8, 15, and 22 of the SSRI-treatment. Results: Treatment with both doses of paroxetine, but not fluvoxamine, delayed ejaculation. 8-OH-DPAT strongly accelerated ejaculation under vehicle conditions. Pretreatment with paroxetine reduced the effects of 8-OH-DPAT on ejaculation in a dose-dependent manner and more strongly than fluvoxamine. Conclusions: SSRIs affect 5-HT 1A receptors involved in ejaculation. The degree to which this occurs, with paroxetine exerting a stronger effect than fluvoxamine, might determine the extent of SSRI-induced delayed ejaculation.
Introduction. Over the past 20 years our knowledge of premature ejaculation (PE) has significantl... more Introduction. Over the past 20 years our knowledge of premature ejaculation (PE) has significantly advanced.
Specifically, we have witnessed substantial progress in understanding the physiology of ejaculation, clarifying the real
prevalence of PE in population-based studies, reconceptualizing the definition and diagnostic criterion of the
disorder, assessing the psychosocial impact on patients and partners, designing validated diagnostic and outcome
measures, proposing new pharmacologic strategies and examining the efficacy, safety and satisfaction of these new
and established therapies. Given the abundance of high level research it seemed like an opportune time for the
International Society for Sexual Medicine (ISSM) to promulgate an evidenced-based, comprehensive and practical
set of clinical guidelines for the diagnosis and treatment of PE.
Aim. 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. Review of the literature.
Results. This article contains the report of the ISSM PE Guidelines Committee. It affirms the ISSM definition of
PE and suggests that the prevalence is considerably lower than previously thought. Evidence-based data regarding
biological and psychological etiology of PE are presented, as is population-based statistics on normal ejaculatory
latency. 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. Therefore, it is strongly
recommended that these guidelines be re-evaluated and updated by the ISSM every 4 years.
Sexual medicine, 2014
The International Society for Sexual Medicine (ISSM) Ad Hoc Committee for the Definition of Prema... more 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. 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. 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. 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...
Nederlands tijdschrift voor geneeskunde, 2012
In 2010 the International Society of Sexual Medicine published its practice guideline for the dia... more In 2010 the International Society of Sexual Medicine published its practice guideline for the diagnosis and treatment of premature ejaculation. This guideline was translated and adapted on a number of points by a committee consisting of members of two Dutch sexological societies, the 'WVSD' and the 'NVVS'. The most important subjects in this guideline are: (a) the case history is the most important diagnostic tool; (b) a physical examination is usually not necessary; (c) determination of the subtype of premature ejaculation can guide treatment; (d) pharmacotherapy alone is only applicable for primary premature ejaculation; (e) combination therapy is preferable for the secondary form of premature ejaculation, and pharmacotherapy is contraindicated for the other 2 subtypes.
Research and Perspectives in Endocrine Interactions, 2008
... acutely or chronically, did not inhibit sexual behaviour by itself but when combined with a .... more ... acutely or chronically, did not inhibit sexual behaviour by itself but when combined with a ... Beside selective 5-HT1A receptor agonists, a selective dopamine D2 receptor agonist, SND-919 (Ferrari ... in rats, although its effects were much less pronounced compared to the effects of 5 ...
Biological Basis of Sex …, 2011
Serotonin plays an important role in both male and female sexual behaviour. In general, reduction... more Serotonin plays an important role in both male and female sexual behaviour. In general, reduction of 5-HT function facilitates, whereas enhancement inhibits sexual behaviour. Most fundamental research on the involvement of 5-HT in sex has been performed in rats. Selective serotonin reuptake inhibitors (SSRIs) have comparable effects on male and female sexual behaviour in rats; they inhibit it but only after chronic administration. Activation of the 5-HT(1A) receptor facilitates sexual behaviour in male rats but inhibits sexual behaviour in female rats, suggesting a differential role for 5-HT(1A) receptors in male and female rats. Research on sexual behaviour in rats with null mutations in the serotonin transporter (SERT) indicated also a differential role for 5-HT(1A) receptors in male and female sexual behaviour. Evidence exists that different pools of 5-HT(1A) receptors have differential roles in various parts of the cascade of sexual events occurring during sexual interactions. Roles for other 5-HT receptors are less well defined although 5-HT(1B), 5-HT(2A/B) and 5-HT(7) receptors seem to be involved. Identification of putative differential or comparable roles in female and male sexual activities requires more research.
International Journal of Impotence Research, 2006
Most of our current understanding of the neurobiology, neuroanatomy and psychopharmacology of sex... more Most of our current understanding of the neurobiology, neuroanatomy and psychopharmacology of sexual behavior and ejaculatory function has been derived from preclinical studies in the rat. When a large population of male rats is tested on sexual activity during a number of successive tests, over time individual rats display a very stable sexual behavior that is either slow, normal or
European Journal of Pharmacology, 2007
Apomorphine is a non-selective dopaminergic receptor agonist. Because of its pro-erectile effects... more Apomorphine is a non-selective dopaminergic receptor agonist. Because of its pro-erectile effects, apomorphine is clinically used for treatment of erectile dysfunction. We investigated the effects of subcutaneous apomorphine administration (0.4 mg/kg rat) on sexual behavior and mating-induced Fos-expression following acute (day 1) or chronic apomorphine treatment (days 8 and 15) in sexually experienced male rats. Consistent facilitatory effects of apomorphine were
World Journal of Urology, 2005
Disorders of orgasm and ejaculation are erroneously mixed up in the DSM-IV classification system.... more Disorders of orgasm and ejaculation are erroneously mixed up in the DSM-IV classification system. Male Orgasmic Disorder to denote “delayed ejaculation” is inadequate as orgasm and ejaculation represent clinical expressions of different neurobiological phenomena. Unfortunately, the DSM-IV criteria for delayed ejaculation were accepted regardless of any research with appropriate methodology and design. The psychological approach and associated psychotherapy to solve
Asian Journal of Andrology, 2014
It has been postulated that the persistent short intravaginal ejaculation latency time (IELT) of ... more It has been postulated that the persistent short intravaginal ejaculation latency time (IELT) of men with lifelong premature ejaculation (LPE) is related to 5-hydroxytryptamine (HT)2C receptor functioning. The aim of this study was to investigate the relationship of Cys23Ser 5-HT2C receptor gene polymorphism and the duration of IELT in men with LPE. Therefore, a prospective study was conducted in 64 Dutch Caucasian men with LPE. Baseline IELT during coitus was assessed by stopwatch over a 1-month period. All men were genotyped for Cys23Ser 5-HT2C receptor gene polymorphism. Allele frequencies and genotypes of Cys and Ser variants of 5-HT2C receptor gene polymorphism were determined. Association between Cys/Cys and Ser/Ser genotypes and the natural logarithm of the IELT in men with LPE were investigated. As a result, the geometric mean, median and natural mean IELT were 25.2, 27.0, 33.9 s, respectively. Of all men, 20.0%, 10.8%, 23.1% and 41.5% ejaculated within 10, 10-20, 20-30 and 30-60 s after vaginal penetration. Of the 64 men, the Cys/Cys and Ser/Ser genotype frequency for the Cys23Ser polymorphism of the 5-HT2C receptor gene was 81% and 19%, respectively. The geometric mean IELT of the wildtypes (Cys/Cys) is significantly lower (22.6 s; 95% CI 18.3-27.8 s) than in male homozygous mutants (Ser/Ser) (40.4 s; 95% CI 20.3-80.4 s) (P = 0.03). It is concluded that Cys23Ser 5-HT2C receptor gene polymorphism is associated with the IELT in men with LPE. Men with Cys/Cys genotype have shorter IELTs than men with Ser/Ser genotypes.
Korean Journal of Urology, 2014
Lifelong premature ejaculation (LPE) is characterized by persistent intravaginal ejaculation late... more 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 Յ 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. Janssen PKC, Bakker SC, Réthelyi J, Zwinderman AH, Touw DJ, Olivier B, and Waldinger MD. Serotonin transporter promoter region (5-HTTLPR) polymorphism is associated with the intravaginal ejaculation latency time in Dutch men with lifelong premature ejaculation. J Sex Med 2009;6:276-284.
PLoS ONE, 2014
Objective: To analyze a recently published meta-analysis of six studies on 5-HTTLPR polymorphism ... more Objective: To analyze a recently published meta-analysis of six studies on 5-HTTLPR polymorphism and lifelong premature ejaculation (PE).
Psychopharmacology, 2002
The selective serotonin re-uptake inhibitors (SSRIs) delay orgasm and ejaculation in men. In men ... more The selective serotonin re-uptake inhibitors (SSRIs) delay orgasm and ejaculation in men. In men with rapid ejaculation it was shown that, of the SSRIs, paroxetine exerted the strongest delay in ejaculation and fluvoxamine the weakest. In the present study, we compared the acute and chronic effects of fluvoxamine and paroxetine on sexual behavior in the male rat in order to compare their differential inhibitory effects on sexual behavior. During a 4-week period, 48 male Wistar rats, selected on the basis of their sexual performance, were repeatedly tested for sexual behavior. All male rats received vehicle (saline, n=12), fluvoxamine (30 mg/kg, n=12), or paroxetine (10 mg/kg, n=12) daily for 2 weeks. Sexual behavioral tests were performed on days 1 (acute), 7, and 14. After acute oral administration, fluvoxamine and paroxetine did not inhibit sexual behavior. After 7 days and 14 days treatment, fluvoxamine mildly inhibited certain parameters of sexual behavior but ejaculation was ne...
Korean Journal of Urology, 2014
Purpose: Nonresponse to any selective serotonin reuptake inhibitor (SSRI) treatment is rare. In t... more Purpose: Nonresponse to any selective serotonin reuptake inhibitor (SSRI) treatment is rare. In this study, we aimed to investigate ejaculation delay nonresponse to paroxetine treatment in men with lifelong premature ejaculation (PE) who were also known to be nonresponders to other SSRIs. Materials and Methods: Five males with lifelong PE who were known nonresponders to paroxetine and other serotonergic antidepressants and eight males with lifelong PE who were specifically recruited were included. Blood sampling occurred 1 month and 1 day before the start of treatment and at the end of three consecutive series of 4 weeks of daily treatment with 10-, 20-, and 30-mg paroxetine, respectively. Blood samples for measurement of leptin and paroxetine were taken at 8:30 AM, 9:30 AM, 10:30 AM, and 11:30 AM, respectively. At 9:00 AM, one tablet of 10-, 20-, or 30-mg paroxetine was taken during the first, second, and third month, respectively. Intravaginal ejaculatory latency time (IELT) was measured with a stopwatch. The main outcome measures were the fold increase in the geometric mean IELT, serum leptin and paroxetine concentrations, body mass index (BMI), 5-HT1A receptor C-1019G polymorphism, and CYP2D6 mutations. Results: Between the 7 paroxetine responders and 6 nonresponders, the fold increase in the geometric mean IELT was significantly different after daily 10-mg (p=0.003), 20-mg (p=0.002), and 30-mg paroxetine (p=0.026) and ranged from 2.0 to 8.8 and from 1.1 to 1.7, respectively. BMI at baseline and at the end of the study was not significantly different between responders and nonresponders. Serum leptin levels at baseline were similar in responders and nonresponders and did not change during treatment. The serum paroxetine concentration increased with increasing dosage and was not significantly different between responders and nonresponders. There was no association between the fold increase in the geometric mean IELT and serum paroxetine levels during the three treatment periods nor between leptin levels during the treatment periods and serum paroxetine levels. For the 5-HT1A receptor C-1019G variation, all responders had the CC genotype and all nonresponders had the GC genotype, respectively. Conclusions: Complete absence of paroxetine-induced ejaculation delay is presumably related to pharmacodynamic factors and perhaps to 5-HT1A receptor gene polymorphism.
Sexual medicine, 2014
The International Society for Sexual Medicine (ISSM) Ad Hoc Committee for the Definition of Prema... more 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. 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. 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. 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...
Journal of Sexual Medicine, 2006
In former days, information obtained from randomized well-controlled clinical trials and epidemio... more In former days, information obtained from randomized well-controlled clinical trials and epidemiological studies on premature ejaculation (PE) was not available, thereby hampering the efforts of the consecutive DSM Work Groups on Sexual Disorders to formulate an evidence-based definition of PE. The current DSM-IVTR definition of PE is still nonevidence based. In addition, the requirement that persistent self-perceived PE, distress, and
International Journal of Impotence Research, 2004
The aim of this systematic review and meta-analysis is to evaluate whether the design and methodo... more The aim of this systematic review and meta-analysis is to evaluate whether the design and methodology of drug-treatment studies of premature ejaculation affect the efficacy outcome differently. Therefore, methodological, design and efficacy data from 79 studies (3034 males), published between 1943 and 2003, are reviewed. A meta-analysis is performed on 43 selective serotonin reuptake inhibitors (SSRIs) and clomipramine studies (1514
World Journal of Urology, 2005
Most of our current understanding of the neurobiology of sexual behavior and ejaculatory function... more Most of our current understanding of the neurobiology of sexual behavior and ejaculatory function has been derived from animal studies using rats with normal sexual behaviour. However, none of these proposed models adequately represents human ejaculatory disorders. Based on the "ejaculation distribution theory", which postulates that the intravaginal ejaculation latency time in men is represented by a biological continuum, we have developed an animal model for the research of premature and delayed ejaculation. In this model, a large number of male Wistar rats are investigated during 4-6 weekly sexual behavioural tests. Based on the number of ejaculations during 30 min tests, rapid and sluggish ejaculating rats are distinguished, each representing approximately 10% at both ends of a Gaussian distribution. Together with other parameters, such as ejaculation latency time, these rats at either side of the spectrum resemble men with premature and delayed ejaculation, respectively. Comparable to the human situation, in a normal population of rats, endophenotypes exist with regard to basal sexual (ejaculatory) performance.
Psychopharmacology, 2002
Rationale: The selective serotonin re-uptake inhibitors (SSRIs) delay orgasm and ejaculation in m... more Rationale: The selective serotonin re-uptake inhibitors (SSRIs) delay orgasm and ejaculation in men. In men with rapid ejaculation it was shown that, of the SSRIs, paroxetine exerted the strongest delay in ejaculation and fluvoxamine the weakest. Objectives: In the present study, we compared the acute and chronic effects of fluvoxamine and paroxetine on sexual behavior in the male rat in order to compare their differential inhibitory effects on sexual behavior. Methods: During a 4-week period, 48 male Wistar rats, selected on the basis of their sexual performance, were repeatedly tested for sexual behavior. All male rats received vehicle (saline, n=12), fluvoxamine (30 mg/kg, n=12), or paroxetine (10 mg/kg, n=12) daily for 2 weeks. Sexual behavioral tests were performed on days 1 (acute), 7, and 14. Results: After acute oral administration, fluvoxamine and paroxetine did not inhibit sexual behavior. After 7 days and 14 days treatment, fluvoxamine mildly inhibited certain param-eters of sexual behavior but ejaculation was never delayed. In contrast, paroxetine, after 7 days and particularly after 14 days treatment, strongly inhibited sexual behavior, including ejaculation. Conclusions: These results strongly concur with clinical data, suggesting that paroxetine, but not fluvoxamine, delays ejaculation. Because fluvoxamine does not delay ejaculation it may serve as an optimal treatment for depressive illness when sexual side effects, such as a delayed ejaculation, are undesired. The mechanisms whereby paroxetine and fluvoxamine, both being selective serotonin uptake inhibitors, differentially inhibit sexual behavior are unclear.
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Papers by Marcel Waldinger
Specifically, we have witnessed substantial progress in understanding the physiology of ejaculation, clarifying the real
prevalence of PE in population-based studies, reconceptualizing the definition and diagnostic criterion of the
disorder, assessing the psychosocial impact on patients and partners, designing validated diagnostic and outcome
measures, proposing new pharmacologic strategies and examining the efficacy, safety and satisfaction of these new
and established therapies. Given the abundance of high level research it seemed like an opportune time for the
International Society for Sexual Medicine (ISSM) to promulgate an evidenced-based, comprehensive and practical
set of clinical guidelines for the diagnosis and treatment of PE.
Aim. 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. Review of the literature.
Results. This article contains the report of the ISSM PE Guidelines Committee. It affirms the ISSM definition of
PE and suggests that the prevalence is considerably lower than previously thought. Evidence-based data regarding
biological and psychological etiology of PE are presented, as is population-based statistics on normal ejaculatory
latency. 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. Therefore, it is strongly
recommended that these guidelines be re-evaluated and updated by the ISSM every 4 years.
Specifically, we have witnessed substantial progress in understanding the physiology of ejaculation, clarifying the real
prevalence of PE in population-based studies, reconceptualizing the definition and diagnostic criterion of the
disorder, assessing the psychosocial impact on patients and partners, designing validated diagnostic and outcome
measures, proposing new pharmacologic strategies and examining the efficacy, safety and satisfaction of these new
and established therapies. Given the abundance of high level research it seemed like an opportune time for the
International Society for Sexual Medicine (ISSM) to promulgate an evidenced-based, comprehensive and practical
set of clinical guidelines for the diagnosis and treatment of PE.
Aim. 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. Review of the literature.
Results. This article contains the report of the ISSM PE Guidelines Committee. It affirms the ISSM definition of
PE and suggests that the prevalence is considerably lower than previously thought. Evidence-based data regarding
biological and psychological etiology of PE are presented, as is population-based statistics on normal ejaculatory
latency. 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. Therefore, it is strongly
recommended that these guidelines be re-evaluated and updated by the ISSM every 4 years.