Dapoxetine treatment of premature ejaculation.
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Benzylamines↗
Biomedical subjects
Dave H Schweitzer
Publications and source records attributed to Dave H Schweitzer.
Changing paradigms from a historical DSM-III and DSM-IV view toward an evidence-based definition of premature ejaculation. Part I--validity of DSM-IV-TR.
BACKGROUND: 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-IV-TR definition of PE is still nonevidence based. In addition, the requirement that persistent self-perceived PE, distress, and interpersonal difficulties, in absence of a quantified ejaculation time, are necessary to establish the diagnosis remains disputable. AIM: To investigate the validity and reliability of DSM and ICD diagnosis of premature ejaculation. METHODS: The historical development of DSM and ICD classification of mental disorders is critically reviewed, and two studies using the DSM-IV-TR definition of PE is critically reanalyzed. RESULTS: Reanalysis of two studies using the DSM-IV-TR definition of PE has shown that DSM-diagnosed PE can be accompanied by long intravaginal ejaculation latency time (IELT) values. The reanalysis revealed a low positive predictive value for the DSM-IV-TR definition when used as a diagnostic test. A similar situation pertains to the American Urological Association (AUA) definition of PE, which is practically a copy of the DSM-IV-TR definition. CONCLUSION: It should be emphasized that any evidence-based definition of PE needs objectively collected patient-reported outcome (PRO) data from epidemiological studies, as well as reproducible quantifications of the IELT.
Coitus↗
Changing paradigms from a historical DSM-III and DSM-IV view toward an evidence-based definition of premature ejaculation. Part II--proposals for DSM-V and ICD-11.
BACKGROUND: In the Diagnostic and Statistical Manual of Mental Disorders (DSM), a descriptive definition for premature ejaculation (PE) that was based on historical assumptions has been accepted. AIM: To formulate a new functional definition of PE in the DSM. METHODS: A "syndrome" approach instead of a "complaint" approach is applied and evidence-based data from epidemiological and clinical studies are used. RESULTS: A new functional definition of PE should pertain to a cluster of "symptoms" of a distinct "syndrome." A syndrome rather than a descriptive definition should distinguish Lifelong and Acquired PE variants. Evidence-based data also suggest another PE type "Natural Variable PE," which is not a typical syndrome but rather a cluster of inconsistent symptoms of rapid ejaculation. Moreover, in "Natural Variable PE" the occurrence of rapid ejaculation is not based on neurobiological or psychological pathology, but belongs to the normal variability of sexual performance. Its prevalence is probably much higher than that of Lifelong and Acquired PE. We propose three separate operationalized definitions of these three PE types for the pending DSM-V and ICD-11, which include a quantification of the ejaculation time (intravaginal ejaculation latency time), inability of ejaculatory control, and a description of severity of PE in terms of psychological distress. CONCLUSION: The use of the intravaginal ejaculation latency time into the DSM-V and ICD-11 would mean that statistical evidence becomes accepted as one of the mainstays for establishing an evidence-based definition of the three PE types.
Coitus↗
Retarded ejaculation in men: an overview of psychological and neurobiological insights.
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 this problem is rather disappointing. The neurobiological approach, which started with animal studies, has demonstrated various neurotransmitters with the potency to inhibit ejaculation. Indeed, several experimental drugs have been tested in rats, showing the successful acceleration of ejaculation. We propose that human research should start with the development of an operational definition of delayed ejaculation. To achieve this goal, we propose unselected epidemiological stopwatch studies which also provide information on the prevalence and incidence of delayed ejaculation in men. Currently, no effective and safe drugs are available to accelerate ejaculation time in men. The best way to treat lifelong delayed ejaculation is, thus far, to inform the patients about biological and psychological inhibiting factors which they need to avoid, and to remain critical about unrealistic expectations from psychotherapy. Psychotherapy may be useful in subgroups, particularly in the absence of effective and safe drugs.
Animals↗
Proposal for a definition of lifelong premature ejaculation based on epidemiological stopwatch data.
INTRODUCTION: Consensus on a definition of premature ejaculation has not yet been reached because of debates based on subjective authority opinions and nonstandardized assessment methods to measure ejaculation time and ejaculation control. AIM: To provide a definition for lifelong premature ejaculation that is based on epidemiological evidence including the neurobiological and psychological approach. METHODS: We used the 0.5 and 2.5 percentiles as accepted standards of disease definition in a skewed distribution. We applied these percentiles in a stopwatch-determined intravaginal ejaculation latency time (IELT) distribution of 491 nonselected men from five different countries. The practical consequences of 0.5% and 2.5% cutoff points for disease definition were taken into consideration by reviewing current knowledge of feelings of control and satisfaction in relation to ejaculatory performance of the general male population. MAIN OUTCOME MEASURES: Literature arguments to be used in a proposed consensus on a definition of premature ejaculation. RESULTS: The stopwatch-determined IELT distribution is positively skewed. The 0.5 percentile equates to an IELT of 0.9 minute and the 2.5 percentile an IELT of 1.3 minutes. However, there are no available data in the literature on feelings of control or satisfaction in relation to ejaculatory latency time in the general male population. Random male cohort studies are needed to end all speculation on this subject. Exact stopwatch time assessment of IELT in a multinational study led us to propose that all men with an IELT of less than 1 minute (belonging to the 0.5 percentile) have "definite" premature ejaculation, while men with IELTs between 1 and 1.5 minutes (between 0.5 and 2.5 percentile) have "probable" premature ejaculation. Severity of premature ejaculation (nonsymptomatic, mild, moderate, severe) should be defined in terms of associated psychological problems. CONCLUSION: We define lifelong premature ejaculation as a neurobiological dysfunction with an unacceptable increase of risk to develop sexual and psychological problems anywhere in a lifetime. By defining premature ejaculation from an authority-defined disorder into a dysfunction based on epidemiological evidence it is possible to establish consensus based on epidemiological evidence. Additional epidemiological stopwatch studies are needed for a final decision of IELT values at both percentile cutoff points.
Age Factors↗
A multinational population survey of intravaginal ejaculation latency time.
INTRODUCTION: Intravaginal ejaculation latency time (IELT), defined as the time between the start of vaginal intromission and the start of intravaginal ejaculation, is increasingly used in clinical trials to assess the amount of selective serotonin reuptake inhibitor-induced ejaculation delay in men with premature ejaculation. Prospectively, stopwatch assessment of IELTs has superior accuracy compared with retrospective questionnaire and spontaneous reported latency. However, the IELT distribution in the general male population has not been previously assessed. AIM: To determine the stopwatch assessed-IELT distribution in large random male cohorts of different countries. METHODS: A total of 500 couples were recruited from five countries: the Netherlands, United Kingdom, Spain, Turkey, and the United States. Enrolled men were aged 18 years or older, had a stable heterosexual relationship for at least 6 months, with regular sexual intercourse. The surveyed population were not included or excluded by their ejaculatory status and comorbidities. This survey was performed on a "normal" general population. Sexual events and stopwatch-timed IELTs during a 4-week period were recorded, as well as circumcision status and condom use. MAIN OUTCOME MEASURES: The IELT, circumcision status, and condom use. RESULTS: The distribution of the IELT in all the five countries was positively skewed, with a median IELT of 5.4 minutes (range, 0.55-44.1 minutes). The median IELT decreased significantly with age, from 6.5 minutes in the 18-30 years group, to 4.3 minutes in the group older than 51 years (P<0.0001). The median IELT varied between countries, with the median value for Turkey being the lowest, i.e., 3.7 minutes (0.9-30.4 minutes), which was significantly different from each of the other countries. Comparison of circumcised (N=98) and not-circumcised (N=261) men in countries excluding Turkey resulted in median IELT values of 6.7 minutes (0.7-44.1 minutes) in circumcised compared with 6.0 minutes (0.5-37.4 minutes) in not-circumcised men (not significant). The median IELT value was not affected by condom use. CONCLUSION: The IELT distribution is positively skewed. The overall median value was 5.4 minutes but with differences between countries. For all five countries, median IELT values were independent of condom usage. In countries excluding Turkey, the median IELT values were independent of circumcision status.
Adolescent↗
Thyroid-stimulating hormone assessments in a Dutch cohort of 620 men with lifelong premature ejaculation without erectile dysfunction.
INTRODUCTION: Apart from the involvement of central serotonergic neurotransmission on lifelong premature ejaculation, interference of thyroid function has been speculated. AIM: To study thyroid function in a large group of men with lifelong premature ejaculation (LPE). METHODS: Lifelong premature ejaculation was defined as an intravaginal ejaculation latency time (IELT) of less than 1 minute. Any consecutive man with LPE and no erectile dysfunction assessed by medical history and the International Index of Erectile Function (IIEF-5) was eligible for the study. Apart from the assessment of thyroid-stimulating hormone (TSH) also free thyroxin (f T4) was determined in case of a TSH of <0.3 mU/L or TSH of >4.0 mU/L (being the lower and upper limits of normal values, respectively). Blood samples were drawn throughout the day within office hours. MAIN OUTCOME MEASURES: Thyroid-stimulating hormone and f T4. RESULTS: Included were 620 men; age (mean+/-SD) was 39.9+/-9.4 years (range 19-65). TSH concentrations from morning, early and late afternoon samples did not differ. The geometrical mean TSH concentration was 0.85 mU/L (95% confidence intervals: 0.82-0.90) with a coefficient of variation of 57.9%. Fourteen men had a TSH of <0.3 mU/L (2.2%), while five men (0.8%) of >4.0 mU/L. All men with an abnormal TSH had a normal f T4 (between 10 and 20 pmol/L). No relationship was found between age and TSH concentrations. CONCLUSION: Thyroid-stimulating hormone distribution was analyzed in a cohort of Dutch men with lifelong premature ejaculation and no erectile dysfunction. According to statistical analysis, there appeared to be no interaction between this ejaculatory complaint and the prevalence of thyroidal dysfunction. However, further studies are needed to gain more insight into the role of thyroid dysfunction and regulation of ejaculation time.
Adult↗
On-demand SSRI treatment of premature ejaculation: pharmacodynamic limitations for relevant ejaculation delay and consequent solutions.
INTRODUCTION: Recently, the idea has emerged that on-demand use of serotonin reuptake inhibitors (SSRIs), particularly short half-life, should be equally effective in delaying ejaculation as daily SSRI treatment of premature ejaculation. AIM: To provide evidence that SSRI-induced ejaculation delay is mainly dependent on pharmacodynamic properties of the drug and hardly on pharmacokinetic factors, and that combined SSRI administration with specific 5-hydroxytryptamine (5-HT) receptor antagonism leads acutely to stronger ejaculation delay than acute SSRI monoadministration. METHODS: We performed a detailed analysis of serotonin neurotransmission and reviewed animal studies with 5-HT(1A) receptor antagonists. In addition, we critically reviewed existing on-demand SSRI treatments publications and the current debate on a definition of premature ejaculation. MAIN OUTCOME MEASURES: Intravaginal ejaculation latency time (IELT). RESULTS: Acute SSRI administration leads to only a mild or no increase of 5-HT neurotransmission and concomitant stimulation of postsynaptic 5-HT receptors. Existing on-demand SSRI treatment studies suffer from methodological insufficiencies, and the reported high-fold increases of ejaculation time contradict with neuropharmacological insights from serotonin metabolism. Animal studies show that SSRI coadministration with 5-HT(1A) receptor antagonists significantly increases the ejaculation time acutely compared to acute SSRI monoadministration. CONCLUSION: On-demand SSRI treatment has less ejaculation-delaying effects than daily SSRI treatment. SSRIs with a short half-life are likely leading to much less ejaculation delay than current registered SSRIs. Combined use of SSRIs with 5-HT(1A) receptor antagonists increases the likelihood of clinically relevant ejaculation delay after on-demand treatment. On-demand SSRIs with short half-life that insufficiently delay ejaculation in men with IELTs less than 1 minute should be called ejaculation-delaying drugs rather than drugs against premature ejaculation.
Animals↗
Different cycle ergometer outcomes in severely obese men and women without documented cardiopulmonary morbidities before bariatric surgery.
STUDY OBJECTIVES: The number of severely obese patients undergoing bariatric surgery is increasing. No incremental cycle ergometer data are available in this category of patients. The current study was undertaken to provide information and to compare outcomes between severely obese men and women during physical exercise. DESIGN: Cross-sectional study. PARTICIPANTS: Twenty-two men and 34 women, all with a body mass index (BMI) of at least 40 kg/m(2), were selected from among persons participating in a dedicated weight management program that was carried out in the outpatient clinic of a large teaching hospital. MEASUREMENTS AND RESULTS: Body composition was estimated with bioelectrical impedance. Oxygen uptake (Vo(2)) was obtained by breath-by-breath minute ventilation (ventilated hood) and was measured under resting energy expenditure (REE) conditions. Endurance was measured with an incremental cycle ergometer test. Male and female groups were balanced for mean (+/- SD) age (42.7 +/- 7.6 vs 41.8 +/- 8.9 years, respectively), BMI (43.0 +/- 4.9 vs 41.3 +/- 5.2 kg/m(2), respectively), and fat weight (55.5 +/- 14.0 vs 56.8 +/- 2.2 kg, respectively). Fat-free mass (FFM), FFM index, fasting blood glucose level, insulin level, REE, and Vo(2) at rest and during subjective maximal endurance were higher in the male group. However, maximal Vo(2) (women, 119 +/- 19% predicted; men, 92 +/- 16% predicted) and anaerobic threshold were higher in the female group (women, 64 +/- 12% predicted; men, 48 +/- 76% predicted, respectively; p < 0.0001). CONCLUSIONS: Severely obese men were more carbohydrate-intolerant and sustained less physical endurance than was predicted according to standards in comparison with obese women. The cycle ergometer data indicated that male gender was associated with less physical fitness.
Adult↗
Daily high doses of fluoxetine for weight loss and improvement in lifestyle before bariatric surgery.
BACKGROUND: The number of gastric restrictive bariatric operations is increasing each year, but about one-fifth of patients will become disappointed due to unsatisfactory weight reduction or annoying complications. We questioned whether weight reduction by taking high doses of fluoxetine improves lifestyle before surgery. METHODS: 84 severely obese subjects were referred by one bariatric surgeon for medical weight reduction and dietary counseling, before bariatric surgery. Subjects were voluntarily treated with fluoxetine, 60 mg per day, and followed-up at 1, 3, 6 and 12 months. Surgery was scheduled between 6 to 12 months after subjects started to take fluoxetine. Endpoints of this study were body weight reductions, the number of individuals who decided for themselves to postpone surgery for at least 6 months, and side-effects of fluoxetine therapy. RESULTS: 84 severely obese subjects consisting of 28 men (group 1) and 41 women (group 2) consented to take fluoxetine for its anorectic effects, whereas 12 men and 3 women who did not want to take fluoxetine served as the control group (group 3). Weight in these 3 groups at baseline was 149+/-26, 124+/-17, and 132+/-23 (controls) (P<0.05) with BMI 46+/-3, 44+/-3, and 45+/-2 (controls) kg/m(2) (NS). Maximum weight reduction before surgery in male and female fluoxetine users occurred at 3 and 6 months, respectively. At 6 months, men had achieved a weight reduction (kg) of -8.3 (95% CI: -9.3 to -5.9), women of -13.3 (95% CI: -16.3 to -8.8), sex difference P<0.001, and controls of -1.6 (95% CI: -3.8 to -2.5) kg, group difference P<0.0001. Only 2 men stopped fluoxetine because of annoying sexual side-effects. At 6 months, 25 fluoxetine users (29.7%) and none of the controls consented to postpone the time of surgery for at least another 6 months. CONCLUSION: Fluoxetine is effective to reduce weight in severely obese men and women who originally had requested to undergo bariatric surgery. One-third of subjects who consented to take fluoxetine as an anorectic drug agreed to delay surgery for at least 6 months later than scheduled.
Adult↗
Early effects of metformin on glucose dynamics in women with oligoamenorrhea and regular menstrual cycles who were wearing a subcutaneous glucose sensor.
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Blood Glucose↗
Dual energy X-ray absorptiometry outcomes in male COPD patients after treatment with different glucocorticoid regimens.
STUDY OBJECTIVES: To compare bone mineral density (BMD) outcomes of patients who received continuous oral systemic glucocorticoids (GCs) with BMD outcomes of patients who received multiple GC courses, oral or IV. DESIGN: Cross-sectional study. PARTICIPANTS: Eighty-six white men with COPD selected from the outpatient clinic for pulmonary diseases. INTERVENTION: Data analysis from medical records, bone densitometry, and pulmonary function tests of consecutive selected patients. Inclusion period into the study was exactly 1 year. MEASUREMENTS AND RESULTS: Ten patients received oral prednisolone daily (group 1). Eleven patients were treated for several exacerbations with multiple systemic prednisolone courses, up to a period of 2 weeks per course, with a cumulative dose of > or = 1,000 mg (group 2). Likewise, 28 patients were treated with multiple systemic prednisolone courses, but with a cumulative dose < 1,000 mg (group 3). Thirty-seven patients were never treated with systemic prednisolone, and partly with inhaled corticosteroids (ICS) [group 4]. All groups were balanced for age and pack-years of smoking. In group 2, body mass index (BMI) and FEV(1) were lowest and hyperinflation was highest. The cumulative systemic prednisolone dose was highest in group 1, irrespective of the additional ICS treatments. Dual energy x-ray absorptiometry scanning of the lumbar spine, total hip, and femoral neck regions revealed a T score < or = 2.5 SD in 27 patients (31%), 31 patients (36%), and 34 patients (40%), respectively. BMD outcomes at any site were lower in patients receiving multiple systemic prednisolone courses > 1,000 mg, cumulatively (group 2), compared to the other groups, and these values were (mean +/- 1 SD) 0.759 +/- 0.238 g/cm(2), 0.683 +/- 0.115 g/cm(2), and 0.686 +/- 0.125 g/cm(2), respectively (p < 0.0001). Multivariate regression analysis revealed a correlation between the cumulative dose of prednisolone in group 2 and BMD of the lumbar spine (adjusted r = 0.48; p < 0.01). At the total hip and femoral neck regions, only a correlation between BMI and BMD was observed (adjusted r = 0.65 and 0.58, respectively; p < 0.0001 for both sites). CONCLUSIONS: Despite a far lower cumulative GC dose in comparison with patients treated with systemic corticosteroids continuously, after adjusting for BMI and lung function, osteoporosis of the lumbar spine was most frequent in patients receiving > 1,000 mg of prednisolone cumulatively, administered in multiple courses for the treatment of exacerbations of COPD.
Absorptiometry, Photon↗
Postorgasmic illness syndrome: two cases.
We describe the symptoms of a postejaculatory syndrome in two men with spontaneous ejaculations. The syndrome consists of severe fatigue, intense warmth, and a flulike state, with generalized myalgia. These symptoms occur rapidly after ejaculation and only disappear after 4 to 7 days. The symptoms are so severe that sexual activity is avoided. The cluster of symptoms is named postorgasmic illness syndrome (POIS). To date, no explanation has been offered for the etiology and pathogenesis of the symptoms, and the prevalence is unknown. Both cases are presented to draw attention to this syndrome for further research regarding etiology, pathogenesis, and treatment.
Adult↗