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      • KCI등재

        Nonresponders to Daily Paroxetine and Another SSRI in Men With Lifelong Premature Ejaculation: A Pharmacokinetic Dose-Escalation Study for a Rare Phenomenon

        Paddy K.C. Janssen,Daan Touw,Dave H. Schweitzer,Marcel D. Waldinger 대한비뇨의학회 2014 Investigative and Clinical Urology Vol.55 No.9

        Purpose: Nonresponse to any selective serotonin reuptake inhibitor (SSRI) treatmentis rare. In this study, we aimed to investigate ejaculation delay nonresponse to paroxetinetreatment in men with lifelong premature ejaculation (PE) who were also knownto be nonresponders to other SSRIs. Materials and Methods: Five males with lifelong PE who were known nonrespondersto paroxetine and other serotonergic antidepressants and eight males with lifelong PEwho were specifically recruited were included. Blood sampling occurred 1 month and1 day before the start of treatment and at the end of three consecutive series of 4 weeksof daily treatment with 10-, 20-, and 30-mg paroxetine, respectively. Blood samples formeasurement of leptin and paroxetine were taken at 8:30 AM, 9:30 AM, 10:30 AM, and11:30 AM, respectively. At 9:00 AM, one tablet of 10-, 20-, or 30-mg paroxetine was takenduring the first, second, and third month, respectively. Intravaginal ejaculatory latencytime (IELT) was measured with a stopwatch. The main outcome measures were the foldincrease in the geometric mean IELT, serum leptin and paroxetine concentrations, bodymass index (BMI), 5-HT1A receptor C-1019G polymorphism, and CYP2D6 mutations. Results: Between the 7 paroxetine responders and 6 nonresponders, the fold increasein 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 from1.1 to 1.7, respectively. BMI at baseline and at the end of the study was not significantlydifferent between responders and nonresponders. Serum leptin levels at baseline weresimilar in responders and nonresponders and did not change during treatment. Theserum paroxetine concentration increased with increasing dosage and was not significantlydifferent between responders and nonresponders. There was no associationbetween the fold increase in the geometric mean IELT and serum paroxetine levels duringthe three treatment periods nor between leptin levels during the treatment periodsand serum paroxetine levels. For the 5-HT1A receptor C-1019G variation, all respondershad the CC genotype and all nonresponders had the GC genotype, respectively. Conclusions: Complete absence of paroxetine-induced ejaculation delay is presumably relatedto pharmacodynamic factors and perhaps to 5-HT1A receptor gene polymorphism.

      • KCI등재

        Serotonin Transporter Promoter Region (5-HTTLPR) Polymorphism Is Not Associated With Paroxetine-Induced Ejaculation Delay in Dutch Men With Lifelong Premature Ejaculation

        Paddy K.C. Janssen,Aeilko H. Zwinderman,Berend Olivier,Marcel D. Waldinger 대한비뇨의학회 2014 Investigative and Clinical Urology Vol.55 No.2

        Purpose: To investigate the association between the 5-HT-transporter-gene-linkedpromoter region (5-HTTLPR) polymorphism and 20-mg paroxetine-induced ejaculationdelay in men with lifelong premature ejaculation (LPE). Materials and Methods: This was a prospective study of 10 weeks of paroxetine treatmentin 54 men with LPE. Intravaginal ejaculation latency time (IELT) was measuredby stopwatch. Controls consisted of 92 Caucasian men. All men with LPE were genotypedfor the 5-HTTLPR polymorphism. Allele frequencies and genotypes of short (S)and long (L) variants of the polymorphism were compared between patients andcontrols. Associations between the LL, SL, and SS genotypes and fold increase of meanIELT were investigated. Results: Of the 54 patients, 43 (79.6%) responded to 20-mg paroxetine treatment withan ejaculation delay, whereas 11 patients (20.4%) did not respond; 44%, 18%, and 18%of the patients showed a fold increase in mean IELT of 2-10, 10-20, and more than 20,respectively. Of the 54 men, 14 (25.9%) had the LL genotype, 29 (53.7%) had the SLgenotype, and 11 (20.4%) had the SS genotype. In the 92 controls, the LL, SL, and SSgenotypes were present in 27 (29.3%), 41 (44.6%), and 24 (26.1%), respectively. No statisticallysignificant differences were found in 5-HTTLPR allelic variations or in5-HTTLPR gene variations. In all men treated with 20 mg paroxetine, analysis of varianceof the natural logarithm of fold increase in the IELT showed no statistically significantdifference according to genotype (p=0.83). Conclusions: The 5-HTTLPR polymorphism is not associated with daily 20-mg paroxetinetreatment-induced ejaculation delay in men with LPE.

      • KCI등재

        The mathematical formula of the intravaginal ejaculation latency time (IELT) distribution of lifelong premature ejaculation differs from the IELT distribution formula of men in the general male population

        Paddy K.C. Janssen,Marcel D. Waldinger 대한비뇨의학회 2016 Investigative and Clinical Urology Vol.57 No.2

        Purpose: To find the most accurate mathematical description of the intravaginal ejaculation latency time (IELT) distribution in the general male population. Materials and Methods: We compared the fitness of various well-known mathematical distributions with the IELT distribution of two previously published stopwatch studies of the Caucasian general male population and a stopwatch study of Dutch Caucasian men with lifelong premature ejaculation (PE). The accuracy of fitness is expressed by the Goodness of Fit (GOF). The smaller the GOF, the more accurate is the fitness. Results: The 3 IELT distributions are gamma distributions, but the IELT distribution of lifelong PE is another gamma distribution than the IELT distribution of men in the general male population. The Lognormal distribution of the gamma distributions most accurately fits the IELT distribution of 965 men in the general population, with a GOF of 0.057. The Gumbel Max distribution most accurately fits the IELT distribution of 110 men with lifelong PE with a GOF of 0.179. There are more men with lifelong PE ejaculating within 30 and 60 seconds than can be extrapolated from the probability density curve of the Lognormal IELT distribution of men in the general population. Conclusions: Men with lifelong PE have a distinct IELT distribution, e.g., a Gumbel Max IELT distribution, that can only be retrieved from the general male population Lognormal IELT distribution when thousands of men would participate in a IELT stopwatch study. The mathematical formula of the Lognormal IELT distribution is useful for epidemiological research of the IELT.

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