Paddy K C Janssen1, R van Schaik2, Aeilko H Zwinderman3, Berend Olivier4, Marcel D Waldinger5. 1. Division Pharmacology, Utrecht Institute for Pharmaceutical Sciences and Rudolf Magnus Institute for Neurosciences, Utrecht University, Utrecht, The Netherlands; Department of Central Hospital Pharmacy, Viecuri Hospital Venlo, Venlo, The Netherlands. 2. Department of Clinical Chemistry (AKC), Erasmus University Medical Center (Erasmus MC), Rotterdam, The Netherlands. 3. Department of Medical Statistics, Clinical Epidemiology and Biostatistics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. 4. Division Pharmacology, Utrecht Institute for Pharmaceutical Sciences and Rudolf Magnus Institute for Neurosciences, Utrecht University, Utrecht, The Netherlands; Yale University School of Medicine, New Haven, CT, USA. 5. Division Pharmacology, Utrecht Institute for Pharmaceutical Sciences and Rudolf Magnus Institute for Neurosciences, Utrecht University, Utrecht, The Netherlands; Outpatient Department of Neurosexology, HagaZiekenhuis, The Hague, The Netherlands. Electronic address: md@waldinger.demon.nl.
Abstract
INTRODUCTION: Lifelong premature ejaculation (LPE) is characterized by persistent intravaginal ejaculation latency times (IELTs) of less than 1 min, and has been postulated as a neurobiological dysfunction related to diminished serotonergic neurotransmission with 5-HT₁A receptor hyperfunction and 5-HT₂C hypofunction. AIM: To investigate the relationship between 5-HT₁A receptor gene (HTR₁A)-C(1019)G promoter polymorphism and IELT in men with LPE. This polymorphism is known to increase 5-HT1A receptor expression. METHODS: A prospective study was conducted in 54 Dutch Caucasian men with LPE. Baseline IELT during coitus was assessed by stopwatch over a 1-month period. All men were genotyped for HTR₁A gene polymorphism. Allele frequencies and genotypes of C and G variants of HTR₁A polymorphism were determined. Association between CC, CG, and GG genotypes and the IELT in men with LPE were investigated. MAIN OUTCOME MEASURES: IELT measured by stopwatch, HTR₁A polymorphism. RESULTS: In this cohort of men with LPE, the geometric mean IELT was 23.8 s. Of the 54 men, the CC, CG and GG genotype frequency for the C(1019)G polymorphism of the 5-HT₁A gene was 33%, 43% and 24%, respectively. The geometric mean IELT for the CC, CG and GG genotypes were 14.5, 27.7 and 36.0 s, respectively (p=0.019). Compared to GG and CG genotypes, men with CC genotype had a 250% and 190% shorter ejaculation time, respectively. CONCLUSIONS: HTR₁A gene polymorphism is associated with the IELT in men with LPE. Men with CC genotype have shorter IELTs than men with GG and CG genotypes.
INTRODUCTION: Lifelong premature ejaculation (LPE) is characterized by persistent intravaginal ejaculation latency times (IELTs) of less than 1 min, and has been postulated as a neurobiological dysfunction related to diminished serotonergic neurotransmission with 5-HT₁A receptor hyperfunction and 5-HT₂C hypofunction. AIM: To investigate the relationship between 5-HT₁A receptor gene (HTR₁A)-C(1019)G promoter polymorphism and IELT in men with LPE. This polymorphism is known to increase 5-HT1A receptor expression. METHODS: A prospective study was conducted in 54 Dutch Caucasian men with LPE. Baseline IELT during coitus was assessed by stopwatch over a 1-month period. All men were genotyped for HTR₁A gene polymorphism. Allele frequencies and genotypes of C and G variants of HTR₁A polymorphism were determined. Association between CC, CG, and GG genotypes and the IELT in men with LPE were investigated. MAIN OUTCOME MEASURES: IELT measured by stopwatch, HTR₁A polymorphism. RESULTS: In this cohort of men with LPE, the geometric mean IELT was 23.8 s. Of the 54 men, the CC, CG and GG genotype frequency for the C(1019)G polymorphism of the 5-HT₁A gene was 33%, 43% and 24%, respectively. The geometric mean IELT for the CC, CG and GG genotypes were 14.5, 27.7 and 36.0 s, respectively (p=0.019). Compared to GG and CG genotypes, men with CC genotype had a 250% and 190% shorter ejaculation time, respectively. CONCLUSIONS: HTR₁A gene polymorphism is associated with the IELT in men with LPE. Men with CC genotype have shorter IELTs than men with GG and CG genotypes.