Korean J Urol.  2014 Feb;55(2):129-133. 10.4111/kju.2014.55.2.129.

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

Affiliations
  • 1Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands. m.d.waldinger@uu.nl
  • 2Department of Central Hospital Pharmacy, Viecuri Hospital, Venlo, The Netherlands.
  • 3Department of Medical Statistics, Clinical Epidemiology and Biostatistics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
  • 4Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, USA.
  • 5Outpatient Department of Neurosexology, HagaHospital, The Hague, The Netherlands.

Abstract

PURPOSE
To investigate the association between the 5-HT-transporter-gene-linked promoter region (5-HTTLPR) polymorphism and 20-mg paroxetine-induced ejaculation delay in men with lifelong premature ejaculation (LPE).
MATERIALS AND METHODS
This was a prospective study of 10 weeks of paroxetine treatment in 54 men with LPE. Intravaginal ejaculation latency time (IELT) was measured by stopwatch. Controls consisted of 92 Caucasian men. All men with LPE were genotyped for the 5-HTTLPR polymorphism. Allele frequencies and genotypes of short (S) and long (L) variants of the polymorphism were compared between patients and controls. Associations between the LL, SL, and SS genotypes and fold increase of mean IELT were investigated.
RESULTS
Of the 54 patients, 43 (79.6%) responded to 20-mg paroxetine treatment with an 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 SL genotype, and 11 (20.4%) had the SS genotype. In the 92 controls, the LL, SL, and SS genotypes were present in 27 (29.3%), 41 (44.6%), and 24 (26.1%), respectively. No statistically significant differences were found in 5-HTTLPR allelic variations or in 5-HTTLPR gene variations. In all men treated with 20 mg paroxetine, analysis of variance of the natural logarithm of fold increase in the IELT showed no statistically significant difference according to genotype (p=0.83).
CONCLUSIONS
The 5-HTTLPR polymorphism is not associated with daily 20-mg paroxetine treatment-induced ejaculation delay in men with LPE.

Keyword

5-HTTLPR polymorphism; Ejaculation delay; Lifelong premature ejaculation; Paroxetine; SSRIs

MeSH Terms

Ejaculation*
Gene Frequency
Genotype
Humans
Male
Paroxetine
Premature Ejaculation*
Promoter Regions, Genetic*
Prospective Studies
Serotonin Plasma Membrane Transport Proteins*
Serotonin*
Paroxetine
Serotonin
Serotonin Plasma Membrane Transport Proteins

Figure

  • FIG. 1 Distribution of fold increase (FI) of the geometric mean intravaginal ejaculation latency time (IELT) on daily paroxetine 20-mg treatment in men with lifelong premature ejaculation: 20% had no paroxetine-induced ejaculation delay (FI, 0-2), whereas 80% had an ejaculation delay (FI, >2).

  • FIG. 2 Photograph of DNA fragments on a gel under ultraviolet light. Lane 1, patient homozygous for the L allele (LL); lane 2, patient homozygous for the S allele (SS); lane 3, heterozygous patient (LS).


Reference

1. Waldinger MD. Toward evidence-based genetic research on lifelong premature ejaculation: a critical evaluation of methodology. Korean J Urol. 2011; 52:1–8.
2. Janssen PK, Bakker SC, Rethelyi J, Zwinderman AH, Touw DJ, Olivier B, et al. 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.
3. Janssen PK, van Schaik R, Zwinderman AH, Olivier B, Waldinger MD. The 5-HT1A receptor C(1019)G polymorphism influences the intravaginal ejaculation latency time in Dutch Caucasian men with lifelong premature ejaculation. Pharmacol Biochem Behav. 2014; 01. 15. [Epub]. http://dx.doi.org/10.1016/j.pbb.2014.01.004.
4. Janssen PK, van Schaik R, Olivier B, Waldinger MD. The 5-HT2C receptor gene Cys23Ser polymorphism influences the intravaginal ejaculation latency time in Dutch Caucasian men with lifelong premature ejaculation. Asian J Androl. 2014; Forthcoming.
5. Waldinger MD, Zwinderman AH, Schweitzer DH, Olivier B. Relevance of methodological design for the interpretation of efficacy of drug treatment of premature ejaculation: a systematic review and meta-analysis. Int J Impot Res. 2004; 16:369–381.
6. Waldinger MD, Hengeveld MW, Zwinderman AH, Olivier B. Effect of SSRI antidepressants on ejaculation: a double-blind, randomized, placebo-controlled study with fluoxetine, fluvoxamine, paroxetine, and sertraline. J Clin Psychopharmacol. 1998; 18:274–281.
7. Waldinger MD. Towards evidence-based drug treatment research on premature ejaculation: a critical evaluation of methodology. Int J Impot Res. 2003; 15:309–313.
8. Ahlenius S, Larsson K, Svensson L, Hjorth S, Carlsson A, Lindberg P, et al. Effects of a new type of 5-HT receptor agonist on male rat sexual behavior. Pharmacol Biochem Behav. 1981; 15:785–792.
9. Foreman MM, Love RL, Hall JL. Effects of LY237733, a selective 5-HT2 receptor antagonist, on copulatory behavior of male rats [abstract 374]. In : Neuroscience 1998; 1988 Nov. 13-18; Toronto, Canada. Washington, DC: Society for Neuroscience;1988.
10. Waldinger MD, Hengeveld MW, Zwinderman AH. Paroxetine treatment of premature ejaculation: a double-blind, randomized, placebo-controlled study. Am J Psychiatry. 1994; 151:1377–1379.
11. McMahon CG, Althof SE, Waldinger MD, Porst H, Dean J, Sharlip ID, et al. An evidence-based definition of lifelong premature ejaculation: report of the International Society for Sexual Medicine (ISSM) ad hoc committee for the definition of premature ejaculation. J Sex Med. 2008; 5:1590–1606.
12. Jungerius BJ, Hoogendoorn ML, Bakker SC, Van't Slot R, Bardoel AF, Ophoff RA, et al. An association screen of myelin-related genes implicates the chromosome 22q11 PIK4CA gene in schizophrenia. Mol Psychiatry. 2008; 13:1060–1068.
13. Janssen PK, Olivier B, Zwinderman AH, Waldinger MD. Measurement errors in polymerase chain reaction are a confounding factor for a correct interpretation of 5-HTTLPR polymorphism effects on lifelong premature ejaculation: a critical analysis of a previously published meta-analysis of six studies. Plos One. 2014; Forthcoming.
Full Text Links
  • KJU
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr