Analysis of association between the 5-HTTLPR and STin2 polymorphisms in the serotonin-transporter gene and clinical response to a selective serotonin reuptake inhibitor (sertraline) in patients with premature ejaculation

Study Type – Therapy (cohort) Level of Evidence 2b

OBJECTIVE

To test the hypothesis that polymorphism within the gene-linked polymorphic region (5-HTTLPR) and second intron of SLC6A4 gene (STin2) is associated with selective serotonin-reuptake inhibitors (SSRIs) response in subjects with premature ejaculation (PE).

PATIENTS AND METHODS

In all, 246 men with PE were recruited in this study. They were asked to take sertraline 50 mg daily for 2 weeks, and thereafter 100 mg daily, for a 12-week treatment period. Pretreatment evaluation included history and physical examination, intravaginal ejaculatory latency time (IELT), and International Index of Erectile Function (IIEF). The efficacy of treatment was assessed using responses to IIEF, and geometric mean IELT evaluation. 5-HTTLPR was genotyped using polymerase chain reaction techniques. A repeated-measures analysis of variance of geometric mean IELT was done to test a genotype effect on treatment outcome with SSRI (sertraline).

RESULTS

Of 227 participants who completed the study, 175 (77.1%) responded to sertraline (IELT >1 min). Overall the patients had a 3.7-fold (95% confidence interval, CI, 1.72–5.46) increase of the geometric mean IELT (P = 0.001). The results showed that responses were significantly better for the L_A/L_A genotype of the 5-HTTLPR polymorphism than for S-allele carriers (P = 0.001). The STin2 12/12 genotype was found more often in those responding to sertraline than in those not responding (P = 0.001). The probability of patients responding sufficiently to sertraline with an L_A/L_A genotype was highest (odds ratio 4.66, 95% CI, 2.48–6.14).

CONCLUSIONS

These findings indicate that the genotype of 5-HTT contributes in unique ways to the variation in the outcome of PE treatment with SSRIs.