The association of serotonin transporter genotypes and selective serotonin reuptake inhibitor (SSRI)-associated sexual side effects: possible relationship to oral contraceptives

Objective To study the relationship between functional variants in the serotonin transporter gene (SLC6A4) and selective serotonin reupake inhibitor (SSRI)-associated sexual dysfunction. Methods One hundred fifteen subjects aged 18-40 years and currently being treated with an SSRI for depression were assessed for clinical variables known to affect sexual well-being. SSRI-associated sexual difficulties were assessed with the Changes in Sexual Functioning Questionnaire (CSFQ). Subjects were subsequently genotyped for the SLC6A4 promoter region (5HTTLPR) insertion/deletion variant and a variable number of tandem repeats (VNTR) in the second intron. Results The 5HTTLPR insertion/deletion variant was associated with sexual dysfunction in this study sample [odds ratio (OR) = 2.7; 95% confidence interval (CI) 1.2, 6.4; p = 0.02]. The relationship between promoter genotypes and sexual well-being differed in males and females and was re ated to whether females were taking an oral contraceptive (OC) medication. Females with the II genotype were nearly eight times more likely to be categorized as having sexual dysfunction if they were taking OCs, while no relationship was observed in those not taking OCs. Conclusion These results suggest that a functional variant in the serotonin transporter gene is associated with sexual difficulties in persons taking an SSRI for depression. This relationship may differ by sex and be dependent on OC status in females. Copyright (C) 2009 John Wiley & Sons, Ltd.