title: Efficacy of testosterone combined with a PDE5 inhibitor and testosterone combined with a serotonin (1A) receptor agonist in women with SSRI-induced sexual dysfunction. A preliminary study.
abstract: Selective serotonin reuptake inhibitors (SSRIs) are known to cause sexual dysfunction, such as decreased sexual motivation, desire, arousal, and orgasm difficulties. These SSRI-induced sexual complaints have a high prevalence rate, while there is no approved pharmacological treatment for SSRI-induced sexual dysfunction. It is hypothesized that a polymorphisms in the androgen receptor gene, encoded by the nucleotides cysteine, adenine, and guanine (CAG), influence the effect of testosterone on sexual functioning. In an explorative, randomized, double-blind, placebo-controlled, crossover study we investigated the possible effects of sublingual testosterone combined with a serotonin (5-HT)1A receptor agonist, and of sublingual testosterone combined with a phosphodiesterase type 5 inhibitor (PDE5-i) on sexual functioning in women with SSRI-induced sexual dysfunction. Furthermore, we did an exploratory analysis to assess if the CAG polymorphism influences this effect. 21 pre- and postmenopausal women with SSRI-induced sexual dysfunction participated and underwent the following interventions: a combination of testosterone (0.5 mg) sublingually and the PDE5-i sildenafil (50 mg) and a combination of testosterone (0.5 mg) sublingually and the 5-HT1A receptor agonist buspirone (10 mg). The results show that women who use a low dose of SSRI and have relatively long CAG repeats report a marked improvement in sexual function in response to both treatments compared to placebo. This explorative study and preliminary results indicate that in women with SSRI-induced sexual dysfunction, a combination of testosterone sublingually and a PDE5-i or testosterone sublingually and a 5-HT1A receptor agonist might be promising treatments for certain subgroups of women with this condition.
authors.affiliation: Emotional Brain B.V., Almere, The Netherlands; Utrecht Institute for Pharmaceutical Sciences and Rudlof Magnus Institute of Neuroscience, Utrecht University, Utrecht, The Netherlands. Electronic address: k.vanrooij@emotionalbrain.nl.
authors.forename: Kim
authors.initials: K
authors.lastname: van Rooij
authors.affiliation: Emotional Brain B.V., Almere, The Netherlands; Utrecht Institute for Pharmaceutical Sciences and Rudlof Magnus Institute of Neuroscience, Utrecht University, Utrecht, The Netherlands.
authors.forename: Saskia
authors.initials: S
authors.lastname: Poels
authors.affiliation: Emotional Brain B.V., Almere, The Netherlands.
authors.forename: Petra
authors.initials: P
authors.lastname: Worst
authors.affiliation: Emotional Brain B.V., Almere, The Netherlands; Utrecht Institute for Pharmaceutical Sciences and Rudlof Magnus Institute of Neuroscience, Utrecht University, Utrecht, The Netherlands.
authors.forename: Jos
authors.initials: J
authors.lastname: Bloemers
authors.affiliation: Emotional Brain B.V., Almere, The Netherlands.
authors.forename: Hans
authors.initials: H
authors.lastname: Koppeschaar
authors.affiliation: Center for Vulvovaginal Disorders, Washington, DC, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Goldstein
authors.affiliation: Utrecht Institute for Pharmaceutical Sciences and Rudlof Magnus Institute of Neuroscience, Utrecht University, Utrecht, The Netherlands; Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Berend
authors.initials: B
authors.lastname: Olivier
authors.affiliation: Emotional Brain B.V., Almere, The Netherlands; Department of Psychopharmacology, Utrecht University, Utrecht, The Netherlands.
authors.forename: Adriaan
authors.initials: A
authors.lastname: Tuiten
mesh_terms: D000286:Administration, Sublingual; D000328:Adult; D002065:Buspirone / Q000627:therapeutic use; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D058986:Phosphodiesterase 5 Inhibitors / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide; D011944:Receptors, Androgen / Q000235:genetics; D058825:Serotonin 5-HT1 Receptor Agonists / Q000627:therapeutic use*; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects*; D020018:Sexual Dysfunctions, Psychological / Q000139:chemically induced* / Q000188:drug therapy* / Q000235:genetics; D000068677:Sildenafil Citrate / Q000627:therapeutic use; D013739:Testosterone / Q000008:administration & dosage / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D002065:Buspirone; D058986:Phosphodiesterase 5 Inhibitors; D011944:Receptors, Androgen; D058825:Serotonin 5-HT1 Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; D000068677:Sildenafil Citrate; D013739:Testosterone
keywords: CAG repeat length; Phosphodiesterase type 5 inhibitors; SSRI-induced sexual dysfunction; Serotonin; Serotonin 1A receptor agonist; Sublingual testosterone