Efficacy and Safety of On-Demand Use of 2 Treatments Designed for Different Etiologies of Female Sexual Interest/Arousal Disorder: 3 Randomized Clinical Trials.

Autor:	Tuiten A; Emotional Brain BV, Almere, The Netherlands. Electronic address: A.Tuiten@EmotionalBrain.nl., van Rooij K; Emotional Brain BV, Almere, The Netherlands; Utrecht Institute for Pharmaceutical Sciences and Rudolf Magnus Institute of Neuroscience, Utrecht University, Utrecht, The Netherlands., Bloemers J; Emotional Brain BV, Almere, The Netherlands; Utrecht Institute for Pharmaceutical Sciences and Rudolf Magnus Institute of Neuroscience, Utrecht University, Utrecht, The Netherlands., Eisenegger C; Neuropsychopharmacology and Biopsychology Unit, University of Vienna, Vienna, Austria., van Honk J; Department of Experimental Psychology, Utrecht University, Utrecht, The Netherlands; Institute of Infectious Disease and Molecular Medicine (IDM), University of Cape Town, South Africa; Department of Psychiatry and Mental Health, University of Cape Town, South Africa., Kessels R; Emotional Brain BV, Almere, The Netherlands., Kingsberg S; Reproductive Biology and Psychiatry, Case Western Reserve University, Cleveland, OH, USA; MacDonald Women's Hospital, Cleveland, OH, USA., Derogatis LR; Johns Hopkins University School of Medicine, Baltimore, MD, USA; Maryland Center for Sexual Health, Lutherville, MD, USA., de Leede L; Exelion Bio-Pharmaceutical Consultancy BV, Waddinxveen, The Netherlands., Gerritsen J; Emotional Brain BV, Almere, The Netherlands; Utrecht Institute for Pharmaceutical Sciences and Rudolf Magnus Institute of Neuroscience, Utrecht University, Utrecht, The Netherlands., Koppeschaar HPF; Emotional Brain BV, Almere, The Netherlands., Olivier B; Department of Psychopharmacology, Utrecht University, Utrecht, The Netherlands; Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA; Groningen Institute for Evolutionary Life Sciences, University of Groningen, Groningen, The Netherlands., Everaerd W; Department of Psychology, University of Amsterdam, Amsterdam, The Netherlands., Frijlink HW; Research Group of Pharmaceutical Technology and Biopharmacy, University of Groningen, Groningen, The Netherlands., Höhle D; Alan Turing Institute Almere, Almere, The Netherlands., de Lange RPJ; Alan Turing Institute Almere, Almere, The Netherlands., Böcker KBE; Alan Turing Institute Almere, Almere, The Netherlands., Pfaus JG; Center for Studies in Behavioral Neurobiology, Concordia University, Montreal, QC, Canada.
Jazyk:	angličtina
Zdroj:	The journal of sexual medicine [J Sex Med] 2018 Feb; Vol. 15 (2), pp. 201-216. Date of Electronic Publication: 2017 Dec 27.
DOI:	10.1016/j.jsxm.2017.11.226
Abstrakt:	Background: In women, low sexual desire and/or sexual arousal can lead to sexual dissatisfaction and emotional distress, collectively defined as female sexual interest/arousal disorder (FSIAD). Few pharmaceutical treatment options are currently available. Aim: To investigate the efficacy and safety of 2 novel on-demand pharmacologic treatments that have been designed to treat 2 FSIAD subgroups (women with low sensitivity for sexual cues and women with dysfunctional over-activation of sexual inhibition) using a personalized medicine approach using an allocation formula based on genetic, hormonal, and psychological variables developed to predict drug efficacy in the subgroups. Methods: 497 women (21-70 years old) with FSIAD were randomized to 1 of 12 8-week treatment regimens in 3 double-blinded, randomized, placebo-controlled, dose-finding studies conducted at 16 research sites in the United States. Efficacy and safety of the following on-demand treatments was tested: placebo, testosterone (T; 0.5 mg), sildenafil (S; 50 mg), buspirone (B; 10 mg) and combination therapies (T 0.25 mg + S 25 mg, T 0.25 mg + S 50 mg, T 0.5 mg + S 25 mg, T 0.5 mg + S 50 mg, and T 0.25 mg + B 5 mg, T 0.25 mg + B 10 mg, T 0.5 mg + B 5 mg, T 0.5 mg + B 10 mg). Outcomes: The primary efficacy measure was the change in satisfying sexual events (SSEs) from the 4-week baseline to the 4-week average of the 8-week active treatment period after medication intake. For the primary end points, the combination treatments were compared with placebo and the respective monotherapies on this measure. Results: In women with low sensitivity for sexual cues, 0.5 mg T + 50 mg S increased the number of SSEs from baseline compared with placebo (difference in change [Δ] = 1.70, 95% CI = 0.57-2.84, P = .004) and monotherapies (S: Δ = 1.95, 95% CI = 0.44-3.45, P = .012; T: Δ = 1.69, 95% CI = 0.58-2.80, P = .003). In women with overactive inhibition, 0.5 mg T + 10 mg B increased the number of SSEs from baseline compared with placebo (Δ = 0.99, 95% CI = 0.17-1.82, P = .019) and monotherapies (B: Δ = 1.52, 95% CI = 0.57-2.46, P = .002; T: Δ = 0.98, 95% CI = 0.17-1.78, P = .018). Secondary end points followed this pattern of results. The most common drug-related side effects were flushing (T + S treatment, 3%; T + B treatment, 2%), headache (placebo treatment, 2%; T + S treatment, 9%), dizziness (T + B treatment, 3%), and nausea (T + S treatment, 3%; T + B treatment, 2%). Clinical Implications: T + S and T + B are promising treatments for women with FSIAD. Strengths and Limitations: The data were collected in 3 well-designed randomized clinical trials that tested multiple doses in a substantial number of women. The influence of T + S and T + B on distress and the potentially sustained improvements after medication cessation were not investigated. Conclusions: T + S and T + B are well tolerated and safe and significantly increase the number of SSEs in different FSIAD subgroups. Tuiten A, van Rooij K, Bloemers J, et al. Efficacy and Safety of On-Demand Use of 2 Treatments Designed for Different Etiologies of Female Sexual Interest/Arousal Disorder: 3 Randomized Clinical Trials. J Sex Med 2018;15:201-216. (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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