1 Emotional Brain BV, Almere, The Netherlands. Electronic address: A.Tuiten@EmotionalBrain.nl.
2 Emotional Brain BV, Almere, The Netherlands; Utrecht Institute for Pharmaceutical Sciences and Rudolf Magnus Institute of Neuroscience, Utrecht University, Utrecht, The Netherlands.
3 Neuropsychopharmacology and Biopsychology Unit, University of Vienna, Vienna, Austria.
4 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.
5 Emotional Brain BV, Almere, The Netherlands.
6 Reproductive Biology and Psychiatry, Case Western Reserve University, Cleveland, OH, USA; MacDonald Women's Hospital, Cleveland, OH, USA.
7 Johns Hopkins University School of Medicine, Baltimore, MD, USA; Maryland Center for Sexual Health, Lutherville, MD, USA.
8 Exelion Bio-Pharmaceutical Consultancy BV, Waddinxveen, The Netherlands.
9 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.
10 Department of Psychology, University of Amsterdam, Amsterdam, The Netherlands.
11 Research Group of Pharmaceutical Technology and Biopharmacy, University of Groningen, Groningen, The Netherlands.
12 Alan Turing Institute Almere, Almere, The Netherlands.
13 Center for Studies in Behavioral Neurobiology, Concordia University, Montreal, QC, Canada.

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 Feb;15(2):201-216

Authors: Tuiten A, van Rooij K, Bloemers J, Eisenegger C, van Honk J, Kessels R, Kingsberg S, Derogatis LR, de Leede L, Gerritsen J, Koppeschaar HPF, Olivier B, Everaerd W, Frijlink HW, Höhle D, de Lange RPJ, Böcker KBE, Pfaus JG

Abstract

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 [?] = 1.70, 95% CI = 0.57-2.84, P = .004) and monotherapies (S: ? = 1.95, 95% CI = 0.44-3.45, P = .012; T: ? = 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 (? = 0.99, 95% CI = 0.17-1.82, P = .019) and monotherapies (B: ? = 1.52, 95% CI = 0.57-2.46, P = .002; T: ? = 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