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Efficacy and safety of on-demand use of 2 treatments designed for different etiologies of female sexual interest/arousal disorder: 3 randomized clinical trials

Tuiten, A1; van Rooij, K2; Bloemers, J2; Eisenegger, C3; van Honk, J4; Kessels, R1; Kingsberg, S5; Derogatis, LR6; de Heede, L7; Gerritsen, J8; Koppeschaar, HPF1; Olivier, B9; Everaerd, W10; Frijlink, HW11; Höhle, D12

1: Emotional Brain BV, Almere, The Netherlands; 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; (IDM), University of Cape Town, Department of Psychiatry and Mental Health, University of Cape Town, South Africa;; 5: Reproductive Biology and Psychiatry, Case Western Reserve University, Cleveland, OH, USA; MacDonald Women’s Hospital, Cleveland, OH, USA; 6: Johns Hopkins University School of Medicine, Baltimore, MD, USA; Maryland Center for Sexual Health, Lutherville, MD, USA;; 7: Exelion Bio-Pharmaceutical Consultancy BV, Waddinxveen, The Netherlands; 8: Emotional Brain BV, Almere, The Netherlands;; 9: Department of Psychopharmacology, Utrecht University, The Netherlands Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA; Groningen Institute for Evolutionary Life Sciences, University of 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

Background: In women, low sexual desire and/or sexual arousal may 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 two novel, on-demand pharmacological treatments that have been designed to treat two FSIAD subgroups (women with low sensitivity for sexual cues and women with dysfunctional over-activation of sexual inhibition), employing 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 (aged 21 to 70) with FSIAD were randomized to one of twelve, 8-week treatment regimens in three double-blind, randomized, placebo-controlled dose-finding studies, conducted at 16 research sites in the US. Efficacy and safety of the following on-demand treatments was tested: placebo, testosterone (T;0.5mg), sildenafil (S;50mg), buspirone (B;10mg), and the combination therapies T0.25mg+S25mg, T0.25mg+S50mg, T0.5mg+S25mg, T0.5mg+S50mg, and T0.25mg+B5mg, T0.25mg+B10mg, T0.5mg+B5mg, T0.5mg+B10mg.

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, following medication intake. For the primary endpoints, the combination treatments were compared with placebo and the respective monotherapies on this measure.  

Results: In women with low sensitivity for sexual cues, T0.5mg+S50mg increased the number of SSEs from baseline as compared to placebo (difference in change (Δ)=1.70 SSEs, 95% Confidence Interval (CI)=0.57–2.84, P=0.004) and monotherapies (S:Δ=1.95, 95% CI=0.44–3.45, P=0.012; T:Δ=1.69, 95% CI=0.58–2.80, P=0.003). In women with overactive inhibition, T0.5mg+B10mg increased the number of SSEs from baseline as compared to placebo (Δ=0.99, 95% CI=0.17–1.82, P=0.019) and monotherapies (B: Δ=1.52, 95% CI=0.57–2.46, P=0.002; T: Δ=0.98, 95% CI=0.17–1.78, P=0.018). Secondary endpoints 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 three well-designed randomized clinical trials, testing multiple doses in a substantial number of women. The influence of T+S and T+B on distress was not investigated, nor were the potentially sustained improvements following medication cessation.

Conclusions: T+S and T+B are well-tolerated and safe and significantly increase the number of SSEs in different FSIAD subgroups.  

Disclosure:

Work supported by industry: yes, by Emotional Brain BV, Almere, the Netherlands. The presenter or any of the authors act as a consultant, employee (part time or full time) or shareholder of an industry.

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