Efficacy and Safety of On-Demand Use of 2 Treatments Designed for Different Etiologies of Female Sexual Interest/Arousal Disorder: 3 Randomized Clinical Trials
Authors: Tuiten Adriaan , van Rooij Kim , Bloemers Jos , Eisenegger Christoph , van Honk Jack , Kessels Rob , Kingsberg Sheryl , Derogatis Leonard R. , de Leede Leo , Gerritsen Jeroen , Koppeschaar Hans P.F. , Olivier Berend , Everaerd Walter , Frijlink Henderik W. , Höhle Daniël , de Lange Robert P.J. , Böcker Koen B.E. , Pfaus James G. 
Published: December 2017

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 [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.