Get access

Toward Personalized Sexual Medicine (Part 1): Integrating the “Dual Control Model” into Differential Drug Treatments for Hypoactive Sexual Desire Disorder and Female Sexual Arousal Disorder

Authors

  • Jos Bloemers MSc,

    1. Emotional Brain B.V., Almere, The Netherlands
    2. Utrecht Institute for Pharmaceutical Sciences and Rudolf Magnus Institute of Neuroscience, Utrecht University, Utrecht, The Netherlands
    Search for more papers by this author
  • Kim van Rooij MD,

    1. Emotional Brain B.V., Almere, The Netherlands
    2. Utrecht Institute for Pharmaceutical Sciences and Rudolf Magnus Institute of Neuroscience, Utrecht University, Utrecht, The Netherlands
    Search for more papers by this author
  • Saskia Poels MD,

    1. Emotional Brain B.V., Almere, The Netherlands
    2. Utrecht Institute for Pharmaceutical Sciences and Rudolf Magnus Institute of Neuroscience, Utrecht University, Utrecht, The Netherlands
    Search for more papers by this author
  • Irwin Goldstein MD,

    1. San Diego Sexual Medicine, San Diego, CA, USA
    Search for more papers by this author
  • Walter Everaerd PhD,

    1. Department of Psychology, University of Amsterdam, Amsterdam, The Netherlands
    Search for more papers by this author
  • Hans Koppeschaar MD, PhD,

    1. Emotional Brain B.V., Almere, The Netherlands
    Search for more papers by this author
  • Meredith Chivers PhD,

    1. Department of Psychology, Queen's University, Kingston, ON, Canada
    Search for more papers by this author
  • Jeroen Gerritsen MSc,

    1. Emotional Brain B.V., Almere, The Netherlands
    2. Utrecht Institute for Pharmaceutical Sciences and Rudolf Magnus Institute of Neuroscience, Utrecht University, Utrecht, The Netherlands
    3. Turing Institute Almere, Almere, The Netherlands
    Search for more papers by this author
  • Diana van Ham MSc,

    1. Emotional Brain B.V., Almere, The Netherlands
    2. Utrecht Institute for Pharmaceutical Sciences and Rudolf Magnus Institute of Neuroscience, Utrecht University, Utrecht, The Netherlands
    Search for more papers by this author
  • Berend Olivier PhD,

    1. Utrecht Institute for Pharmaceutical Sciences and Rudolf Magnus Institute of Neuroscience, Utrecht University, Utrecht, The Netherlands
    2. Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA
    Search for more papers by this author
  • Adriaan Tuiten PhD

    Corresponding author
    1. Emotional Brain B.V., Almere, The Netherlands
    2. Utrecht Institute for Pharmaceutical Sciences and Rudolf Magnus Institute of Neuroscience, Utrecht University, Utrecht, The Netherlands
    Search for more papers by this author

  • Role of funding source: Funding for this study was provided by Emotional Brain B.V.

Adriaan Tuiten, PhD, Emotional Brain B.V., Louis Armstrongweg 78, 1311 RL Almere, The Netherlands. Tel: 0031-5-46-83-46; Fax: 0031-5-49-71-86; E-mail: a.tuiten@emotionalbrain.nl

ABSTRACT

In three related manuscripts we describe our drug development program for the treatment of Hypoactive Sexual Desire Disorder (HSDD). In this first theoretical article we will defend the hypothesis that different causal mechanisms are responsible for the emergence of HSDD: low sexual desire in women (with HSDD) could be due to either a relative insensitive brain system for sexual cues or to enhanced activity of sexual inhibitory mechanisms. This distinction in etiological background was taken into account when designing and developing new pharmacotherapies for this disorder.

Irrespective of circulating plasma levels of testosterone, administration of sublingual 0.5 mg testosterone increases the sensitivity of the brain to sexual cues. The effects of an increase in sexual sensitivity of the brain depend on the motivational state of an individual. It might activate sexual excitatory mechanisms in low sensitive women, while it could evoke (or strengthen) sexual inhibitory mechanisms in women prone to sexual inhibition. Sexual stimulation in the brain is necessary for phosphodiesterase type 5 inhibitor (PDE5i)-mediated increase in genital sexual response. Accordingly, a single dose of T+PDE5i might enhance sexual responsiveness, especially in women with low sensitivity to sexual cues. In other women sexual stimulation might elicit a prefrontal cortex (PFC)-mediated phasic increase in sexual inhibition, in which activity of 5-hydroxytryptamine (5-HT, serotonin) is involved. We hypothesize that a single dose of 5-hydroxytryptamine1A receptor agonist (5-HT1Ara) will reduce the sexual-stimulation-induced PFC-mediated sexual inhibition during a short period after administration. Consequently, treatment with T+5-HT1Ara will be more effective, in particular in women exhibiting sexual inhibition.

Based on the results of our efficacy studies described in parts 2 and 3 of the series, we conclude that tailoring on-demand therapeutics to different underlying etiologies might be a useful approach to treat common symptoms in subgroups of women with HSDD. Bloemers J, van Rooij K, Poels S, Goldstein I, Everaerd W, Koppeschaar H, Chivers M, Gerritsen J, van Ham D, Olivier B, and Tuiten A. Toward personalized sexual medicine (part 1): Integrating the “dual control model” into differential drug treatments for hypoactive sexual desire disorder and female sexual arousal disorder. J Sex Med 2013;10:791–809.

Ancillary