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Toward Personalized Sexual Medicine (Part 3): Testosterone Combined with a Serotonin1A Receptor Agonist Increases Sexual Satisfaction in Women with HSDD and FSAD, and Dysfunctional Activation of Sexual Inhibitory Mechanisms

Authors

  • 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
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  • 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
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  • 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
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  • Irwin Goldstein MD, PhD,

    1. San Diego Sexual Medicine, San Diego, CA, USA
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  • 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. Alan Turing Institute Almere, Almere, The Netherlands
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  • 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
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  • Frederiek van Mameren MD,

    1. Department of Gynaecology and Obstetrics, Flevo Hospital, Almere, The Netherlands
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  • Meredith Chivers PhD,

    1. Department of Psychology, Queen's University, Kingston, ON, Canada
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  • Walter Everaerd PhD,

    1. Department of Psychology, University of Amsterdam, Amsterdam, The Netherlands
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  • Hans Koppeschaar MD, PhD,

    1. Emotional Brain B.V., Almere, The Netherlands
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  • 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
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  • 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
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  • Role of funding source: Funding for this study was provided by Emotional Brain B.V.

  • Trial registration: trialregister.nl identifier: NTR1228.

Adriaan Tuiten, PhD, Emotional Brain B.V., Louis Armstrongweg 78, 1311 RL Almere, The Netherlands. Tel: 0031-36-5468346; Fax: 0031-36-5497186; E-mail: a.tuiten@emotionalbrain.nl

ABSTRACT

Introduction.  Among other causes, low sexual desire in women may result from dysfunctional activation of sexual inhibition mechanisms during exposure to sex. Administration of sublingual 0.5 mg testosterone (T) increases the sensitivity of the brain to sexual cues, which might amplify sexual inhibitory mechanisms further in women already prone to sexual inhibition. 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. A single dose of 5-HT1A receptor agonist (5-HT1Ara) might reduce the sexual stimulation induced PFC-mediated sexual inhibition during a short period after administration. Consequently, treatment with a single dose of T+5-HT1Ara might enhance sexual responsiveness, particularly in women exhibiting sexual inhibition.

Aim.  To investigate if treatment with a single dosage of T+5-HT1Ara will produce improvement in sexual functioning in women with Hypoactive Sexual Desire Disorder (HSDD) as the result of dysfunctional high sexual inhibition.

Methods.  Fifty-four women were divided on the basis of their excitatory or inhibitory responses during T+phosphodiesterase type 5 inhibitor (PDE5i) in low (N = 26) and high inhibitors (N = 28). Physiological and subjective indices of sexual functioning were measured in a participant-controlled ambulatory psychophysiological experiment at home (the first week of each drug treatment). In a bedroom experiment (the subsequent 3 weeks), sexual functioning was evaluated by event, week, and monthly diaries.

Main Outcome Measures.  Subjective: sexual satisfaction, experienced genital arousal, sexual desire. Physiological: vaginal pulse amplitude.

Results.  Women with high inhibition show a marked improvement in sexual function in response to treatment with T+5-HT1Ara relative to placebo and relative to T+PDE5i.

Conclusions.  The present study demonstrated that on-demand T+5-HT1Ara is a potentially promising treatment for women with HSDD, particularly for those women who are prone to sexual inhibition. van Rooij K, Poels S, Bloemers J, Goldstein I, Gerritsen J, van Ham D, van Mameren F, Chivers M, Everaerd W, Koppeschaar H, Olivier B, and Tuiten A. Toward personalized sexual medicine (part 3): Testosterone combined with a serotonin1A receptor agonist increases sexual satisfaction in women with HSDD and FSAD, and dysfunctional activation of sexual inhibitory mechanisms. J Sex Med 2013;10:824–837.

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