title: 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.
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-hydroxytryptamine receptor agonist (5-HT(1A)ra) will reduce the sexual-stimulation-induced PFC-mediated sexual inhibition during a short period after administration. Consequently, treatment with T+5-HT(1A)ra 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.
authors.affiliation: Emotional Brain BV, Almere, The Netherlands.
authors.forename: Jos
authors.initials: J
authors.lastname: Bloemers
authors.forename: Kim
authors.initials: K
authors.lastname: van Rooij
authors.forename: Saskia
authors.initials: S
authors.lastname: Poels
authors.forename: Irwin
authors.initials: I
authors.lastname: Goldstein
authors.forename: Walter
authors.initials: W
authors.lastname: Everaerd
authors.forename: Hans
authors.initials: H
authors.lastname: Koppeschaar
authors.forename: Meredith
authors.initials: M
authors.lastname: Chivers
authors.forename: Jeroen
authors.initials: J
authors.lastname: Gerritsen
authors.forename: Diana
authors.initials: D
authors.lastname: van Ham
authors.forename: Berend
authors.initials: B
authors.lastname: Olivier
authors.forename: Adriaan
authors.initials: A
authors.lastname: Tuiten
mesh_terms: D000279:Administration, Cutaneous; D000286:Administration, Sublingual; D000728:Androgens / Q000627:therapeutic use; D000818:Animals; D001921:Brain / Q000502:physiology; D001931:Brain Mapping; D003071:Cognition / Q000502:physiology; D003463:Cues; D004359:Drug Therapy, Combination; D004882:Erotica; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D058986:Phosphodiesterase 5 Inhibitors / Q000627:therapeutic use; D011987:Receptors, Steroid / Q000502:physiology; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D012725:Sexual Behavior / Q000187:drug effects / Q000502:physiology; D020018:Sexual Dysfunctions, Psychological / Q000188:drug therapy*; D013739:Testosterone / Q000502:physiology / Q000627:therapeutic use
chemical_list: D000728:Androgens; D058986:Phosphodiesterase 5 Inhibitors; D011987:Receptors, Steroid; D012738:Sex Hormone-Binding Globulin; D013739:Testosterone