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

ABSTRACTIntroductionAmong 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.AimTo 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.MethodsFifty-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 MeasuresSubjective: sexual satisfaction, experienced genital arousal, sexual desire. Physiological: vaginal pulse amplitude.ResultsWomen 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.ConclusionsThe 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.