Search

Phenotype Prediction Scores (PPS) might be powerful tools to predict traits or the efficacy of treatments based on combinations of Single-Nucleotide Polymorphism (SNPs) in large samples. We developed a novel method to produce PPS models for small samples sizes. The set of SNPs is first filtered on those known to be relevant in biological pathways involved in a clinical condition, and then further filtered repeatedly in a survival strategy to select stabile positive/negative risk alleles. This method is applied on Female Sexual Interest/Arousal Disorder (FSIAD), for which two subtypes has been proposed: 1) a relatively insensitive excitatory system in the brain for sexual cues, and 2) a dysfunctional activation of brain mechanisms for sexual inhibition. A double-blind, randomized, placebo-controlled cross-over experiment was conducted on 129 women with FSIAD. The women received three different on-demand drug-combination treatments during 3 two-week periods: testosterone (0.5 mg) + sildenafil (50 mg), testosterone (0.5 mg) + buspirone (10 mg), or matching placebos. The resulted PPS were independently validated on patient-level and group-level. The AUC scores for T+S of the derivation set was 0.867 (95% CI = 0.796–0.939; p<0.001) and was 0.890 (95% CI = 0.778–1.000; p<0.001) on the validation set. For T+B the AUC of the derivation set was 0.957 (95% CI = 0.921–0.992; p<0.001) and 0.869 (95% CI = 0.746–0.992; p<0.001) for the validation set. Both formulas could reliably predict for each drug who benefit from the on-demand drugs and could therefore be useful in clinical practice. [ABSTRACT FROM AUTHOR]

Data from clinical trials investigating on-demand medication often consist of an intentionally varying number of measurements per patient. These measurements are often observations of discrete events of when the medication was taken, including for example data on symptom severity. In addition to the varying number of observations between patients, the data have another important feature: they are characterized by a hierarchical structure in which the events are nested within patients. Traditionally, the observed events of patients are aggregated into means and subsequently analyzed using, for example, a repeated measures ANOVA. This procedure has drawbacks. One drawback is that these patient means have different standard errors, first, because the variance of the underlying events differs between patients and second, because the number of events per patient differs. In this paper, we argue that such data should be analyzed by applying a multilevel analysis using the individual observed events as separate nested observations. Such a multilevel approach handles this drawback and it also enables the examination of varying drug effects across patients by estimating random effects. We show how multilevel analyses can be applied to on-demand medication data from a clinical trial investigating the efficacy of a drug for women with low sexual desire. We also explore linear and quadratic time effects that can only be performed when the individual events are considered as separate observations and we discuss several important statistical topics relevant for multilevel modeling. Taken together, the use of a multilevel approach considering events as nested observations in these types of data is advocated as it is more valid and provides more information than other (traditional) methods. [ABSTRACT FROM AUTHOR]

The study aimed to compare the kinetics of two novel combination drug products for Female Sexual Interest/Arousal Disorder (FSIAD). Thirteen women received testosterone via the sublingual route followed 2.5 hours later by a buspirone tablet, versus a single combination tablet swallowed at once. The first clinical prototype consisted of a sublingual solution containing testosterone (0.5 mg) complexed with cyclodextrin and a tablet containing 10 mg buspirone, in a gelatin capsule to ensure blinding during the clinical studies. The innovative fixed-combination tablet consists of an inner-core component of 10 mg buspirone coated with a polymeric time-delay coating and an outer polymeric coating containing testosterone with hydroxypropyl-beta cyclodextrin. We observed an immediate testosterone pulse absorption from both formulations. We also demonstrated that there was adequate absorption of buspirone (>80 % relative to the conventional tablet) and a time delay in release of buspirone of 3.3 hours, close to the 3.0 hours of the reference formulation that showed clinical efficacy in early proof-of-principle studies. The newly developed combination tablet fulfils its design criteria and is a convenient tablet for further clinical studies in FSIAD. [ABSTRACT FROM AUTHOR]

In two experiments selective attention to angry faces was investigated in relation to trait anger and anxiety. A pictorial emotional Stroop task comparing colour-naming latencies for neutral and angry faces was employed. In Experiment 1 using an unmasked task, individuals scoring high on trait anger showed an attentional bias for angry faces. In Experiment 2, unmasked and masked versions of the task were used. Individuals were selected on low and high trait anxiety, but there was no indication of a relation between attentional bias scores and anxiety. When individuals were subsequently reallocated to groups on the basis of trait anger scores, the high anger group showed an attentional bias for angry faces in the unmasked and the masked task. Results are discussed in relation to recent neurobiological findings from our laboratory, as reflecting an evolutionary-evolved, content-specific response to the facial expression of anger. [ABSTRACT FROM AUTHOR]

Presents a study which examined whether exogenous testosterone would induce cardiac acceleration in response to angry faces in young women. Methodology; Results; Discussion.

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. [ABSTRACT FROM AUTHOR]

Introduction. Female sexual dysfunction (FSD) may be associated with reduced central sensitivity for sexual cues. A single dose of testosterone might induce an increase in sensitivity for sexual stimuli, which in turn allows a PDE5 inhibitor to be effective in boosting the physiological sexual response. Negative sexual experience—like childhood sexual abuse (CSA)—might be an important intervening factor in these drugs-induced alterations. Aim. To investigate if the combination of testosterone and vardenafil causes an increase in sensitivity for sexual cues and an increase in physiological sexual responding in women suffering from hypoactive sexual desire disorder (HSDD). Methods. Thirteen women with HSDD underwent four different drug treatments: (i) placebo; (ii) vardenafil; (iii) testosterone; and (iv) combination of testosterone and vardenafil. During each treatment, they performed an emotional Stroop task and watched neutral and erotic film clips. Main Outcome Measures. A masked version of the emotional Stroop task, and the vaginal pulse amplitude (VPA). Results. We found different effects in women who had reported CSA (N = 5) compared with those who had not (N = 8). In women without CSA, testosterone induced an increase in their originally low levels of preconscious attention for sexual cues, while women with CSA showed a decrease in their originally high levels of attention. In these groups, we also found different effects of the combination of testosterone and vardenafil on the VPA: women without CSA revealed a statistically significant increase in their VPA during treatment with the combination of testosterone and vardenafil as compared with placebo. Women with CSA, however, showed no alterations in their physiological sexual responding during this combined drug treatment. Conclusion. In women without CSA, testosterone appears to activate central sexual mechanisms resulting in higher VPA under the combination of testosterone and vardenafil. This effect did not occur in women with CSA. van der Made F, Bloemers J, van Ham D, El Yassem W, Kleiverda G, Everaerd W, Olivier B, and Tuiten A. Childhood sexual abuse, selective attention for sexual cues and the effects of testosterone with or without vardenafil on physiological sexual arousal in women with sexual dysfunction: A pilot study. J Sex Med 2009;6:429–439. [ABSTRACT FROM AUTHOR]