Efficacy and Safety of On-Demand Use of 2 Treatments Designed for Different Etiologies of Female Sexual Interest/Arousal Disorder: 3 Randomized Clinical Trials

Tuiten, Adriaan; Rooij, Kim van; Bloemers, Jos; Eisenegger, Christoph; Honk, Jack van; Kessels, Rob; Kingsberg, Sheryl A.; Derogatis, Leonard R.; Leede, Leo de; Gerritsen, Jeroen; Koppeschaar, H. P. F.; Olivier, Berend; Everaerd, Walter; Frijlink, Henderik W.; Höhle, Daniël; Lange, Robert P.J. de; Böcker, K.B.E.; Pfaus, James G.

doi:10.1016/j.jsxm.2017.11.226

Cited by 30 publications

(21 citation statements)

References 43 publications

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“…Current evidence from women with adrenal insufficiency (44) or normal adrenal function (45) does not support DHEA use for HSDD treatment (A). Besides, two drug combinations, based on known neurobiological mechanisms that are critically important in sexual excitation and inhibition (46,47),…”

Section: Testosterone Therapy For Sexual Desire Dysfunctionmentioning

confidence: 99%

“…One consists of a tablet that combines a testosterone coating for sublingual administration and an innercore component containing the phosphodiesterase type 5 inhibitor sildenafil. Sublingual testosterone could potentially increase the brain's responses to sexual cues, leading to increases in sexual motivation, while sildenafil could increase genital vasocongestion (46,47). The other drug is a tablet which combines an innercore component containing the 5-hydroxytryptamine (5-HT)1A receptor agonist buspirone coated with a delayed-release matrix impregnated with testosterone, which could ensure that the pharmacologic effects of both components coincide (46,47).…”

Section: Testosterone Therapy In Womenmentioning

confidence: 99%

“…Sublingual testosterone could potentially increase the brain's responses to sexual cues, leading to increases in sexual motivation, while sildenafil could increase genital vasocongestion (46,47). The other drug is a tablet which combines an innercore component containing the 5-hydroxytryptamine (5-HT)1A receptor agonist buspirone coated with a delayed-release matrix impregnated with testosterone, which could ensure that the pharmacologic effects of both components coincide (46,47). However, these investigational drugs have not advanced yet to Phase III clinical trials and further progress are needed before considering as a treatment option.…”

Section: Testosterone Therapy In Womenmentioning

confidence: 99%

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Testosterone therapy for women with low sexual desire: a position statement from the Brazilian Society of Endocrinology and Metabolism

Weiss¹,

Hohl²,

Athayde³

et al. 2019

Archives of Endocrinology and Metabolism

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Objective: To summarize current evidence regarding testosterone treatment for women with low sexual desire. Materials and methods: The Female Endocrinology and Andrology Department of the Brazilian Society of Endocrinology and Metabolism invited nine experts to review the physiology of testosterone secretion and the use, misuse, and side effects of exogenous testosterone therapy in women, based on the available literature and guidelines and statements from international societies. Results: Low sexual desire is a common complaint in clinical practice, especially in postmenopausal women, and may negatively interfere with quality of life. Testosterone seems to exert a positive effect on sexual desire in women with sexual dysfunction, despite a small magnitude of effect, a lack of long-term safety data, and insufficient evidence to make a broad recommendation for testosterone therapy. Furthermore, there are currently no testosterone formulations approved for women by the relevant regulatory agencies in the United States, Brazil, and most other countries, and testosterone formulations approved for men are not recommended for use by women. Conclusion: Therefore, testosterone therapy might be considered if other strategies fail, but the risks and benefits must be discussed with the patient before prescription. A prospective longitudinal study of serum testosterone, dehydroepiandrosterone sulfate, and sex hormone-binding globulin levels through the menopause transition. J Clin Endocrinol Metab. 2000;85(8):2832-8.

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Section: Testosterone Therapy For Sexual Desire Dysfunctionmentioning

confidence: 99%

Section: Testosterone Therapy In Womenmentioning

confidence: 99%

Section: Testosterone Therapy In Womenmentioning

confidence: 99%

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Testosterone therapy for women with low sexual desire: a position statement from the Brazilian Society of Endocrinology and Metabolism

Weiss¹,

Hohl²,

Athayde³

et al. 2019

Archives of Endocrinology and Metabolism

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“…The neurobiological mechanism involved in this inhibitory effect likely involves a phasic increase in serotonergic activity in the left dorsolateral prefrontal cortex (DLPFC), 5 , 12 which is elicited by sexual stimulation. This subgroup division is based on the dual-control model of sexual response 16 and is substantiated by cognitive, 15 , 17 psychophysiological, 13 – 15 , 17 , 18 subjective, 13 – 15 , 19 neuroanatomical, 12 , 20 and pharmacological evidence. 13 – 15 , 17 , 19 Unfortunately, it is not readily apparent to which category a patient belongs because the symptoms, low desire and/or low arousal, manifest in the same manner in both these subgroups.…”

mentioning

confidence: 99%

“…To predict which of the two drug treatments will be effective for a woman diagnosed with FSIAD, we have searched for (combinations of) biological and psychological markers related to either one or both of the two distinct neurobiological mechanisms underlying FSIAD. An emotional Stroop task 13 , 15 , 17 and a combination of questionnaires and biological markers 19 were to a sufficient extent effective in separating T + S and T + B responders; however, this solution was deemed impractical for the clinical setting. Therefore, we searched for combinations of genetic markers that reflect the aetiology of the phenotype and thus predict the responses to these drugs.…”

mentioning

confidence: 99%

Genotype scores predict drug efficacy in subtypes of female sexual interest/arousal disorder: A double-blind, randomized, placebo-controlled cross-over trial

Tuiten

Michiels²,

Böcker³

et al. 2018

Womens Health (Lond Engl)

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Attempts to develop a drug treatment for female sexual interest/arousal disorder have so far been guided by the principle of ‘one size fits all’, and have failed to acknowledge the complexity of female sexuality. Guided by personalized medicine, we designed two on-demand drugs targeting two distinct hypothesized causal mechanisms for this sexual disorder. The objective of this study was to design and test a novel procedure, based on genotyping, that predicts which of the two on-demand drugs will yield a positive treatment response. In a double-blind, randomized, placebo-controlled cross-over experiment, 139 women with female sexual interest/arousal disorder received three different on-demand drug-combination treatments during three 2-week periods: testosterone 0.5 mg + sildenafil 50 mg, testosterone 0.5 mg + buspirone 10 mg, and matching placebo. The primary endpoint was change in satisfactory sexual events. Subjects’ genetic profile was assessed using a microarray chip that measures 300,000 single-nucleotide polymorphisms. A preselection of single-nucleotide polymorphisms associated with genes that are shown to be involved in sexual behaviour were combined into a Phenotype Prediction Score. The Phenotype Prediction Score demarcation formula was developed and subsequently validated on separate data sets. Prediction of drug-responders with the Phenotype Prediction Score demarcation formula gave large effect sizes (d = 0.66 through 1.06) in the true drug-responders, and medium effect sizes (d = 0.51 and d = 0.47) in all patients (including identified double, and non-responders). Accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the Phenotype Prediction Score demarcation formula were all between 0.78 and 0.79, and thus sufficient. The resulting Phenotype Prediction Score was validated and shown to effectively and reliably predict which women would benefit from which on-demand drug, and could therefore also be useful in clinical practice, as a companion diagnostic establishing the way to a true personalized medicine approach.

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A multilevel structural equation model for assessing a drug effect on a patient‐reported outcome measure in on‐demand medication data

et al. 2021

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We analyze data from a clinical trial investigating the effect of an on-demand drug for women with low sexual desire. These data consist of a varying number of measurements/events across patients of when the drug was taken, including data on a patient-reported outcome consisting of five items measuring an unobserved construct (latent variable). Traditionally, these data are aggregated prior to analysis by composing one sum score per event and averaging this sum score over all observed events. In this paper, we explain the drawbacks of this aggregating approach. One drawback is that these averages have different standard errors because the variance of the underlying events differs between patients and because the number of events per patient differs. Another drawback is the implicit assumption that all items have equal weight in relation to the latent variable being measured. We propose a multilevel structural equation model, treating the events (level 1) as nested observations within patients (level 2), as alternative analysis method to overcome these drawbacks. The model we apply includes a factor model measuring a latent variable at the level of the event and at the level of the patient. Then, in the same model, the latent variables are regressed on covariates to assess the drug effect. We discuss the inferences obtained about the efficacy of the on-demand drug using our proposed model. We further illustrate how to test for measurement invariance across grouping covariates and levels using the same model.

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Efficacy and Safety of On-Demand Use of 2 Treatments Designed for Different Etiologies of Female Sexual Interest/Arousal Disorder: 3 Randomized Clinical Trials

Cited by 30 publications

References 43 publications

Testosterone therapy for women with low sexual desire: a position statement from the Brazilian Society of Endocrinology and Metabolism

Testosterone therapy for women with low sexual desire: a position statement from the Brazilian Society of Endocrinology and Metabolism

Genotype scores predict drug efficacy in subtypes of female sexual interest/arousal disorder: A double-blind, randomized, placebo-controlled cross-over trial

A multilevel structural equation model for assessing a drug effect on a patient‐reported outcome measure in on‐demand medication data

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