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1.
Expert Opin Drug Saf ; 19(1): 1-8, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31855607

RESUMO

Introduction: Hypoactive sexual desire disorder (HSDD) is the most prevalent sexual dysfunction in women, previously managed with off-label therapies. Indicated for premenopausal women, flibanserin is the first FDA-approved medication to treat HSDD.Areas covered: This review summarizes flibanserin's pharmacokinetics, proposed mechanism of action, and safety data in clinical trials with a focus on sedation- and hypotension-related adverse events, and drug interactions with alcohol and antidepressants. Sources included peer-reviewed publications and internal data from the manufacturer.Expert opinion: Flibanserin is a well-tolerated and effective treatment that decreases distress and restores sexual desire to a level that is normative for the individual patient with HSDD. Simplification of a risk mitigation program for flibanserin in the US is likely to increase the number of prescribing clinicians if accompanied with educational efforts to clarify flibanserin's risk-benefit profile. As flibanserin is dosed daily and may be used for a decade or more in the typical premenopausal patient, long-term pharmacovigilance data will be essential. Over time, HSDD will be treated by more nonspecialist health care professionals and flibanserin will likely become established as a significant treatment option along with other medications approved for this indication in the context of a holistic biopsychosocial treatment paradigm.


Assuntos
Benzimidazóis/administração & dosagem , Pré-Menopausa , Disfunções Sexuais Psicogênicas/tratamento farmacológico , Benzimidazóis/efeitos adversos , Interações Medicamentosas , Humanos , Hipotensão/induzido quimicamente , Hipotensão/epidemiologia
2.
Obstet Gynecol ; 134(5): 899-908, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31599840

RESUMO

OBJECTIVE: To evaluate the safety and efficacy of bremelanotide for the treatment of premenopausal women with hypoactive sexual desire disorder. METHODS: Two identical phase 3, randomized, double-blind, placebo-controlled, multicenter clinical trials (RECONNECT) evaluated the safety and efficacy of bremelanotide 1.75 mg administered subcutaneously as needed in premenopausal women with hypoactive sexual desire disorder. Patients were randomized 1:1 to 24 weeks of treatment with bremelanotide or placebo. Sample size was estimated based on simulations from key endpoints in patients with hypoactive sexual desire disorder from a prior trial. Coprimary efficacy endpoints were change from baseline to end-of-study in the Female Sexual Function Index-desire domain score and Female Sexual Distress Scale-Desire/Arousal/Orgasm item 13. RESULTS: Study 301 began on January 7, 2015, and concluded on July 26, 2016. Study 302 began on January 28, 2015, and concluded on August 4, 2016. Of the 1,267 women randomized, 1,247 and 1,202 were in the safety and efficacy (modified intent-to-treat) populations, respectively. Most participants were white (85.6%), from U.S. sites (96.6%), and had a mean age of 39 years. From baseline to end-of-study, women taking bremelanotide had statistically significant increases in sexual desire (study 301: 0.30, P<.001; study 302: 0.42, P<.001; integrated studies 0.35, P<.001) and statistically significant reductions in distress related to low sexual desire (study 301: -0.37, P<.001; study 302: -0.29, P=.005; integrated studies -0.33, P<.001) compared with placebo. Patients taking bremelanotide experienced more nausea, flushing, and headache (10% or more in both studies) compared with placebo. CONCLUSIONS: Both studies demonstrated that bremelanotide significantly improved sexual desire and related distress in premenopausal women with hypoactive sexual desire disorder. The safety profile was favorable. Most treatment-emergent adverse events were related to tolerability and the majority were mild or moderate in intensity. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02333071 (study 301) and NCT02338960 (study 302). FUNDING SOURCE: Palatin Technologies, Inc., and AMAG Pharmaceuticals, Inc.


Assuntos
Libido/efeitos dos fármacos , Peptídeos Cíclicos , Receptor Tipo 3 de Melanocortina/agonistas , Receptor Tipo 4 de Melanocortina/agonistas , Disfunções Sexuais Psicogênicas , alfa-MSH/análogos & derivados , Adulto , Fármacos do Sistema Nervoso Central/administração & dosagem , Fármacos do Sistema Nervoso Central/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Injeções Subcutâneas , Peptídeos Cíclicos/administração & dosagem , Peptídeos Cíclicos/efeitos adversos , Pré-Menopausa/fisiologia , Pré-Menopausa/psicologia , Angústia Psicológica , Disfunções Sexuais Psicogênicas/tratamento farmacológico , Disfunções Sexuais Psicogênicas/fisiopatologia , Disfunções Sexuais Psicogênicas/psicologia , Resultado do Tratamento , alfa-MSH/administração & dosagem , alfa-MSH/efeitos adversos
3.
Obstet Gynecol ; 134(5): 909-917, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31599847

RESUMO

OBJECTIVE: To evaluate the long-term safety and efficacy of bremelanotide as treatment for hypoactive sexual desire disorder in premenopausal women. METHODS: Women who completed the 24-week double-blind core phase of RECONNECT, composed of two parallel phase 3 trials (301 and 302) examining the safety and efficacy of bremelanotide compared with placebo in premenopausal women with hypoactive sexual desire disorder, could enroll in the 52-week open-label extension, provided they had not experienced serious adverse events during the core phase. Efficacy was assessed using the coprimary endpoints from the core phase, and all adverse events were collected during the open-label extension. All statistical analyses were descriptive. RESULTS: The study 301 open-label extension began on July 17, 2015, and concluded on July 13, 2017; the study 302 open-label extension began on October 5, 2015, and concluded on June 29, 2017. Of the 856 eligible patients who completed the core phase, 684 elected to participate in the open-label extension, and 272 completed it. The most common treatment-emergent adverse events considered related to study drug were nausea (40.4%), flushing (20.6%), and headache (12.0%), and the only severe treatment-emergent adverse event experienced by more than one participant in both studies was nausea during the open-label extension. The change in Female Sexual Function Index-desire domain score and Female Sexual Distress Scale-Desire/Arousal/Orgasm item 13 from baseline to end of the open-label extension ranged from 1.25 to 1.30 and -1.4 to -1.7, respectively, for patients who received bremelanotide during the core phase, and 0.70-0.77 and -0.9, respectively, for patients who received placebo during the core phase. CONCLUSION: During the 52-week open-label extension of RECONNECT, no new safety signals were observed, and premenopausal women treated with bremelanotide exhibited sustained improvements in hypoactive sexual desire disorder symptoms. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02333071 (study 301) and NCT02338960 (study 302). FUNDING SOURCE: Palatin Technologies, Inc., and AMAG Pharmaceuticals, Inc.


Assuntos
Libido/efeitos dos fármacos , Efeitos Adversos de Longa Duração , Peptídeos Cíclicos , Disfunções Sexuais Psicogênicas , alfa-MSH/análogos & derivados , Adulto , Fármacos do Sistema Nervoso Central/administração & dosagem , Fármacos do Sistema Nervoso Central/efeitos adversos , Feminino , Humanos , Injeções Subcutâneas , Efeitos Adversos de Longa Duração/induzido quimicamente , Efeitos Adversos de Longa Duração/diagnóstico , Peptídeos Cíclicos/administração & dosagem , Peptídeos Cíclicos/efeitos adversos , Angústia Psicológica , Receptor Tipo 3 de Melanocortina/agonistas , Receptor Tipo 4 de Melanocortina/agonistas , Estudos Retrospectivos , Disfunções Sexuais Psicogênicas/tratamento farmacológico , Disfunções Sexuais Psicogênicas/fisiopatologia , Disfunções Sexuais Psicogênicas/psicologia , Tempo , Resultado do Tratamento , alfa-MSH/administração & dosagem , alfa-MSH/efeitos adversos
5.
Drugs ; 79(14): 1599-1606, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31429064

RESUMO

Bremelanotide (Vyleesi™) is a melanocortin receptor agonist recently approved in the USA for the treatment of premenopausal women with acquired, generalized hypoactive sexual desire disorder (HSDD), as characterized by low sexual desire that causes marked distress or interpersonal difficulty. It is a self-administered, on-demand subcutaneous therapy. Initially developed by Palatin Technologies who sponsored the Phase 3 clinical trials, bremelanotide was subsequently out-licensed to AMAG Pharmaceuticals Inc. for exclusive North American rights to develop and commercialize the drug, including submitting the New Drug Application to the US FDA. Bremelanotide is a synthetic peptide analogue of the neuropeptide hormone alpha melanocyte-stimulating hormone (α-MSH) with high affinity for the melanocortin type 4 receptor (thought to be important for sexual function), giving it the potential to modulate brain pathways involved in sexual response. This article summarizes the milestones in the development of bremelanotide leading to this first regulatory approval.


Assuntos
Peptídeos Cíclicos/uso terapêutico , alfa-MSH/uso terapêutico , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Ensaios Clínicos Fase III como Assunto , Humanos , Disfunções Sexuais Psicogênicas/tratamento farmacológico , Disfunções Sexuais Psicogênicas/metabolismo , alfa-MSH/metabolismo
6.
PLoS One ; 14(8): e0221063, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31415608

RESUMO

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.


Assuntos
Nível de Alerta , Libido , Disfunções Sexuais Psicogênicas , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Disfunções Sexuais Psicogênicas/tratamento farmacológico , Disfunções Sexuais Psicogênicas/fisiopatologia
8.
Turk Psikiyatri Derg ; 30(1): 67-70, 2019.
Artigo em Turco | MEDLINE | ID: mdl-31170309

RESUMO

Persistent Genital Arousal Disorder is characterized with unwanted, uncontrollable and persistent genital arousal symptoms that occur spontaneously in the absence of simultaneous sexual fantasy, sexual desire or sexual stimulation. The condition may last for hours or days. Patients often find it difficult to share this condition with their health care providers because they are afraid of being diagnosed with hypersexuality and they often get different psychiatric diagnoses such as Obsessive Compulsive Disorder and Major Depressive Disorder. Therefore, little is known about the real prevalence, pathophysiology or etiology of Persistent Genital Arousal Disorder. In addition, since there is no study conducted in this field, our information in this area is limited to case reports. Although there is no consensus about the treatment of Persistent Genital Arousal Disorder in the psychiatric literature, there are some case reports about the use of pregabaline, clomipramine, duloxetine, clonazepam, varenicline, olanzapine, risperidone in addition to the case reports on treatment with hypnotherapy, pelvic floor physiotherapy and electroconvulsive therapy (ECT). In this case report, we aimed to present the detailed description of a successful treatment procedure with duloxetine in a forty two years old female patient diagnosed with Persistent Genital Arousal Disorder. She had been using various antidepressants, antipsychotics, anxiolytics and mood stabilizers for sixteen years with different psychiatric misdiagnoses like Bipolar Disorder, Obsessive Compulsive Disorder, Anxiety Disorder and Major Depressive Disorder and yet, had not shared her symptoms of genital arousal with any psychiatrist previously.


Assuntos
Cloridrato de Duloxetina/uso terapêutico , Inibidores da Recaptação de Serotonina e Norepinefrina/uso terapêutico , Disfunções Sexuais Psicogênicas/diagnóstico , Adulto , Diagnóstico Diferencial , Feminino , Humanos , Escalas de Graduação Psiquiátrica , Disfunções Sexuais Psicogênicas/tratamento farmacológico , Disfunções Sexuais Psicogênicas/psicologia
9.
Sex Med Rev ; 7(4): 575-586, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31196764

RESUMO

INTRODUCTION: Flibanserin, a multifunctional serotonin receptor agonist and antagonist, is currently approved in the United States and Canada for the treatment of acquired, generalized hypoactive sexual desire disorder (HSDD) in premenopausal women. A post hoc analysis of HSDD clinical trial data found that flibanserin treatment was associated with statistically significant weight loss relative to placebo, even though study patients were not selected for being overweight/obese and were provided no expectation for weight reduction or interventions intended to promote weight loss. AIM: To understand possible mechanisms by which flibanserin may produce weight loss. METHODS: A literature review was performed using Medline database for relevant publications on the mechanisms of action by which flibanserin may provide weight loss and the links between sexual function and weight management. MAIN OUTCOME MEASURES: Examination of (i) biopsychosocial factors regulating sexual desire, food intake, and weight regulation; (ii) clinical pharmacology of flibanserin; (iii) neurobiology of brain reward circuitry; and (iv) identification of possible mechanisms common to flibanserin and weight loss. RESULTS: Based on flibanserin clinical trial data, there was no consistent correlation between weight loss and improvement in sexual function, as assessed by HSDD outcome measures. Nausea, a common adverse event associated with flibanserin use, also did not appear to be a contributing factor to weight loss. Hypothetical links between flibanserin treatment and weight loss include modulation of peripheral 5-HT2A receptors and factors such as improved mood and improved sleep. CONCLUSION: Mechanisms of flibanserin-induced weight loss have not been well characterized but may involve indirect beneficial effects on peripheral 5-HT2A receptors and central regulation of mood and sleep. Future research may better elucidate the links between sexual function and weight management and the mechanism(s) by which flibanserin use may result in weight loss. Simon JA, Kingsberg SA, Goldstein I, et al. Weight Loss in Women Taking Flibanserin for Hypoactive Sexual Desire Disorder (HSDD): Insights into Potential Mechanisms. Sex Med Rev 2019;7:575-586.


Assuntos
Benzimidazóis/efeitos adversos , Antagonistas da Serotonina/efeitos adversos , Agonistas do Receptor de Serotonina/efeitos adversos , Disfunções Sexuais Psicogênicas/tratamento farmacológico , Perda de Peso/efeitos dos fármacos , Nível de Alerta/efeitos dos fármacos , Benzimidazóis/farmacologia , Ingestão de Energia/efeitos dos fármacos , Feminino , Humanos , Libido/efeitos dos fármacos , Antagonistas da Serotonina/farmacologia , Agonistas do Receptor de Serotonina/farmacologia
10.
BMC Womens Health ; 19(1): 58, 2019 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-31039769

RESUMO

BACKGROUND: Studies have demonstrated that women with low desire and low excitement have negative feelings regarding their physical and emotional satisfaction, as well as their happiness. In this study, we evaluate the efficacy of Libicare® - a multi-ingredient food supplement - to improve sexual function in postmenopausal women. METHODS: This was an exploratory, prospective, non-controlled, observational study. Postmenopausal women aged 45-65 with a risk of sexual dysfunction (Female Sexual Function Index (FSFI) < 25.83) were included during routine clinical visits and treated with 2 tablets of Libicare® daily for 2 months. Libicare® is an oral food supplement containing Trigonella foenum graecum, Turnera diffusa, Tribulus terrestris, and Ginkgo biloba dry extracts. Primary endpoint: change vs. baseline in FSFI score. Secondary endpoints: 1) changes in testosterone and serum steroid levels of free testosterone and sex hormone-binding globulin (SHBG) levels and 2) tolerability. RESULTS: A total of 29 patients (mean age: 54.69 years) were included. FSFI mean (SD) score showed a significant increase: 20.15 (4.48) vs 25.03 (6.94), baseline vs final; p = 0.0011, paired t-test. Most patients (86.2%) increased their FSFI score. All FSFI domains, except dyspareunia, showed significant increases. The highest increase was observed in the desire domain (p = 0.0004). Testosterone and SHBG levels were assessed in 21 patients. A significant increase in testosterone level was observed: 0.41 (0.26) vs. 0.50 (0.34) pg/mL, baseline vs. final; p = 0.038, Wilcoxon test. 52.4% of patients increased their testosterone levels. Finally, a significant decrease was observed in SHBG level: 85 (32.9) vs. 73 (26.8) nmol/L, baseline vs. final; p = 0.0001; paired t-test. 95.2% of patients decreased their SHBG levels. CONCLUSION: In this pilot study, a significant improvement in sexual function and related hormone levels was observed with Libicare®. Further studies must be conducted to confirm these exciting results. TRIAL REGISTRATION: Current Controlled Trial ISRCTN12928573 . Date of registration: 28/March/2019. Retrospectively registered.


Assuntos
Suplementos Nutricionais , Preparações de Plantas/administração & dosagem , Disfunções Sexuais Fisiológicas/tratamento farmacológico , Disfunções Sexuais Psicogênicas/tratamento farmacológico , Feminino , Humanos , Libido/efeitos dos fármacos , Pessoa de Meia-Idade , Satisfação Pessoal , Projetos Piloto , Extratos Vegetais/administração & dosagem , Estudos Prospectivos , Resultado do Tratamento
11.
J Sex Med ; 16(3): 375-382, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30773497

RESUMO

BACKGROUND: The effects of phosphodiesterase-type 5 (PDE5) inhibitors on the in vivo clitoral structure of women with diabetes have never been investigated. AIM: To study the in vivo structural and hemodynamic changes of the clitoris in premenopausal women with type 1 diabetes on PDE5 inhibitors. METHODS: 38 premenopausal women with type 1 diabetes aged 36 -46 years. A randomized 1:1 study design was used: Study Group (group A) on Tadalafil 5 mg daily, and control group (group B). Blood samples were taken from each woman to measure HbA1c, testosterone, and Free Androgen Index. The women underwent microbiopsy of the clitoral body by means of semiautomatic gun during total anesthesia for surgery therapy of a benign gynecological pathology. The tissue removed was processed for electron microscopy. Translabial color Doppler ultrasound was used to measure the peak systolic velocity (PSV), the end diastolic velocity (EDV), and the pulsatility index (PI) of clitoral arteries. MAIN OUTCOME MEASURES: Micro-ultrastructure observation of clitoral tissue and color Doppler sonography of clitoral blood flow. RESULTS: Of the 38 women, 13 (68.4%) of group A and 15 (78.9%) of group B completed the study. Group A showed a mean PSV and EDV increase, and a mean PI decrease with respect to baseline (P < .001). Group B did not show any change in both the parameters (P = NS). By a quantitative study in both groups a variable degree of ultrastructural abnormalities of smooth muscle cells (SMCs) was observed, consisting in increased glycogen and lipoic deposits, cytoplasmic vacuoles, and focal increase of electron density of SMCs. Moreover, the mean SMC thickness of group A (1.83 ± 0.68 µm) was larger than that of group B (1.3 ± 0.41 µm) (P = .02). CLINICAL IMPLICATIONS: PDE5 inhibitors could be used to treat diabetic women with genital arousal disorder. STRENGTHS & LIMITATIONS: The study shows a clear effect of PDE5 inhibitors on clitoral SMCs. However, a limit was to not have investigated the sexual function/behavior of women of both groups, this was because of the short time of the study. CONCLUSION: This study could help to understand in what way PDE5 inhibitors act on the ultrastructural pathophysiological clitoral cavernous tissue of women with diabetes. It could support PDE5 inhibitor usage in women with genital sexual arousal disorder due to metabolic diseases. Caruso S, Cianci A, Cianci S, et al. Ultrastructural Study of Clitoral Cavernous Tissue and Clitoral Blood Flow From Type 1 Diabetic Premenopausal Women on Phosphodiesterase-5 Inhibitor. J Sex Med 2019;16:375-382.


Assuntos
Clitóris/irrigação sanguínea , Diabetes Mellitus Tipo 1/fisiopatologia , Inibidores da Fosfodiesterase 5/farmacologia , Tadalafila/farmacologia , Adulto , Feminino , Hemodinâmica , Humanos , Pessoa de Meia-Idade , Pré-Menopausa , Disfunções Sexuais Psicogênicas/tratamento farmacológico , Ultrassonografia Doppler em Cores
12.
Subst Abuse Treat Prev Policy ; 14(1): 9, 2019 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-30795785

RESUMO

BACKGROUND: Methadone maintenance treatment (MMT) might be associated with the symptoms of depression and anxiety, sleep disturbances and sexual dysfunctions. This study was designed to determine the effects of crocin on psychological parameters in patients under MMT. METHODS: Patients under MMT were randomly allocated into two groups to receive either 30 mg/day crocin (2 plus crocin tablet, 15 mg BID) (n = 25) or placebo (2 tablets per day, 15 mg BID) (n = 25), one hour after taking food, for 8 weeks. Psychological parameters were evaluated at baseline and end of the trial to determine related associations between crocin and patients' mental health status. RESULTS: After 8-week intervention, crocin significantly decreased Beck Depression Inventory (b - 6.66; 95% CI, - 9.88, - 3.45; P < 0.0001), Beck Anxiety Inventory (b - 4.35; 95% CI, - 5.94, - 2.75; P < 0.0001), general health questionnaire (b - 4.45; 95% CI, - 7.68, - 1.22; P = 0.008) and Pittsburgh Sleep Quality Index (b - 2.73; 95% CI, - 3.74, - 1.73; P < 0.0001) in patients under MMT, compared with the placebo. Crocin also significantly improved International Index of Erectile Functions (b 4.98; 95% CI, 2.08, 7.88; P = 0.001) rather than placebo. CONCLUSION: Our findings indicated that taking crocin for 8 weeks by patients under MMT had beneficial effects on their mental health status. Crocin can be recommended as an adjunct to methadone in opioid withdrawal protocols because of the ability to improve the quality of life and decrease opioids side effects in these patients. This trial was registered in the Iranian website for clinical trials registry as http://www.irct.ir : IRCT2017110537243N1. CLINICAL TRIAL REGISTRATION NUMBER: www.irct.ir: http://www.irct.ir: IRCT2017110537243N1 .


Assuntos
Ansiedade/tratamento farmacológico , Carotenoides/uso terapêutico , Depressão/tratamento farmacológico , Metadona/uso terapêutico , Disfunções Sexuais Psicogênicas/tratamento farmacológico , Transtornos do Sono-Vigília/tratamento farmacológico , Adulto , Ansiedade/complicações , Carotenoides/efeitos adversos , Depressão/complicações , Método Duplo-Cego , Quimioterapia Combinada , Humanos , Tratamento de Substituição de Opiáceos/métodos , Escalas de Graduação Psiquiátrica , Transtornos do Sono-Vigília/complicações
13.
Sex Med Rev ; 7(3): 380-392, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30803922

RESUMO

INTRODUCTION: Flibanserin, a multifunctional serotonin agonist and antagonist, is approved by the U.S. Food and Drug Administration (FDA) for treatment of acquired, generalized hypoactive sexual desire disorder in premenopausal women. During the FDA's review of flibanserin, concerns were raised about the risks of hypotension, syncope, and sedation-related adverse events, which increase with alcohol use. Based on the results of an alcohol challenge study, the FDA required a boxed warning and alcohol contraindication in the flibanserin prescribing information, as part of a risk evaluation and mitigation strategy program. AIM: To evaluate the adverse event profile of flibanserin in the context of that seen with other medications that affect serotonin in the brain and are commonly prescribed for women. METHODS: This was a review of data provided in the product prescribing information for flibanserin, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, other serotonergic antidepressants, and triptans. MAIN OUTCOME MEASURES: The incidence of adverse events was assessed. RESULTS: The incidences of hypotension, syncope, and sedation-related adverse events (eg, dizziness, somnolence, fatigue) in studies of flibanserin were within the ranges observed for serotonergic antidepressants; the rates of these adverse events were generally lower with triptan medications. Other flibanserin-associated adverse events (eg, nausea, insomnia, dry mouth) occurred more commonly in patients taking antidepressant medications. CONCLUSION: Although medications that affect the serotonin system have varying adverse event profiles (likely mediated by differences in serotonin-related mechanisms of action, specific brain structures affected, and effects on other neurotransmitter systems), the occurrence of central nervous system-related adverse events was not dissimilar between flibanserin and serotonergic antidepressants. Kingsberg SA, McElroy SL, Clayton AH. Evaluation of Flibanserin Safety: Comparison with Other Serotonergic Medications. Sex Med Rev 2019;7:380-392.


Assuntos
Benzimidazóis/uso terapêutico , Libido/efeitos dos fármacos , Pré-Menopausa , Serotoninérgicos/uso terapêutico , Disfunções Sexuais Psicogênicas/tratamento farmacológico , Feminino , Humanos , Disfunções Sexuais Psicogênicas/fisiopatologia
15.
Acta Med Port ; 31(11): 680-690, 2018 Nov 30.
Artigo em Português | MEDLINE | ID: mdl-30521462

RESUMO

INTRODUCTION: Female sexual dysfunction is a common problem, affecting more than 1/3 of women during their lives. The aim of this review is to review the evidence for the effectiveness of testosterone in sexual dysfunction in postmenopausal women, particularly in the improvement of sexual desire. MATERIAL AND METHODS: The authors searched in international databases National Guidelines Clearinghouse, Guidelines Finder, Cochrane Library and MEDLINE/PubMed, for guidelines, systematic reviews, meta-analysis and randomized controlled trials, published between January 2005 and February 2017, using the MeSH terms 'testosterone', 'androgens', 'libido', 'sexual dysfunctions' and 'menopause'. RESULTS: From a pool of 506 articles, 11 were selected: three guidelines, one systematic review with meta-analysis and seven randomized controlled trials. The selected articles showed testosterone's efficacy on global sexual function and improvement of sexual desire in postmenopausal women, when both are used in monotherapy or in association with other hormones. No study showed changes in hepatic enzymes or serious adverse effects. DISCUSSION: The small sample size and short follow-up used in the included studies limits the ability to assess testosterone's long-term benefits and effects. CONCLUSION: At short-term, testosterone seems to improve sexual function in postmenopausal women, particularly sexual desire. Nevertheless, more studies with larger sample size and longer follow-up are needed to understand its long-term safety and effectiveness.


Assuntos
Androgênios/uso terapêutico , Medicina Baseada em Evidências , Libido/efeitos dos fármacos , Pós-Menopausa , Disfunções Sexuais Psicogênicas/tratamento farmacológico , Testosterona/uso terapêutico , Androgênios/efeitos adversos , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Humanos , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Revisões Sistemáticas como Assunto , Testosterona/efeitos adversos
16.
Anticancer Res ; 38(12): 6615-6620, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30504369

RESUMO

BACKGROUND/AIM: Hypoactive sexual desire disorder (HSDD) is hypothesised to manifest in postmenopausal women at onset of menopause due to decreased oestrogen levels. Transdermal testosterone is a potential treatment option. This systematic review explores the relationship between the incidence of breast cancer and transdermal testosterone use. MATERIALS AND METHODS: Searches were conducted on the PubMed and Ovid databases. In Ovid, the advanced search function was used: 'transdermal testosterone not male'. In PubMed, the following search terms were used: 'transdermal, testosterone, menopausal, women, breast cancer, women'. Abstracts that fitted our initial criteria were further investigated. RESULTS: A total of 25 publications from PubMed and 192 publications from Ovid were initially assessed. Three randomised control trials were judged to have sufficiently met our inclusion criteria. However, these trials were too heterogeneous for a meta-analysis. A systematic review was deemed the most appropriate analysis of the data available. CONCLUSION: The publications examined in this systematic review suggest that the use of transdermal testosterone to treat HSDD in postmenopausal women does not increase breast cancer incidence. However, further research in the form of adequately powered randomised controlled trials with breast cancer incidence being the primary end point is required in order to confirm this.


Assuntos
Neoplasias da Mama/epidemiologia , Testosterona/administração & dosagem , Testosterona/efeitos adversos , Administração Cutânea , Neoplasias da Mama/induzido quimicamente , Feminino , Humanos , Menopausa/efeitos dos fármacos , Fatores de Risco , Disfunções Sexuais Psicogênicas/tratamento farmacológico , Adesivo Transdérmico
17.
Expert Opin Pharmacother ; 19(15): 1705-1709, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30220233

RESUMO

INTRODUCTION: Persistent genital arousal disorder (PGAD) is a presumably rare, although debilitating condition, which was first defined only at the beginning of this century and has not yet found consideration by any of the international classification systems of diseases. As affected patients can suffer tremendously, this report aims at providing an overview and an expert opinion on the few existing studies and case reports, guiding clinicians in the treatment and pharmacotherapy of PGAD. Areas covered: In this article case reports, case series and surveys on drugs that may both alleviate or worsen/induce PGAD are reported. Expert opinion: Data on pharmacological treatment options in PGAD are sparse and mainly rely on case reports making conclusions difficult. Most importantly, some drugs such as serotonin reuptake inhibitors (SSRIs) may even induce or worsen PGAD during treatment or withdrawal. We now need an initial spark in order to promote basic research on the etiology of PGAD as well as clinical trials on possible treatment options. In the meanwhile, clinicians should provide careful diagnostics and counseling for affected patients. In case pharmacotherapy is desired, drugs that are able to inhibit sexual excitation and/or modulate sensory perception such as pregabalin or duloxetin might be worth a trial.


Assuntos
Inibidores de Captação de Serotonina/uso terapêutico , Disfunções Sexuais Psicogênicas/tratamento farmacológico , Nível de Alerta , Feminino , Humanos , Inibidores de Captação de Serotonina/farmacologia , Disfunções Sexuais Psicogênicas/patologia
18.
Expert Opin Emerg Drugs ; 23(3): 223-230, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30251897

RESUMO

INTRODUCTION: Female sexual dysfunction (FSD) is a highly prevalent, yet commonly underdiagnosed and undertreated condition. This paper reviews the diagnostic terminology for FSD, and basic sexual physiology in women. The Food and Drug Administration (FDA) approved drugs for FSD are discussed, followed by investigational drugs for FSD currently in phase 2 or 3 clinical trials, reasons for failure of drug development, and potential future drug targets. Areas covered: A literature review was conducted for available treatments for FSD: flibanserin, estrogen, ospemifene and prasterone. Potential treatments are assessed, as was the Pharmaprojects database which includes clinical trial information. Testosterone, bremelanotide, bupropion-trazodone, PDE-5 inhibitors, prostaglandins, tibolone and combination therapies, and the theoretical basis of potential drug targets are discussed. Expert opinion: The lack of established endpoints for phase 3 studies of FSD has impeded approval of new treatments, and required additional studies for validation, resulting in proposed changes to the FDA draft guidance for FSD clinical trials in October 2016. Current DSM-5 diagnostic nosology also fails to capture the full range of symptomology. Several promising compounds have shown no movement for several years limiting women's options. Overcoming socio-cultural bias against women's sexual and reproductive health will be critical in the approval of new treatments for FSD.


Assuntos
Drogas em Investigação/uso terapêutico , Disfunções Sexuais Fisiológicas/tratamento farmacológico , Disfunções Sexuais Psicogênicas/tratamento farmacológico , Animais , Aprovação de Drogas , Desenho de Fármacos , Drogas em Investigação/farmacologia , Feminino , Humanos , Disfunções Sexuais Fisiológicas/diagnóstico , Disfunções Sexuais Fisiológicas/fisiopatologia , Disfunções Sexuais Psicogênicas/diagnóstico , Disfunções Sexuais Psicogênicas/fisiopatologia , Estados Unidos , United States Food and Drug Administration
19.
Obstet Gynecol ; 132(2): 453-458, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29995725

RESUMO

OBJECTIVE: To quantify the placebo effect of various pharmacologic modalities including neuromodulators, hormonal agents, and onabotulinum toxin A for female sexual dysfunction. DATA SOURCES: Using Meta-analyses Of Observational Studies in Epidemiology guidelines, we conducted a systematic review of PubMed, EMBASE, ClinicalTrials.gov, and the Cochrane Review databases. METHODS OF STUDY SELECTION: Eleven search terms, "female sexual dysfunction" "treatment" in combination with "hypoactive sexual desire," "arousal disorder," "sexual pain disorder," "genitourinary syndrome of menopause," "orgasmic disorder," "vulvovaginal atrophy," "vaginismus," "vaginal atrophy," "vulvodynia," and "vestibulitis," were used. Studies were included if their design was randomized, included a placebo arm, and used the Female Sexual Function Index as an outcome measure. TABULATION, INTEGRATION, AND RESULTS: The placebo effect on the Female Sexual Function Index was compared with each respective study's treatment effect using inverse-variance weighting in a random-effects analysis model. Six hundred five relevant articles were retrieved. Twenty-four randomized controlled trials included a placebo arm. Of these, eight studies used the Female Sexual Function Index. Across these studies, 1,723 women with clinical pretreatment female sexual dysfunction received placebo. Two thousand two hundred thirty-six women were in the treatment arm of the respective studies and received various pharmacologic interventions including flibanserin, bupropion, onabotulinum toxin A, intravaginal prasterone, intranasal oxytocin, ospemifene, and bremelanotide. Women receiving placebo improved 3.62 (95% CI 3.29-3.94) on the Female Sexual Function Index. The treatment arm had a corresponding increase of 5.35 (95% CI 4.13-6.57). CONCLUSION: This meta-analysis of Level I evidence demonstrates that 67.7% of the treatment effect for female sexual dysfunction is accounted for by placebo. Our findings suggest that the current treatments for female sexual dysfunction are, overall, minimally superior to placebo, which emphasizes the ongoing need for more efficacious treatment for female sexual dysfunction.


Assuntos
Toxinas Botulínicas Tipo A/uso terapêutico , Hormônios/uso terapêutico , Neurotransmissores/uso terapêutico , Efeito Placebo , Disfunções Sexuais Fisiológicas/tratamento farmacológico , Disfunções Sexuais Psicogênicas/tratamento farmacológico , Feminino , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Disfunções Sexuais Fisiológicas/psicologia , Disfunções Sexuais Psicogênicas/psicologia , Resultado do Tratamento
20.
Womens Health (Lond) ; 14: 1745506518788970, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30016917

RESUMO

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.


Assuntos
Androgênios/uso terapêutico , Buspirona/uso terapêutico , Disfunções Sexuais Fisiológicas/tratamento farmacológico , Disfunções Sexuais Psicogênicas/tratamento farmacológico , Citrato de Sildenafila/uso terapêutico , Testosterona/uso terapêutico , Adulto , Estudos Cross-Over , Relação Dose-Resposta a Droga , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Libido/efeitos dos fármacos , Pessoa de Meia-Idade , Resultado do Tratamento
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