Potential future options in the pharmacotherapy of female sexual dysfunction

Female sexual dysfunction (FSD) is considered a common medical problem estimated to affect millions of women in the westernized countries. FSD has been classified into four different categories including sexual arousal disorder (FSAD), sexual desire disorder (HSDD), orgasmic disorder and sexual pain disorder. The focus of this article is the potential role of pharmacological compounds currently under development, in the treatment of sexual arousal and orgasmic disorders in order to enhance the sexual response in adult females. While a number of potential therapeutic options are available to date, not one of the pharmacological treatment regimens has been yet considered the Gold standard in the management of symptoms of FSD. This article reviews the rationale and potential benefits of using distinct drug formulations in the treatment of FSD.     

Progress in female sexual dysfunction

INTRODUCTION: Female sexual dysfunction (FSD) is a significant age-related, progressive and highly prevalent problem that affects a substantial number of women that causes personal distress and has negative effects on quality of life and interpersonal relationships. DEFINITIONS: The female sexual response cycle consists of three phases: desire, arousal, and orgasm, and is initiated by non-adrenergic/non-cholinergic, e.g. vasoactive intestinal polypeptide and nitric oxide, neurotransmitters that maintain vascular and non-vascular smooth muscle relaxation resulting in increased pelvic blood flow, vaginal lubrication, and clitoral and labial engorgement. Furthermore, hormonal status may influence female sexual function. For the diagnosis of FSD, a detailed history should be taken initially, followed by a physical examination and laboratory studies. CONCLUSION: Due to the fact that there has been little research and attention on FSD, our knowledge in this field is quite limited and there is still no approved therapy. Future advances in evaluation and treatment of female sexual problems are forthcoming.     

Anatomy and physiology of female sexual function and dysfunction: classification, evaluation and treatment options

Female sexual dysfunction is a significant age-related, progressive and highly prevalent problem that affects a substantial number of women in the United States. The female sexual response cycle is initiated by neurotransmitter-mediated vascular and nonvascular smooth muscle relaxation resulting in increased pelvic blood flow, vaginal lubrication, and clitoral and labial engorgement. These mechanisms are mediated by a combination of neuromuscular and vasocongestive events. Physiological impairments that interfere with the normal female sexual response bring about complaints associated with diminished sexual arousal, libido, vaginal lubrication, genital sensation, and ability to achieve orgasm. Therapy aimed at restoring hormone levels as well as genital blood flow will be discussed.     

Impact of hormones on female sexual function and dysfunction

The female sexual response cycle is a complex system composed of physiologic changes, psychological, and cultural factors. Female sexual dysfunction (FSD) encompasses a variety of sexual problems, including low desire or interest, diminished arousal, difficulties with orgasm, and dyspareunia. Research in female sexual function and dysfunction has lagged significantly behind males despite our current knowledge that FSD can occur in as many of 80% of the female population. Basic science research exists but also identifies serious gaps in our fundamental knowledge of this area. The purpose of this article was to review our current understanding of the effects of hormones on normal physiologic sexual responses in women, female sexual function and dysfunction, and the available treatment options for the various components of FSD.     

Female sexual dysfunction

Female sexual dysfunction (FSD) is a very common disorder in Germany with a prevalence of approximately 38%. FSD includes persistent or recurrent disorders of sexual desire, disorders of subjective or genital arousal and pain during intercourse. An overview of the epidemiology, the current definitions of the single domains of FSD, the pathophysiology and recommendations on the treatment of FSD is given.     

女性性功能障碍的治疗进展

随着社会的进步和性医学的发展,女性性功能障碍的治疗水平不断提高。本文综述了女性性功能障碍的基本治疗方法,包括心理治疗、性行为疗法、机械治疗、生活方式调整和体育锻炼、针灸、药物、手术及基因治疗,提出要客观认识现有治疗手段的局限性,强调以患者为中心的综合治疗原则,以及加强患者认知教育,全面改善女性性功能障碍的治疗现状。     

Prevalence and degree of sexual dysfunction in a sample of women seeking bariatric surgery

BackgroundSexual functioning has been shown to be impaired in women who are obese, particularly those seeking bariatric surgery. However, most previous studies evaluating sexual function in these populations have not used validated measures. We used the validated Female Sexual Function Index (FSFI) to assess the prevalence of female sexual dysfunction (FSD) in a sample of >100 women evaluated for bariatric surgery.MethodsThe FSFI was administered to reportedly sexually active women during their preoperative evaluation. The scores for the individual FSFI domains (desire, arousal, lubrication, orgasm, satisfaction, and pain) ranging from 0 (or 1.2) to 6 were summed to produce a FSFI total score (range 2–36). A FSFI total cutoff score of ≤26.55 was used to identify participants with FSD. The participants' FSFI total and domain scores were compared with previously published norms available for women diagnosed with female sexual arousal disorder and healthy controls.ResultsOf the 102 women, 61 (59.8%) had FSFI total scores of ≤26.55, indicative of FSD. Older age and menopause were associated with FSD. Compared with published norms, bariatric surgery candidates had FSFI domain scores that were lower than those of the control group (all P values < 0.0001) but greater than those of the female sexual arousal disorder group (all P values < 0.0001), except for desire, for which the scores were similar.ConclusionWomen seeking bariatric surgery are clearly a population with substantial sexual function impairment, with 60% of participants reporting FSD. These findings highlight the need to initiate routine assessment of sexual functioning in this population and examine whether the weight loss after bariatric surgery contributes to a reversal of FSD.     

Impact of pelvic floor disorders and prolapse on female sexual function and response

Pelvic floor disorders and FSD are prevalent and challenging problems. These disorders include prolapse of the uterus, cervix, vagina, bladder, and rectum and incontinence. These diseases likely affect women's sexual well-being through physical and emotional effects. Women with pelvic floor disorders often have co-existing urologic and sexual complaints. Patients who present with these urologic problems should be questioned about their sexual function. Surgical treatment in these patients may be curative of their sexual disorders (e.g., by repairing incontinence) but may also have undesired effects on sensation, blood flow, and the anatomy. These effects can affect sexual arousal and orgasm or cause dyspareunia. It is hoped that a better understanding of the anatomy of this area will guide us in a more targeted approach to management of these conditions.     

Experimental models for the investigation of female sexual function and dysfunction

There have been limited anatomic and physiological investigations of the female sexual arousal response. A broader understanding of the physiologic mechanisms of female sexual arousal function is required to improve the management of women with sexual dysfunction. Three experimental test systems have been developed to understand better the biochemical and physiological mechanisms of female sexual arousal response. An in vivo animal model was developed to record physiological and hemodynamic changes in the clitoris and vagina following pelvic nerve stimulation and administration of vasoactive agents and physiological modulators. In vitro organ baths of clitoral and vaginal tissue were utilized to investigate mechanisms involved in the regulation of smooth muscle contractility. In addition, primary cell cultures of human and animal clitoral and vaginal smooth muscle cells were developed to investigate signal transduction pathways modulating smooth muscle tone. In vivo studies revealed hemodynamic changes in vagina and clitoris in response to pelvic nerve stimulation, vasodilators and physiological modulators. Organ bath studies have demonstrated that clitoral and vaginal smooth muscle tone is affected by non-adrenergic and non-cholinergic neurotransmitters, and the presence of functional alpha 1 and alpha 2 adrenergic receptors in these tissues has been established through biochemical studies. These changes are regulated by the tone of vascular and non-vascular smooth muscle in the vagina and clitoris. Primary cell culture studies have suggested that several physiological modulators such as vasoactive intestinal polypeptide (VIP), nitric oxide (NO), and prostaglandin E (PGE) regulate vaginal smooth muscle contractility. Data from experimental models have provided a preliminary understanding of the mechanisms of the female sexual arousal response.     

妇科良性疾病与女性性功能障碍相关性分析

目的探讨妇科良性疾病与女性性功能障碍(FSD)相关性,为防治FSD的发生及防治提供理论依据。方法采用横断面调查方法,选取中等收入城市及农村居民区20岁及其以上女性进行问卷调查,收集其人口学特征及目前所患妇科疾病(经诊断确诊过的疾病)等信息。采用中文版女性性功能量表(FSFI)进行FSD评估,总分小于26.55说明存在FSD。应用多因素非条件Logistic回归模型分析妇科良性疾病与FSD相关性。结果发放问卷1 130份,收回1 068份(回收率94.5%),去除不符合要求问卷80份,共纳入有效问卷988份。988例被访者中妇科良性疾病患者占39.8%(393/988),为患病组,其余为健康组。393例患者中,性功能障碍者占71.2%(280/393),高于健康组性功能障碍患病率(P0.05)。与健康组相比,患病组在总分及性欲、性唤起、性高潮方面的评分分值均较健康组低(P0.05)。多因素非条件Logistic回归分析显示,妇科良性疾病、年龄(≥40岁)及绝经是FSD的独立危险因素,较高的教育水平是其保护性因素。结论 FSD是一个重要的公共卫生问题,甘肃省在妇科良性疾病者中FSD现患率较高,应加强性健康教育,降低FSD发生率。     

Noncontrast dynamic magnetic resonance imaging for quantitative assessment of female sexual arousal

PURPOSE: We evaluated a noncontrast, dynamic magnetic resonance imaging (MRI) technique for quantitative evaluation of the female sexual arousal response and compared these results with those of a previously described, contrast enhanced MRI technique. MATERIALS AND METHODS: Eight normal, healthy volunteer women underwent 2 separate MRI sessions, during which they were shown audiovisual material consisting of interleaved neutral and audiovisual sexual stimulation segments. Serial high resolution MRI of the genital structures was done at 3-minute intervals during a 45-minute period. Images were analyzed in blinded fashion and measurements of clitoral volume with time were obtained for each subject. Measured clitoral volumes together with the percent change in clitoral volume during audiovisual sexual stimulation for MRI sessions 1 and 2 were compared within subjects. Results were also compared to those of prior contrast enhanced MRI studies in the same subjects. RESULTS: There was excellent intrasubject reproducibility between sessions 1 and 2 using the noncontrast MRI technique (r = 0.99). There was also excellent agreement between the current noncontrast study and prior contrast enhanced studies with a correlation coefficient of 0.89. CONCLUSIONS: Dynamic, noncontrast MRI of the female genitalia appears to be a reproducible, nonintrusive and objective way to assess quantitatively the sexual arousal response in women without sexual difficulties.     

The epidemiology and definition of female sexual disorders

Female sexual dysfunction (FSD) is a multifactorial condition that has anatomical, physiological, medical, psychological, and social components. Similar to erectile dysfunction in men, FSD is highly prevalent and often undertreated. Due to the development of successful treatment for male erectile dysfunction, FSD is receiving increased attention. Only a few studies dealing with epidemiology of female sexual dysfunction are available in the literature. However, research efforts in the field are increasing. This overview presents currently used classification systems, recently updated definitions, as well as prevalence data on the different entities of female sexual disorders.     

Sildenafil augments pelvic nerve-mediated female genital sexual arousal in the anesthetized rabbit

The NO-cGMP pathway has been implicated in clitoral and vaginal smooth muscle relaxation based on previous immunochemical, biochemical and physiologic studies. There are limited data from in vivo studies demonstrating enhancement of the genital sexual arousal response by pharmacologic agents influencing the NO-cGMP pathway. The goal of this study was to investigate if sildenafil, a phosphodiesterase type-5 inhibitor, facilitated female genital sexual arousal in an animal model in response to pelvic nerve stimulation (PNS). Using female New Zealand White rabbits, we measured the following parameters before, during and after PNS at 4, 16, and 32 Hz: a) hemoglobin concentration and oxygen saturation in female genital (vaginal, labial, clitoral) tissues by laser oximetry; b) clitoral blood flow by laser Doppler flowmetry; c) vaginal luminal pressure by a balloon catheter pressure transducer; d) vaginal lubrication by tampon. Sildenafil was administered intravenously (0.21 microg/kg, 0.42 microg/kg, 2.1 microg/kg) to achieve a systemic concentration of 5, 10 and 50 nM, respectively. After 20 minutes, physiologic measurements were repeated. Sildenafil (50 nM) caused a significant increase in genital oxyhemoglobin concentration and a significant decrease in genital deoxyhemoglobin concentration. Sildenafil also increased the duration of response following PNS, relative to genital hemoglobin concentration and mean clitoral blood flow. Sildenafil caused a decrease in vaginal luminal pressure and resulted in an increase in vaginal lubrication. These data indicate that the NO-cGMP pathway is involved in the physiologic mechanism of female genital arousal and that sildenafil facilitates this response in an in vivo animal model.     

Remission of female sexual dysfunction in morbidly obese female patients with the Scopinaro procedure

BackgroundThe prevalence of obesity has increased in Spain in recent years. Obese women are at increased risk for sexual dysfunction, and important remission of this condition has been previously reported with bariatric surgery.ObjectivesThe major aim of this study was to assess the effects of the Scopinaro biliopancreatic diversion on female sexual dysfunction (FSD) using a validated Female Sexual Function Index (FSFI).MethodsEighty sexually active women with morbid obesity and with FSD underwent surgery. All patients completed the FSFI before surgery, as well as 6 and 12 months after surgery. The FSFI evaluates the sexual function using 6 items: desire, arousal, lubrication, orgasm, satisfaction, and pain. We used a<26.5 cut-point to assess the presence of FSD. This cut-point is used as a standard for the investigation.ResultsBefore surgery, all patients had FSD (mean 19.9±1.6). Six months after surgery, the FSD improved (mean 25.4±4.1; P<.001), and 12 months after surgery FSD resolved in most of the patients (mean 30.4±3.5; P<.001). All of the parameters evaluated by the FSFI (P<.001) improved significantly in all patients.ConclusionFSD improved significantly 6 months after biliopancreatic diversion among obese women with preoperative sexual dysfunction and continued improving up to 12 months later.     

高血压对女性性功能的影响

女性性功能障碍(FSD)是一种与年龄相关的进展性疾病,可能影响多达半数的成年妇女,长期以来,FSD未得到重视.高血压是一种常见病、多发病.高血压及抗高血压药物与FSD有密切关系,其中高血压引起的动脉粥样硬化和内皮功能障碍、抗高血压药物对女性性功能的影响尤为显著,现就高血压对女性性功能的影响机制及研究进展作一综述.     

女性性功能障碍的常见病因

女性的性功能障碍是一种常见和多发疾病,给夫妻生活带来显著的不良影响,而明确其病因是合理诊治的基础。本文介绍了女性性功能障碍的常见病因,主要包括心理与社会因素、神经因素、性激素异常、疾病因素、药物因素和产后。     

Evaluation and treatment of female sexual disorders

Prevalence data suggest that more than 40% of women experience sexual problems and that 12% of these women are distressed by the problem. In the 1960s, Masters and Johnson introduced what is now considered the classic linear model of female sexual response based on a physiologic foundation. Recently, Rosemary Basson introduced a nonlinear interconnected model which emphasizes the importance of emotional intimacy and satisfaction as integral components of the female sexual response cycle. According to the Diagnostic and Statistical Manual (DSM-IV TR), there are six female sexual disorders: hypoactive sexual desire disorder, aversion disorder, sexual arousal disorder, female orgasmic disorder, vaginismus, and dyspareunia. Despite the high prevalence, few healthcare professionals take the time or feel adequately trained to assess and treat these sexual problems. Sexuality questionnaires play an integral role in the diagnosis and treatment of male and female sexual dysfunctions. They are used to (1) identify/diagnose individuals with a particular dysfunction, (2) assess the severity of the dysfunction, (3) measure improvement or satisfaction with treatment, (4) examine the impact of the dysfunction on the individual’s quality of life (relationship satisfaction, mood, sexual confidence), and (5) study the impact of the dysfunction on the partner and his or her quality of life. Patient-reported outcomes (PRO) are increasingly important in both clinical practice and research settings. The instruments reviewed have played a significant role in furthering our understanding of the impact of female sexual function on the patient and partner and its treatment. It is important for the clinician and researcher to familiarize themselves with the best available measures for identifying specific dysfunctions, measuring distress due to the sexual dysfunction, assessing treatment efficacy, and objectively evaluating the quality of life issues of women with these dysfunctions. However, even the best PRO cannot replace the clinician–patient interview and the careful gathering of the patient’s sexual history. PROs should always be interpreted and integrated with the woman’s history.     

Weibliche sexuelle Dysfunktion

Female sexual dysfunction (FSD) is a very common disorder in Germany with a prevalence of approximately 38%. FSD includes persistent or recurrent disorders of sexual desire, disorders of subjective or genital arousal and pain during intercourse. An overview of the epidemiology, the current definitions of the single domains of FSD, the pathophysiology and recommendations on the treatment of FSD is given.     

Regulatory issues in female sexual dysfunction

Female sexual dysfunction (FSD) remains an enigmatic area to some, a controversial area to others and the subject of continued, intense debate in the literature. Questions remain regarding the legitimacy of FSD as a bona fide disease; the definition of FSD; the methods of diagnosis; and, the treatment of FSD. In this timely perspective, Jean Fourcroy, Consultant in Urology, Endocrinology and Regulatory Issues, discusses the controversies that continue to plague FSD.     

Female sexual dysfunction in a healthy Austrian cohort: prevalence and risk factors

Purpose:Data on prevalence and risk factors for female sexual dysfunction (FSD) are rare, particularly from Europe. Aim of our study was therefore to investigate this issue in a cohort of women undergoing a health investigation.Patients and Methods:A consecutive series of women aged 20–80 years participating in a health-screening project in Vienna underwent a detailed health investigation and completed a 23-item questionnaire on several aspects of FSD including desire, arousal, pain and orgasmic disorders. Prevalence of FSD in different age groups and risk factors for FSD were calculated.Results:A total of 703 women aged 43 ± 15 years entered this study. Within the total study population, 22% reported on desire disorders, 35% on arousal disorders, and 39% on orgasmic problems, all of which increased significantly with age. Pain disorders were reported by 12.8% being most frequently in the women aged 20–39 years. In women aged 60–69 years, still 50% reported having at least “occasionally” sexual desire and 30% had more than two sexual intercourses per month. In this age group, 50% stated that a healthy sexual life is at least moderately important to them. Apart from age few risk factors for FSD were identified. Sportive activity was the only correlate to desire- and arousal disorders, psychological stress for orgasmic disorders.Conclusions:This study provides insights into age-specific changes of FSD in apparently healthy women. The importance of this subject is underlined by the high prevalence of FSD particularly in the elderly paralleled by a persisting interest in sexual activity.