Sexual Arousal Disorder Research Articles

Topical Alprostadil for the Treatment of Female Sexual Arousal Disorder

Female sexual dysfunction is a common disorder that is present in over 40% of women in the USA. An evaluation of female sexual dysfunction differs greatly from male erectile dysfunction in that female sexual dysfunction is a very general term that encompasses a variety of sexual complaints in women, rather than a specific physiological disorder. No pharmacological treatment is presently approved for the treatment of the myriad of disorders that are involved in female sexual dysfunction. One of the more common disorders of female sexual dysfunction involves disturbances in objective or subjective sexual arousal. Sexual arousal in women has a central component and a peripheral, or vulvar, component. Disorders in vulvar blood flow and stimulation may lead to decreased genital and central arousal. A logical corollary of this statement is that an improvement in local blood flow by the use of a local or systemic vasodilator may lead to an increase in overall sexual arousal and an increase in sexual satisfaction. This article will explore the use of topical alprostadil as a local vasodilator to improve sexual arousal and sexual satisfaction in women with female sexual arousal disorder.

Sexual Desire and Arousal Disorders in Women

A 46-year-old woman, married for 16 years, reports having had a low level of sexual desire and minimal sexual arousal during sexual activity for the past 10 years. Sexual thoughts, fantasies, and orgasms are all extremely rare. Lubrication is sufficient to allow painless intercourse. She and her husband have an eight-year-old son who was born after in vitro fertilization for unexplained infertility. How should this patient be assessed and treated?

Sildenafil improves sexual functioning in premenopausal women with type 1 diabetes who are affected by sexual arousal disorder: a double-blind, crossover, placebo-controlled pilot study

To verify whether sildenafil is effective in type 1 premenopausal women affected by sexual arousal disorder (SAD). Double-blind, crossover, placebo-controlled study. Gynecological diabetic outpatient clinic and sexual clinic. Thirty-six type 1 premenopausal diabetic women affected by SAD. Two 8-week periods of sildenafil 100 mg, washout, and placebo, by two possible sequences. Each woman submitted blood samples to measure HbA(1c), and T, free T (FT), and PRL. Efficacy was assessed [1] subjectively by the Personal Experiences Questionnaire based on the 5-point Likert scale, quantifying arousal, desire, orgasm, enjoyment of sexual activities, and frequency of sexual relationships; and [2] objectively by translabial color Doppler ultrasound to measure the resistance index (RI), pulsatility index (PI), peak systolic velocity (PSV), and end diastolic velocity of clitoral arteries. Thirty-two women completed the study. The mean HbA(1c) value was 8.0% +/- 1.8%, and plasma concentrations of T, FT, and PRL were normal. Sildenafil seems to improve arousal, orgasm and sexual enjoyment, and dyspareunia in women affected by type 1 diabetes. However, by flowmetric measurements, the mean RI was significantly lower and both the mean PI and PSV of the clitoral arteries were significantly higher compared with baseline and placebo. Sildenafil seems to improve subjective sexual aspects and can be used to treat objectively genital arousal disorder of premenopausal women with type 1 diabetes.

ORIGINAL RESEARCH—OUTCOMES RESEARCH: The Sensitivity of Event Logs, Self‐Administered Questionnaires and Photoplethysmography to Detect Treatment‐Induced Changes in Female Sexual Arousal Disorder (FSAD) Diagnosis

ABSTRACT Introduction The literature provides little evidence on what type of endpoints should be used to assess treatment-induced improvement in female sexual function. Aim The main goal of this study was to provide empiric evidence on the sensitivity of different types of measures for detecting treatment-induced changes in female sexual dysfunction diagnosis. Methods The measures investigated in this study included event logs, self-administered questionnaires (Female Sexual Functioning Index; FSFI), vaginal photoplethysmography, and continuous subjective sexual arousal measured during exposure to erotic videos. Participants were 24 women with female sexual arousal disorder (FSAD) who received sex therapy, placebo, or gingko biloba in a four-arm double-blind placebo-controlled clinical trial. FSAD was diagnosed utilizing a semistructured interview administered at pre- and post-treatment. Those women who did not meet FSAD criteria at post-treatment (N = 10) were labeled as “improved,” while women who still met FSAD criteria (N = 14) were categorized as “not improved” even if they showed signs of improvements. Main Outcome Measure Change scores from pre- to post-treatment on the FSFI, event logs, vaginal photoplethysmography, and continuous subjective levels of sexual arousal were used to predict whether women improved at post-treatment. Results were checked with exact logistic regression to control for the small sample size. Results The FSFI was the only measure to significantly predict whether women improved at post-treatment. The findings from this study lend support for the use of validated questionnaires as endpoint criteria in detecting treatment-induced changes in women's sexual dysfunction.

Brain activation by visual erotic stimuli in healthy middle aged males

The objective of the present study was to identify brain centers, whose activity changes are related to erotic visual stimuli in healthy, heterosexual, middle aged males. Ten heterosexual, right-handed males with normal sexual function were entered into the present study (mean age 52 years, range 46-55). All potential subjects were screened over 1 h interview, and were encouraged to fill out questionnaires including the Brief Male Sexual Function Inventory. All subjects with a history of sexual arousal disorder or erectile dysfunction were excluded. We performed functional brain magnetic resonance imaging (fMRI) in male volunteers when an alternatively combined erotic and nonerotic film was played for 14 min and 9 s. The major areas of activation associated with sexual arousal to visual stimuli were occipitotemporal area, anterior cingulate gyrus, insula, orbitofrontal cortex, caudate nucleus. However, hypothalamus and thalamus were not activated. We suggest that the nonactivation of hypothalamus and thalamus in middle aged males may be responsible for the lesser physiological arousal in response to the erotic visual stimuli.

Pharmacologic Treatment Strategies for Sexual Dysfunction in Patients with Epilepsy and Depression

Sexual dysfunction is a frequently encountered comorbid condition in patients with many medical and psychiatric conditions, such as epilepsy and depression. Most depressed patients experience some type of sexual dysfunction, decreased sexual desire being the most common. The association of sexual dysfunction with epilepsy is less clear. Changes in sex hormone levels are common in patients with epilepsy and may be attributable to the disease or to antiepileptic drugs (AEDs). Sexual dysfunction associated with depression or epilepsy is generally treated according to standard guidelines for the management of sexual disorders, since data from special populations are not available. The most common forms of female sexual dysfunction are lack of sexual desire and difficulty achieving orgasm. There are no approved pharmacotherapies for female hypoactive sexual desire disorder or female orgasmic disorder. Female sexual arousal disorder is treated with estrogen replacement therapy when indicated or vaginal lubricants. The most common male sexual dysfunction disorders are premature ejaculation and erectile dysfunction. Phosphodiesterase type-5 inhibitor drugs are now the first-line treatment for erectile dysfunction, and selective serotonin reuptake inhibitors and topical anesthetic creams are nonapproved but effective treatments for premature ejaculation. Testosterone and aromatase inhibitors have been used investigationally to treat sexual dysfunction in men taking AEDs. Patient education and follow-up appointments are essential to ensure optimal outcomes of pharmacologic treatments for sexual dysfunction.

Topical alprostadil (PGE1) for the treatment of female sexual arousal disorder: In-clinic evaluation of safety and efficacy

This multi-center, randomized, placebo-controlled, crossover design study evaluated the effects of a topical alprostadil solution for the treatment of female sexual arousal disorder (FSAD). A total of 79 naturally or surgically post menopausal women with FSAD were treated with either 100 or 400 micrograms of alprostadil solution and placebo, delivered on separate clinic visits in random order. Study drug was applied to the external genitalia and was followed by 30 minutes of visual sexual stimulation. Study evaluations included investigator assessments of genital vasocongestion and patient assessments of physical and emotional sexual arousal, and sexual satisfaction. Genital vasocongestion in response to PGE1 was significantly greater than placebo (p < 0.0001) at each dose level and at all post dosing time points. Patient assessments of physical and emotional arousal and sexual satisfaction were significantly greater than placebo with the 400 mcg dose, but not with the 100 mcg dose of alprostadil. Topical alprostadil was well tolerated with no reports of significant systemic side effects. The most common adverse event was mild, transient genital burning typically < 1 minute duration. Other side effects were mild–moderate, resolving within two hours of application. These data suggest topical alprostadil should be further researched as a potentially appropriate on-demand therapeutic choice for women experiencing FSAD.

Biologic basis of serotonin reuptake inhibitor antidepressant-associated female sexual dysfunction: A novel signaling perspective

Depression, which affects women twice as often as it does men, is rapidly becoming the second major cause of disability worldwide. This is true despite evidence that 80% to 90% of major depressive disorder patients respond to the first or second agent prescribed, and they can prevent relapse with continuing medication. Although “improved” serotonin reuptake inhibitor antidepressant agents advance treatment, most patients do not continue their prescribed medication for extended periods, resulting in premature treatment withdrawal rates approaching 68% in the first 3 months of treatment. This makes rates of relapse and recurrence three to four times higher. The principal reasons for premature withdrawal are side effects—mainly sexual dysfunction, which is under-recognized, occurs early in treatment, is dose related, is reversible, and rarely remits spontaneously. Assessment requires comprehensive evaluation of sexual function, pre-existing depression, depression associated with antidepressant treatment, and other related factors (eg, concurrent medical conditions, treatments, lifestyle risk factors, and response to treatments). Research on treatments for sexual dysfunction caused by serotonin reuptake inhibitor antidepressants relied on open label reports and clinical wisdom but lacked supporting double-blind placebo-controlled studies. This resulted in random pharmacology being given to patients. Advances in novel signal transduction and the use of phosphodiesterase type 5 (PDE5) inhibitors offer new opportunities for the development of evidence-based treatments for sexual dysfunction and for improving depression management outcomes. However, although evidence for PDE5 inhibitor effectiveness is extensive, it has predominantly focused on erectile dysfunction in men. Considerations for using PDE5 inhibitors to treat sexual dysfunction in women have begun to emerge and suggest potential treatment options for female sexual arousal disorder associated with the use of selective serotonin reuptake inhibitors.

Validation of the McCoy Female Sexuality Questionnaire in an Italian Sample

This article presents the result of a study that translated into Italian and validated the McCoy Female Sexuality Questionnaire (MFSQ) on an Italian sample. The questionnaire was first administered to a sample of 240 Italian women (age range, 18-65 years) recruited from a gynecology clinic. A principal component analysis identified 2 factors: sexuality (9 items) and partnership (5 items). Both factors showed an adequate inter-item reliability (Cronbach's alpha of .88 and .75, respectively). The validity of the Italian MFSQ was then tested by administering the questionnaire to a sample of 16 women with sexual dysfunction and 46 control women. Sexual dysfunction diagnoses were assessed through a semi-standardized interview based on the DSM-IV-TR diagnoses for Female Sexual Arousal Disorder, Female Orgasmic Disorder, Dyspareunia, and Hypoactive Sexual Desire Disorder. A discriminant validity test showed significant differences between women with and without female sexual dysfunction. These results indicate that the translated version of the MFSQ is a reliable and valid measure of sexual dysfunction among Italian women. The results also indicated a difference in factor structure between the Italian and the original version of the MFSQ, which warrants further investigation.

Phosphodiesterase inhibitors in female sexual dysfunction

Based on the increasing knowledge on both the physiology of penile erection and the pathophysiology of erectile dysfunction, selective phosphodiesterase (PDE) inhibitors have been successfully introduced in the oral treatment of male erectile dysfunction. Because of their central role in smooth muscle tone regulation, PDEs remain an attractive target for drug development in urology. Since the distribution and functional significance of PDE isoenzymes vary in different tissues, selective inhibitors of the isoenzymes have the potential to exert at least partially specific effects on the target tissue. Currently, PDE inhibitors are under investigation with potential uses in urinary stone disease, overactive bladder and the so-called benign prostatic syndrome. The convincing clinical data on the use of the orally active PDE5 inhibitors sildenafil (VIAGRA), vardenafil (LEVITRA) and tadalafil (CIALIS) in the treatment of erectile dysfunction are accompanied by boosting research activities on intracellular signal transduction and PDE characterisation in female genital tissues with the aid of immunohistochemistry and immunocytochemistry and molecular biology. The expression of various PDE isoforms in the human clitoris, vagina and labia minora was shown by means of immunohistochemistry and RT-PCR analyses and it was concluded from functional studies that an increase in cGMP or cAMP might be involved in the regulation of female genital blood flow and the control of genital non-vascular smooth muscle. As a consequence, the efficacy and safety of the PDE5 inhibitor sildenafil in the treatment of symptoms of female sexual dysfunction (FSD), including female sexual arousal disorders (FSAD), have been evaluated. Although the experiences from these early clinical studies have so far not been conclusive, they suggest that, after appropriate evaluation of patients, inhibition of PDE5 might be of benefit for selected individuals with FSAD. Such research efforts will possibly allow the identification of efficacious and diagnostic tools for erectile dysfunction and of even more selective drugs in its therapy.

A Randomized, Placebo-Controlled, Double-Blind, Parallel Design Study of the Efficacy and Safety of Specially Formulated Alprostadil Topical Cream in Patients With Female Sexual Arousal Disorder

Female sexual arousal disorder (FSAD) is a common disorder, affecting approximately 14% of the general female population. Up to date, few clinical trials have been conducted and no approved medications are available. The purpose of this study was to evaluate the clinical efficacy and safety of a novel alprostadil topical cream for the treatment of FSAD.

Excitatory Effects Produced by Topical Application of a Specially Formulated Alprostadil Cream on Hypothelamic and Amygdala Neuronal Activities

Female sexual arousal disorder (FSAD) is complex and may involve both the central nervous system (CNS) and peripheral nervous system. Our previous study showed that application of a novel and specially formulated alprostadil cream to the clitoris and the G-spot during visual sexual stimulation could elicit cerebral activations in various brain receptors using functional magnetic resonance imaging (fMRI) in both healthy and FSAD women. However, the neuropsychological mechanisms of FSAD are still poorly understood.

Enhanced Effects of Specially Formulated Topical Alprostadil Cream by a Continuous Dosing Remedy for the Treatment of Female Sexual Arousal Disorder (FSAD) in a Double-Blind, Multicenter, Randomized, and Placebo-Controlled Clinical Trial

Female sexual arousal disorder (FSAD) affects both pre- and postmenopausal women and is one of the major disorders in female sexual dysfunction. To this date, no approved medications for the indication of FSAD are available. In the analysis of the current study, the aim was to explore the treatment cycle effects of using a specially formulated alprostadil topical cream to treat FSAD women and its enhanced therapeutic effect for the treatment of FSAD by comparing the short and long term efficacy and safety treatment profiles.

Subtypes of Sexual Arousal Disorder Identified

Subtypes of Sexual Arousal Disorder Identified

The Use of the Sexual Function Questionnaire as a Screening Tool for Women with Sexual Dysfunction

To determine if the validated Sexual Function Questionnaire (SFQ), developed to assess efficacy in female sexual dysfunction (FSD) clinical trials, may also have utility in identifying target populations for such studies. Data from five clinical trials and two general population surveys were used to analyze the utility of the SFQ as a tool to discriminate between the presence of specific components of FSD (i.e., hypoactive sexual desire disorder, female sexual arousal disorder, female orgasmic disorder, and dyspareunia). Sensitivity/specificity analysis and logistic regression analysis, using data from all five clinical studies and the general population surveys, confirmed that the SFQ domains have utility in detecting the presence of specific components of FSD and provide scores indicative of the presence of a specific sexual disorder. The SFQ is a valuable new tool for detecting the presence of FSD and identifying the specific components of sexual functions affected (desire, arousal, orgasm, or dyspareunia).

Dopamine and Norepinephrine Responses to Film-Induced Sexual Arousal in Sexually Functional and Sexually Dysfunctional Women

This study was designed to assess potential differences between sexually functional and dysfunctional women in dopamine (DA) and norepinephrine (NE) responses to erotic stimuli. Blood levels of homovanillic acid (HVA; the major metabolite of DA) and NE were taken during the showing of a nonsexual and a sexual film from 9 women with female sexual arousal disorder and hypoactive sexual desire disorder and from 13 sexually functional women. We assessed sexual arousal subjectively using a self-report scale and physiologically using a vaginal photoplethysmograph. HVA levels significantly decreased in sexually functional and dysfunctional women during the erotic versus during the neutral film. NE levels were not significantly different for either group of women during the neutral and erotic films. Sexually dysfunctional women had significantly higher levels of NE during both the neutral and erotic films compared with functional women. Subjective or physiological arousal differences between neutral and erotic films were not significantly different between functional and dysfunctional women.

Diabetes and female sexual dysfunction: Moving beyond "benign neglect"

Female sexual response is a complex, nonlinear progression from desire to arousal and orgasm. Diabetes may affect all these, but it particularly affects arousal with decreased genital sensation and lubrication. Vaginal dryness and infections may lead to dyspareunia. Predictors of sexual dysfunction in women include depression. Neither age, duration of diabetes, glycemic control, nor complications predict sexual dysfunction in women as they do in men. Objective measures of decreased genital sensation or lubrication do not correlate with a subjective sense of female sexual arousal disorder. Low androgens and possibly estrogens may be etiologic, as may numerous medications used by patients with diabetes. Practitioners should recognize the high prevalence of female sexual dysfunction (up to 50%) and potential increase, in tandem with that of diabetes. In the absence of definitive treatment evidence, psychological counseling, improvised vaginal lubricants, and low doses of estrogens or androgens have been used to relieve the personal distress of female sexual dysfunction.

Arginase: Structure, Mechanism, and Physiological Role in Male and Female Sexual Arousal

AbstractFor Abstract see ChemInform Abstract in Full Text.

Evaluation of the role of pudendal nerve integrity in female sexual function using noninvasive techniques

Using quantitative sensory testing and a validated questionnaire, we investigated the role of pudendal nerve integrity in sexual function among women. Participants completed the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ). Vibratory and pressure thresholds were measured at the S2 dermatome reflecting pudendal nerve distribution. A total of 56 women enrolled; 29 (51.8%) were asymptomatic and 27 (48.2%) had 1 or more forms of female sexual dysfunction (total sexual dysfunction) including: desire disorder 16.1%, arousal disorder 26.8%, orgasmic disorder 25%, and pain disorder 12.5%. Age, parity, menopausal status, and body mass index were similar between groups. PISQ scores were lower in symptomatic subjects compared with controls (P < .001). Decreased tactile sensation was found at the clitoris for women with total sexual dysfunction, desire disorder, and arousal disorder. Women with arousal disorder also had decreased tactile sensation at the perineum. Pudendal nerve integrity may play a role in female sexual dysfunction.

Persistent Sexual Arousal Syndrome: A Descriptive Study

Persistent sexual arousal disorder (PSAS) is a poorly documented condition characterized by persistent genital arousal in the absence of conscious feelings of sexual desire. To determine whether there are replicable features associated with PSAS, to describe salient characteristics of women reporting this condition, and to determine predictors of distress. A 46-item Internet survey containing demographic information, symptom description, triggers, exacerbation and relief measures, distress ratings, and life and sexual satisfaction was placed on a secure server. Frequency analyses of descriptive data, and stepwise multiple regression analysis to identify independent predictors of level of distress. Of the 103 respondents, most were in good health, well educated, and in long-term relationships. Ninety-eight percent of respondents met at least one criterion for PSAS and 53% met all five criteria. Involuntary genital and clitoral arousal persisting for extended time periods, genital arousal unrelated to subjective feelings of sexual desire, and genital arousal not relieved with orgasms were the most frequently endorsed features associated with this syndrome. Symptom triggers included sexual stimulation, masturbation, stress, and anxiety. Distress about the condition was low in 25%, moderate in 35%, and high in 40% of respondents. The strongest predictors of distress were intrusive and unwanted feelings of genital arousal (P < 0.0001), continuous symptoms (P < 0. 001), feelings of unhappiness (P < 0.03), shame (P = 0.0001) and worry (P = 0.01), reduced sexual satisfaction (P < 0.004), enjoyment of symptoms some of the time (P = 0.01), and relationship status (P < 0.004). The results of this research support the description of a condition (persistent sexual arousal) involving involuntary genital and clitoral arousal unrelated to subjective feelings of sexual desire which persists despite one or more orgasms and which usually feels intrusive and unwanted. Varying levels of distress were identified with this condition as well as a variety of primarily negative emotional reactions.