Safety of topical sildenafil cream, 3.6% in a randomized, placebo-controlled trial for the treatment of female sexual arousal disorder.

BACKGROUND: There are currently no Food and Drug Administration-approved treatments for female sexual arousal disorder (FSAD), which is physiologically analogous to male erectile dysfunction. AIMS: The study sought to test the systemic and local genital safety of topical sildenafil cream, 3.6% (sildenafil cream) among healthy premenopausal women with FSAD and their sexual partners over a 12-week treatment period. METHODS: This was a phase 2b, exploratory, randomized, placebo-controlled, double-blind study of sildenafil cream among healthy premenopausal women with FSAD. Safety was assessed by the frequency and incidence of treatment-emergent adverse events (TEAEs) among participants and their sexual partners. Participants recorded the incidence of TEAEs in a daily eDiary (electronic diary). Sexual partners were contacted within 72 hours of each sexual event in which investigational product was used. All participants used placebo cream for 1 month, during a single-blind run-in period, and then if eligible, were randomized 1:1 to sildenafil cream or placebo cream. Participants used their assigned investigational product over a 12-week double-blind dosing period. They attended monthly follow-up visits, in which their eDiary TEAE data were reviewed by the study staff and graded for severity and relationship to study product. OUTCOMES: The frequency and incidence of TEAEs among participants and their sexual partners. RESULTS: During the 12-week double-blind dosing period, there were 78 TEAEs reported by 29 of 99 sildenafil-assigned participants and 65 TEAEs reported by 28 of 94 placebo-assigned participants (P = .76). All TEAEs were mild or moderate in severity. The most common treatment-related TEAE among active and placebo-assigned participants was application site discomfort. There were no differences in the number of treatment-related TEAEs among sildenafil cream vs placebo cream users (P > .99). Four sildenafil cream participants and 3 placebo cream participants discontinued the study due to TEAEs involving application site discomfort (P > .99). There were 9 TEAEs reported by 7 of 91 sexual partners exposed to sildenafil cream vs 4 TEAEs reported by 4 of 84 sexual partners exposed to placebo cream (P = .54). CLINICAL IMPLICATIONS: These data support further clinical development of topical sildenafil cream for the treatment of FSAD. STRENGTHS AND LIMITATIONS: Safety was assessed among participants and their sexual partners after 1357 and 1160 sexual experiences in which sildenafil cream or placebo cream were used, respectively. The phase 2b study was powered for the primary objectives of efficacy, rather than safety. CONCLUSION: These data demonstrate that topically applied sildenafil cream was safe and well tolerated by exposed users and their sexual partners.

What should we be studying? Research priorities according to women and gender-diverse individuals with sexual interest/arousal disorder and their partners.

BACKGROUND: Sexual interest/arousal disorder (SIAD) is one of the most common sexual problems for women. In clinical research, there are often misalignments between the research priorities of patients and researchers, which can negatively impact care, and gender-diverse individuals are often excluded from research. Inclusion of patient perspectives when establishing research priorities may help to reduce these gaps; however, the research priorities of couples coping with SIAD remain unclear. AIM: Identify the research priorities of women and gender-diverse individuals with SIAD and their partners. METHODS: In an online survey, couples coping with SIAD provided consent and responded to an open-ended question asking them to list the top 3 things they think are important for researchers to focus on related to couples coping with low sexual desire. A team-based content analysis was conducted to identify themes and their frequency of endorsement. OUTCOMES: An author-developed open-ended question. RESULTS: Analysis of 1279 responses (n = 667 from women and gender-diverse individuals with SIAD, n = 612 from partners) resulted in our identification of 6 main themes: general causes, general treatment and coping, biophysiological, relationship, psychological, and environmental/contextual. Additionally, we identified 4 sub-themes within each of the latter 4 main themes: general, cause, treatment, and impact. For women and gender-diverse individuals with SIAD, their partners, and specifically gender-diverse participants, the 3 most endorsed themes were psychological general factors (24.3%, 21.2%, 24.3%; eg, stress and the link between SIAD and anxiety), relationship general factors (15.7%, 13.2%, 18.6%; eg, relationship length and communication on sexual desire), and biophysiological general factors (12.3%, 12.4%, 14.3%; eg, research on medications and hormones). CLINICAL IMPLICATIONS: Clinical researchers should consider the research priorities of couples coping with SIAD to ensure their work aligns with the needs of the affected population. STRENGTHS AND LIMITATIONS: This study is the first to identify the research priorities of both women and gender-diverse individuals with SIAD and their partners. Most participants identified as heterosexual, North American, and of middle to high socioeconomic status; results may not generalize. Responses were sometimes brief and/or vague; interpretation of these responses was therefore limited and may have required more contextual information. CONCLUSION: Findings suggest that women and gender-diverse individuals with SIAD, their partners, and gender-diverse participants have similar research priorities that are consistent with a biopsychosocial approach to research. Heterogeneity of responses across themes supports a multidisciplinary, patient-oriented approach to SIAD research.

Comparisons and correlations of 1-month recall vs 24-hour recall in patient-reported outcomes of an exploratory, phase 2b, randomized, double-blind, placebo-controlled clinical trial of sildenafil cream, 3.6% for the treatment of female sexual arousal disorder.

BACKGROUND: Efficacy assessments in clinical trials of treatments for female sexual arousal disorder (FSAD) and other female sexual dysfunction (FSD) diagnoses rely on various patient-reported outcomes (PROs). AIMS: We sought to compare 1-month recall PRO measures among participants enrolled in a clinical trial who provided these data without (test population) vs with (control population) use of an at-home, 24-hour recall electronic diary (eDiary), capturing similar data. METHODS: Preplanned subset analysis as performed during a phase 2b, exploratory, randomized, placebo-controlled, double-blind study of sildenafil cream, 3.6% (sildenafil cream) among healthy premenopausal women with FSAD. Preliminary product efficacy was assessed via 1-month recall and 24-hour recall questionnaires. A subset of the participants, the Evaluation of Recall Subset [ERS] provided PROs via the 1-month recall instruments but did not provide data via the 24-hour recall eDiary. OUTCOMES: Responses to the 1-month recall instruments were compared among ERS (test) vs non-ERS (control) participants. Among the non-ERS population, correlations between 1-month and 24-hour recall endpoints were calculated. RESULTS: There were no significant differences in the study co-primary 1-month recall efficacy endpoints, the Arousal Sensation (AS) domain of the 28-item Sexual Function Questionnaire (SFQ28) and the Female Sexual Distress Scale - Desire, Arousal, Orgasm question 14, among ERS vs non-ERS participants during the initial 1-month no-drug run-in period or the 1-month single-blind placebo run-in period (P values > .47). Scores on these 1-month recall PROs continued to be similar after randomization for sildenafil cream (P values > .30) and placebo cream (P values > .20) assigned ERS and non-ERS participants during the 3-month double-blind dosing period. There were strong correlations between the SFQ28 AS and eDiary AS scores during the no-drug run-in (R = 0.79, P < .01) and the single-blind run-in (R = 0.73 P < .001). During the double-blind dosing period, the SFQ28 AS score continued to be highly correlated with the eDiary AS score among sildenafil cream users (R = 0.83; P < .001) and placebo cream users (R = 0.8; 2 P < .001). CLINICAL IMPLICATIONS: There was no evidence that 1-month recall PRO instruments introduce recall bias; assessing arousal sensations with 24-hour vs 1-month PRO instruments is similar and either method could be used to assess efficacy depending on study objectives. STRENGTHS AND LIMITATIONS: This preplanned subset analysis compared efficacy of PROs based on recall duration. While the subset was preplanned, the study was powered to detect significant differences in the primary efficacy objectives, not among this subset analyses. CONCLUSION: These data will be used in planning future efficacy assessments of sildenafil cream for FSAD. CLINICAL TRIAL REGISTRATION: This clinical trial was registered with ClinicalTrials.gov, NCT04948151.

Systemic testosterone for the treatment of female sexual interest and arousal disorder (FSIAD) in the postmenopause.

INTRODUCTION: Female sexual interest and arousal disorder (FSIAD) is the most prevalent female sexual dysfunction in the postmenopause. OBJECTIVE: The aim of this review is to provide a summary of the currently available evidence on the use of testosterone in the treatment of FSIAD in postmenopausal women. METHODS: A narrative review on the topic was performed. Only randomized controlled trials (RCTs) and systematic reviews and meta-analysis were considered. 123 articles were screened, 105 of them assessed for eligibility, and finally 9 were included in qualitative synthesis following the PRISMA declaration. RESULTS: Current evidence recommends, with moderate therapeutic benefit, the use of systemic transdermal testosterone within the premenopausal physiological range in postmenopausal women with Hypoactive Sexual Desire Disorder (HSDD), the previous entity for low desire dysfunction, not primarily related to modifiable factors or comorbidities such as relationship or mental health problems. The available evidence is based on studies with heterogeneity on their design (different testosterone doses, routes of administration, testosterone use in combination and alone, sexual instruments of measurement). There is no data indicating severe short-term adverse effects, although long-term safety data is lacking. CONCLUSIONS: Despite having testosterone as a valuable tool, therapeutic strategies are lacking in the pharmacological field of HSDD/FSIAD. Neuroimaging studies could provide valuable information regarding the sexual desire substrate and suggest the potential application of already approved drugs for women with a good safety profile. The use of validated instruments for HSDD in postmenopausal women, considering the level of distress, is necessary to be able to draw robust conclusions on the evaluated treatments.

Impact of mindfulness versus supportive sex education on stress in women with sexual interest/arousal disorder.

Low desire in women is the most common sexual difficulty, and stress has been identified as a significant predictor of symptoms. We evaluated a mindfulness-based cognitive therapy (MBCT) group treatment versus a sex education comparison group treatment (STEP) on self-reported stress and on the physiological stress response measured via morning-to-evening cortisol slope in 148 women with a diagnosis of sexual interest/arousal disorder (SIAD). Perceived stress decreased following treatment in both groups, and significantly more after MBCT. The cortisol slope was steeper (indicative of better stress system regulation) from pre-treatment to 6-month follow-up, with no differences between the groups. As an exploratory analysis, we found that the reduction in perceived stress predicted increases in sexual desire and decreases in sex-related distress for participants after MBCT only. These findings suggest that group mindfulness targeting women with low sexual desire leads to improvements in self-reported and physiological stress, with improvements in self-reported stress partially accounting for improvements in sexual desire and distress.

Pudendal nerve blockade for persistent genital arousal disorder (PGAD): A clinical review and case report.

BACKGROUND: Persistent genital arousal disorder (PGAD) is a condition characterized by unwanted and potentially painful genital sensations or spontaneous orgasms without stimulation. We present a case of a 55-year-old woman with refractory genital arousal disorder that was treated with serial pudendal nerve blocks. CASE: RW is a 55-year-old woman with chronic pelvic pain, pudendal neuralgia, MDD, SI, GAD, CRPS, and persistent genital arousal disorder for 11 years. Her PGAD was refractory to conservative management, physical therapy, and bilateral clitoral artery embolization. We performed bilateral pudendal nerve blocks with Kenalog and Bupivacaine, which provided almost complete relief for 2-3 months. We performed a bilateral pudendal nerve radiofrequency ablation; however, there was minimal benefit. RW continues to have significant relief with serial pudendal nerve blocks. SUMMARY AND CONCLUSION: Persistent genital arousal disorder is often refractory to medication and physical therapy requiring significant intervention such as entrapment surgery or artery embolization. Our case demonstrates pudendal nerve blocks as a potential treatment modality with minimal side effects.

Analysis of hsa-miR-19a-3p and hsa-miR-19b-3p modulation and phosphodiesterase type 5 expression in the vaginal epithelium of premenopausal women with genital arousal disorder.

BACKGROUND: Few studies have investigated the role of the phosphodiesterase type 5A (PDE5A) isoenzyme in female genital tissue disorders, exclusively taken from cadavers, as well as the epigenetic mechanisms responsible for the regulation of PDE5A levels. AIM: The aim was to study the in vivo association between microRNA (miRNA) expression and the expression levels of PDE5A in women with female genital arousal disorder (FGAD) compared with healthy women. METHODS: Premenopausal women affected by FGAD (cases) and sexually healthy women (control group) underwent microbiopsy of the periclitoral anterior vaginal wall for the collection of tissue samples. Computational analyses were preliminarily performed in order to identify miRNAs involved in the modulation of PDE5A by using miRNA-messenger RNA interaction prediction tools. Differences in the expression levels of miRNAs and PDE5A were finally investigated in cases and control subjects by using the droplet digital polymerase chain reaction amplification system and stratifying women considering their age, number of pregnancies, and body mass index. OUTCOMES: Expression levels of miRNAs were able to target PDE5A and the tissue expression in women with FGAD compared with healthy women. RESULTS: The experimental analyses were performed on 22 (43.1%) cases and 29 (56.9%) control subjects. Two miRNAs with the highest interaction levels with PDE5A, hsa-miR-19a-3p (miR-19a) and hsa-miR-19b-3p (miR-19b), were identified and selected for validation analyses. A reduction of the expression levels of both miRNAs was observed in women with FGAD compared with the control subjects (P < .05). Moreover, PDE5A expression levels were higher in women with FGAD and lower in women without sexual dysfunctions (P < .05). Finally, a correlation between body mass index and the expression levels of miR-19a was found (P < .01). CLINICAL IMPLICATIONS: Women with FGAD had higher levels of PDE5 compared with control subjects; therefore, the administration of PDE5 inhibitors (PDE5 inhibitors) could be useful in women with FGAD. STRENGTHS AND LIMITATIONS: The strength of the current study was to analyze genital tissue obtained in vivo from premenopausal women. A limitation was to not investigate other factors, including endothelial nitric oxide synthetases, nitric oxide, and cyclic guanosine monophosphate. CONCLUSION: The results of the present study indicate that the modulation of selected miRNAs could influence PDE5A expression in genital tissues in healthy women or in those with FGAD. Such findings further suggest that treatment with PDE5 inhibitors, as a modulator of PDE5A expression, could be indicated for women with FGAD.

Lumbar endoscopic spine surgery for persistent genital arousal disorder/genitopelvic dysesthesia resulting from lumbosacral annular tear-induced sacral radiculopathy.

BACKGROUND: Persistent genital arousal disorder/genitopelvic dysesthesia (PGAD/GPD) is characterized by distressing, abnormal genitopelvic sensations, especially unwanted arousal. In a subgroup of patients with PGAD/GPD, cauda equina Tarlov cyst-induced sacral radiculopathy has been reported to trigger the disorder. In our evaluation of lumbosacral magnetic resonance images in patients with PGAD/GPD and suspected sacral radiculopathy, some had no Tarlov cysts but showed lumbosacral disc annular tear pathology. AIM: The aims were 2-fold: (1) to utilize a novel multidisciplinary step-care management algorithm designed to identify a subgroup of patients with PGAD/GPD and lumbosacral annular tear-induced sacral radiculopathy who could benefit from lumbar endoscopic spine surgery (LESS) and (2) to evaluate long-term safety and efficacy of LESS. METHODS: Clinical data were collected on patients with PGAD/GPD who underwent LESS between 2016 and 2020 with at least 1-year follow-up. LESS was indicated because all had lumbosacral annular tear-induced sacral radiculopathy confirmed by our multidisciplinary management algorithm that included the following: step A, a detailed psychosocial and medical history; step B, noninvasive assessments for sacral radiculopathy; step C, targeted diagnostic transforaminal epidural spinal injections resulting in a temporary, clinically significant reduction of PGAD/GPD symptoms; and step D, surgical intervention with LESS and postoperative follow-up. OUTCOMES: Treatment outcome was based on the validated Patient Global Impression of Improvement, measured at postoperative intervals. RESULTS: Our cohort included 15 cisgendered women and 5 cisgendered men (mean ± SD age, 40.3 ± 16.8 years) with PGAD/GPD who fulfilled the criteria of lumbosacral annular tear-induced sacral radiculopathy based on our multidisciplinary management algorithm. Patients were followed for an average of 20 months (range, 12-37) post-LESS. Lumbosacral annular tear pathology was identified at multiple levels, the most common being L4-L5 and L5-S1. Twenty-two LESS procedures were performed in 20 patients. Overall, 80% (16/20) reported improvement on the Patient Global Impression of Improvement; 65% (13/20) reported improvement as much better or very much better. All patients were discharged the same day. There were no surgical complications. CLINICAL IMPLICATIONS: Among the many recognized triggers for PGAD/GPD, this subgroup exhibited lumbosacral annular tear-induced sacral radiculopathy and experienced long-term alleviation of symptoms by LESS. STRENGTHS AND LIMITATIONS: Strengths include long-term post-surgical follow-up and demonstration that LESS effectively treats patients with PGAD/GPD who have lumbosacral annular tear-induced sacral radiculopathy, as established by a multidisciplinary step-care management algorithm. Limitations include the small study cohort and the unavailability of a clinical measure specific for PGAD/GPD. CONCLUSION: LESS is safe and effective in treating patients with PGAD/GPD who are diagnosed with lumbosacral annular tear-induced sacral radiculopathy.

Symptoms and associated impact in pre- and postmenopausal women with sexual arousal disorder: a concept elicitation study.

BACKGROUND: Approximately 26% of adult women in the United States suffer from female sexual arousal disorder (FSAD), yet little has been done to compare the experience of FSAD in pre- and postmenopausal women, which is critical to enhance the current understanding of FSAD and inform the development and assessment of treatment options for these patient populations. AIM: To explore the experience of condition-associated symptoms and the relative importance of FSAD symptoms, including their severity, bother, and impact, on participants' health-related quality of life (HRQoL) in pre- and postmenopausal women with FSAD. METHODS: In-depth, qualitative, semistructured concept elicitation interviews were conducted with premenopausal (n = 23) and postmenopausal (n = 13) women who were clinically diagnosed with FSAD by a trained sexual medicine clinician. All interviews were audio recorded and transcribed verbatim by a professional transcription company. Thematic analysis was performed with the assistance of NVivo qualitative analysis software. OUTCOMES: Outcomes included qualitative interview data about FSAD symptoms and HRQoL, as well as a comparison between pre- and postmenopausal populations. RESULTS: The most frequently reported symptom in both cohorts was "inability or difficulty with orgasm" (premenopausal, n = 21; postmenopausal, n = 13). The symptom that premenopausal women most desired to have treated was lubrication, and for postmenopausal women, it was a lack of lubrication or wetness and loss of feeling/sensation. In total, 21 of 23 premenopausal women and all 13 postmenopausal women reported a lack of feeling or sensation in the genitals. The most frequently reported HRQoL impact in both groups was decreased confidence. CLINICAL IMPLICATIONS: Results from this study suggest that the manifestation and experience of FSAD are similar in pre- and postmenopausal women and that the unmet need for an FSAD treatment in the postmenopausal population is just as great as that of the premenopausal population. STRENGTHS AND LIMITATIONS: This study involved in-depth qualitative interviews with a relatively small group of women (N = 36) recruited from only 5 study sites across the United States. CONCLUSION: The analysis of qualitative data from the concept elicitation interviews revealed a substantial physical and emotional burden of FSAD, underscoring the need for Food and Drug Administration-approved treatment options for pre- and postmenopausal women with FSAD.

History of Sexual Assault as a Predictor of Response to a Self-Guided Online Program for Sexual Desire and Arousal Difficulties in Women.

Sexual Interest/Arousal Disorder (distressing, long-lasting impairments in sexual desire and/or arousal) is common in women, but few have access to efficacious psychotherapies, including cognitive-behavioral therapy (CBT) and mindfulness-based therapy (MBT). eSense, an online program meant to maximize treatment access, has been shown to be a feasible, satisfactory, and potentially efficacious intervention. However, subpopulations such as sexual assault survivors may find the program less usable or efficacious. The current study compared women with and without a history of sexual assault (SA) regarding their ability to use and benefit from eSense. Forty-four women (22 with a history of SA; M age = 34.20 years) used eSense (CBT or MBT) and completed validated self-report scales of sexual function, sexual distress, treatment satisfaction, and homework compliance. A history of SA did not predict differences in attrition or changes in clinical outcomes. Exploratory analyses suggested that women with a history of SA reported slightly higher difficulty completing homework assignments, but also slightly higher treatment satisfaction. These preliminary results suggest that eSense may be usable and helpful for women with a history of SA. We discuss ways to maximize the acceptability and efficacy of online programs for women with a history of SA.

Psychological Treatment of Persistent Genital Arousal Disorder/Genitopelvic Dysesthesia Using an Integrative Approach.

Persistent genital arousal disorder/genitopelvic dysesthesia (PGAD/GPD) is characterized by persistent, unwanted physiological genital arousal (i.e., sensitivity, fullness, and/or swelling) in the absence of sexual excitement or desire which can persist for hours to days and causes significant impairment in psychosocial well-being (e.g., distress) and daily functioning. The etiology and course of PGAD/GPD is still relatively unknown and, unsurprisingly, there are not yet clear evidence-based treatment recommendations for those suffering from PGAD/GPD. We present the case of a 58-year-old woman with acquired persistent genital arousal disorder, which began in March 2020; she believed she developed PGAD/GPD due to a period of significant distress and anxiety related to the COVID-19 pandemic. After seeking medical diagnosis and treatment from multiple healthcare providers and trying a combination of pharmacological and medical treatment modalities, she presented for psychological treatment. An integrative therapy approach (3 assessment sessions, 11 treatment sessions), which included cognitive behavior therapy, distress tolerance and emotion regulation skills from dialectical behavior therapy, and mindfulness practice, was utilized. The patient reported improvements anecdotally (e.g., decreased impact on occupational and social functioning, greater self-compassion, less frequent and shorter duration of PGAD/GPD flare-ups, improved ability to cope with PGAD/GPD symptoms, and decreased need for sleeping medication) and on self-report measures (e.g., lower PGAD/GPD catastrophizing, lower anxiety and depression, and greater overall quality of life).We report the use of an integrative (i.e., psychoeducational, cognitive behavioral, dialectical behavioral, and mindfulness-based) intervention, which may be an effective psychological treatment for PGAD/GPD.

Treatments for Persistent Genital Arousal Disorder in Women: A Scoping Review.

BACKGROUND: Persistent genital arousal disorder (PGAD) is characterized by elevated discomfort associated with persistent genital arousal in the absence of sexual desire. AIM: To perform a scoping review of the proposed treatments for PGAD and their efficacy. METHODS: A scoping review was carried out (PRISMA-Scr) that included articles on PGAD as the main disorder, only in women, which explained, in detail, the treatment and its efficacy, was empirical, was written in English and Spanish. No prior filtering by years was performed. OUTCOMES: Three different effective treatments were found (Physical therapies, pharmacological therapies, and psychotherapeutics in combination with other therapies). RESULTS: Thirty-eight articles were selected. From physical therapies, treatments using neuromodulation, transcutaneous electrical stimulation, Botox, surgery, electroconvulsive therapy, manual therapy, pelvic floor therapy, dietary changes, and transcranial magnetic stimulation showed effectiveness. Using the pharmacological approach, paroxetine, duloxetine, pramipexole, ropinirole, and clonazepam treatments were effective. Psychotherapy treatments showed effectiveness only in combination with other types of treatments, specifically a combination of cognitive-behavioral strategies with pharmacological treatment. CLINICAL IMPLICATIONS: Pharmacological treatment, specifically SSRIs, have proven to be the therapy of choice for different subtypes of patients. STRENGTHS AND LIMITATIONS: This study analyzed treatment effectiveness with different approaches and took into consideration those articles where psychotherapy was used as a combination treatment with pharmacological and physical therapy. The main limitation is that it was focused exclusively on women, and the results cannot be generalized to include men. CONCLUSIONS: To date, a combination of pharmacological interventions with physical therapy and, in some occasions, with psychological therapy is main strategy followed to accomplish effective treatment of PGAD. Martín-Vivar M, Villena-Moya A, Mestre-Bach G, et al. Treatments for Persistent Genital Arousal Disorder in Women: A Scoping Review. J Sex Med 2022;19:961-974.

What has the new 11th revision of International Classification of Diseases classification brought in the categorization of female sexual dysfunctions?

In January 2022, the classification of female sexual dysfunctions under the new eleventh revision of International Classification of Diseases came into force. Its definitive integration into practice is expected after a 5-year transition period. The new nomenclature is based on a circular model of female sexual activity, eliminating the Cartesian-dualistic concept of separating individual pathophysiological entities with "non-organic" and "organic" etiology. Sexual dysfunctions are evaluated as a complex interaction of psychological, interpersonal, social, cultural, physiological, and by gender-related processes. The new 11th revision of International Classification of Diseases established clear criteria for symptomatology and duration of disorders according to duration, frequency, and exposure to distress. Female sexual dysfunctions may be diagnosed regardless of etiology. The system of qualifiers allows the identification of etiological factors related to health condition; psychological and mental disorders; use of psychoactive substances or medication; lack of knowledge or experience; relational, cultural or gender-related factors. This article summarizes the current situation in the classification of female sexual dysfunctions in a historical context and presents the modus operandi for clinical practice according to current classifications.

Changes of Apomorphine-Induced Vaginal Hemodynamics in an Ovariectomized Rat Model Using Near-Infrared Spectroscopic Probe.

INTRODUCTION: Female sexual arousal disorder (FSAD) can be caused by the change in vaginal structure due to the decline of estrogen and one of the main symptoms is vaginal dryness. FSAD is a prevalent problem afflicting women all over the world and thus the interest is growing on the matter, but related studies of monitoring FSAD using a non-invasive optical method barely have been carried out. AIM: This study aims to investigate the longitudinal changes in female sexual arousal response induced by apomorphine (APO) administration in the ovariectomized rat using near-infrared spectroscopy (NIRS) probe. METHODS: To elicit sexual arousal, APO was administered subcutaneously to animals (n = 6) before and after ovariectomy, and the changes in oxyhemoglobin (OHb), deoxyhemoglobin (RHb), total hemoglobin (THb) concentration, and temperature on the vaginal wall after APO administration were monitored bi-weekly for 8 weeks. Furthermore, estradiol hormone, vaginal secretion, and body weight have been measured for comparison with the results from vaginal hemodynamics. RESULTS: APO administration caused the increase of vaginal OHb and RHb concentration but a decrease in temperature. The amplitude of OHb, RHb, and THb increase induced by APO gradually decreased over 8 weeks after ovariectomy while the decrease in vaginal temperature became profound. The level of estradiol and vaginal secretions also decreased over 8 weeks after ovariectomy, but bodyweight showed an increasing trend. CONCLUSIONS: A comparison between the parameters measured from the NIRS probe and the others (estradiol level, amount of vaginal secretion, and body weight) proved that the NIRS has the potential as a monitoring tool to evaluate female sexual arousal response. Jeong H, Lee HS, Seong M, et al. Changes of Apomorphine-Induced Vaginal Hemodynamics in an Ovariectomized Rat Model Using Near-Infrared Spectroscopic Probe. J Sex Med 2021;18:1328-1336.

Developing Cognitive Bias Modification Scenarios for Women with Sexual Interest Arousal Disorder and Comparing Effectiveness with Mindfulness Therapy.

The aim of the present study was to develop and validate the scenarios of cognitive bias modification of interpretation (CBM-I) in women with sexual interest arousal disorder (SIAD) and comparing its effectiveness with mindfulness therapy in Iran. This study was performed by mixed method in two phases. In the first phase of the study, CBM treatment scenarios were developed. In the second phase, 45 women with SIAD were selected and randomly divided into three groups (two experimental groups and one control group). In the qualitative phase of the research on the evaluation of the designed scenarios, 80 scenarios remained among the 100 scenarios by meeting the content validity criteria, fidelity, acceptance, and satisfaction with the treatment. Both experimental treatments exceeded the no treatment control but that mindfulness was more effective than CBM-I as measured by the Female Sexual Function Index Questionnaire (p < 0.001). According to the findings, the use of CBM-I to replace positive interpretations with negative interpretations of cognitive bias in SIAD has a clinical application. Therefore, CBM-I can be used as practical treatment along with other treatments to reduce the symptoms of sexual dysfunction.

Persistent Genital Arousal Disorder: A Study on an Italian Group of Female University Students.

There are very few studies in literature about Persistent Genital Arousal Disorder (PGAD) prevalence to date, and no one has ever been done in Italy. This study replicated the earlier Canadian research in order to investigate the prevalence of PGAD diagnostic criteria in an Italian group of 679 female university students and to compare the results with those obtained in the Canadian group. In addition, the research aimed at verifying if the type or number of PGAD criteria met and the intensity of symptoms are associated with more negative emotions, and if they can be related to age and sexual orientation. The results confirm that some women can experience spontaneous genital sensations that can vary in intensity and duration, and can be associated with a wide range of emotions. However, the results seem to suggest the importance of other factors in the evaluation of the symptoms, rather than factors related to their nature and intensity or age and sexual orientation. Moreover, 2 participants (0.29%) met all five criteria and reported high distress, confirming that there is a potential clinical condition called PGAD, in which the hypertrophic, intense and intrusive spontaneous genital arousal might determine the presence of extremely negative emotions.

Guideline No. 422d: Menopause and Sexuality.

OBJECTIVE: Provide strategies for improving the care of perimenopausal and postmenopausal women based on the most recent published evidence. TARGET POPULATION: Perimenopausal and postmenopausal women. BENEFITS, HARMS, AND COSTS: Target population will benefit from the most recent published scientific evidence provided via the information from their health care provider. No harms or costs are involved with this information since women will have the opportunity to choose among the different therapeutic options for the management of the symptoms and morbidities associated with menopause, including the option to choose no treatment. EVIDENCE: Databases consulted were PubMed, MEDLINE, and the Cochrane Library for the years 2002-2020, and MeSH search terms were specific for each topic developed through the 7 chapters. VALIDATION METHODS: The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See online Appendix A (Tables A1 for definitions and A2 for interpretations of strong and weak recommendations). INTENDED AUDIENCE: physicians, including gynaecologists, obstetricians, family physicians, internists, emergency medicine specialists; nurses, including registered nurses and nurse practitioners; pharmacists; medical trainees, including medical students, residents, fellows; and other providers of health care for the target population. SUMMARY STATEMENTS: RECOMMENDATIONS.

Feasibility of a cognitive behavioral online intervention for women with Sexual Interest/Arousal Disorder.

OBJECTIVES: Difficulties with sexual desire and arousal are common in women, but most lack access to effective treatment such as cognitive-behavioral therapy (CBT). eSense is a recently created online CBT intervention for sexual difficulties with promising evidence of usability. The current study assessed the feasibility of women completing the full eSense CBT program without guidance. METHODS: Eleven women with Sexual Interest/Arousal Disorder completed eSense and provided feedback via semi-structured interviews. RESULTS: Participants reported high satisfaction with eSense's functionality, improved knowledge about sexuality, greater awareness of their thought patterns, and better perspective around their sexual difficulties. Despite some difficulty completing homework, participants exhibited statistically significant pre-post improvements in sexual desire (d = 1.04), sexual arousal (d = 1.83), sexual satisfaction (d = 1.35), and sexual distress (d = 1.79). CONCLUSION: The findings add to the growing evidence that self-guided online interventions are feasible and potentially efficacious in treating female sexual dysfunction.

Prevalence of Persistent Genital Arousal Disorder in 2 North American Samples.

BACKGROUND: Persistent genital arousal disorder (PGAD) is a highly distressing, understudied condition characterized by persistent genital arousal (eg, genital sensations, sensitivity) in the absence of sexual desire. Currently, there is limited information about the prevalence of PGAD based on its proposed diagnostic criteria ("PGAD criteria"). AIM: This study sought to assess the prevalence of PGAD criteria in 2 North American samples: a large, non-clinical sample of Canadian undergraduate students (Study 1), and a nationally representative sample from the U.S. (Study 2). METHODS: The incoming class of undergraduate students (N = 1,634) enrolled in the Introduction to Psychology course at a Canadian university and a nationally representative sample of U.S. participants (N = 1,026) responded to questions about each PGAD criterion, and distress associated with these experiences. OUTCOMES: 5 self-report questions were developed based on each of the Leiblum and Nathan 2001 PGAD criteria, and a measure of associated distress was included. The U.S. sample (Study 2) also responded to questions about medical comorbidities and their knowledge of the term "PGAD." RESULTS: 1.1% (n = 4; Study 1) to 4.3% (n = 22; Study 2) of men and 0.6% (n = 7; Study 1) to 2.7% (n = 14; Study 2) of women reported experiencing all 5 PGAD criteria at a moderate to high frequency. Even greater proportions of participants reported experiencing all 5 criteria at any frequency (6.8-18.8%). Although ratings of associated distress varied, participants who were distressed by these symptoms most frequently endorsed the first PGAD criterion: physiological genital arousal in the absence of sexual excitement or desire. These results are similar to previously reported rates of PGAD. CLINICAL IMPLICATIONS: A non-trivial number of individuals may experience PGAD, and it should be screened for by healthcare practitioners. STRENGTHS & LIMITATIONS: This study is the first to use 2 large, non-clinical samples to assess the prevalence of PGAD symptoms. However, barriers to reporting symptoms, such as shame or embarrassment, may have resulted in underestimates of prevalence in the present sample. CONCLUSION: The prevalence of the 5 PGAD criteria in 2 large non-clinical samples ranged from similar to higher than rates reported in previous research. However, distress ratings associated with each of the 5 criteria varied, with most respondents describing them primarily as neutral or non-distressing. Jackowich RA, Pukall CF. Prevalence of Persistent Genital Arousal Disorder in 2 North American Samples. J Sex Med 2020;17:2408-2416.

Partner Responses to Low Desire: Associations With Sexual, Relational, and Psychological Well-Being Among Couples Coping With Female Sexual Interest/Arousal Disorder.

BACKGROUND: The experience of distressing low sexual interest/arousal-female sexual interest/arousal disorder (FSIAD)-is prevalent in women of all ages and is associated with poorer sexual, relationship, and psychological well-being than women without this difficulty. Women who are partnered are almost 5 times more likely to be distressed by low desire and to receive a diagnosis of FSIAD than unpartnered women, indicating that interpersonal factors are highly relevant, although largely neglected in past research. AIM: In a dyadic cross-sectional and longitudinal study, we examined whether partner responses to FSIAD were associated with the sexual, relationship, and psychological well-being of couples, and whether any effects persisted 1 year later. METHODS: Women diagnosed with FSIAD (N = 89) completed a validated measure of perceived partner positive vs negative responses to their low sexual interest/arousal and their partners reported on their own responses, as well as measures of sexual desire, sexual satisfaction, relationship satisfaction, sexual distress, and anxiety. 1 year later, couples (N = 66) completed the outcome measures again. Data were analyzed according to the Actor-Partner Interdependence Model. OUTCOMES: Outcomes included were the Sexual Desire Inventory-Solitary and Partner-Focused Subscales; Global Measure of Sexual Satisfaction; Female Sexual Distress Scale; Couple Satisfaction Index; and State-Trait Anxiety Inventory-Short-Form. RESULTS: When women with FSIAD perceived more positive partner responses (eg, warm, supportive, compassionate) than negative responses (eg, hostile, unsupportive, indifferent), they were more satisfied with the relationship and they and their partners reported lower anxiety. When partners reported more positive than negative responses, they had greater relationship and sexual satisfaction and lower sexual distress and anxiety. Exploratory analyses revealed that women's perceptions of their partners' responses accounted for the link between partners' own responses and women's relationship satisfaction and anxiety. Partner responses did not predict any change in outcomes over time. CLINICAL IMPLICATIONS: Findings support interpersonal conceptualizations of FSIAD and may inform the development of future couple-based interventions. STRENGTHS & LIMITATIONS: This study is one of the few dyadic investigations of FSIAD, as diagnosed via a clinical interview. Significant associations were only observed cross-sectionally, limiting causal conclusions. There was limited power to detect longitudinal effects. CONCLUSION: More positive responses to women's low sexual interest/arousal by partners is linked to better adjustment among couples affected by FSIAD. Rosen NO, Corsini-Munt S, Dubé JP, et al. Partner Responses to Low Desire: Associations With Sexual, Relational, and Psychological Well-Being Among Couples Coping With Female Sexual Interest/Arousal Disorder. J Sex Med 2020;17:2168-2180.