Immunohistochemical staining with CD117 and PGP9.5 of excised vestibular tissue from patients with neuroproliferative vestibulodynia.

BACKGROUND: Neuroproliferative vestibulodynia (NPV), a provoked genital pain characterized by severe allodynia and hyperalgesia, is confirmed in excised vestibular tissue by immunohistochemical staining (>8 CD117-positive immunostained cells/100× microscopic field) rather than by hematoxylin and eosin staining. AIM: In this study we sought to assess immunostaining of tissue samples obtained during vestibulectomy surgery and to correlate results with patient outcomes. METHODS: Patients (n = 65) meeting criteria for NPV who underwent vestibulectomy during the period from June 2019 through December 2022 formed the study cohort. We performed assessment of pathology of vestibular tissues by use of immunohistochemical staining, including quantitation of mast cells by CD117 (mast cell marker) and nerve fibers by protein gene product (PGP) 9.5 (neuronal marker). We analyzed 725 photomicrographs of immunostained tissue sections (100× and 200×) by manual counting and computer-assisted histometry and correlated these data to clinical assessments. OUTCOMES: Outcomes included density of CD117 and PGP9.5 immunostaining in the 1:00-11:00 o'clock and 12:00 o'clock vestibular regions, and patient-reported outcomes assessing sexual function, pain, distress, and symptom improvement. RESULTS: All 65 NPV patients (median age 26 years), 45 with lifelong and 20 with acquired NPV, had severe pain documented by PROs and vulvoscopy and had >8 CD117-immunopositive cells/100× microscopic field. Median cell count values were similar in the 1:00-11:00 o'clock and 12:00 vestibular regions (28.5 and 29.5/100× field, respectively). Likewise, the marker) and nerve fibers by protein gene product (PGP) 9.5 (neuronal marker). We analyzed 725 photomicrographs of immunostained tissue sections (100× and 200×) by manual counting and computer-assisted histometry and correlated these data to clinical assessments. OUTCOMES: Outcomes included density of CD117 and PGP9.5 immunostaining in the 1:00-11:00 o'clock and 12:00 o'clock vestibular regions, and patient-reported outcomes assessing sexual function, pain, distress, and symptom improvement. RESULTS: All 65 NPV patients (median age 26 years), 45 with lifelong and 20 with acquired NPV, had severe pain documented by PROs and vulvoscopy and had >8 CD117-immunopositive cells/100× microscopic field. Median cell count values were similar in the 1:00-11:00 o'clock and 12:00 vestibular regions (28.5 and 29.5/100× field, respectively). Likewise, the median area of CD117 immunostaining was similar in both regions (0.69% and 0.73%). The median area of PGP9.5 immunostaining was 0.47% and 0.31% in these same regions. Pain scores determined with cotton-tipped swab testing were nominally higher in lifelong vs acquired NPV patients, reaching statistical significance in the 1:00-11:00 o'clock region (P < .001). The median score for the McGill Pain Questionnaire affective subscale dimension was also significantly higher in lifelong vs acquired NPV patients (P = .011). No correlations were observed between hematoxylin and eosin results and density of mast cells or neuronal markers. Of note, 63% of the patient cohort reported having additional conditions associated with aberrant mast cell activity. CLINICAL IMPLICATIONS: The pathology of NPV is primarily localized to the vestibular epithelial basement membrane and subepithelial stroma with no visible vulvoscopic findings, making clinical diagnosis challenging. STRENGTHS AND LIMITATIONS: Strengths of this study include the large number of tissues examined with what is to our knowledge the first-ever assessment of the 12:00 vestibule. Major limitations are specimens from a single timepoint within the disease state and lack of control tissues. CONCLUSIONS: Performing immunohistochemical staining of excised vestibular tissue with CD117 and PGP9.5 led to histometric confirmation of NPV, indications that NPV is a field disease involving all vestibular regions, validation for patients whose pain had been ignored and who had experienced negative psychosocial impact, and appreciation that such staining can advance knowledge.

Vestibular tissue changes following administration of intravaginal prasterone: a vulvoscopic open-label pilot study in menopausal women with dyspareunia.

Background: Prasterone, an intravaginal dyspareunia treatment in menopausal women, improves vaginal health through intracellular conversion of dehydroepiandrosterone into androgens and estrogens. Phase 3 trials for prasterone showed significant improvement in vaginal tissue health and reduction of pain. Aim: To assess vestibular changes with daily use of intravaginal prasterone in menopausal women with moderate to severe dyspareunia. Methods: This open-label prospective pilot study was conducted over 20 weeks. It included 11 menopausal women (median age, 56 years) who were treated daily with intravaginal inserts of 6.5-mg prasterone and assessed monthly. During vulvoscopy, vestibular pain was assessed by cotton-tipped swab testing, and vestibular and vaginal health was independently assessed with the Visual Scale (VS). In addition, vulvoscopic photographs were obtained and assessed via the Vulvoscopic Genital Tissue Appearance (VGTA) scale to evaluate overall genital tissue health. Mean changes from baseline for genital tissue health and pain assessments were analyzed by repeated measures 1-way analysis of variance, followed by a Dunnett post hoc test. Sexual event diaries were completed and adverse events recorded. Outcomes: Outcomes included indices of genital tissue health: pain assessment by cotton-tipped swab testing, VS of the vestibule and vagina, VGTA, and sexual event diary. Results: Aggregate scores from the cotton-tipped swab test progressively improved, reaching statistical significance at week 16, which was maintained through week 20 (-7.27, P = .019). VS scores significantly improved from baseline by week 4 and were maintained through week 20 for the vestibule (-3.00, P = .004) and vagina (-4.00, P = .002). An overall 1607 vulvoscopic photographs were examined; all showed reduction in vestibular erythema and pallor at the end of the study. The mean change from baseline at week 20 for the VGTA score was -7.9 (P = .0016). Intercourse associated with pain was reduced from 81.3% of initiated events during the first month of the study to 8.3% during the last month. Sexual activities that were discontinued due to discomfort were reduced from 45.8% to 6.3%. No prasterone-related serious adverse events were reported. Clinical Implications: Prasterone, a safe and effective intravaginal hormone treatment, significantly improves vestibular health parameters. Strengths and Limitations: Strengths are the prospective study design and the use of multiple outcome measures to assess vestibular tissue health and pain associated with sexual activity. Limitations are the small study cohort and use of nonvalidated outcome measures. Conclusion: Our findings suggest that intravaginal prasterone exerts biologic activity on the androgenic endodermal vestibule, as the medication passes from vagina to vestibule, resulting in amelioration of pain associated with sexual activity.

Safety and efficacy of fractional CO2 laser treatment to the vestibule: a randomized, double-blind, sham-controlled, prospective 3-site clinical study in women with vestibular pain.

BACKGROUND: Data are limited regarding fractional CO2 laser as a nonhormonal treatment for vestibular pain. AIM: We sought to perform what is, to our knowledge, the first multisite prospective randomized, double-blind, sham-controlled clinical trial to assess the safety and efficacy of fractional CO2 laser treatment to the vestibule in women with vestibular pain. METHODS: Subjects (n = 70) meeting inclusion/exclusion criteria at each of 3 sites were randomized 2:1 to active or sham (zero energy) fractional CO2 laser treatment using the vestibular probe (SmartXide2 V2LR - MonaLisa Touch, DEKA, Florence, Italy). Subjects in each treatment arm received 3 treatments 4 weeks apart. At the initial follow-up (week 12), subjects were unblinded and those initially assigned to sham started active treatment. OUTCOMES: Outcome measures included changes from baseline in sexual activity diaries and scores for the Vulvoscopic Genital Tissue Appearance Scale (VGTA), vestibular cotton-tipped swab testing, McGill Pain Questionnaire, Female Sexual Function Index (FSFI), Female Sexual Distress Scale-Revised (FSDS-R), and the O'Leary-Sant voiding and pain indices, the Interstitial Cystitis Symptom Index (ICSI) and Interstitial Cystitis Problem Index (ICPI). RESULTS: After active treatment, VGTA scores significantly improved in 5 parameters. Pain associated with cotton-tipped swab testing was significantly reduced at weeks 4 through 16 (mean change from baseline -0.64 [95% CI, -0.79 to -0.50] and -1.31 [95% CI, -1.46 to -1.16], respectively). FSFI pain domain scores improved significantly at weeks 12 and 16 (mean change from baseline 0.925 [95% CI, 0.10-1.75] and 1.22 [95% CI, 0.40-2.05], respectively). FSFI total scores increased significantly at weeks 12 and 16 (mean change from baseline 6.24 [95% CI, 2.64-9.85] and 4.96 [95% CI, 1.36-8.57], respectively). FSDS-R scores decreased significantly at weeks 12 and 16 (mean change from baseline -5.84 [95% CI, -8.80 to -2.87] and -9.15 [95% CI, -12.11 to -6.18], respectively). ICSI scores decreased significantly at weeks 12 and 16 (mean change from baseline -0.91 [95% CI, -1.65 to -0.18] and -0.754 [95% CI, -1.49 to -0.02], respectively). ICPI scores decreased significantly at week 16 (mean change from baseline -0.99 [95% CI, -1.63 to -0.34]). In contrast, there were no significant changes in outcomes in the sham arm. No serious adverse events occurred. CLINICAL IMPLICATIONS: Fractional CO2 laser treatment in women with vestibular pain resulted in improvement from baseline in multiple key outcome measures of vestibular health. STRENGTHS AND LIMITATIONS: Strengths of the study were that it was a multisite prospective randomized double-blind, sham-controlled clinical trial that included multiple measures related to vestibular pain and sexual function. Limitations were the nonvalidated primary outcome measure and limited study cohort. CONCLUSION: Fractional CO2 laser therapy is a safe and effective nonhormonal treatment for vestibular pain.

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.

International Society for the Study of Women's Sexual Health Clinical Practice Guideline for the Use of Systemic Testosterone for Hypoactive Sexual Desire Disorder in Women.

BACKGROUND: The Global Consensus Position Statement on the Use of Testosterone Therapy for Women (Global Position Statement) recommended testosterone therapy for postmenopausal women with hypoactive sexual desire disorder (HSDD). AIM: To provide a clinical practice guideline for the use of testosterone including identification of patients, laboratory testing, dosing, post-treatment monitoring, and follow-up care in women with HSDD. METHODS: The International Society for the Study of Women's Sexual Health appointed a multidisciplinary panel of experts who performed a literature review of original research, meta-analyses, review papers, and consensus guidelines regarding testosterone use in women. Consensus was reached using a modified Delphi method. OUTCOMES: A clinically useful guideline following a biopsychosocial assessment and treatment approach for the safe and efficacious use of testosterone in women with HSDD was developed including measurement, indications, formulations, prescribing, dosing, monitoring, and follow-up. RESULTS: Although the Global Position Statement endorses testosterone therapy for only postmenopausal women, limited data also support the use in late reproductive age premenopausal women, consistent with the International Society for the Study of Women's Sexual Health Process of Care for the Management of HSDD. Systemic transdermal testosterone is recommended for women with HSDD not primarily related to modifiable factors or comorbidities such as relationship or mental health problems. Current available research supports a moderate therapeutic benefit. Safety data show no serious adverse events with physiologic testosterone use, but long-term safety has not been established. Before initiation of therapy, clinicians should provide an informed consent. Shared decision-making involves a comprehensive discussion of off-label use, as well as benefits and risks. A total testosterone level should not be used to diagnose HSDD, but as a baseline for monitoring. Government-approved transdermal male formulations can be used cautiously with dosing appropriate for women. Patients should be assessed for signs of androgen excess and total testosterone levels monitored to maintain concentrations in the physiologic premenopausal range. Compounded products cannot be recommended because of the lack of efficacy and safety data. CLINICAL IMPLICATIONS: This clinical practice guideline provides standards for safely prescribing testosterone to women with HSDD, including identification of appropriate patients, dosing, and monitoring. STRENGTHS & LIMITATIONS: This evidence-based guideline builds on a recently published comprehensive meta-analysis and the Global Position Statement endorsed by numerous societies. The limitation is that testosterone therapy is not approved for women by most regulatory agencies, thereby making prescribing and proper dosing challenging. CONCLUSION: Despite substantial evidence regarding safety, efficacy, and clinical use, access to testosterone therapy for the treatment of HSDD in women remains a significant unmet need. Parish SJ, Simon JA, Davis SR, et al. International Society for the Study of Women's Sexual Health Clinical Practice Guideline for the Use of Systemic Testosterone for Hypoactive Sexual Desire Disorder in Women. J Sex Med 2021;18:849-867.

International Society for the Study of Women's Sexual Health Clinical Practice Guideline for the Use of Systemic Testosterone for Hypoactive Sexual Desire Disorder in Women.

Background: The Global Consensus Position Statement on the Use of Testosterone Therapy for Women (Global Position Statement) recommended testosterone therapy for postmenopausal women with hypoactive sexual desire disorder (HSDD). Aim: To provide a clinical practice guideline for the use of testosterone including identification of patients, laboratory testing, dosing, post-treatment monitoring, and follow-up care in women with HSDD. Methods: The International Society for the Study of Women's Sexual Health appointed a multidisciplinary panel of experts who performed a literature review of original research, meta-analyses, review papers, and consensus guidelines regarding testosterone use in women. Consensus was reached using a modified Delphi method. Outcomes: A clinically useful guideline following a biopsychosocial assessment and treatment approach for the safe and efficacious use of testosterone in women with HSDD was developed including measurement, indications, formulations, prescribing, dosing, monitoring, and follow-up. Results: Although the Global Position Statement endorses testosterone therapy for only postmenopausal women, limited data also support the use in late reproductive age premenopausal women, consistent with the International Society for the Study of Women's Sexual Health Process of Care for the Management of HSDD. Systemic transdermal testosterone is recommended for women with HSDD not primarily related to modifiable factors or comorbidities such as relationship or mental health problems. Current available research supports a moderate therapeutic benefit. Safety data show no serious adverse events with physiologic testosterone use, but long-term safety has not been established. Before initiation of therapy, clinicians should provide an informed consent. Shared decision-making involves a comprehensive discussion of off-label use, as well as benefits and risks. A total testosterone level should not be used to diagnose HSDD, but as a baseline for monitoring. Government-approved transdermal male formulations can be used cautiously with dosing appropriate for women. Patients should be assessed for signs of androgen excess and total testosterone levels monitored to maintain concentrations in the physiologic premenopausal range. Compounded products cannot be recommended because of the lack of efficacy and safety data. Clinical Implications: This clinical practice guideline provides standards for safely prescribing testosterone to women with HSDD, including identification of appropriate patients, dosing, and monitoring. Strengths & Limitations: This evidence-based guideline builds on a recently published comprehensive meta-analysis and the Global Position Statement endorsed by numerous societies. The limitation is that testosterone therapy is not approved for women by most regulatory agencies, thereby making prescribing and proper dosing challenging. Conclusion: Despite substantial evidence regarding safety, efficacy, and clinical use, access to testosterone therapy for the treatment of HSDD in women remains a significant unmet need.

International Society for the Study of Women's Sexual Health Clinical Practice Guideline for the Use of Systemic Testosterone for Hypoactive Sexual Desire Disorder in Women.

AIM: To provide a clinical practice guideline for the use of testosterone including identification of patients, laboratory testing, dosing, post-treatment monitoring, and follow-up care in women with hypoactive sexual desire disorder (HSDD). METHODS: The International Society for the Study of Women's Sexual Health appointed a multidisciplinary panel of experts who performed a literature review of original research, meta-analyses, review papers, and consensus guidelines regarding testosterone use in women. Consensus was reached using a modified Delphi method. OUTCOMES: A clinically useful guideline following a biopsychosocial assessment and treatment approach for the safe and efficacious use of testosterone in women with HSDD was developed including measurement, indications, formulations, prescribing, dosing, monitoring, and follow-up. RESULTS: Although the Global Position Statement endorses testosterone therapy for only postmenopausal women, limited data also support the use in late reproductive age premenopausal women, consistent with the International Society for the Study of Women's Sexual Health Process of Care for the Management of HSDD. Systemic transdermal testosterone is recommended for women with HSDD not primarily related to modifiable factors or comorbidities such as relationship or mental health problems. Current available research supports a moderate therapeutic benefit. Safety data show no serious adverse events with physiologic testosterone use, but long-term safety has not been established. Before initiation of therapy, clinicians should provide an informed consent. Shared decision-making involves a comprehensive discussion of off-label use, as well as benefits and risks. A total testosterone level should not be used to diagnose HSDD, but as a baseline for monitoring. Government-approved transdermal male formulations can be used cautiously with dosing appropriate for women. Patients should be assessed for signs of androgen excess and total testosterone levels monitored to maintain concentrations in the physiologic premenopausal range. Compounded products cannot be recommended because of the lack of efficacy and safety data. CLINICAL IMPLICATIONS: This clinical practice guideline provides standards for safely prescribing testosterone to women with HSDD, including identification of appropriate patients, dosing, and monitoring. STRENGTHS AND LIMITATIONS: This evidence-based guideline builds on a recently published comprehensive meta-analysis and the Global Position Statement endorsed by numerous societies. The limitation is that testosterone therapy is not approved for women by most regulatory agencies, thereby making prescribing and proper dosing challenging. CONCLUSION: Despite substantial evidence regarding safety, efficacy, and clinical use, access to testosterone therapy for the treatment of HSDD in women remains a significant unmet need.

International Society for the Study of Women's Sexual Health (ISSWSH) Review of Epidemiology and Pathophysiology, and a Consensus Nomenclature and Process of Care for the Management of Persistent Genital Arousal Disorder/Genito-Pelvic Dysesthesia (PGAD/GPD).

BACKGROUND: Persistent genital arousal disorder (PGAD), a condition of unwanted, unremitting sensations of genital arousal, is associated with a significant, negative psychosocial impact that may include emotional lability, catastrophization, and suicidal ideation. Despite being first reported in 2001, PGAD remains poorly understood. AIM: To characterize this complex condition more accurately, review the epidemiology and pathophysiology, and provide new nomenclature and guidance for evidence-based management. METHODS: A panel of experts reviewed pertinent literature, discussed research and clinical experience, and used a modified Delphi method to reach consensus concerning nomenclature, etiology, and associated factors. Levels of evidence and grades of recommendation were assigned for diagnosis and treatment. OUTCOMES: The nomenclature of PGAD was broadened to include genito-pelvic dysesthesia (GPD), and a new biopsychosocial diagnostic and treatment algorithm for PGAD/GPD was developed. RESULTS: The panel recognized that the term PGAD does not fully characterize the constellation of GPD symptoms experienced by patients. Therefore, the more inclusive term PGAD/GPD was adopted, which maintains the primacy of the distressing arousal symptoms and acknowledges associated bothersome GPD. While there are diverse biopsychosocial contributors, there is a common underlying neurologic basis attributable to spontaneous intense activity of the genito-pelvic region represented in the somatosensory cortex and its projections. A process of care diagnostic and treatment strategy was developed to guide the clinician, whenever possible, by localizing the symptoms as originating in any of five regions: (i) end organ, (ii) pelvis/perineum, (iii) cauda equina, (iv) spinal cord, and (v) brain. Psychological treatment strategies were considered critical and should be performed in conjunction with medical strategies. Pharmaceutical interventions may be used based on their site and mechanism of action to reduce patients' symptoms and the associated bother and distress. CLINICAL IMPLICATIONS: The process of care for PGAD/GPD uses a personalized, biopsychosocial approach for diagnosis and treatment. STRENGTHS AND LIMITATIONS: Strengths and Limitations: Strengths include characterization of the condition by consensus, analysis, and recommendation of a new nomenclature and a rational basis for diagnosis and treatment. Future investigations into etiology and treatment outcomes are recommended. The main limitations are the dearth of knowledge concerning this condition and that the current literature consists primarily of case reports and expert opinion. CONCLUSION: We provide, for the first time, an expert consensus review of the epidemiology and pathophysiology and the development of a new nomenclature and rational algorithm for management of this extremely distressing sexual health condition that may be more prevalent than previously recognized. Goldstein I, Komisaruk BR, Pukall CF, et al. International Society for the Study of Women's Sexual Health (ISSWSH) Review of Epidemiology and Pathophysiology, and a Consensus Nomenclature and Process of Care for the Management of Persistent Genital Arousal Disorder/Genito-Pelvic Dysesthesia (PGAD/GPD). J Sex Med 2021;18:665-697.

The International Society for the Study of Women's Sexual Health Process of Care for the Identification of Sexual Concerns and Problems in Women.

Sexual problems are common in women of all ages. Despite their frequency and impact, female sexual dysfunctions (FSDs) are often unrecognized and untreated in clinical settings. In response, the International Society for the Study of Women's Sexual Health convened a multidisciplinary, international expert panel to develop a process of care (POC) that outlines recommendations for identification of sexual problems in women. This POC describes core and advanced competencies in FSD for clinicians who are not sexual medicine specialists and serve as caregivers of women and, therefore, is useful for clinicians with any level of competence in sexual medicine. The POC begins with the expectation of universal screening for sexual concerns, proceeds with a 4-step model (eliciting the story, naming/reframing attention to the problem, empathic witnessing of the patient's distress and the problem's impact, and referral or assessment and treatment) that accommodates all levels of engagement, and delineates a process for referral when patients' needs exceed clinician expertise. Distressing problems related to desire, arousal, and orgasm affect 12% of women across the lifespan. Low desire is the most common sexual problem, but sexual pain and other less common disorders of arousal and orgasm are also seen in clinical practice. Screening is best initiated by a ubiquity statement that assures the patient that sexual concerns are common and can be revealed. Patient-centered communication skills facilitate and optimize the discussion. The goal of the POC is to provide guidance to clinicians regarding screening, education, management, and referral for women with sexual problems.

Toward a More Evidence-Based Nosology and Nomenclature for Female Sexual Dysfunctions-Part III.

INTRODUCTION: In 2016 the International Society for the Study of Women's Sexual Health (ISSWSH) published an expert consensus report on new nomenclature that addressed the need for comprehensive, evidence-based criteria for new diagnoses in desire, arousal, and orgasm, with the definition on arousal focusing exclusively on female genital arousal disorder (FGAD). AIM: A new expert panel solely focused on mechanisms of arousal disorders convened to revise the nomenclature to include female cognitive arousal disorder (FCAD) and FGAD. METHODS: The ISSWSH co-chairs identified experts on arousal disorders in women. The 10 participants included clinicians, researchers, and educators, representing a diverse, multidisciplinary group. Pre-meeting preparation included evidence-based literature review as the basis of presentations panelists made at the meeting on the current knowledge in cognitive arousal. Consensus was reached using a modified Delphi method. Writing assignments were made as a basis of manuscript development. MAIN OUTCOME MEASURES: The new definition of FCAD is characterized by distressing difficulty or inability to attain or maintain adequate mental excitement associated with sexual activity, as manifested by problems with feeling engaged and mentally turned on or sexually aroused for a minimum of 6 months. RESULTS: Female sexual arousal disorder encompasses both FGAD (revised definition) and FCAD (new definition). Recommendations regarding diagnosis include a clinical interview to assess for FCAD using targeted questions. Patient-reported outcomes that contain questions to assess FCAD are described, including limitations for differentiating between cognitive arousal, genital arousal, and sexual desire. Laboratory measures of cognitive and genital arousal are discussed, including the relationships between genital and cognitive arousal patterns. Biopsychosocial risk factors for FCAD and FGAD, as well as exclusionary conditions, are presented. CLINICAL IMPLICATIONS: The revision of the ISSWSH nomenclature regarding the criteria for the 2 arousal categories, FCAD and FGAD, and the recommended diagnostic strategies offers a framework for management of women with arousal disorders. STRENGTHS & LIMITATIONS: This nomenclature allows for basic science and clinical research in subtypes of arousal in order to develop better diagnostic and treatment options for use by clinicians, scientists, and regulatory agencies. There are limited validated measures of cognitive arousal, including the Female Sexual Function Index, the most commonly used measure, which does not effectively distinguish between cognitive excitement, genital sensations, and event-related desire. CONCLUSION: Future directions include the refinement of FCAD and FGAD and development and validation of patient-reported outcomes that distinguish between the cognitive processes and genital responses to enhance clinical care and research in this area. Parish SJ, Meston CM, Althof SE, et al. Toward a More Evidence-Based Nosology and Nomenclature for Female Sexual Dysfunctions-Part III. J Sex Med 2019;16:452-462.