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Introduction: Mast cell accumulation and nerve proliferation has been hypothesized to lead to pain symptoms for patients with neuroproliferative vestibulodynia (NPV). A clinically suspected diagnosis of NPV can be confirmed by examining immunohistochemical (IHC) staining of excised vestibular specimens. Compared to controls, specimens from NPV patients have been found to contain >8 mast cells per high-power field (HPF) and increased density of nerves. Objective: To assess for correlations between patient reported pain-related measures and computer-assisted histometry of excised vestibulectomy specimen IHC staining with CD117 (marker for mast cells) and PGP9.5 (marker for nerves) in a cohort of histopathologically confirmed NPV patients. Methods: Patients (n=65) with lifelong or acquired NPV undergoing vestibulectomy had IHC-staining of excised vestibular tissue. Tissue sections from the 1:00-11:00 and/or 12:00 regions of the vestibule were examined and high-resolution images were captured using a microscope at 100x and 200x magnification. A minimum of 2 photomicrographs per magnification were taken for each tissue section that included epithelial basement membrane and adjacent subepithelium representative of the majority of immunostained tissue. Fractional area of positive immunostaining of all photomicrographs was determined using computer-assisted histometry by ImageJ. Mean fractional area was determined from 3 separate measurements of each photomicrograph. Correlations were made between density of IHC staining and the following assessments: pain domain of the Female Sexual Function Index (FSFI), the Short Form McGill Pain Questionnaire (SF-MPQ), and cotton-tipped swab testing. We also examined correlations with the Patient Global Impression of Improvement (PGI-I), a treatment response index and indirect assessment of pain. Data were analyzed using Spearman correlations and the Mann-Whitney test. Results: The study cohort had a median age of 26 (IQR = 23-31) years and experienced symptoms for a median duration of 11 (IQR = 6-15) years. While all patients reported high levels of pain (median FSFI pain domain score = 0.0), there were no correlations between CD117- or PGP9.5-immunopositive mean fractional area and FSFI pain domain or SF-MPQ scores. There was no difference in immunopositive mean fractional area between lifelong and acquired NPV. A positive correlation between fractional area of CD117 immunostaining in the 1:00-11:00 region of the vestibule and cotton-tipped swab test pain score approached but did not reach statistical significance (r = 0.24, p = 0.063). No correlations were observed between immunostaining and PGI-I or cotton-tipped swab testing scores. Likewise, SF-MPQ domain scores had no correlation to PGI-I or cotton-tipped swab testing. Median cotton-tipped swab testing pain scores were significantly higher (p < 0.001) in patients with lifelong NPV (7.6) compared to those with acquired NPV (5.7). Conclusions: Our findings suggest that the high levels of pain experienced by NPV patients over a prolonged period of time may be dissociated from the density of mast cells and nerves in vestibular tissue. We postulate that any potential threshold of mast cell accumulation and increased nerve density that results in symptoms of vestibulodynia has been exceeded in our patient cohort. Disclosure: Any of the authors act as a consultant, employee or shareholder of an industry for: Dare Bioscience; Pfizer; Prometheus Laboratories; Sprout Pharmaceuticals. [ABSTRACT FROM AUTHOR]

Introduction: As pain symptoms from neuroproliferative vestibulodynia (NPV) often arise at initial attempt at tampon insertion or penetrative sex, most vestibulodynia patients present in their 20's or 30's. Consequently, individuals who reached this age prior to 2004-when Dr. Bornstein and colleagues delineated the excess mast cell and nerve pathology-had limited opportunity for successful NPV diagnosis and treatment. Menopausal patients often experience vulvar pain with genitourinary syndrome of menopause (GSM) due to the paucity of sex steroid hormonal support of their genital tissues. While symptoms of painful penetration are similar in both of these conditions, NPV is diagnosed when severe allodynia/hyperalgesia is still present with a normal or corrected hormonal milieu. A treatment for NPV is complete vestibulectomy surgery, performed in premenopausal eugonadal patients. However, in hormonally depleted patients with GSM, the vaginal tissue is thinner and less robust making it less optimal for reconstructive surgery. Objective: To examine the intersection of genitourinary syndrome of menopause and neuroproliferative vestibulodynia symptoms in a subgroup of at-risk patients and to report techniques for optimizing management of this patient population. Methods: We reviewed charts of two menopausal patients with NPV and report a clinical strategy for successful management. Results: Two patients, ages 58 and 63 reported histories consistent with NPV during their reproductive years-one with lifelong entrance pain with any insertion and one with pain-free penetration prior to experiencing severe burning upon use of topical miconazole for candidiasis. At presentation, both had entry pain symptoms consistent with GSM and NPV. Since NPV is a diagnosis of exclusion, each was treated for GSM with intravaginal DHEA and vestibular topical compounded testosterone/estradiol cream. After 6 months, vestibular pallor and erythema resolved, however, cotton-tip swab testing scores did not improve. A positive improvement with vestibular anesthesia testing was consistent with NPV. Each underwent a complete vestibulectomy with vaginal advancement flap with successful wound healing and no adverse events despite their age and prior GSM diagnosis. Both patients report "very much better" symptoms on post-op Patient Global Impression of Improvement. Immunohistochemical staining of excised vestibular tissue confirmed a high density of CD117 and PGP9.5 staining consistent with an NPV diagnosis. Each patient has continued their menopause treatments post-op. Conclusions: We report on two menopausal patients with NPV who had classic symptoms of severe allodynia/hyperalgesia in their reproductive years but who were not managed as NPV patients due to lack of knowledge at that time. Treating the GSM first with hormone replacement may restore health to vaginal tissues, thereby allowing the excised vestibular region to be covered with a vaginal advancement flap. Managing GSM symptoms prior and then undergoing vestibulectomy allowed them to have pain-free penetration. Disclosure: No. [ABSTRACT FROM AUTHOR]

Introduction: Vestibulodynia is a prevalent problem in individuals with vulvas, with as many as 30% reporting complaints consistent with entry dyspareunia. Distinctive vestibulodynia pathophysiologies may include psychosocial factors, pelvic floor muscle dysfunction, dermatologic disorders, inflammatory disorders, hormonal deficiencies, neuroproliferative pathology, and pudendal neuropathy. Sacral radiculopathy is considered an inflammatory irritation of S2-S3 nerve roots in the cauda equina by various pathologies such as lumbosacral annular tear. S2-S3 nerve roots are formed by the convergence of the pelvic, pudendal, and sciatic nerves and genito-pelvic clinical symptoms may result from inflammatory involvement of the sensory fields of these nerves. Vestibulodynia may occur from sacral radiculopathy since the somatic and visceral afferent innervation of the vestibule occurs via the pudendal and pelvic nerves, respectively; however, to the best of our knowledge, there has not been a case series of such patients previously reported. Objective: To perform a chart review of patients with vestibulodynia secondary to lumbosacral annular tear-induced sacral radiculopathy. Methods: Vestibulodynia patients who presented to our sexual medicine clinic were evaluated by detailed history, vulvoscopy, vestibular anesthesia testing, neurogenital testing and lumbosacral MRI. When these tests warranted it, a transforaminal epidural spinal injection with 1 ml lidocaine 1% was performed to substantiate the diagnosis. If appropriate, spine surgery was performed. Improvement was assessed using the Patient Global Impression of Improvement (PGI-I). Results: Four patients, 3 cis-gender women and 1 trans-man, mean age 33 years (range 25-42), were diagnosed with vestibulodynia secondary to lumbosacral annular tear-induced sacral radiculopathy. Concomitant sacral radiculopathy symptoms included: clitoral hypersensitivity (50%), bladder urgency/frequency (75%), umbilical hypersensitivity (75%), vaginal dysesthesia (25%), vulvar itching (50%), low back pain (100%), and sciatica (75%). Vulvoscopy was performed to exclude other forms of vestibulodynia. All patients had: a) positive cotton-tipped swab testing throughout the entire vestibule; b) negative vestibular anesthesia testing; c) abnormal neurogenital testing; d) lumbosacral MRI that revealed surgically treatable lumbosacral annular tear (L5-S1, L4-L5); e) transforaminal epidural spinal injection resulting in clinically significant symptom reduction. Lumbar endoscopic spine surgery resulted in improvement in 75% reporting PGI-I 1-3 (very much better - somewhat better). Conclusions: We report the first series of patients with vestibulodynia resulting from lumbosacral annular tear-induced sacral radiculopathy. Clinicians should be aware that bothersome vestibulodynia in patients with vulvas can occur from cauda equina pathology (Region 3) outside the genitals (Region 1) and/or pelvis/perineum (Region 2). Disclosure: Any of the authors act as a consultant, employee or shareholder of an industry for: Elliquence. [ABSTRACT FROM AUTHOR]

Introduction: Persistent Genital Arousal Disorder/Genito-Pelvic Dysesthesia (PGAD/GPD) is characterized by persistent, unwanted genital arousal and/or other dysesthesia, including burning, itch and/or pain in the genito-pelvic area such as clitoris, vulva, perineal region and/or peri-anal region (pudendal nerve), umbilicus, urethra, bladder, vagina, and/or rectum (pelvic nerve) and also including the lower extremity buttock, thigh, calf, foot (sciatic nerve). Patients with PGAD/GPD are significantly bothered/distressed, and catastrophization and suicidal ideation are common. In 2012 Komisaruk reported that PGAD/GPD could result from Tarlov cyst-induced sacral radiculopathy. We developed a multidisciplinary step-care management algorithm with specialists in sexual medicine, spine surgery, sex therapy, physical therapy, and neurophysiology to diagnose and treat Tarlov cyst-induced sacral radiculopathy. Objective: To utilize a multidisciplinary step-care management algorithm to identify PGAD/GPD patients with Tarlov cyst-induced sacral radiculopathy who could benefit from Tarlov cyst spine surgery and to evaluate long-term safety and efficacy of the surgery. Methods: Clinical data were collected on PGAD/GPD patients who underwent Tarlov cyst spine surgery between 2016 and 2020 with at least 1-year follow-up. The management algorithm used to identify and treat Tarlov cyst-induced sacral radiculopathy involves: detailed psychosocial assessment and medical history; non-invasive diagnostic assessments for sacral radiculopathy; sacral MRI with Tarlov cyst protocol; targeted diagnostic caudal epidural injection; and if appropriate, Tarlov cyst spine surgery using minimally invasive surgery techniques. Treatment outcome was based on the validated Patient Global Impression of Improvement (PGI-I) measured at regular intervals post-operatively. Results: Ten patients (8 women, 2 men), mean age 40 years (range 19-66), met inclusion criteria. Patients were discharged the same day or following morning post-operatively. No serious complications occurred. Follow-up was >12 months (range 13-22 months). Seven (70%) patients reported post-operative clinical improvement on PGI-I at last follow up: two patients reported "very much better", three patients reported "much better" and two patients reported "little better". Two patients had no improvement. Only one patient was much worse, however we believe that the PGI-I score of 6 reflected the worsening of the PGAD/GPD condition and not specifically the result of the surgical procedure. Conclusions: Distressing PGAD/GPD symptoms can be caused by Tarlov cyst-induced sacral radiculopathy. A multidisciplinary step-care management algorithm allows selection of appropriate surgical candidates. To the best of our knowledge, this is the largest case series of patients with PGAD/GPD treated with Tarlov cyst spine surgery with at least 1 year follow-up. Using minimally invasive spine surgery techniques, spine surgery on the Tarlov cyst was associated with clinical improvement in 70% of select patients. Disclosure: Any of the authors act as a consultant, employee or shareholder of an industry for: Elliquence. [ABSTRACT FROM AUTHOR]

Introduction: Low intensity shockwave therapy (LiSWT) has been used to treat sexual dysfunction by inducing genital tissue mechanotransduction. Mechanotransduction is the ability of a cell to actively convert contraction/expansion mechanical stimuli induced by exposure to the shockwave energy into biochemical signals with physiological effects including synthesis of nitic oxide, upregulation of vascular endothelial growth factors, recruitment of endothelial progenitor cells, vasodilation, and expression of tumor necrosis factor alpha mRNA with anti-inflammatory activity. The greater the shockwave energy absorbed in genital tissues, the greater the opportunity for mechanotransduction physiologic effects to occur and improve sexual function. Therefore, effectiveness of LiSWT depends, in part, on applied energy (mJ/mm2) and number of applications (total shocks). In 2019, our sexual medicine clinic began utilizing the SoftWave (Urogold 100™) LiSWT device, FDA cleared for pain amelioration, connective tissue activation, wound healing, and improved blood flow, to treat individuals with vulvas with sexual dysfunction. Objective: To review the various sexual health concerns in individuals with vulvas effectively treated by LiSWT. Methods: A chart review was performed of individuals with vulvas with various sexual dysfunctions, including genital pain and genito-pelvic dysesthesia (GPD), who received LiSWT between April 2019 and June 2023. In general, 2400 shocks were applied at energy flux density 0.05-0.08 mJ/mm2, Hz = 3, membrane pressure = 1. The Patient Global Impression of Improvement (PGI-I) was used to assess post-LiSWT outcome; improvement was positive if the post-LiSWT PGI-I ranged from 1-3. Results: 189 women, mean age 32 (range 18–67) years, with sexual dysfunction underwent LiSWT treatments in the 38 months. 18 women with neuroproliferative vestibulodynia (NPV) who underwent vestibulectomy received 3-6 post-operative vestibular LiSWT to reduce post-operative pain and improve wound healing; 83% reported improved PGI-I. 24 patients with hormone-mediated vestibulodynia who elected not to use hormone treatment, underwent vestibular LiSWT; 54% reported improved PGI-I. 25 menopausal patients with persistent symptoms of Genito-Urinary Syndrome of Menopause (GSM) received multiple vestibular LiSWT treatments; 64% improved PGI-I, including reduction of urinary incontinence. 36 women with PGAD/GPD from lumbosacral annular tear-and/or Tarlov cyst-induced sacral radiculopathy who were not candidates for minimally invasive spine surgery or continued to have symptoms after recovering from spine surgery, underwent multiple treatments of lumbosacral spine LiSWT; 58% reported improved PGI-I. 86 patients with neuroproliferative vestibulodynia (NPV) underwent 2-3 pre-operative sessions of vestibular LiSWT immediately prior to complete subepithelial vestibulectomy surgery; they used significantly fewer opioids post-op than those without pre-operative LiSWT based on historical data prior to 2019. All patients received multiple LiSWT sessions to maximize mechanotransduction effects on genital tissues. There were no significant adverse events noted with LiSWT use. Conclusions: Multiple LiSWT sessions are utilized in individuals with vulvas with sexual dysfunction to maximize mechanotransduction. LiSWT is associated with improved sexual health symptoms ranging from 54% - 75%, not associated with any side effects. More research is needed regarding the role of LiSWT for management of various sexual dysfunctions. Disclosure: Any of the authors act as a consultant, employee or shareholder of an industry for: Softwave TRT. [ABSTRACT FROM AUTHOR]

Introduction: Neuroproliferative vestibulodynia (NPV) is a chronic genital pain condition characterized by severe vestibular allodynia and hyperalgesia. The clinically suspected diagnosis of NPV is confirmed in excised vestibular tissue by immunohistochemical staining of > 8 cells per 100x magnification positively immunostained for CD 117, a mast cell marker, and 10 times the area compared to controls positively immunostained for PGP 9.5, a neuronal marker, Endometriosis, on the other hand, is a chronic pelvic pain condition associated with growth of ectopic endometrial-like tissue outside the uterus. The clinically suspected diagnosis is confirmed in excised endometriosis tissue revealing, in some patients, endometrial type glands and/or stroma. In patients with NPV and endometriosis, it is hypothesized that excess mast cells release cytokines and growth factors that promote neuroproliferation in their respective tissues, resulting in chronic genital and pelvic pain symptoms, respectively. In a study involving 65 patients with pathologically confirmed NPV, 63% reported having additional conditions associated with aberrant mast cell activity, including endometriosis. The conditions of NPV and endometriosis may both be focal to the vestibule and pelvis, respectively, but both may also share pathologies of aberrant mast cell activity with other systemic disorders. Objective: To perform immunostaining for markers of mast cells and nerves in excised vestibular and endometriosis implant tissues from a single patient. Methods: Fixed, paraffin-embedded vestibular tissue specimens from the 1:00-11:00 and 12:00 vestibule, and from excised endometriosis fibroadipose tissue on the rectosigmoid colon, were sectioned and immunostained for CD 117 (C-kit) and PGP 9.5. The immunostained slides were examined and digital photomicrographs taken. A minimum of 2 photomicrographs were examined at 100x magnification for each stained slide, identifying representative regions of the excised tissue. Manual counting of CD117 and PGP 9.5 immunopositive profiles, cells/nerves per 100x magnification, was performed for each photomicrograph. Results: A 23-year-old woman presented with a history marked by painful and prolonged menstrual periods, inability to insert tampons, and discomfort with both entry and deep thrusting during intercourse. After excluding other forms of vestibulodynia, she underwent complete 1:00-11:00 and 12:00 subepithelial vestibulectomy with vaginal advancement flap reconstruction. Post-operatively, she reported "very much better" symptoms, with a reduction of entrance dyspareunia, but continued to experience deep thrusting pain with penetrative sexual activity. She subsequently underwent endometriosis excision surgery with positive lesions identified in 12 locations in the pelvis and retroperitoneum. Tissue stained for CD117 and PGP9.5 analyzed by manual counting exhibited > 20 immunopositive cells and nerves per 100x microscopic field in the epithelial basement membrane and adjacent subepithelial regions of the 1:00-11:00 and 12:00 vestibule, as well as in the endometriosis fibroadipose tissue on the rectosigmoid colon. Conclusions: We report for the first time, in a single patient diagnosed with both NPV and endometriosis, immunostaining findings of high densities of mast cells and nerves in their respective tissues. These findings reinforce the hypothesis that NPV and endometriosis are linked to a broader condition associated with aberrant mast cell activity. Disclosure: No. [ABSTRACT FROM AUTHOR]

Introduction: Among patients with neuroproliferative vestibulodynia (NPV) experiencing pain on cotton-tip swab testing at the 1:00-11:00 vestibule prior to complete vestibulectomy surgery, a subset also had pain at the 12:00 vestibule. Excision of the 12:00 core region may be performed concomitantly or after healing from the vestibulectomy. Given that a vaginal flap cannot be advanced to this area, only a core excision is removed and closed using surrounding 12:00 tissue. Differences between the post-operative improvement in the 1:00-11:00 and the 12:00 regions have not been examined to date. To better understand the success of core excision of the 12:00 region, we assessed post-operative patient-reported outcomes specifically of this vestibular region. Objective: To characterize patients who underwent 12:00 excision as well as assess Patient Global Impression of Improvement (PGI-I) specifically regarding 12:00 core excision in individuals with NPV. Methods: We performed a retrospective chart review of patients from one clinic who had undergone a 12:00 core excision. Preoperative baseline assessments included Vulvar Pain Functional Questionnaire (V-Q), Female Sexual Function Index (FSFI), Short Form McGill Pain Questionnaire (SF-MPQ), cotton-tip swab test results. Dimensions of the excised tissue as determined by pathology report, responses to the PGI-I scale at > 6 months post-op, and any adverse events were collected. Descriptive statistics were conducted to analyze the PGI-I scores and other outcomes. Results: The majority of patients (67%, n=21), with an average age of 26, rated their 12:00 pain as "much improved" or "very much improved" on the PGI-I scale. Mean duration of follow up since surgery was one year and five months, with a minimum follow up of 9 months. Most patients (90%) did not have regrets about having the 12:00 region removed. Most patients (83%) would recommend this surgery to other patients who have 12:00 pain. There were no significant post-operative adverse events with 12:00 excision. Mean dimensions of the excised specimen were 1.01 cm x 0.60 cm x 0.21 cm, 3% of the size of the 1:00-11:00 vestibule excised. Preoperatively, patient reported mean FSFI pain domain was 0.67, SF-MPQ 16.80, affective 5.15 and PPI 3.42. Mean V-Q prior to surgery was 11.68, mean cotton-tip swab test result for the 12:00 region was 6.15. Conclusions: Performing core excision of a very small volume of tissue during surgery in patients with 12:00 pain is associated with an improved PGI-I score in 67% of patients. Further research with larger sample sizes and longer follow-up periods is warranted to confirm these findings and optimize the management of vestibulodynia. In patients who fail 12:00 core excision surgery, buccal mucosal grafting of the entire 12:00 vestibule may be a future option. Disclosure: No. [ABSTRACT FROM AUTHOR]

Introduction: Neuroproliferative vestibulodynia (NPV) is suspected in individuals with vulvas with complaints of entrance dyspareunia, vestibular allodynia and hyperalgesia, after ruling out other causes. When conservative biopsychosocial treatments for suspected NPV are unsuccessful, vestibulectomy may be an appropriate option. Excised vestibular surgical specimens are routinely sent for pathologic assessment including hematoxylin and eosin (H&E) staining. Objective: To review reports of gross and microscopic pathology examinations of excised vestibular specimens from a cohort of patients with NPV and compare immunohistochemical staining density among subgroups classified by severity of subepithelial inflammatory infiltrate. Methods: Excised specimens from vestibulectomy surgeries were placed in 10% neutral buffered formalin prior to pathology examination. Routine pathology assessment included gross examination and cytological characterization of H&E-stained vestibular tissue for malignancy, viral nuclear changes (in addition to P16 staining as needed), and quality of the vestibular epithelium and subepithelial inflammatory infiltrate. Severity of this infiltrate was classified by the pathologist as mild, mild-moderate, moderate, or severe. Additional vestibular tissue sections were processed for immunohistochemical staining for CD117 and PGP9.5, protein markers consistent with mast cells and nerves, respectively. Separating the tissues into subgroups based on severity of subepithelial inflammatory infiltrate, they were compared to mast cell counts and immunopositive mean fractional area for CD117 and PGP9.5 using the Kruskal-Wallis test. Results: Gross examinations of the 1:00-11:00 (n = 63) and 12:00 (n = 54) regions of vestibular tissue showed mean dimensions (length, width, thickness) to be 5.8 x 2.1 x 0.6 cm and 1.0 x 0.7 x 0.3 cm, respectively. Microscopic examinations revealed no malignant cells in any specimen, and viral nuclear findings were consistent with HPV in 3 specimens. Vestibular tissue was characterized as non-reactive squamous epithelium in 91% and 93% of specimens for the 1:00-11:00 and 12:00 regions, respectively. Mature lymphocytes were found in the subepithelial stromal infiltrate of 67% of specimens in both the 1:00-11:00 and 12:00 regions. Severity of subepithelial stromal infiltrate was reported as: mild in 67% and 65%; mild-moderate in 5% and 4%; moderate in 14% and 15%; and severe in 14% and 17% of cases for the 1:00-11:00 and 12:00 regions, respectively. Among the subgroups categorized by severity of inflammatory infiltrate, there were no significant differences for CD117-immunopositive cell counts or mean fractional area of CD117 and PGP9.5 in the 1:00-11:00 and 12:00 regions. Conclusions: Routine pathology examination including H&E staining is standard for vestibulectomy specimens. There were no significant differences found among subgroups comparing severity of subepithelial inflammatory infiltrate with immunohistochemical data. Thus, information gleaned from routine pathology examination did not provide confirmation of the diagnosis of NPV. To better understand NPV, excised vestibular tissue should also be immunostained for CD117 and PGP9.5. Disclosure: No. [ABSTRACT FROM AUTHOR]

Introduction: Low sexual desire (LSD) is a syndrome of symptoms including diminished sexual interest or desire and absence of sexual thoughts or fantasies. Hypoactive sexual desire disorder (HSDD) is a subtype of persistent LSD associated with marked distress with no known cause. LSD/HSDD in men frequently occurs with other sexual dysfunctions such as erectile dysfunction and delayed orgasms. Flibanserin is a centrally-acting serotonergic medication approved in the United States to treat acquired, generalized HSDD in certain premenopausal women. Improvement in symptoms following the initiation of flibanserin treatment may take up to eight weeks. Objective: Given the paucity of research available on the off-label use of flibanserin in men, this survey study was conducted to capture general information on the safety and outcomes of flibanserin in men with LSD/HSDD. Methods: Dispensing data from sexual health clinics were used to identify males older than 18 years prescribed flibanserin between July 1 to December 31, 2022. Invitational emails containing a secure survey link were sent to eligible males. Survey questions captured changes in sexual function and sleep quality during active treatment. Patients not currently on treatment were excluded from the survey after the first question. In addition, 10-minute physician interviews were conducted to capture general safety information and outcomes. Study results are summarized using descriptive statistics. Results: Thirty-four of 75 eligible males (45%) from 5 centers responded to the survey. The mean age was 55 years (range 30 to 81 years). Among respondents actively taking flibanserin (n=20), 12 selected low sexual desire, and 8 selected difficulties in reaching orgasm as their primary indication. Eleven of 16 respondents (69%) with treatment durations longer than 2 months indicated treatment-related benefits since starting flibanserin (TABLE). For the sleep quality question, 53% reported no change, 31% reported some improvement, and 16% reported worsening sleep. The most common reasons cited by physicians for treatment discontinuation were lack of effect and insomnia, followed by somnolence and fatigue. Conclusions: Select male patients at sexual health clinics may experience benefits in LSD/HSDD and the ability to reach orgasm following 2 months of flibanserin treatment. Physician interviews suggest flibanserin is well tolerated in men with a safety profile similar to women. It is important to acknowledge survey study limitations when interpreting these findings. These results suggest that more research on the use of flibanserin in men with sexual dysfunctions is warranted. Disclosure: Yes, this is sponsored by industry/sponsor: Sprout Pharmaceuticals, Inc. Clarification: Industry initiated, executed and funded study. Any of the authors act as a consultant, employee or shareholder of an industry for: Sprout Pharmaceuticals, Inc. [ABSTRACT FROM AUTHOR]

Introduction: Bremelanotide (Vyleesi) is an FDA approved medication for the safe and efficacious treatment of hypoactive sexual desire disorder in premenopausal women, however phase 3 trials revealed it improved arousal and orgasm as well. As a centrally acting drug it was expected to be effective to treat sexual dysfunctions in men and has been prescribed off label routinely in our practice. Objective: The primary aim of this study was to evaluate the use of bremelanotide in men with various sexual dysfunctions, the reasons why the medication was prescribed, improvements in sexual function and overall satisfaction, and side effects experienced. Methods: This one-group study design involved men from a single clinic with various sexual dysfunctions prescribed bremelanotide beginning May 1, 2021. After signing consent participants answered the Quality of Life (QOL) Dimension of Sexual Quality of Life Questionnaire, the Patient Global Impression of Improvement (PGI-I) and the General Assessment Questions (GAQ) online. After confirming they had used the medication at least twice, participants completed a structured interview over the telephone with a single interviewer. Descriptive statistics were used to characterize the study cohort. Adverse events were collected. Results: To date a total of 21 men signed consent and 19 completed the online questionnaires. 80% of these men were more satisfied with their lovemaking and duration of lovemaking; 93% reported vaginal insertion was easier and 71% said it was easier to orgasm. With regard to feelings about initiating lovemaking, 86% were more at ease and 79% anticipated it would be more pleasurable and more carefree. 69% believed orgasm was more pleasurable and 73% said that lovemaking was more pleasurable while 79% reported that the partner's overall experience was more pleasurable. Using the PGI-I, 53% of participants felt that sexual function after using bremelanotide was a little better, much better, or very much better. Additional questions online revealed similar results. Twelve men completed the one-on-one interview: 69% of participants were prescribed bremelanotide for erectile dysfunction. 64% had at least other one sexual health issue, including anxiety about sex (54%), low sexual desire (45%), not enjoying sex (36%), orgasm difficulties (18%), and ejaculation difficulties and sensation loss (9% each). A total of 91% experienced improvements in sexual function, all with improved erectile function. 100% of those with complaints of low sexual desire and/or complaints of anxiety around sex reported improvement; 64% had decreased anxiety around sex; 55% had more enjoyment with sex; and orgasm improved for 36% of participants. Men reported longer erection and ability for additional erection for 18-24 hours after bremelanotide injection, better connection between genitals and brain, improved sensitivity, and increased confidence. Side effects included flushing (36%), nausea (36%), headache (27%), bothersome spontaneous erections without sexual stimulation for about 24 hours after injection (27%), and incontinence, cramping and abdominal burning (9% each). All adverse events were transient. Conclusions: While bremelanotide is approved for hypoactive sexual desire disorder in premenopausal women, it has been prescribed and used successfully for men with erectile dysfunction and other concomitant sexual health issues. Disclosure: Yes, this is sponsored by industry/sponsor: Palatin Technologies. Clarification: Industry funding only - investigator initiated and executed study. Any of the authors act as a consultant, employee or shareholder of an industry for: Palatin Technologies. [ABSTRACT FROM AUTHOR]

Introduction: Neuroproliferative vestibulodynia (NPV) is a provoked vestibular pain, shown to be associated with excess immunohistochemical staining for CD117 and PGP9.5, consistent with mast cells and nerves, respectively. It is hypothesized that NPV occurs in genetically predisposed patients in whom mast cells accumulate in the vestibular sub-epithelial stroma where they release various cytokines/growth factors that stimulate the growth of nerves, causing severe allodynia and hyperalgesia throughout the entire vestibule. Objective: To assess, in our patient cohort with histopathologically confirmed diagnosis of NPV, the prevalence of concomitant conditions involving aberrant mast cell activity. Methods: Medical records from people with vulvas who underwent vestibulectomy between June 1, 2019 and December 31, 2022 were retrospectively reviewed. This research protocol was IRB-exempt. Histories from these patients, all of whom had histopathologically confirmed NPV after observing > 8 immunopositive CD117 stained cells per high-power field in the sub-epithelial stroma, were reviewed. The prevalence was noted for the presence of concomitant conditions where aberrant mast cell activity has been reported to play a critical role in symptomatology. The focus was on the following eight conditions: asthma, chronic sinusitis, endometriosis, food allergy/intolerance, interstitial cystitis, irritable bowel syndrome, migraine, and postural orthostatic tachycardia syndrome. Results: A total of 65 NPV patients were included in this chart review. While 24 (37%) reported none, 41 (63%) had at least one other concomitant condition involving aberrant mast cell activity. A total of 25 (38%), 10 (15%), 4 (6%) and 2 (3%) had one, two, three and five other conditions, respectively, involving aberrant mast cell activity. The most common such condition was migraine (n=14; 22%), followed by endometriosis (n=12; 19%), food allergy/intolerance (n=11; 17%), interstitial cystitis (n=10; 15%), irritable bowel syndrome (n=8; 12%), asthma (n=7; 11%), chronic sinusitis (n=5; 8%) and postural orthostatic tachycardia syndrome (n=2; 3%). There was no correlation between the number of concomitant conditions with aberrant mast cell activity reported and the density of CD117-immunopositive staining in the overall cohort of patients with NPV or within the subgroups of those with either lifelong or acquired NPV. Conclusions: Patients with histopathologically confirmed NPV have a high prevalence of concomitant conditions associated with aberrant mast cell activity. While more studies are needed, NPV is likely part of a broader systemic collection of conditions associated with aberrant mast cell activity. This finding is relevant in terms of future diagnostic and treatment options for patients with NPV. Disclosure: No. [ABSTRACT FROM AUTHOR]

Introduction: Neuroproliferative vestibulodynia (NPV) is suspected in women with entrance dyspareunia, vestibular allodynia, and hyperalgesia, after ruling out other causes. If conservative biopsychosocial treatments in patients with suspected NPV are unsuccessful, vestibulectomy may be an appropriate option. Excised vestibular surgical specimens are sent for routine pathology assessment, including hematoxylin and eosin (H&E) staining. Objective: To review reports of gross and microscopic pathology examinations of excised vestibular specimens from a cohort of patients with NPV and compare immunohistochemical (IHC) staining density between subgroups classified by severity of subepithelial inflammatory infiltrate. Methods: Excised specimens from NPV patients, the 1:00-11:00 region (n = 63) and 12:00 region (n = 54) of the vestibule, were placed in 10% formalin prior to pathology examination. Routine pathology assessment included gross examination and cytological characterization of H&E-stained vestibular tissue for malignancy, viral nuclear changes (in addition to P16 staining), and quality of the vestibular epithelium and subepithelial inflammatory infiltrate. Severity of this infiltrate was classified by the pathologist as mild, mild-moderate, moderate, or severe. Additional vestibular tissue sections were processed for IHC staining for CD117 and PGP9.5, protein markers consistent with mast cells and nerves, respectively. Mast cell counts and immunopositive mean fractional area for CD117 and PGP9.5, separated into subgroups based on severity of subepithelial inflammatory infiltrate, were compared using Kruskal-Wallis test. Results: Gross examinations of the 1:00-11:00 and 12:00 regions of vestibular tissue showed mean dimensions (length, width, thickness) to be 5.8 x 2.1 x 0.6 cm and 1.0 x 0.7 x 0.3 cm, respectively. Microscopic examinations revealed no malignant cells in any specimen and viral nuclear findings were consistent with HPV in 3 specimens. Vestibular tissue was characterized as non-reactive squamous epithelium in 90.5% and 92.6% of specimens for the 1:00-11:00 and 12:00 regions, respectively. Mature lymphocytes were found in the subepithelial stromal infiltrate of 67% of specimens in both the 1:00-11:00 and 12:00 regions. Severity of subepithelial stromal infiltrate was reported as: mild in 67% and 65%; mild-moderate in 5% and 4%; moderate in 14% and 15%; and severe in 14% and 17% of cases for the 1:00-11:00 and 12:00 regions, respectively. Amongst the subgroups categorized by severity of inflammatory infiltrate, there were no significant differences for CD117-immunopositive cell counts or mean fractional area of CD117 and PGP9.5 in the 1:00-11:00 and 12:00 regions. Conclusions: No significant differences were found between subgroups of severity of subepithelial inflammatory infiltrate and IHC data. While routine pathology examination including H&E staining is standard for vestibulectomy specimens, such standardized assessment did not provide any insight into the severe allodynia and hyperalgesia associated with NPV, and further, was not useful for confirmation of the diagnosis of NPV. To better understand NPV, excised vestibular tissue should also be stained for CD117 and PGP9.5. Disclosure: No. [ABSTRACT FROM AUTHOR]

Introduction: Bremelanotide is a centrally acting, cyclic heptapeptide analog of the neuropeptide α-melanocyte-stimulating hormone with elevated affinity for the melanocortin-4 receptor. Bremelanotide modulates dopaminergic pathways involved in sexual desire and arousal. In an fMRI study, compared to placebo, bremelanotide was shown to improve connectivity between the amygdala and the insula during visual sexual stimulation, improve sexual brain processing, enhance cerebellar and supplementary motor area activity, and deactivate the secondary somatosensory cortex. Bremelanotide 1.75 mg/0.3 ml (Vyleesi®) is subcutaneously delivered by a single-use auto injector which has been shown to result in increased genital blood flow within hours of administration in both men and women. While phase 2 studies were performed in men with erectile dysfunction (ED), bremelanotide is currently FDA approved as an on-demand treatment for premenopausal women with generalized, acquired hypoactive sexual desire disorder (HSDD). Since its availability in September 2019, providers in our facility have been prescribing bremelanotide to premenopausal women, but off label to postmenopausal women, and to men diagnosed with ED and other types of sexual dysfunction after undergoing a biopsychosocial evaluation. Objective: To better understand the use at our sexual medicine clinic of bremelanotide in men, we analyzed on and off label prescribing patterns and refill rates over a 46-month period in both our male and female patients with various sexual dysfunctions. Methods: Bremelanotide prescription dispensing data specific to our sexual medicine facility during the period of September 2019 (inception) through June 30, 2023, was compiled. The analysis included the breakdown of prescription dispenses for men, premenopausal women (categorized by age 18-50) and postmenopausal women (categorized by age >50), with further analysis regarding refills and refill rates. Results: Over the 46-month period, bremelanotide has been dispensed for various sexual dysfunctions: 76 times to premenopausal women, 104 times to postmenopausal women, and 444 times to men in our clinic. For premenopausal women, 29% of these dispenses were refills, for postmenopausal women, 52% of these dispenses were refills, and for men, 65% of these dispenses were refills. Over the last 18 months (January 1, 2022, through June 30, 2023), refill rates have been 47% for premenopausal women (n = 30), 52% for postmenopausal women (n = 29), and 73% for men (n = 219). Conclusions: The refill rate and prescribing practices of any medication reflects, in part, the safety and efficacy of the treatment in a real-world setting. We observed increasing refill rates of bremelanotide in all patients. Of note, our male patients have particularly high refill rates, implying that bremelanotide, a centrally acting agent, can be used on demand to successfully treat a variety of sexual dysfunctions. Disclosure: Any of the authors act as a consultant, employee or shareholder of an industry for: Palatin Technologies, Sprout Pharmaceuticals. [ABSTRACT FROM AUTHOR]

Introduction: Hard flaccid syndrome (HFS), characterized by the penis in an unwanted persistent semi-rigid flaccid state, is an acquired, painful, and bothersome sexual dysfunction that is poorly understood. We have previously postulated that HFS is, in part, a consequence of pathological activation of a somato-visceral and/or a viscero-visceral reflex that we term the "pelvic/pudendal-hypogastric" reflex. In patients with HFS, physical examination reveals a hypercontracted flaccid penis that feels hard on palpation. Biological complaints include penile morphometric changes such as wrinkles or indents; cold-feeling glans with decreased penile sensation; urinary symptoms such as decreased force of stream; constipation; high tone pelvic floor; perineal and penile pain during ejaculation; and erectile dysfunction. Since there is limited understanding of HFS and its pathophysiologic triggers, men with these complaints often seek help from online support groups. Objective: To assess the prevalence of lumbosacral annular tears in individuals participating in an HFS online support group and compare this to the prevalence reported in asymptomatic individuals in the peer-reviewed literature. Methods: A sexual medicine clinic patient with HFS likely from a lumbosacral annular tear causing sacral radiculopathy who leads an HFS online support group shared his information regarding the suspected pathophysiology. Consequently, other members of the group contacted the sexual medicine clinic to share lumbar MRI images for the spine surgeon to read. All lumbar MRIs had been performed within the last year. They were uploaded to an image sharing service for the spine surgeon to read the sagittal and axial views to assess for the presence of lumbosacral annular tears. For comparison, the literature was reviewed regarding the prevalence of lumbosacral spine disease in asymptomatic individuals. Results: A total of 21 individuals, mean age 28 (range 19-42) years, with symptoms consistent with HFS contacted our sexual medicine clinic. Symptoms were verified during the courtesy triage call after which a lumbar MRI was submitted by each individual for evaluation. 16/21 (76%) had surgically treatable annular tears, the most common location being L5-S1 and L4-L5. In addition to HFS symptoms, 38% had concomitant complaints of low back pain and lower extremity sciatica. In a systematic review of 33 peer-reviewed articles reporting imaging findings for >3000 asymptomatic individuals, the prevalence of lumbosacral annular tear varied from 19% to 29% in individuals aged 20 to 80 years [Brinjikji et al, 2015]. Conclusions: There is a higher prevalence of lumbosacral annular tears among HFS individuals in this support group who had a lumbar MRI compared to the rate in asymptomatic individuals from peer-reviewed literature. This further supports our hypothesis that HFS is the result of a hyperactive "pelvic/pudendal-hypogastric" reflex. In those men with lumbosacral annular tears, HFS may be triggered by the cauda equina pathology causing sacral radiculopathy that reflexively induces excess sympathetic activity in the efferent hypogastric nerve causing the unwanted HFS symptoms. Disclosure: No. [ABSTRACT FROM AUTHOR]

Introduction: Low intensity shockwave therapy (LiSWT) has been used to treat erectile dysfunction since 2010 by inducing mechanotransduction. The greater the shockwave energy absorbed in cavernosal erectile tissue, the greater the opportunity for mechanotransduction regenerative mechanisms to occur and improve erectile function. Effectiveness of LiSWT depends, in part, on applied energy (mJ/mm2) and number of applications (total shocks). Although intensity of LiSWT energy cannot be arbitrarily increased due to side effects, energy absorption may be improved by performing treatment to an erect vs flaccid penis. Intracavernosal pressure and penile volume are both determinants of velocity of the energy wave in tissue and therefore absorption of shockwave energy in tissue. Intracavernosal penile pressure when erect (100 mmHg) is 16-fold higher than flaccid (6 mmHg), and blood volume when erect (142.6 cm3) is >2 times more than flaccid (62.18 cm3), therefore LiSWT in the erect state with larger blood-filled lacunar spaces should be associated with greater shockwave energy absorption. Use of a symmetry-matched secondary reflector can further increase the energy absorption of each applied shockwave by reflecting the wave back. Objective: The aim of this study was to perform a simulation of energy absorption during LiSWT with a reflector in both the flaccid and erect penis. Methods: This energy model used the MTS UroGold electrohydraulic shockwave device [Softwave TRT]. When sound waves pass through an interface between 2 media with different impedances, sound propagation can be significantly altered. If impedances of the media are different, part of the sound energy is reflected into the incident medium; the rest of the sound energy is transferred to the second medium. Sound propagation in tissue can be illustrated via computer simulation by mathematically calculating the damping and deflection of the sound wave by different tissue structures. Finite Element Method (FEM) simulation models are particularly suitable for the mathematical description of complex processes of shockwave propagation, such as in the flaccid and erect penis. Based on results, a "prediction" of propagation of LiSWT in tissue is possible. This patient-specific procedure is based on consideration of individual anatomical structures: corporal lacunar spaces and physical-acoustic laws. For FEM modeling of LiSWT propagation, program systems ANSYS, MATLAB and PZFLEX/ONSCALE were used. Results: Using the FEM calculation model of the simulation analyses, the shockwave pulse is applied at the bottom edge of the model (Fig 1). It propagates through the erect (Fig 2a) and flaccid (Fig 2b) states, with the most energy absorption in the erect penis, shown in red. The effect of increased penile pressure on energy absorption with a constant volume is shown in Fig 3. Conclusions: More energy is absorbed in cavernosal tissue during erection than in the flaccid state, with a further increase in absorption with use of a symmetric reflector. This provides greater opportunity for beneficial mechanotransduction regenerative mechanism due, in part, to increased intracavernosal pressure and tissue volume with larger blood-filled lacunar spaces during erection. LiSWT to treat erectile dysfunction should be more effective when performed in the erect state utilizing a reflector. Disclosure: Any of the authors act as a consultant, employee or shareholder of an industry for: MTS Medical, Softwave TRT. [ABSTRACT FROM AUTHOR]

Introduction: Unrelenting, bothersome sexual medicine problems in individuals with a vulva or penis sometimes do not respond to conventional therapies, frustrating both patient and provider. These distressing problems can be categorized as a genito-pelvic dysesthesia (GPD), including genito-pelvic (penile, scrotal, clitoral, vulvar, vestibular, vaginal, bladder, rectal) pain, persistent genital arousal disorder (PGAD), sleep related prolonged erections (SRPE) and hard-flaccid syndrome (HFS), currently considered as "zebras" in sexual medicine. We recently published a study on 20 patients with PGAD/GPD who underwent a multi-disciplinary management algorithm, were determined to have lumbosacral annular tear induced sacral radiculopathy, and with one year follow-up post-spine surgery, 80% revealed improvement in symptoms. Objective: To apply our (spine-sexual medicine) multi-disciplinary management algorithm to sexual medicine "zebras". Methods: Patients who presented between July 1, 2021, and June 30, 2023, to our sexual medicine clinic were included in the study cohort. The management algorithm was as follows: biopsychosocial history, multiple validated instruments, physical examination, neurogenital testing, regional anesthesia testing, lumbosacral MRI, and when appropriate, a caudal epidural or transforaminal epidural spinal injection. Those with clinically significant symptom reduction from the spinal injection were offered appropriate spine surgery. Patient Global Impression of Improvement (PGI-I) was assessed post-operatively (1 = very much better, 2 = much better, 3 = better, 4 = no change, 5 = worse, 6 = much worse and 7 = very much worse. Results: Our study cohort consisted of 24 patients, 14 with a vulva and 10 with a penis, mean age 42 years (range 25-69) who presented to our clinic over a period of two years. The patients' GPD complaints included genital pain (13), PGAD (6), SRPE (2), HFS (1), bladder pain (1) and rectal pain (1). All patients had results of neurogenital and regional anesthesia tests consistent with sacral radiculopathy, then underwent a diagnostic focal lidocaine spinal injection. Each had a positive response to either a transforaminal epidural spinal injection and underwent lumbar endoscopic spine surgery (n = 21) or a caudal epidural and underwent Tarlov cyst surgery (n = 3). PGI-I scores after surgery indicative of improvement (PGI-I = 1, 2, 3) at one week was 10/22 (45%), at 6 weeks was 9/17 (53%) at 3 months was 9/16 (56%) and at 6 months was 5/6 (83%). Conclusions: Patients presenting with sexual medicine complaints not successfully managed by routine treatment strategies often experienced delay in diagnosis and excessive healthcare-seeking behavior resulting in significant distress. In our experience, GPD can result from triggers in the cauda equina, far from the location of the presenting genito-pelvic symptom(s). Our cohort of sexual medicine "zebras" who underwent our multi-disciplinary management algorithm were diagnosed with sacral radiculopathy. These patients opted for spine surgery and reported improvement of symptoms that continued to get better over time. Disclosure: Any of the authors act as a consultant, employee or shareholder of an industry for: Eliquence. [ABSTRACT FROM AUTHOR]

Introduction: Prasterone (DHEA), a daily 6.5 mg intravaginal insert, is approved in the US and Canada for moderate to severe dyspareunia, a symptom of vulvovaginal atrophy from menopause. Prasterone converts intracellularly in vaginal epithelial cells into active androgens and estrogens without affecting systemic hormone blood levels. Although prasterone is a vaginal insert, the significant reduction of pain in the phase 3 registration trials suggests improvement of the vestibular endodermal genital tissue health associated with dyspareunia in androgen and estrogen deficient states like menopause. To the best of our knowledge, there have not been previous prospective studies documenting visible changes to the vestibule with daily administration of 6.5 mg prasterone in menopausal women with vulvovaginal atrophy and moderate to severe dyspareunia. Objective: It is the aim of this study to investigate whether an intravaginal therapy, prasterone, could affect the vestibular tissue, assessing for changes in visual appearance, pain, and responses on sexual event diaries over the 20-week administration of intravaginal 6.5 mg prasterone. Methods: This 20-week, open-label, prospective, pilot study included 11 menopausal women (median age = 56 y) treated daily with 6.5 mg prasterone intravaginal inserts and assessed every 4 weeks. During vulvoscopy, vestibular pain was assessed by cotton-tipped swab testing and vestibular and vaginal health were independently assessed using the Visual Scale (VS). In addition, vulvoscopic photographs were obtained and assessed using 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 one-way analysis of variance, followed by Dunnett's post-hoc test. Sexual event diaries were completed, and adverse events recorded. Results: Eleven participants completed the study, with a total of 1607 vulvoscopic photographs, showing reduction in vestibular erythema and pallor at end of study. Total VGTA scores at week 20 showed improvement from baseline (mean change = -7.9, p = 0.0016). Changes in VS scores were significantly reduced from baseline after active treatment by week 4 and maintained through week 20 for the vestibule (3.00, p = 0.004) and vagina (4.00, p = 0.002) respectively), suggesting improved vestibular and vaginal tissue health. Cotton-tipped swab test scores were significantly reduced from baseline after week 8 through week 20 (mean change = (-7.27, p = 0.019), suggesting decreased pain. Diary results showed decrease in pain from 81.3% during the first month to 8.3% during the last month of the study, with sexual activities discontinued due to discomfort reduced from 45.8% to 6.3% respectively. No prasterone related adverse events were reported. Conclusions: This is the first prospective vulvoscopic study showing that intravaginal hormone therapy significantly improves total VGTA, VS and cotton-tipped swab test scores. This observation may explain the robust effect of prasterone in lowering dyspareunia in menopausal women with moderate to severe dyspareunia. 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. Disclosure: Yes, this is sponsored by industry/sponsor: AMAG Pharmaceuticals, Inc. Clarification: Industry funding only - investigator initiated and executed study. [ABSTRACT FROM AUTHOR]

Introduction: In 2004, Bornstein and colleagues performed immunohistochemical (IHC) staining of excised vestibular specimens in patients with vestibular pain. They demonstrated that these specimens contained > 8 CD117 immunopositive stained cells per high-power field (HPF), consistent with mast cells, and excess S100 stained immunopositive cells, consistent with nerves-far more compared to control tissue. However, Bornstein et al. only studied the 1:00-11:00 vestibule in this condition, now referred to as neuroproliferative vestibulodynia (NPV). To the best of our knowledge, the 12:00 region of the vestibule, below the clitoral frenulae and above the urethral meatus, has not been examined with IHC staining. Pain in the 12:00 region can be particularly bothersome for patients and poses several challenges for successful treatment. Objective: To report IHC staining findings in the excised 12:00 vestibule specimen and associated clinical characteristics of NPV patients. Methods: Retrospective chart review performed. Slides of IHC-stained vestibular tissue specimens from the 12:00 vestibule were examined and high-resolution digital microscopy images were captured under 100x and 200x magnification. A least 2 photomicrographs at both magnifications were taken for each slide that included representative areas of epithelial basement membrane and the adjacent subepithelial regions. Fractional area of positive immunostaining in all photomicrographs was assessed and mean values calculated using computer-assisted histometry by ImageJ. Results: A total of 50 patients had complete vestibulectomy including 12:00 and 3 had regional vestibulectomy for only the 12:00 area. Using manual counting as applied by Bornstein et al., 53 excised 12:00 specimens stained for CD117 had a median immunopositive cell count, consistent with mast cells, of 29.5, greater than the described 8 mast cells per HPF. Using computer-assisted histometry, tissue stained for CD117 had a median fractional area of 0.73 in the 12:00 region. Tissues stained for PGP9.5 had a median fractional area of 0.31 in the 12:00 region. Overall, there was no difference between lifelong NPV (LNPV) and acquired NPV (ANPV) patients in the cell count or median fractional area for CD117-immunopositive or PGP9.5-immunopositive staining in the 12:00 region. In LNPV patients who had excision of both the 1:00-11:00 and 12:00 regions, the 12:00 region had significantly less PGP9.5 immunopositive fractional area than the 1:00-11:00 region of the vestibule (p = 0.001). Their H&E pathology findings, including severity grading of the subepithelial inflammatory infiltrate, did not predict the IHC assessment of either CD117 or PGP9.5 in the 12:00 region. The median cotton-tipped swab test pain score was 5 out of 10 for the 12:00 region vs 7 for the rest of the vestibule. Conclusions: Current surgical practices often do not include the 12:00 region, likely due to lack of data demonstrating excess mast cells and nerves in this specific region. Our results suggest that there are, in fact, a high density of immunopositive histochemical stains consistent with mast cells and nerves in the 12:00 region and high reported pain scores in both 12:00 and 1:00-11:00 vestibule. Thus, NPV surgical treatments should include, when appropriate, the 12:00 vestibule, as NPV is a field disease involving the entire vestibule. Disclosure: No. [ABSTRACT FROM AUTHOR]

Persistent Genital Arousal Disorder/Genito-Pelvic Dysesthesia (PGAD/GPD) is characterized by persistent, distressing genital arousal sensations for > 3 months and may include other genito-pelvic dysesthesia. PGAD/GPD is associated with biopsychosocial triggers, originating in any of 5 regions: end organ; pelvis/perineum; cauda equina; spinal cord; brain. In the cauda equina, surgically treatable PGAD/GPD triggers include Tarlov cyst and annular tear visualized on MRI. Sacral radiculopathy is confirmed by ruling out other triggers, combined with abnormal neurogenital tests and positive anesthetic lumbar/caudal epidural injections. We hypothesize that there are other treatable cauda equina lesions producing sacral radiculopathy despite a "normal" MRI. We describe a new cauda equina PGAD/GPD trigger, associated with sacral radiculopathy, termed "sacral foraminal (S2-3) radiculopathy syndrome (SFRS)." Women with PGAD/GPD > 3 months with sacral radiculopathy symptoms underwent a comprehensive biopsychosocial diagnostic evaluation including: sex therapy assessment; local anesthesia testing of suspected PGAD/GPD triggers in the end organ and pelvis/perineum; neurogenital testing: integrity of pudendal and sciatic nerves, bulbocavernosus reflex latency. PGAD/GPD patients with suspected SFRS had: no triggers in the end organ or pelvis/perineum; abnormal neurogenital test results; no evidence of surgically treatable Tarlov cyst or annular tear pathology on lumbosacral MRI; an anesthetic caudal epidural whenever possible, based on Tempest et al (2011). They reported on 4 women with GPD without lumbosacral MRI pathology who demonstrated temporary resolution of their dysesthesia with an anesthetic caudal epidural. Patients who met criteria for SFRS were offered non-significant risk treatment with low intensity sacral shockwave therapy (LiSWT). A total of 5 women (mean age 28 ± 6 years) who had a history of blunt trauma to the coccyx or sacrum from: a fall down icy stairs (n=1); childbirth (n=2); slipping/falling on wet concrete (n=1) and stretching while exercising (n=1) were identified. They were suspected of having sacral radiculopathy based on: i) history of dysesthesia symptoms involving genito-pelvic region (pelvic and pudendal nerve, n=5) and lower extremity region (sciatic nerve, n=3), ii) negative local anesthesia testing ruling out PGAD/GPD triggers in the end organ and/or pelvis/perineum, (n=5) iii) abnormal neurogenital tests showing a pattern consistent with cauda equina pathology, (n=5) and iv) clinically significant PGAD/GPD temporary symptom reduction with anesthetic caudal epidural, (n=3). As LiSWT is anti-inflammatory, 4 of the 5 women have undergone this therapy directed to the region overlying the sacral foramina, with very much (n=2) and much better (n=2) improvement of PGAD/GPD symptoms based on PGI-I after an average of 4 treatments. The pelvic, pudendal and sciatic nerves enter at the S2 and S3 foramina where they converge to form the common S2-3 nerve roots. At this location, these nerve roots are only covered by thin peri- and epineurium, not thick, tough dura mater. We postulated that abrasion within the foramina from trauma to the sacrum locally irritated and inflamed these vulnerable nerve roots. Crucial supportive evidence is that clinically significant reduction of PGAD/GPD symptoms in 3 patients was observed in response to anesthetic injection directly into the caudal sacrum. Further research is needed. No [ABSTRACT FROM AUTHOR]

Introduction: Neuroproliferative vestibulodynia (NPV) is a genetic form of vestibulodynia associated with increased density of mast cells and nerves in vestibular tissue. In congenital NPV, umbilical hypersensitivity and a history of absent pain-free penetration including tampon insertion is associated. In acquired NPV, entrance dyspareunia often occurs after severe or recurrent candidiasis or allergic reaction to a topical agent. The diagnosis of NPV is primarily made by excluding other forms of vestibulodynia including: pelvic floor muscle hypertonicity (in part because of pain throughout the entire vestibule); dermatologic pathology (e.g. lichen sclerosus, lichen planus) is absent; inflammatory pathology (e.g. vaginitis, candidiasis) is absent; hormonally-mediated pathology is ruled- out (normal calculated free testosterone or following unsuccessful treatment with local vestibular testosterone/estradiol or systemic testosterone); and cauda equina or pudendal nerve pathology is ruled out (vestibular anesthesia testing temporarily eliminates pain). Few providers performing surgical treatment of NPV by complete vestibulectomy and vaginal advancement flap reconstruction confirm the increased density of CD117-positive cells (consistent with mast cells) and PGP9.5 positive cells (consistent with nerves) in the vestibular epithelium and/or stroma of excised vestibular tissue specimens. Objectives: To confirm the diagnosis of NPV, surgical specimens from patients undergoing complete vestibulectomy were examined using immunohistochemical staining to observe if there was an increased density of CD117-positive cells and PGP9.5 positive cells in the vestibular epithelium and/or stroma, consistent with excess mast cells and nerves, respectively. Methods: Vestibular tissues were placed in fixed formalin paraffin embedded blocks. 5 um sections from each block were stained with hematoxylin and eosin and the slides analyzed by light microscopy. Antibodies to CD117 and PGP 9.5 were used for immunostaining. Multiple regions of the immunohistochemically stained slides were examined and photographed using a Zeiss AxioCam HR high resolution digital microscopy. The density of CD117-positive cells and PGP9.5 positive cells were determined by counting the number of dark brown stained cells in a high-power field (HPF = x 20 magnification). Specimens from control subjects have values of 8 mast cells or less per hpf as reported by Bornstein. Results: Specimens from 21 women (mean age 29+/−13 years) who had complete vestibulectomy with vaginal advancement flap surgery between June 2019 and November 2020 underwent immunohistochemical staining, with NPV confirmed in all. High densities of both CD117-positive cells (mean density of 39+/−15 per HPF) in vestibular epithelium and stroma, and high densities of PGP9.5-positive cells (mean density of 27+/−16 per HPF) were noted in vestibular stroma in all specimens. Figures 1 and 2 show CD117-positive cells and PGP9.5 positive cells, consistent with excess mast cells and nerves, respectively. Findings and photos of immunohistochemical staining are shared with patients post-operatively, which validates the surgery for them. Conclusions: Patients are empowered knowing the underlying pathology of their entrance dyspareunia which was previously only suspected to be NPV. Future considerations include pre-operative vestibular biopsies to determine the necessity of surgery and immunohistochemical staining with calcitonin gene-related peptide to determine the possibility of medical management of NPV. Disclosure: No. [ABSTRACT FROM AUTHOR]

Introduction: Congenital neuroproliferative vestibulodynia (NPV) is associated with lifelong entrance dyspareunia, starting with initial tampon insertion. Acquired NPV is associated with pain-free penetration until after a severe candidiasis infection and/or allergic reaction to a locally applied agent. NPV is diagnosed by ruling out other forms of vestibulodynia. Based on immunohistochemical examination of excised vestibular tissue specimens from women with NPV, the pathophysiology is related to high density of mast cells and nerves throughout the entire surgical specimen If conservative, non-operative strategies fail, or are not appropriate, surgical excision may be considered as vestibulectomy has a high success rate. The extent of surgical excision, however, varies by surgeon, from an excision of the posterior vestibule to a wider excision involving posterior vestibule along with left and right anterior vestibule, millimeters next to the urethral meatus. Few providers perform an even wider excision when appropriate including vestibular tissue inferior to the clitoris/right and left frenulum, and superior to the urethral meatus, the "12:00" vestibule. The extent of vestibular tissue excision related to patient outcome in NPV has not been studied. Objectives: This study compares the density of mast cells and nerves from the 12:00 vestibule to the posterior and left and right anterior vestibule using immunohistochemistry. Methods: Surgical specimens (12:00 vestibule; posterior and left and right anterior vestibule) from 6 women (mean age 27 +/− 11 years) were fixed in formalin, paraffin embedded blocks and labelled. 5 um sections from each block were stained with hematoxylin and eosin and slides analyzed by light microscopy. Antibodies to CD117 and PGP 9.5 were used for immunostaining. Multiple regions were examined and photographed using a Zeiss AxioCam HR high resolution digital microscope. Density of CD117 and PGP9.5 positive cells were determined by counting the number of dark brown stained cells per high-power field (hpf = x 20 magnification). Specimens from control subjects have values of 8 mast cells or less per hpf, as reported by Bornstein. Results: High densities of CD117-positive cells in vestibular epithelium and stroma were noted in the 12:00 vestibule (mean density of 43 +/− 18 per hpf) versus in the posterior and left and right anterior vestibule (mean density of 38 +/− 14 per hpf). High densities of PGP9.5-positive cells were noted in vestibular stroma in the 12:00 vestibule (mean density of 31 +/− 20 per hpf) versus the posterior and left and right anterior vestibule (mean density of 33 +/− 18p er hpf). Figures 1 and 2 show CD117-positive cells and PGP9.5 positive cells, consistent with excess mast cells and nerves, respectively at the 12:00 vestibule and from the posterior and left and right anterior vestibule. Conclusions: We demonstrate, for the first time, that the 12:00 vestibule contains the same increased number of mast cells and nerves as the rest of the vestibule. If anesthetizing that region pre-operatively provides pain relief, excision during surgery should be considered. In patients with NPV, excising the 12 o'clock region at the top of the vestibule may result in improved post-operative success rate. Disclosure: No. [ABSTRACT FROM AUTHOR]

There are various treatment options for patients with ED and comorbid BPH-LUTS. Relevant clinical practice guidelines are available to help and guide physicians in making appropriate disease management decisions. However, real-world evidence comparing health-related outcomes between patients treated with tadalafil and those who did not receive any PDE5i therapy is limited. To compare HCRU outcomes in patients with ED and BPH-LUTS treated with tadalafil or not treated with any PDE5i in the US and to compare tadalafil treatment persistence and adherence by dose. This was a retrospective real-world data study of men (aged 45+) with ED and BPH-LUTS treated with tadalafil or not treated with any PDE5i, using the IQVIA PharMetrics® Plus claims database. Outcomes included all-cause and disease-specific HCRU over the 12-month follow-up. Disease-specific was defined as claims with a diagnosis of ED or BPH-LUTS, and/or specific therapy or procedures used in the treatment of ED or BPH-LUTS. Persistence (days till discontinuation) and adherence (proportion of days covered, PDC) to tadalafil therapy was also evaluated, stratified by dose over the follow-up (10 or 20 mg as needed; 2.5 or 5 mg as once daily). Pair-wise comparisons were conducted using t-test for continuous variables and Chi-square test for categorical variables. The final sample comprised 11,351 tadalafil and 48,722 non-PDE5i cohorts. Mean age was 57.1 and 57.9 years, respectively. All-cause HCRU : Mean number of all-cause laboratory/pathology tests (13.8 vs. 16.4) and proportion with at least one outpatient surgical visit (63.0% vs. 68.8%) or radiology exam (59.3% vs. 63.4%) were significantly lower for tadalafil cohort vs. non-PDE5i cohort (all comparisons, p<0.0001). Disease-specific HCRU : Proportion with at least one disease-specific physician office visit (55.1% vs. 91.4%), laboratory/pathology test (34.8% vs. 58.2%), radiology exam (5.8% vs. 10.8%), outpatient surgery (24.3% vs. 38.9%) or outpatient ancillary service (18.0% vs. 29.8%) were significantly lower for tadalafil cohort vs. non-PDE5i cohort (all comparisons, p<0.0001). Persistence toTadalafil : Mean persistence days (179.8 vs 61.2) and % patients without discontinuation (35.8% vs. 6.5%) were higher for daily tadalafil dose vs. as needed tadalafil dose. Adherence toTadalafil : Mean PDC [90% confidence interval] was higher for daily tadalafil dose vs. as needed tadalafil dose (0.50 [0.495,0.508] vs. 0.20 [0.198,0.211]). Patients on tadalafil used less HCRU than patients not on any PDE5i therapy. Persistence and adherence were higher in patients treated with daily tadalafil compared with as needed tadalafil therapy. The results demonstrated tadalafil's benefit in the management of men with ED and BPH-LUTS. Work supported by industry: yes, by Upjohn-a Pfizer division. A consultant, employee (part time or full time) or shareholder is among the authors (Viatris). [ABSTRACT FROM AUTHOR]

Erectile dysfunction (ED) is usually a symptom of another medical condition. People with poor overall health are more likely to develop severe form of coronavirus disease 2019 (COVID-19) and may have unwanted symptoms such as ED. COVID-19-related stress, anxiety, and depression can also impact sexual health and possibly lead to ED. There are various treatment options for patients with ED. However, real-world evidence of the impact of COVID-19 on the treatment and comorbidities of patients with ED is limited. To estimate the impact of COVID-19 on the treatment and comorbidities of patients with ED in the United States. This retrospective real-world data (RWD) analysis used the IQVIA PharMetrics® Plus claims database, which is a patient-Centric, closed claims database of fully adjudicated pharmacy, hospital and medical claims anonymized at the patient level, that captures the complete patient journey for all services billed to and covered by the patient's health plan. We compared the ED treatment and comorbidities in adult males aged 18+ years with ED in the same 3-month periods before (01March - 31May, 2019) and during (01March – 31May, 2020) the COVID-19 pandemic. ED treatment included any ED-related claims, prescriptions of any and individual phosphodiesterase-5 inhibitor (PDE5i) medications (avanafil, sildenafil, tadalafil and vardenafil). See the table below for number of patients having ED-related claims, having any and individual PDE5i prescriptions, number of patients with COVID-19 diagnosis, and percentage of patients with each of the top 10 comorbidities, in the 3-month periods before and during COVID-19. RWD showed that ED-related claims significantly decreased during the COVID-19 pandemic, reflecting the pandemic's impact on ED patients' health. However, the use of PDE5i medications remained stable during the pandemic. Key comorbidities including hypertension, hyperlipidemia, type 2 diabetes mellitus, benign prostatic hyperplasia with lower urinary tract symptoms, testicular hypofunction, and malignant neoplasm of the prostate, during the pandemic, compared with pre-pandemic period, highlighted the impact of the pandemic on ED patients' health and need for managing their other comorbid chronic diseases. Work supported by industry: yes, by Viatris. A consultant, employee (part time or full time) or shareholder is among the authors (Viatris). [ABSTRACT FROM AUTHOR]

Neuroproliferative vestibulodynia (NPV) is a poorly understood chronic debilitating sexual pain condition associated with severe vestibular allodynia and hyperalgesia. In patients with NPV, histopathology of surgical specimens from the usual posterior and right and left anterior locations (1:00 - 11:00 o'clock) has shown high densities of CD117 and PGP9.5 positive staining cells consistent with excessive mast cells and nerves. Such pathologic findings have justified the excision of this usual location of the vestibule. There is, however, a lack of consensus regarding the total extent of complete surgical excision for vestibulectomy. Some of our patients demonstrated pain at the 12:00 region and underwent concomitant 12:00 excision along with the usual vestibule location. We wished to study excised vestibular tissue at the 12:00 region for the presence/absence of CD117 and PGP9.5 positive staining cells. This pathologic finding has critical clinical implications as to the extent of the surgical excision. We assessed immunohistochemical densities of CD117 and PGP9.5 positive staining cells from the 12:00 region from each patient, comparing it to cells stained from posterior and left/right anterior vestibule. We studied specimens from 26 women (mean age 27 +/- 12 years) with the presumptive diagnosis of NPV based on positive vestibular cotton swab testing at 12:00 as well as 1:00, 3:00, 5:00, 6:00, 7:00, 9:00 and 11:00 locations who underwent complete vestibulectomy with vaginal advancement flap including the 12:00 region. Surgical specimens from the 12:00, the posterior and left/right anterior vestibule were prepared separately in formalin and embedded in paraffin blocks. Immunohistochemical staining using antibodies to CD117 and PGP 9.5 was performed on these blocks and sections cut for slides. These stained slides from multiple locations of the vestibule were examined and photographed using a Zeiss AxioCam HR high resolution digital microscope. The density of CD117 and PGP9.5 positive cells were determined by counting the number of dark brown stained cells per high-power field (HPF = x 20 magnifications). Based on the literature, control subjects have values of 8 mast cells or less per HPF. All 26 patients had elevated densities of CD117-positive cells in vestibular epithelium/stroma in the 12:00 (mean density 51 +/- 19 per HPF) as well as posterior and left/right anterior vestibule (mean density 47 +/- 18 per HPF). All 26 patients had high densities of PGP9.5-positive cells noted in vestibular stroma in the 12:00 (mean density 36 +/- 23 per HPF) and posterior and left/right anterior vestibule (mean density 38 +/- 22 per HPF). In 100% of these patients NPV, the 12:00 region of the vestibule contained an increased number of CD117 and PGP9.5 positive staining cells similar to the posterior and left/right anterior vestibule. When performing a vestibulectomy in patients with positive cotton-tip swab testing including the 12:00, excision of the 12:00 vestibule should be considered to optimize treatment. Work supported by industry: no. [ABSTRACT FROM AUTHOR]

Neuroproliferative vestibulodynia (NPV) is a poorly understood chronic debilitating sexual pain condition associated with severe vestibular allodynia and hyperalgesia. In patients with NPV, histopathology of surgical specimens from the usual posterior and right and left anterior locations (1:00 - 11:00 o'clock) has shown high densities of CD117 and PGP9.5 positive staining cells consistent with excessive mast cells and nerves. Such pathologic findings have justified the excision of this usual location of the vestibule. There is, however, a lack of consensus regarding the total extent of complete surgical excision for vestibulectomy. Some of our patients demonstrated pain at the 12:00 region and underwent concomitant 12:00 excision along with the usual vestibule location. We wished to study excised vestibular tissue at the 12:00 region for the presence/absence of CD117 and PGP9.5 positive staining cells. This pathologic finding has critical clinical implications as to the extent of the surgical excision. We assessed immunohistochemical densities of CD117 and PGP9.5 positive staining cells from the 12:00 region We studied specimens from 26 women (mean age 27 +/- 12 years) with the presumptive diagnosis of NPV based on positive vestibular cotton swab testing at 12:00 as well as 1:00, 3:00, 5:00, 6:00, 7:00, 9:00 and 11:00 locations who underwent complete vestibulectomy with vaginal advancement flap including the 12:00 region. Surgical specimens from the 12:00, the posterior and left/right anterior vestibule were prepared separately in formalin and embedded in paraffin blocks. Immunohistochemical staining using antibodies to CD117 and PGP 9.5 was performed on these blocks and sections cut for slides. These stained slides from multiple locations of the vestibule were examined and photographed using a Zeiss AxioCam HR high resolution digital microscope. The density of CD117 and PGP9.5 positive cells were determined by counting the number of dark brown stained cells per high-power field (HPF = x 20 magnifications). Based on the literature, control subjects have values of 8 mast cells or less per HPF. All 26 patients had elevated densities of CD117-positive cells in vestibular epithelium/stroma in the 12:00 (mean density 51 +/- 19 per HPF) as well as posterior and left/right anterior vestibule (mean density 47 +/- 18 per HPF). All 26 patients had high densities of PGP9.5-positive cells noted in vestibular stroma in the 12:00 (mean density 36 +/- 23 per HPF) and posterior and left/right anterior vestibule (mean density 38 +/- 22 per HPF). In 100% of these patients NPV, the 12:00 region of the vestibule contained an increased number of CD117 and PGP9.5 positive staining cells similar to the posterior and left/right anterior vestibule. When performing a vestibulectomy in patients with positive cotton-tip swab testing including the 12:00, excision of the 12:00 vestibule should be considered to optimize treatment. No [ABSTRACT FROM AUTHOR]

IPP infections occur in approximately 1% of cases. The fundamental principle for treatment has always been surgical removal of all components. Explantation/reimplantation surgery, however, may be unsuccessful, require additional surgeries, and/or result in poor patient satisfaction, reduced penile sensation, and decreased penile length. A patient presented 4 weeks post-op with an obvious IPP infection. Culture of scrotal drainage prior to antibiotic administration grew serratia marcescens, enterococcus faecalis, and citrobacter freundii. The patient was informed explanation was required, but he refused and requested we "do what we can" first. He was made aware of the lack of data supporting non-operative strategies for IPP infection. To present, likely for the first time, non-operative strategies including IV/oral antibiotics, low intensity shockwave therapy (LiSWT), and immune therapy can result in successful IPP infection treatment. A 49 yo with a 14 year history of ED underwent insertion of an 20 cm Titan IPP (Coloplast) with submuscular reservoir placement. Four weeks post-op he presented with fever (101°F), elevated WBC (15,400), purulent drainage from a swollen, tender scrotum, and tenderness of all IPP components. We discussed non-operative management. He was admitted for broad spectrum IV antibiotics/antifungal agents: Vancomycin, Piperacillin and Tazobactam, and Fluconazole. After 6 days of IV antibiotics the patient became afebrile, WBC normalized (8,000) but he developed mildly abnormal renal and liver function tests. He was discharged on oral Levofloxacin daily for 30 days. Grayscale ultrasound showed fluid around the pump and scrotal tubing with significant device tenderness and scrotal drainage through two small sinus tracts confirming persistent infection. We assessed the degree of purulent scrotal drainage on gauze kept on the scrotum for 10 hour periods. LiSWT (Urogold 100 MTS, parabolic unfocused probe OPP 155, energy flux density 0.13 mJ/mm2, Hz 3.0, total shocks 6,600/treatment) was administered to the device components and scrotum for two weeks daily, then twice weekly x 2 weeks and then weekly x 4 weeks. Concomitantly he received immune therapy via subcutaneous peptide administration and ozone blood dialysis twice weekly x2 weeks and then weekly x 4 weeks. The patient progressively improved, remaining afebrile, with WBC (5,000) and liver and renal function tests normalized at 1 week. Scrotal drainage stopped at 2 weeks and scrotal sinus tracts healed. There was no pain/tenderness of device components or scrotum at 2.5 weeks. There was no skin fixation to any device component. The patient could easily inflate/deflate the device to full rigidity/flaccidity without pain at 3 weeks and intercourse with orgasm at 5 weeks. Grayscale ultrasound at 4 weeks showed absent fluid around the device components. This is the first case report of successful management of an infected IPP using non-operative novel treatments. The effect of immune therapy is to enhance immune response to infection. Concerning the management of infection with LiSWT, it has been shown to have anti-infective properties, upregulate/recruit anti-bacterial/microbial peptide LL37, increase local blood flow, possibly inhibit biofilm, and result in salvage of infected breast and hip prostheses. Work supported by industry: no. [ABSTRACT FROM AUTHOR]

Flibanserin is a multifunctional serotonin agonist and antagonist for the treatment of acquired, generalized hypoactive sexual desire disorder (HSDD). Flibanserin is approved for use in premenopausal women in the US and in both premenopausal and postmenopausal women ≤60 years old in Canada. A post-hoc analysis of Female Sexual Function Index (FSFI) scores from pivotal trials in premenopausal women with HSDD indicated significant improvements in total and individual domain scores after treatment initiation with flibanserin compared to placebo. The purpose of this case report study is to examine the postmarketing database to determine whether improvements in other aspects of sexual function have also been reported by women who were prescribed flibanserin in real world use outside of clinical trials. A search was performed in the global safety database to identify postmarketing case reports from August 2015 to March 2021. "Therapeutic response unexpected" was the Medical Dictionary for Regulatory Affairs (MedDRA 23.1) preferred term used in this search strategy. Study results include only case reports with narratives containing verbatim terms relevant to the domains on the FSFI (arousal, lubrication, orgasm, pain, satisfaction), excluding desire as this is an expected response. Thirty-two postmarketing case reports, including 13 patient testimonials of "therapeutic response unexpected", were identified during this period. Of these 32 case reports, 12 (38%) contained terms related to unexpected improvements in sexual function. Among the 12 reports of improved sexual function, 10 (83%) included terms related to increases in frequency, intensity, or duration of orgasms, one of which also mentioned improvement in arousal. The remaining 2 cases included 1 report of improvement in lubrication and 1 report of improvement in pain. These postmarketing case reports are consistent with the post-hoc analyses of the data from the flibanserin clinical trials and provide further support that flibanserin therapy can lead to improvement in multiple aspects of sexual function in addition to sexual desire. Yes, this is sponsored by industry/sponsor: Sprout Pharmaceuticals Industry initiated, executed and funded study Any of the authors act as a consultant, employee or shareholder of an industry for: Sprout Pharmaceuticals [ABSTRACT FROM AUTHOR]

The article presents abstracts of research on women's sexual health. They include "Is Sexual Function Different in Obese Women?," "Effects of Hypoactive Sexual Desire Disorder Treatment on Relationships" and "Presence of a Sexual Dysfunction May Not Always Affect Women's Satisfaction From Their Sexual Function."

Daily ospemifene 60 mg was studied in a large phase 3 pivotal clinical trial in 68 sites in women identifying moderate to severe vaginal dryness as their most bothersome symptom (MBS) of vulvo-vaginal atrophy (VVA) due to menopause. The secondary aim was to compare data from the vulvar photographs to visual study measures assessed by investigators at each site, including the Vaginal Health Index (VHI), and Vulvar Health Index (VuHI). VuHI rated vulvar appearance of the labia majora, labia minora, clitoris, introitus appearance/elasticity, color, discomfort and pain as normal/mild/moderate/severe. [Extracted from the article]

Cotton-tipped swab test scores in subjects assigned to active treatment decreased at visits 3-6, whereas there were minimal changes in those in the sham group. Cotton-tipped swab test scores were significantly reduced from baseline after active treatment at week 12 (mean = -1.05; 95% CI [-1.21, -0.89]) and at week 16 (mean = -1.20; 95% CI [-1.36, -1.04]), suggesting decreased pain. These data from an interim exploratory analysis suggest that CO SB 2 sb fractional laser therapy in women with vestibulodynia improves subjective measures of pain and pain related to sexual activity. [Extracted from the article]

Introduction: Vestibular fibroblasts from patients with neuroproliferative vestibulodynia (NPV) versus age-matched controls produced higher proinflammatory cytokine levels of various interleukins when provoked with candida albicans in vitro. In genetically susceptible patients, this enhanced cytokine synthesis is hypothesized, in part, to lead to neuroproliferation in vestibular tissue resulting in allodynia/hyperalgesia. Patients with acquired NPV, who initially experienced pain-free penetration in their early adult reproductive life, may experience persistent severe vestibular burning following an allergic reaction to a topical agent applied to the non-keratinized vestibular epithelium. In contrast, patients with lifelong NPV present with the classic history of inability to insert a tampon at menarche (mean age 12.4 years). Patients with lifelong NPV may have unknowingly been exposed to an allergen early in their childhood, potentially even triggered from ointments used in infancy to protect from diaper rash, resulting in local vestibular mast cell accumulation in genetically susceptible patients. Agents commonly used to prevent are zinc oxide 40%, (Desitin) with inactive ingredients petrolatum, cod liver oil, lanolin, talc, glycerin, sorbitan sesquioleate, beeswax, tocopheryl acetate and fragrance and A+D ointment that includes petroleum jelly, lanolin, lavender oil, light liquid paraffin, vitamin A and vitamin D. It is possible an allergic reaction could result from any of these ingredients when applied to the non-keratinized vestibular epithelium. Objective: We wished to better understand the possible triggering event in patients with lifelong NPV. Methods: A chart review was performed of patients who presented between January 2019 and June 2023 who were clinically suspected to have lifelong NPV based on a history of inability to use tampons and inability to have pain-free penetration and histopathlogically confirmed to have NPV. Information was obtained from a parent or caregiver who regularly changed patient's diapers as to what agents were utilized to manage diaper rash. Results: Our patient cohort included 14 individuals with vulvas, mean age 25 (range 18-37) years. One patient prone to diaper rash was treated with A+D baby diaper rash ointment and Flanders buttocks ointment (zinc oxide, white petrolatum, white beeswax, Peruvian balsam). One patient had a "bad" yeast infection as a baby and received "topical antibiotics". Five patients claimed Desitin and Vaseline were used while six patients claimed Desitin alone, two of whom cryied every time they Desitin was applied. One patient from Puerto Rico, received "a sock filled with cornstarch that dabbed the vaginal area and crevices after wiping the area clean". Conclusions: The endodermal vestibular epithelium is not protected by a keratin layer, including in babies at a very young age. In genetically susceptible babies, an allergic reaction to an active/inactive agent used to prevent or treat diaper rash could have potentially triggered mast cell accumulation in the baby's vestibule leading to increased synthesis of cytokines and growth factors resulting in neuroproliferation consistent with lifelong NPV, evidenced by the inability to place a tampon at menarche. More research into this concern is needed. Disclosure: No. [ABSTRACT FROM AUTHOR]

An analysis of the patient journey was conducted to further explore the initial symptoms, impact of initial treatment, and patients' current mindset about testosterone therapy. Despite reporting satisfaction with treatment, patients identified cost, insurance coverage, and daily inconvenience as key reasons why they chose to discontinue their current treatment. Initial treatment provided by the physician generally resulted in high levels of patient satisfaction; however, patients expressed concerns about cost/insurance and inconvenience of use that were associated with their currently prescribed testosterone therapy. [Extracted from the article]

Basic science research has shown that vaginal epithelial estradiol receptors have a reciprocal relationship with estradiol blood test values: the higher the density of receptors, the lower the values. Hypothetically, a low dose (4 g, 10 g) of intravaginal estradiol, while not increasing estradiol blood values, should act on the highest density of vaginal epithelial estradiol receptors. Being a responder at week 2 highly predicted being a responder at week 12 in the total EE population (OR 13.1; 95% CI, 8.8-19.7) and in the estradiol vaginal insert groups (OR 7.9; 95% CI, 4.7-13.2). [Extracted from the article]

Penile numbness is an unusual, troubling symptom that may cause delayed/muted orgasm. Spinal cord and/or brain pathologies were found in 4/48 (8%) patients based on abnormal vibration/cold/heat perception threshold values in the genitals, normal bulbocavernosus reflex latency testing and abnormal sacral/foot dermatome testing. [Extracted from the article]

The effect of erectile dysfunction (ED) on sexual planning behaviors and outcomes in men taking phosphodiesterase type 5 inhibitors (PDE5Is) is not well studied. To assess the sexual habits, behaviors, and treatment-related outcomes of men with ED who take PDE5Is. Data on demographics, health characteristics, treatment, sexual habits, ED severity, ED-specific quality of life, and satisfaction with treatment were collected. [Extracted from the article]

Liver fat was assessed by MRI-PDFF and liver injury from AST, ALT and GGT. Administration of the T-prodrug LPCN 1144 resolved NAFLD in half the affected patients and normalized liver injury markers in those with elevated levels without any safety signals. [Extracted from the article]

Genitourinary syndrome of menopause (GMS), comprising vulvovaginal atrophy (VVA), impacts the health and quality of life of postmenopausal women. The subject's satisfaction with treatment showed higher percentages of satisfaction in the ospemifene group than the placebo group. Statistically significant superiority in the ospemifene group over the placebo group was demonstrated for the maturation value, the proportion of responders, and overall satisfaction upon treatment. [Extracted from the article]

PGAD is defined as persistent, unwanted, intrusive, distressing feelings of genital arousal or being on the verge of orgasm (genital dysesthesia), not associated with concomitant sexual interest, thoughts, or fantasies. Similar to the assessment of an adult with PGAD, a detailed biopsychosocial assessment should be considered in young PGAD patients. [Extracted from the article]

In women with sexual dysfunction, a bothersome/distressing symptom is persistent numbness in the genitourinary region, the clitoris, vagina and urethra. Office-based neuro-genital testing includes quantitative sensory testing, sacral and foot dermatome testing, bulbocavernosus reflex latency testing, vaginal pelvic afferent nerve testing and urethral pelvic afferent nerve testing. Quantitative sensory testing measures somatic vibration, cold, and heat perception threshold values in the glans clitoris, right and left inner surface of labia minora, and uses the right pulp index finger threshold values as the control. [Extracted from the article]

Introduction: Neuroproliferative vestibulodynia (NPV) is characterized by severe allodynia and hyperalgesia during entry penetration. Multiple psychosocial factors may contribute to the experience of pain from NPV. Concerning psychologic factors, women afflicted with NPV report difficulty with mental health issues such as anxiety and depression, high rates of negative emotions, substantial difficulties with psychosocial adjustment, and experience suicidal ideation. Objective: This study focuses on psychosocial factors identified in a cohort of patients diagnosed with NPV who underwent vestibulectomy. Methods: This is a chart review of 65 patients, median age 26 years (IQR 23-31) clinically diagnosed and pathologically confirmed with NPV. They completed validated instruments administered including the Female Sexual Function Index (FSFI), Sexual Distress Scale-Revised (SDS-R), McGill Pain Questionnaire-Short Form (SF-MPQ), Perceived Stress Scale (PSS), and Patient Health Questionnaire-9 (PHQ-9). The sex therapy evaluation performed on initial patient intake assessed psychosocial issues including effect of symptoms on quality of life, self-image, past trauma, and past/current relationship(s). Patients identified as having significant psychosocial issues were advised to undergo pre-op and/or post-op therapy. Results: Based on history, initial psychological assessment, and psychosocial experiences with vestibular pain, post-operative therapy was recommended to 94% of our study cohort to maximize post-operative outcome. Our study cohort exhibited high levels of anxiety (53.8%) and depression (50.8%). Sexual abuse, assault and/or incest had been experienced by 32.3%. Other psychological issues included eating disorder (10.8%), bipolar (6.2%) as well as suicidal ideation (4.6%). Problems revolving around personal relationships include panic attacks around sex/men (21.5%), not pursuing sexual relationships (9.2%), lack of attraction toward current partner (4.6%) or being attracted to unavailable people (3.1%). A total of 15.4% of this cohort had complaints of low desire and 9.2% had a history of drug or alcohol abuse. Median FSFI total score was 13/36 (<26), with distress (≥11) consistent with sexual dysfunction in 56 of 61 patients. Median FSFI pain domain was 0/6; median FSDS-R (n=61) was 35/52, indicative of significant distress; median PHQ-9 was 6.5/27 with 23 patients' scores consistent with possible need for depression treatment based on clinical judgment and 14 patients with score consistent with warranting treatment for depression. Median PSS was 22/40 with the most common level of stress being moderate (n=54). SF-MPQ median results (n=63) were 15/33 for sensory, 3/12 for affective and 4/5 for present pain intensity. With 3-46 month follow-up, 86.3% of patients (44/51) reported improvement on the Patient Global Impression of Improvement with 72.5% (37/51) reporting significant improvement. Conclusions: While NPV is a biologic diagnosis, psychological factors likely contribute to the development, continuation, and consequences of NPV. We believe that the significant mental health issues in this NPV patient population made recovery from vestibulectomy more protracted than typically experienced after surgery. Psychological therapy would be beneficial in this population and should be continued postoperatively, as needed, to address psychological concerns and enhance quality of life. Disclosure: No. [ABSTRACT FROM AUTHOR]