Menstrual cycle-driven vs noncyclical daily changes in sexual desire.

BACKGROUND: Past research on the association between sexual desire and the menstrual cycle has provided inconclusive results and has not considered the potential influence of psychological and physical changes that are frequently associated with the menstrual cycle. AIM: To test the strength of association between the menstrual cycle (and associated symptoms) and changes in sexual desire. METHODS: Prospective daily reports across 2 full menstrual cycles (2 months) from a sample of female university students (n = 213), were analysed. Analyses tested for average effects of the menstrual cycle on sexual desire, individual differences in these effects, and cyclical and noncyclical associations between sexual desire and the 9 menstrual cycle-related changes. Note that data presented in the current article come from a larger study from which other reports have been published. OUTCOMES: Target variables were (1) daily change in sexual desire and (2) daily reports of 5 psychological changes and 4 physical changes that are commonly associated with the menstrual cycle. RESULTS: Results showed that when considering average effects across participants, the menstrual cycle was associated with a small midcycle increase in sexual desire. However, multilevel analyses showed large individual differences in how the menstrual cycle influences sexual desire. Specifically, some participants showed a midcycle increase, others a perimenstrual increase, and others no change across the menstrual cycle. Moreover, results demonstrated that psychological changes were more important for predicting sexual desire as compared with physical changes. CLINICAL IMPLICATIONS: These results suggest that daily measurement of sexual desire across multiple menstrual cycles may be an important tool in the assessment of sexual desire among some females. STRENGTHS AND LIMITATIONS: Strengths of this study are the daily assessment of sexual desire and all symptoms for 2 menstrual cycles and multilevel analyses that allow the study of individual differences. Limitations include limited measurement of sexual desire based on only 2 questions and the lack of measures of relationship status and sexual orientation. CONCLUSION: Emphasis is placed on the need to apply more rigorous research methods and to abandon simplistic average-effects models that are based on outdated theories and stereotypes.

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

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

The prostate in women: an updated histological and immunohistochemical profile of the female periurethral glands and their relationship to an implanted midurethral sling.

BACKGROUND: There is evidence of glandular tissue in the region of the anterior vaginal wall-female periurethral tissue (AVW-FPT) that has similar morphology and immunohistochemistry to the prostate in men. Surgical injury to this tissue has been suggested as a potential cause of sexual dysfunction following midurethral sling (MUS) procedures. However, the anatomy and embryology of these glands have not been fully resolved. This has led to difficulties in classifying this tissue as a prostate and defining its clinical significance related to MUS procedures. AIM: To describe the histological and immunohistochemical characteristics of the female periurethral glands using markers of prostate tissue and innervation and to examine their anatomical relationships to an implanted MUS. METHODS: Using gross and fine dissection, the AVW-FPT was dissected from 9 cadavers. Prior to dissection, 2 cadavers underwent simulation of the MUS procedure by a urogynecologist. Samples were paraffin embedded and serially sectioned. Immunohistochemistry was performed using markers of prostate tissue and innervation. OUTCOMES: Immunohistochemical localization of markers for prostatic tissue and innervation of the glandular tissue of the AVW-FPT, including the region of MUS implantation. RESULTS: Female periurethral glands were immunoreactive for markers of male prostatic tissue, including prostate-specific antigen, androgen receptor, HOXB13, and NKX3.1. Markers of innervation (protein gene product 9.5, choline acetyl transferase, and vasoactive intestinal polypeptide) also localized to certain regions of the glandular tissue and associated blood supply. Surgical simulation of the MUS procedure demonstrated that some periurethral glands are located in close proximity to an implanted sling. CLINICAL TRANSLATION: The AVW-FPT contains glandular tissue in the surgical field of MUS implantation. Iatrogenic damage to the female periurethral glands and the associated innervation during surgery could explain the negative impacts on sexual dysfunction reported following MUS procedures. STRENGTHS AND LIMITATIONS: This is the first study to characterize the female periurethral glands using markers of prostatic tissue in concert with markers of general and autonomic innervation and characterize their anatomical relationships within the surgical field of MUS implantation. The small sample size is a limitation of this study. CONCLUSION: We provide further evidence that the AVW-FPT contains innervated glands that are phenotypically similar to the male prostate and may share a common embryonic origin. The microscopic and immunohistochemical features of the periurethral glands may be indicative of their functional capacity in sexual responses. The location of these glands in the surgical field of MUS procedures underscores the clinical significance of this tissue.

Patient and provider perspectives on LEEP/LLETZ treatment and outcomes: an interview study.

BACKGROUND: The loop electrosurgical excision procedure (LEEP) and large loop excision of the transformation zone (LLETZ) effectively treat cervical dysplasia, though some women have reported negative outcomes postoperatively (e.g., sexual dysfunction, psychosexual sequalae). There is insufficient understanding of patient experiences with these symptoms and perspectives from the providers who perform LEEP/LLETZ. AIM: To characterize the perceptions and experiences of LEEP/LLETZ treatment from providers and patients, including whether there is a characteristic symptom profile of women who report negative outcomes. METHODS: Patients who had LEEP/LLETZ treatment and reported negative outcomes and providers who perform LEEP/LLETZ completed semistructured interviews about their perceptions and experiences, which were coded through thematic analysis (NVivo 12; QSR International). Patients also completed an online survey assessing demographics, medical history, and sexual function. OUTCOMES: Outcomes included perspectives generated from patient and provider interviews regarding LEEP/LLETZ procedural outcomes, including symptoms and experiences related to sexual functioning. RESULTS: Perspectives and experiences gathered from patient and provider interviews revealed misaligned narratives surrounding LEEP/LLETZ outcomes and treatment. We identified 4 overarching themes encapsulating provider and patient responses: Expectations for Preoperative Consultation; Procedure Experiences; Attitudes; and Resources. Patients reported a unique symptom profile and negative outcome experiences, namely surrounding domains of sexual functioning: decreased physical sensations, orgasm response, and vaginal discharge, as well as loss of arousal, interest, and desire. Patients described changes to overall quality of life, with impacts to interpersonal relationships. Patients discussed preferring open-ended and directed questions to comprehensively elucidate negative outcomes. Provider narratives outlined the current process of care, emphasizing limited experiences with adverse outcomes (e.g., sexual issues) and the use of open-ended questions during counseling. Providers described an evolving intention to create comfortable clinical spaces. Regarding pre- and postoperative resources, patients described seeking support from online patient groups, and providers disclosed limitations to providing resources. CLINICAL IMPLICATIONS: Evidence of discordance between patient and provider perspectives of LEEP/LLETZ reveals a need to reassess clinical practices surrounding this procedure at the level of discussions regarding informed consent, sexual function, and available resources. STRENGTHS AND LIMITATIONS: This study is the first to examine patient and provider perspectives on LEEP/LLETZ treatment. Only patients who self-report negative outcomes were recruited, to elicit narratives from this specific subpopulation. CONCLUSION: Results indicate a characteristic symptom profile of women who undergo LEEP/LLETZ and report negative outcomes and that the perceptions of patients and providers differ regarding several aspects of the treatment experience, supporting the need for directed open conversation and comprehensive pre- and postoperative sexual counseling.

The contribution of the cervix to sexual response: an online survey study.

BACKGROUND: The role of the cervix in sexual response has been poorly studied, despite previous research indicating that some women experience pleasurable sexual sensations from cervical stimulation; given previous reports of sexual issues after cervix electrocautery, it is possible that cervical injury may compromise the role of the cervix in sexual functioning. AIM: The aims of this study were to examine locations of pleasurable sexual sensations, to identify sexual communication barriers, and to investigate if cervical procedures are associated with negative impacts on sexual function. METHODS: Women with (n = 72) and without (n = 235) a history of a gynecological procedure completed an online survey assessing demographics, medical history, sexual function (including locations of sexual pleasure and pain on diagrams), and barriers. The procedure group was divided into subgroups of those who had experienced a cervical (n = 47) or noncervical (n = 25) procedure. Chi-square analyses and t tests were conducted. OUTCOMES: Outcomes included locations and ratings of pleasurable and painful sexual stimulation, as well as sexual function. RESULTS: Over 16% of participants reported experiencing some pleasurable sexual sensations from the cervix. The gynecological procedure group (n = 72) reported significantly higher pain in the vagina and lower rates of pleasure in their external genitals, vagina, deep vagina, anterior and posterior vaginal walls, and clitoris vs the non-gynecological procedure (n = 235) group. The gynecological procedure group and the cervical procedure subgroup (n = 47) reported significant decreases in desire, arousal, and lubrication and increased avoidance of sexual activity due to vaginal dryness. The gynecological procedure group reported significant pain with vaginal stimulation, whereas the cervical subgroup identified significant pain with cervical and clitoral stimulation. CLINICAL IMPLICATIONS: Cervical stimulation elicits some pleasurable sexual sensations for many women, and gynecological procedures that affect the cervix are associated with pain and sexual issues; thus, health care providers should counsel patients about the possibility of related sexual concerns. STRENGTHS AND LIMITATIONS: This study is the first to examine locations of pleasure and pain and experiences of sexual pleasure and function in participants who underwent a gynecological procedure. A hybrid measure was used to assess sexual issues, including symptoms of dysfunction. CONCLUSION: Results indicate an association between cervical procedures and sexual issues, supporting the need to inform patients of this possibility following cervical procedures.

Characterizing the innervation of the vulvar vestibule and the immunohistochemical features of neuroproliferative vestibulodynia.

BACKGROUND: Provoked vestibulodynia (PVD) is a chronic pain condition characterized by allodynia localized to the vulvar vestibule. The finding of increased densities of nerve fibers in the vestibular mucosa of patients with PVD has led to the identification of a neuroproliferative subtype. The etiology of PVD, including neuroproliferative vestibulodynia (NPV), is not fully understood. The gross and microscopic innervation of the vulvar vestibule remains incompletely described, despite the preliminary data supporting the role of peripheral innervation in PVD. AIM: To characterize the gross anatomic and microscopic innervation of the vulvar vestibule through cadaveric dissection and immunohistochemistry. METHODS: The pudendal nerve and inferior hypogastric plexus (IHP) were dissected using 6 cadaveric donors. Histology and immunohistochemistry were used to confirm patterns of innervation identified gross anatomically. Immunohistochemistry was performed on vestibulectomy specimens obtained from 6 patients diagnosed with NPV and compared with cadaveric vestibular tissues. OUTCOMES: Outcomes included (1) dissection of pelvic innervation and (2) immunohistochemical localization of markers for the following: general innervation protein gene product 9.5 (PGP9.5), sensory innervation (calcitonin gene-related peptide), autonomic innervation (vasoactive intestinal polypeptide, tyrosine hydroxylase), neuroproliferation (nerve growth factor [NGF]), and immune activation (C-kit). RESULTS: Perineal (pudendal) nerve branches were traced to the external wall of the vulvar vestibule. Some anatomic heterogeneity was observed in perineal nerve-branching patterns. Fibers from the IHP were identified in close proximity to the vulvar vestibule. Autonomic and sensory nerve fibers were identified in both patient and cadaveric vulvar vestibule samples. Patient samples were characterized by the proliferation of PGP9.5-positive nerve fibers and C-kit-positive mast cells, which were in proximity to neve bundles and showed coexpression with putative NGF-positive cells. NGF expression was localized to a subset of nerves, including those that demonstrated co-expression of sensory and autonomic nerve markers. Increased densities of autonomic fibers positive for vasoactive intestinal polypeptide and tyrosine hydroxylase were observed in 1 patient sample. CLINICAL TRANSLATION: Heterogeneity in gross and microscopic patterns of innervation could explain variability in clinical response to treatment and should be used to inform future therapeutic interventions. STRENGTHS AND LIMITATIONS: This study used a combination of approaches to elucidate the innervation of the vulvar vestibule, including in NPV. The small sample size is a limitation. CONCLUSION: The vulvar vestibule contains both sensory and autonomic innervation, which may originate from the pudendal nerve and IHP. Our results support the existence of a neuroproliferative subtype that is characterized by the proliferation of sensory and autonomic nerve fibers and neuroimmune interactions.

Functional Magnetic Resonance Imaging Studies in Sexual Medicine: A Primer.

BACKGROUND: Over the past 30 years, functional magnetic resonance imaging (fMRI) has emerged as a powerful tool to non-invasively study the activity and function of the human brain. But along with the potential of fMRI to shed light on neurological, psychiatric, and psychological processes, there are methodological challenges and criticisms. AIM: We herein provide an fMRI primer designed for a diverse audience, from the neuroimaging novice to the experienced user. METHODS: This primer is structured as follows: Part 1: Overview: "What is fMRI and what can it tell us?." Part 2: Basic fMRI principles: MR physics, the BOLD signal, and components of a typical scan session. Part 3: Basic fMRI experimental design: why timing is critical, and common sources of noise in the signal. Part 4: Basic fMRI analysis methods: software, the 3 stages of data analysis (preprocessing, individual, and group level), and a survey of advanced topics and methods including connectivity, machine learning, and assessing statistical significance. Part 5: Criticism, crises, and opportunities related to power of studies, computing requirements, logistical, and interpretational challenges, and methodological debate (assessing causality, circular correlations, and open science best practices). OUTCOMES N/A CLINICAL TRANSLATION: fMRI has primarily been used in clinical research to elucidate the brain correlates of sexual behavior. The translational potential of the method into clinical practice has not yet been realizedfMRI has primarily been used in clinical research to elucidate the brain correlates of sexual behavior. The translational potential of the method into clinical practice has not yet been realized STRENGTHS AND LIMITATIONS: fMRI is a useful and powerful tool for understanding the brain basis of human sexuality. However, it is also expensive, requires extensive methods expertise, and lacks the precision needed to be immediately translatable to clinical practice. The recency of the method, need for basic research, technical limitations, as well as inherent variability in individuals brain activity also impact the pace at which fMRI for sexual medicine can move from the scanner to the clinic. CONCLUSION: This primer provides the novice an understanding of the appropriate uses and limitations of fMRI, and for the experienced user, a concise update on current issues and methodological advances. Mills-Finnerty C, Frangos E, Allen K, et al. Functional Magnetic Resonance Imaging Studies in Sexual Medicine: A Primer. J Sex Med 2022;19:1073-1089.

Immunohistochemical Investigation of Autonomic and Sensory Innervation of Anterior Vaginal Wall Female Periurethral Tissue: A Study of the Surgical Field of Mid-Urethral Sling Surgery Using Cadaveric Simulation.

BACKGROUND: Female sexual dysfunction, including female orgasm disorder, has been reported following mid-urethral sling (MUS) surgery to treat bothersome stress urinary incontinence. Anterior vaginal wall-female periurethral tissue (AVW-FPT) likely contains autonomic and sensory innervation involved in the female sexual response, and injury to these nerves may result from MUS implantation. AIM: To characterize, using fresh cadaveric tissue, autonomic and sensory nerves in AVW- FPT using immunohistochemistry (IHC), and to assess their proximity to an implanted MUS. METHODS: AVW-FPT was excised following careful dissection from four fresh cadavers. Prior to dissection, one cadaver underwent simulation of the MUS procedure by a urogynegologist, using a fascial sling. All samples were paraffin embedded, sectioned, and stained with hematoxylin. Serial sectioning and IHC were performed to identify nerves. IHC markers were used to characterize the sensory and autonomic innervation. OUTCOMES: IHC localization of autonomic and sensory nerve markers consistent with neural tissue within the region of MUS implantation. RESULTS: IHC of AVW-FPT using protein gene product 9.5 (PGP9.5), a general nerve stain, revealed innervation throughout the region targeted by the MUS implantation. More specifically, immunoreactivity for both autonomic (tyrosine hydroxylase, TH) and sensory (Nav1.8 and S100ß) nerves were found in close proximity (<1 mm) to the implanted MUS. In addition, a subset of S100ß positive nerves also showed immunoreactivity for calcitonin gene-related peptide (CGRP). Combining the IHC findings with the surgical simulation of the MUS implantation revealed the potential for damage to both autonomic and sensory nerves as a direct result of the MUS procedure. CLINICAL TRANSLATION: The identified autonomic and sensory nerves of the AVW-FPT may contribute to the female sexual response, and yet are potentially negatively impacted by MUS procedures. Given that surgeries performed on male genital tissue, including the prostate, may cause sexual dysfunction secondary to nerve damage, and that urologists routinely provide informed consent regarding this possibility, urogynaecologists are encouraged to obtain appropriate informed consent from prospective patients undergoing the MUS procedure. STRENGTHS & LIMITATIONS: This is the first study to characterize the sensory and autonomic innervation within the surgical field of MUS implantation and demonstrate its relationship to an implanted MUS. The small sample size is a limitation of this study. CONCLUSION: The present study provides evidence of potential injury to autonomic and sensory innervation of AVW-FPT as a consequence of MUS implantation, which may help explain the underlying mechanisms involved in the reported post-operative female sexual dysfunction in some women. Giovannetti O, Tomalty D, Gaudet D, et al. Immunohistochemical Investigation of Autonomic and Sensory Innervation of Anterior Vaginal Wall Female Periurethral Tissue: A Study of the Surgical Field of Mid-Urethral Sling Surgery Using Cadaveric Simulation. J Sex Med 2021;18:1168-1180.

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

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

Male Urogenital System Mapped Onto the Sensory Cortex: Functional Magnetic Resonance Imaging Evidence.

INTRODUCTION: The projection of the human male urogenital system onto the paracentral lobule has not previously been mapped comprehensively. AIM: To map specific urogenital structures onto the primary somatosensory cortex toward a better understanding of sexual response in men. METHODS: Using functional magnetic resonance imaging, we mapped primary somatosensory cortical responses to self-stimulation of the penis shaft, glans, testicles, scrotum, rectum, urethra, prostate, perineum, and nipple. We further compared neural response with erotic and prosaic touch of the penile shaft. MAIN OUTCOME MEASURE: We identified the primary mapping site of urogenital structures on the paracentral lobule and identified networks involved in perceiving touch as erotic. RESULTS: We mapped sites on the primary somatosensory cortex to which components of the urogenital structures project in men. Evidence is provided that penile cutaneous projection is different from deep penile projection. Similar to a prior report in women, we show that the nipple projects to the same somatosensory cortical region as the genitals. Evidence of differential representation of erotic and nonerotic genital self-stimulation is also provided, the former activating sensory networks other than the primary sensory cortex, indicating a role of "top-down" activity in erotic response. CLINICAL IMPLICATIONS: We map primary sites of projection of urogenital structures to the primary somatosensory cortex and differentiate cortical sites of erotic from nonerotic genital self-stimulation. STRENGTH & LIMITATIONS: To our knowledge, this is the first comprehensive mapping onto the primary somatosensory cortex of the projection of the components of the urogenital system in men and the difference in cortical activation in response to erotic vs nonerotic self-stimulation. The nipple was found to project to the same cortical region as the genitals. Evidence is provided that superficial and deep penile stimulation project differentially to the cortex, suggesting that sensory innervation of the penis is provided by more than the (pudendal) dorsal nerve. CONCLUSION: This study reconciles prior apparently conflicting findings and offers a comprehensive mapping of male genital components to the paracentral lobule. We provide evidence of differential projection of light touch vs pressure applied to the penile shaft, suggesting differential innervation of its superficial, vs deep structure. Similar to the response in women, we found nipple projection to genital areas of the paracentral lobule. We also provide evidence of differential representation of erotic and nonerotic genital self-stimulation, the former activating sensory networks other than the primary sensory cortex, indicating a role of top-down activity in erotic response. Allen K, Wise N, Frangos E, et al. Male Urogenital System Mapped Onto the Sensory Cortex: Functional Magnetic Resonance Imaging Evidence. J Sex Med 2020;17:603-613.

Copulation-induced antinociception in female rats is blocked by atosiban, an oxytocin receptor antagonist.

AIMS: We hypothesized that copulation-induced temporary anti-nociception in female rats is mediated by the activation of central and/or peripheral oxytocin receptors. To test this hypothesis, we assessed the effects of intraperitoneal (ip), intrathecal (it), and intra-cerebroventricular (icv) administration of an oxytocin receptor antagonist (atosiban), on copulation-induced temporary anti-nociception in estrous rats. MAIN METHODS: The treatment groups were ovariectomized rats pre-treated subcutaneously (sc) with 10 µg of estradiol benzoate (EB) followed 24 h later by an sc injection of 5 µg EB, and 4 h later, by an sc injection of 2 mg progesterone (P4). Rats were then administered saline vehicle (ip, it, or icv: control groups) or atosiban (500 µg/kg ip; 500 ng it; or 500 ng icv: experimental groups). Thirty minutes after drug or saline administration, their sexual behavior was tested by pairing with a sexually-experienced male rat. Brief pulse trains of 50 Hz, 300 ms duration, supra-threshold tail electrical shocks (STS) were delivered before and during copulatory activity i.e., while the female was receiving mounts, intromissions, or ejaculations, and we recorded whether vocalization occurred in response to each STS. KEY FINDINGS: Replicating our previous findings, the vocalization response to STS in control rats was significantly attenuated during intromissions and ejaculations, compared to their baseline (pre-mating) response, indicative of anti-nociception. By contrast, rats pre-treated with atosiban (each route of administration) failed to show an attenuation of the vocalization response to shock. SIGNIFICANCE: These findings provide evidence that the temporary anti-nociceptive effect of copulation in female rats is mediated by copulation-induced release of endogenous oxytocin in brain, spinal cord and periphery.

Brain Activity Unique to Orgasm in Women: An fMRI Analysis.

BACKGROUND: Although the literature on imaging of regional brain activity during sexual arousal in women and men is extensive and largely consistent, that on orgasm is relatively limited and variable, owing in part to the methodologic challenges posed by variability in latency to orgasm in participants and head movement. AIM: To compare brain activity at orgasm (self- and partner-induced) with that at the onset of genital stimulation, immediately before the onset of orgasm, and immediately after the cessation of orgasm and to upgrade the methodology for obtaining and analyzing functional magnetic resonance imaging (fMRI) findings. METHODS: Using fMRI, we sampled equivalent time points across female participants' variable durations of stimulation and orgasm in response to self- and partner-induced clitoral stimulation. The first 20-second epoch of orgasm was contrasted with the 20-second epochs at the beginning of stimulation and immediately before and after orgasm. Separate analyses were conducted for whole-brain and brainstem regions of interest. For a finer-grained analysis of the peri-orgasm phase, we conducted a time-course analysis on regions of interest. Head movement was minimized to a mean less than 1.3 mm using a custom-fitted thermoplastic whole-head and neck brace stabilizer. OUTCOMES: Ten women experienced orgasm elicited by self- and partner-induced genital stimulation in a Siemens 3-T Trio fMRI scanner. RESULTS: Brain activity gradually increased leading up to orgasm, peaked at orgasm, and then decreased. We found no evidence of deactivation of brain regions leading up to or during orgasm. The activated brain regions included sensory, motor, reward, frontal cortical, and brainstem regions (eg, nucleus accumbens, insula, anterior cingulate cortex, orbitofrontal cortex, operculum, right angular gyrus, paracentral lobule, cerebellum, hippocampus, amygdala, hypothalamus, ventral tegmental area, and dorsal raphe). CLINICAL TRANSLATION: Insight gained from the present findings could provide guidance toward a rational basis for treatment of orgasmic disorders, including anorgasmia. STRENGTHS AND LIMITATIONS: This is evidently the first fMRI study of orgasm elicited by self- and partner-induced genital stimulation in women. Methodologic solutions to the technical issues posed by excessive head movement and variable latencies to orgasm were successfully applied in the present study, enabling identification of brain regions involved in orgasm. Limitations include the small sample (N = 10), which combined self- and partner-induced stimulation datasets for analysis and which qualify the generalization of our conclusions. CONCLUSION: Extensive cortical, subcortical, and brainstem regions reach peak levels of activity at orgasm. Wise NJ, Frangos E, Komisaruk BR. Brain Activity Unique to Orgasm in Women: An fMRI Analysis. J Sex Med 2017;14:1380-1391.

Commentary on "The Evolutionary Origin of Female Orgasm" by M. Pavlicev and G. Wagner, 2016, J. Exp. Zool. (Mol. Dev. Evol.) 326(6):326-337.

Evidence is presented as an alternative to the authors' claims that in the course of evolution, a link between orgasm and ovulation has been lost in women, that evolutionary changes in clitoral anatomy underlie this loss, and that women's orgasm plays no significant role in reproduction.

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

INTRODUCTION: Current Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) definitions of sexual dysfunction do not identify all sexual problems experienced clinically by women and are not necessarily applicable for biologic or biopsychosocial management of female sexual dysfunction. A unified nomenclature system enables clinicians, researchers, and regulatory agencies to use the same language and criteria for determining clinical end points, assessing research results, and managing patients. AIM: To develop nomenclature with classification systems for female sexual desire, arousal, and orgasm disorders with definitions pertinent to clinicians and researchers from multiple specialties who contribute to the field of sexual medicine. METHODS: Key national and international opinion leaders diverse in gender, geography, and areas of expertise met for 2 days to discuss and agree to definitions of female sexual desire, arousal, and orgasm disorders and persistent genital arousal disorder. The attendees consisted of 10 psychiatrists and psychologists; 12 health care providers in specialties such as gynecology, internal medicine, and sexual medicine; three basic scientists; and one sexuality educator, representing an array of societies working within the various areas of sexual function and dysfunction. MAIN OUTCOME MEASURE: A unified set of definitions was developed and accepted for use by the International Society for the Study of Women's Sexual Health (ISSWSH) and members of other stakeholder societies participating in the consensus meeting. RESULTS: Current DSM-5 definitions, in particular elimination of desire and arousal disorders as separate diagnoses and lack of definitions of other specific disorders, were adapted to create ISSWSH consensus nomenclature for distressing sexual dysfunctions. The ISSWSH definitions include hypoactive sexual desire disorder, female genital arousal disorder, persistent genital arousal disorder, female orgasmic disorder, pleasure dissociative orgasm disorder, and female orgasmic illness syndrome. CONCLUSION: Definitions for female sexual dysfunctions that reflect current science provide useful nomenclature for current and future management of women with sexual disorders and development of new therapies.

Does MDMA have treatment potential in sexual dysfunction? A systematic review of outcomes across the female and male sexual response cycles.

INTRODUCTION: Sexual health, an integral component of overall well-being, is frequently compromised by common yet underdiagnosed sexual dysfunctions. Traditional interventions encompass pharmaceutical and psychological treatments. Unconventional therapies, like MDMA, offer hope for sexual dysfunction. This review delves into MDMA's effects on sexual responsiveness and its potential role in treating sexual dysfunction. OBJECTIVES: The purpose of this review is to elucidate effects of MDMA on different domains of the female and male sexual response cycles. METHODS: We conducted a systematic review on the effects of MDMA on each domain of the female and male sexual response cycles. PubMed, MEDLINE, and EMBASE were queried, and results were screened using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Search terms utilized were "MDMA" or "ecstasy" in combination with "desire," "arousal," "lubrication," "orgasm," "pleasure," "libido," "erection," and "ejaculation." Inclusion criteria for this review were MDMA use by study subjects and sexual outcomes in at least 1 domain of the female and/or male sexual response cycles were described and measured. Randomized controlled trials, cohort studies (both prospective and retrospective), surveys, and literature reviews published between January 2000 and June 2022 were included. Case reports and studies that did not address conditions of interest were excluded from analysis. Duplicated search results were screened out. The remaining studies were then read in full text to ensure they met inclusion and exclusion criteria for analysis. RESULTS: We identified 181 studies, of which 6 met criteria for assessment of the female sexual response cycle and 8 met criteria for assessment of the male sexual response cycle. Four of 6 studies reported increased sexual desire with MDMA use among women. Arousal and lubrication were improved with MDMA use in 3 of 4 studies, but they were not affected in 1 randomized control study. In men, 7 studies evaluated the effects of MDMA on desire and/or arousal, 5 studies measured impact on erection, 3 on orgasm, and 2 on ejaculation. Sixty percent of interview-based studies reported increased sexual desire in men, while 40% reported mixed or no effect. Two studies reported impairment of erection, 2 reported mixed effects, and 1 reported fear of erection impairment. In both men and women, all studies evaluating orgasm reported delay in achieving orgasm but increased intensity and pleasure if achieved. Primary outcome measures were variable and largely qualitative. CONCLUSION: Our findings suggest that MDMA generally increases sexual desire and intensifies orgasm when achieved. While producing conflicting evidence on sexual arousal in both sexes, MDMA may impair erectile and ejaculatory function in men.

Prevalence of sacral spinal (Tarlov) cysts in persistent genital arousal disorder.

INTRODUCTION: Neither consistent etiology nor treatment have been established for Persistent Genital Arousal Disorder (PGAD), which is characterized by uninvited, unwelcome, and distressing genital sensation. Sacral (Tarlov) cysts, which form on dorsal (sensory) roots, most commonly of S2 and S3 in the sacral spine, are reported to produce genital symptoms that bear similarities to those described for PGAD. AIMS: The present study ascertained the incidence of Tarlov cysts in the sacral spine of women with PGAD symptoms. METHODS: Women in a PGAD internet support group were asked to submit MRIs of their sacral region to the investigators, who evaluated the MRIs for the presence or absence of Tarlov cysts. MAIN OUTCOME MEASURES: The presence or absence of Tarlov cysts at the level of the sacral spine. RESULTS: Tarlov cysts were present in 12 of the first 18 (66.7%) MRIs submitted to the investigators by women who suffer from PGAD symptoms. By contrast to this incidence, that of Tarlov cysts reported in the literature for large samples of the population observed for various disorders (e.g., lumbosacral pain) is 1.2-9.0%. CONCLUSION: Tarlov cysts have been described in the literature as producing paresthesias and genital sensory disturbances. Hence, at least some cases of PGAD might be considered to be a Tarlov cyst-induced paresthesia. Based on the relatively high occurrence of Tarlov cysts currently observed in women who suffer from PGAD symptoms, it would seem advisable to suspect Tarlov cysts as a possible organic etiological factor underlying PGAD.

Female orgasm(s): one, two, several.

INTRODUCTION: There is general agreement that it is possible to have an orgasm thru the direct simulation of the external clitoris. In contrast, the possibility of achieving climax during penetration has been controversial. METHODS: Six scientists with different experimental evidence debate the existence of the vaginally activated orgasm (VAO). MAIN OUTCOME MEASURE: To give reader of The Journal of Sexual Medicine sufficient data to form her/his own opinion on an important topic of female sexuality. RESULTS: Expert #1, the Controversy's section Editor, together with Expert #2, reviewed data from the literature demonstrating the anatomical possibility for the VAO. Expert #3 presents validating women's reports of pleasurable sexual responses and adaptive significance of the VAO. Echographic dynamic evidence induced Expert # 4 to describe one single orgasm, obtained from stimulation of either the external or internal clitoris, during penetration. Expert #5 reviewed his elegant experiments showing the uniquely different sensory responses to clitoral, vaginal, and cervical stimulation. Finally, the last Expert presented findings on the psychological scenario behind VAO. CONCLUSION: The assumption that women may experience only the clitoral, external orgasm is not based on the best available scientific evidence.

Vagus nerve afferent stimulation: Projection into the brain, reflexive physiological, perceptual, and behavioral responses, and clinical relevance.

The afferent vagus nerves project to diverse neural networks within the brainstem and forebrain, based on neuroanatomical, neurophysiological, and functional (fMRI) brain imaging evidence. In response to afferent vagal stimulation, multiple homeostatic visceral reflexes are elicited. Physiological stimuli and both invasive and non-invasive electrical stimulation that activate the afferent vagus elicit perceptual and behavioral responses that are of physiological and clinical significance. In the present review, we address these multiple roles of the afferent vagus under normal and pathological conditions, based on both animal and human evidence.

Orgasm and Related Disorders Depend on Neural Inhibition Combined With Neural Excitation.

INTRODUCTION: Prevalent models of sexual desire, arousal and orgasm postulate that they result from an excitatory process, whereas disorders of sexual desire, arousal and orgasm result from an inhibitory process based on psychosocial, pharmacological, medical, and other factors. But neuronal excitation and active neuronal inhibition normally interact at variable intensities, concurrently and continuously. We propose herein that in conjunction with neuronal excitation, neuronal inhibition enables the generation of the intense, non-aversive pleasure of orgasm. When this interaction breaks down, pathology can result, as in disorders of sexual desire, arousal, and orgasm, and in anhedonia and pain. For perspective, we review some fundamental behavioral and (neuro-) physiological functions of neuronal excitation and inhibition in normal and pathological processes. OBJECTIVES: To review evidence that the variable balance between neuronal excitation and active neuronal inhibition at different intensities can account for orgasm and its disorders. METHODS: We selected studies from searches on PubMed, Google Scholar, Dialnet, and SciELO for terms including orgasm, neuronal development, Wallerian degeneration, prenatal stress, parental behavior, sensorimotor, neuronal excitation, neuronal inhibition, sensory deprivation, anhedonia, orgasmic disorder, hypoactive sexual desire disorder, persistent genital arousal disorder, sexual pain. RESULTS: We provide evidence that the intensity of neuronal inhibition dynamically covaries concurrently with the intensity of neuronal excitation. Differences in these relative intensities can facilitate the understanding of orgasm and disorders of orgasm. CONCLUSION: Neuronal excitation and neuronal inhibition are normal, continuously active processes of the nervous system that are necessary for survival of neurons and the organism. The ability of genital sensory stimulation to induce concurrent neuronal inhibition enables the stimulation to attain the pleasurable, non-aversive, high intensity of excitation characteristic of orgasm. Excessive or deficient levels of neuronal inhibition relative to neuronal excitation may account for disorders of sexual desire, arousal and orgasm. Komisaruk BR, Rodriguez del Cerro MC. Orgasm and Related Disorders Depend on Neural Inhibition Combined With Neural Excitation. Sex Med Rev 2022;10:481-492.