Clitoral Blood Flow Research Articles

The Intersection of Artificial Intelligence, Wearable Devices, and Sexual Medicine.

The aim of our review paper is to provide a comprehensive overview of the current technologies in artificial intelligence and wearable devices dedicated to sexual health. Currently, AI-powered technologies are enhancing our understanding of reproductive health and sexually transmitted infections, and facilitating empathetic education and outreach to diverse populations. Additionally, innovative wearable devices are providing insights into men's erectile health, addressing ejaculatory concerns, and exploring women's orgasms in relation to pelvic floor muscles and clitoral blood flow. The field of sexual health technology is rapidly expanding, with recent innovations transforming our understanding of sexual health. As technology progresses, it is crucial to address significant ethical considerations to protect users, particularly due to the sensitive nature of the data involved.

Ultrasound-guided staging and reversal of female genital mutilation.

FGM/C is common, effecting over 200 million women worldwide and has substantial associated morbidity. We seek improving the reversal procedure using ultrasound imaging. The use of peri- and intraoperative ultrasound imaging for reconstructive surgery following FGM/C for staging and surgical planning, with focus on the clitoral structures and blood flow. This is a case series of patients with FGM/C who were evaluated and underwent reconstructive surgical management at a single institution between 2018 and 2022. Ultrasound examination with Doppler imaging was performed. The electronic medical record was queried for data regarding patient characteristics, examination and ultrasound findings, and surgical and postoperative course. Seven patients are described in this case series who sustained the FGM/C with classifications ranging from Ia to IIIb. The primary complaints were dyspareunia or apareunia. Six of seven (86%) reported anorgasmia. Four of seven (57%) had prior vaginal deliveries, and one of seven (14%) was delivered only by cesarean sections, two of seven (29%) have not been able to have intercourse. Ultrasound examination was utilized to facilitate recognition of the anatomic structures during the reconstruction, and Doppler was used to evaluate the clitoral blood flow. Doppler was useful to delineate clitoral tissues from a closely involved periclitoral inclusion cyst, aiding in surgical excision while minimizing clitoral vascular or nerve injury. Postoperative anatomical restoration, sexual function, and alleviation of dyspareunia were excellent. None of the patients reported decreased sexual pleasure postoperatively. Ultrasound imaging with Doppler can be utilized to facilitate personalized approaches to optimize both anatomical and functional results in cases of genital reconstruction.

(208) Coital Positions and Clitoral Blood Flow: A Biomechanical and Sonographic Analysis

Abstract Introduction The purported benefits of various coital positions are described in numerous magazines, books, and public forums. However, there is little scientific research that evaluates the association between different coital positions and the ability to produce female orgasm. Objective To create biomechanical models of five coital positions, and evaluate the degree of contact and forces against the clitoris. To evaluate clitoral blood flow before and after engaging in these positions. Methods Biomechanical models were rendered of a male and female pelvis in the following coital positions: face-to-face/female above, sitting/face-to-face, face-to-face/male above (with and without pillow), and kneeling/rear entry. The thrusting force and gravitational force were estimated for the pelvis(es) providing the main forces. The areas of contact between the pelvises were identified and highlighted. Sonography of the clitoris was performed before and after a healthy volunteer couple engaged in each position, using a Philips Lumify™ ultrasound (Koninklijke Philips N.V., Amsterdam, Netherlands) with a L12-4 linear array transducer (4-12 MHz). Results The biomechanical models for each position, with the exception of kneeling/rear entry, reveal a large amount of contact with the clitoris. Clitoral blood flow increased after engaging in each position except for kneeling/rear entry. Positions in which the gravitational force of the thrusting partner was in the same direction of (and thereby augmenting) the thrusting force resulted in intense clitoral blood flow (face-to-face/female above, and face-to-face/male above). Augmenting the face-to-face/male above position with a pillow generated a component of the male pelvic gravitational force in the direction of the clitoris; this resulted in more blood flow to all components of the cavernous body. Conclusions From a biomechanical perspective, different coital positions vary in their potential to stimulate the clitoris. These positions lead to variable increases in clitoral blood flow, concordant with our biomechanical models. Disclosure No

(210) Clitoral Blood Flow After Use of Gel Containing L-Arginine and L-Citrulline

Abstract Introduction L-arginine and its precursor, l-citrulline, are two amino acids involved in the production of nitric oxide (NO); as a result, they increase blood flow and have been used to treat male sexual dysfunction (Alatas and Yagci, 2004). Some lubricants and gels contain l-arginine and are applied directly to the genital area to increase blood flow. Although these products have been evaluated subjectively through patient reports of increased warmth, arousal, and orgasm, to our knowledge, they have not been evaluated quantitatively in women. Moreover, the effect of gels combining both l-arginine and l-citrulline have not been reported in the medical literature. Objective To evaluate whether a topical gel containing l-arginine and l-citrulline increases blood flow to the clitoris. Methods Sonography of the clitoris was performed on a healthy 32-year-old volunteer before and after applying the gel externally to the vulva. The “before” scans were obtained using a neutral ultrasound gel (without l-arginine or l-citrulline). This allowed us to verify that the observations were due to the active ingredients of the gel, and not from massage associated with its application. Control images without gel could not be obtained, since acquisition of ultrasound images requires ultrasound gel in order to reduce acoustic impedance. The scans were obtained with a Philips Lumify™ ultrasound (Koninklijke Philips N.V., Amsterdam, Netherlands) with a L12-4 linear array transducer (4-12 MHz). Clitoral blood flow was assessed qualitatively (color Doppler images), as well as quantitatively (peak systolic velocity, end diastolic velocity, and resistive index of the deep artery of the clitoris). Results Blood flow to the clitoris increased after application of the gel containing l-arginine and l-citrulline at both evaluated time points. The maximum PSV of the deep artery of the clitoris also increased from 6.2 cm/s (before), to 8.6 cm/s (5 minutes) and 13.9 cm/s (15 minutes). The maximum EDV of the deep artery of the clitoris increased from 1.4 cm/s (before), to 1.7 cm/s (5 minutes) and 9.5 cm/s (15 minutes). The RI was 0.8 before and at 5 minutes. After 15 minutes, the RI decreased to 0.3, explained by a disproportional increase in EDV compared to PSV. Conclusions The results of this pilot study suggest that clitoral blood flow increases with the use of a gel containing l-arginine and l-citrulline. These findings can help clinicians inform patients with female sexual dysfunction. Difficulty achieving clitoral stimulation is a major cause of sexual dysfunction. Clinicians can use these findings to counsel patients about using gels to increase clitoral blood flow. Disclosure No

Coital positions and clitoral blood flow: A biomechanical and sonographic analysis

To create biomechanical models of five common coital positions, and evaluate the degree of contact and forces against the clitoris. To evaluate clitoral blood flow before and after engaging in these positions. Biomechanical models were rendered of a male and female pelvis in the following coital positions: face-to-face/female above, sitting/face-to-face, face-to-face/male above (with and without pillow), and kneeling/rear entry. The thrusting force and gravitational force were estimated for the pelvis(es) providing the main forces. The areas of contact between the pelvises were identified and highlighted. Sonography of the clitoris was performed before and after a healthy volunteer couple engaged in each position, using a Philips Lumify™ ultrasound (Koninklijke Philips N.V., Amsterdam, Netherlands) with a L12-4 linear array transducer (4–12 MHz). The biomechanical models for each position, with the exception of kneeling/rear entry, reveal a large amount of contact with the clitoris. Clitoral blood flow increased after engaging in each position except for kneeling/rear entry. Positions in which the gravitational force of the thrusting partner was in the same direction of (and thereby augmenting) the thrusting force resulted in intense clitoral blood flow (face-to-face/female above, and face-to-face/male above). Augmenting the face-to-face/male above position with a pillow generated a component of the male pelvic gravitational force in the direction of the clitoris; this resulted in more blood flow to all components of the cavernous body. From a biomechanical perspective, different coital positions vary in their potential to stimulate the clitoris. These positions lead to variable increases in clitoral blood flow, concordant with our biomechanical models.

Pilot sonographic study of clitoral blood flow and size after use of sexual devices

Over 50% of women in the United States report using sexual devices. These devices, which are often used recreationally to increase the likelihood of arousal and orgasm, can also be used therapeutically in the setting of sexual dysfunction. Despite their widespread use and association with improved sexual wellness, their effect on the clitoris has not been investigated. We aimed to evaluate changes in clitoral blood flow and size in response to stimulation with various sexual devices. Clitoral sonography was performed on a healthy volunteer before and after stimulation with each of the following sexual devices: wand applied externally, internal vibrator inserted vaginally, and air pulse stimulation of the glans clitoris. The scans were obtained with a Philips Lumify™ ultrasound (Koninklijke Philips N.V., Amsterdam, Netherlands) using a L12-4 linear array transducer (4–12 MHz) and a C5-2 broadband curved array transducer (2–5 MHz). We observed that stimulation with sexual devices increased blood flow to different areas of the clitoris, and led to changes in clitoral area and clitoral erectile length (CEL). Our findings suggest that female orgasms are of more than one or two types (clitoral versus vaginal), and likely occupy a spectrum. This may provide insight into using sexual devices as treatment options for female sexual dysfunction. Plus de 50 % des femmes aux États-Unis déclarent utiliser des dispositif sexuels, souvent utilisés à des fins récréatives pour augmenter la probabilité d’excitation et d’orgasme. Ils peuvent être également utilisés à des fins thérapeutiques dans le cadre d’un dysfonctionnement sexuel. Malgré leur utilisation répandue et leur association à l’amélioration du bien-être sexuel, leur effet sur le clitoris n’a pas été étudié. Nous avons cherché à évaluer les modifications du débit sanguin et de la taille du clitoris en réponse à la stimulation par divers sex toys. L’échographie clitoridienne a été réalisée sur une volontaire en bonne santé avant et après la stimulation avec chacun des dispositifs sexuels suivant : wand (masseur à baguette), vibromasseur interne inséré par voie vaginal, et stimulation par impulsion d’air du gland du clitoris. Les scans ont été obtenus avec un système à ultrasons Philips Lumify™ (Koninklijke Philips NV, Amsterdam, Pays-Bas) utilisant un transducteur à réseau linéaire L12-4 (4–12 MHz) et un transducteur à réseau incurvé à large bande C5-2 (2–5 MHz). Nous avons observé que la stimulation avec des jouets sexuels augmentait le flux sanguin vers différentes zones du clitoris et entraînait des modifications de la zone clitoridienne et de la longueur érectile. Nos résultats suggèrent que les orgasmes féminins sont de plus d’un ou deux types (clitoridien versus vaginal) et occupent probablement un large spectre. Cela peut donner un aperçu de l’utilisation de dispositifs sexuels comme options de traitement des dysfonctionnements sexuels féminin.

Effects of testosterone treatment on clitoral haemodynamics in women with sexual dysfunction

ABSTRACT Introduction Preclinical studies show that, in the clitoris, testosterone (T) is necessary to maintain a functional contractile and relaxant machinery, which represents the underlying mechanism of the peripheral arousal response. Although there is clinical evidence suggesting that T treatment significantly improves multiple domains of sexual functioning, the vascularization of clitoral tissue and its regulation by sex steroids are still under-investigated. Objective To explore the effects of 6-month systemic T administration on clitoral color Doppler ultrasound (CDU) parameters in women with female sexual dysfunction (FSD). Methods 81 women with FSD were retrospectively recruited. Data on CDU parameters at baseline and after 6 months with four different treatments were available and thus further longitudinally analyzed: local non-hormonal moisturizers (NH group), n=37; transdermal 2% T gel 300 mcg/day (T group), n=23; local estrogens (E group), n=12; combined therapy (T+E group), n=9. Patients underwent physical, laboratory, and genital CDU examinations at both visits and completed different validated questionnaires, including the Female Sexual Function Index (FSFI). Results At 6-month visit, T therapy significantly increased clitoral artery peak systolic velocity (PSV) when compared to both NH (p < 0.0001) and E (p < 0.0001) groups. A similar increase was found in the T + E group (p = 0.039 vs. E) (Fig.1). In addition, T treatment was associated with significantly higher FSFI desire, pain, arousal, lubrication, orgasm and total scores at 6-month visit vs. baseline. Similar findings were observed in the T + E group. No significant differences in the variations of total and high-density lipoprotein-cholesterol, triglycerides, fasting glycemia, insulin and glycated hemoglobin levels were found among the four groups. No adverse events were observed. Conclusions In women complaining for FSD, systemic T administration, either alone or combined with local estrogens, was associated with a positive effect on clitoral blood flow and a clinical improvement in sexual function, showing a good safety profile. Disclosure Work supported by industry: no.

Cardiometabolic Diseases and Female Sexual Dysfunction: Animal Studies

BackgroundThe association between erectile dysfunction and cardiometabolic disease is well characterized; men are often diagnosed with cardiovascular disease 2–5 years following the incidence of erectile dysfunction. There is evidence that this relationship may also exist for cardiometabolic diseases and female sexual dysfunction (FSD) – particularly sexual arousal disorders. AimTo provide a summary of the preclinical literature related to the evidence of FSD in animal models of cardiometabolic diseases and indicate where further research is needed. MethodsA detailed Medline search of peer-reviewed publications was performed on the associations between animal models of cardiometabolic diseases, FSD and underlying mechanisms. OutcomesA summary of the preclinical evidence of FSD in animal models of cardiometabolic diseases. ResultsCommon methods for assessing female sexual arousal and physiology in animal models include: 1) behavioral assessments (apomorphine-induced genital vasocongestive arousal; hormone-dependent lordosis), 2) nerve-mediated vaginal and clitoral blood flow, 3) pudendal artery, vaginal and clitoral smooth muscle physiology (vasoreactivity and molecular biology), 4) morphology of genital tissues. Twenty-eight studies examined female animal models of atherosclerosis, hypertension, diabetes (type 1 and 2) and obesity. They showed functional alterations, including decreased lordosis, lubrication, or vaginal and clitoral blood flow, and structural impairments, such as increased clitoral and vaginal fibrosis. Several possible mechanisms have been described including increased TGF-β, renin angiotensin system and endothelin/rho-kinase signaling, increased reactive oxygen species, and decreased nitric oxide/cGMP signaling. Clinical TranslationIn line with existing clinical studies, preclinical evidence supports that cardiometabolic diseases alter female genital tissue's function and structure leading to impaired sexual arousal. Strengths and LimitationsThis masterclass paper gives an overview of the preclinical research assessing FSD in cardiometabolic disease. Limitations include the small number of studies that have assessed sexual function and arousal in female cardiometabolic animal models. ConclusionPreclinical evidence exists showing cardiometabolic diseases alter the structure and function of female genital tissues. However, similar to clinical studies, there are few studies to draw from, particularly in models of type 2 diabetes, obesity and metabolic syndrome. More studies are required using optimized animal models and methodology to confirm the mechanisms underlying cardiometabolic disease-induced FSD.Angulo J, Hannan JL. Cardiometabolic Diseases and Female Sexual Dysfunction: Animal Studies. J Sex Med 2022;19:408–420.

Effects of testosterone treatment on clitoral haemodynamics in women with sexual dysfunction

PurposeTo explore the effects of 6-month systemic testosterone (T) administration on clitoral color Doppler ultrasound (CDU) parameters in women with female sexual dysfunction (FSD).Methods81 women with FSD were retrospectively recruited. Data on CDU parameters at baseline and after 6 months with four different treatments were available and thus further longitudinally analyzed: local non-hormonal moisturizers (NH group), n = 37; transdermal 2% T gel 300 mcg/day (T group), n = 23; local estrogens (E group), n = 12; combined therapy (T + E group), n = 9. Patients underwent physical, laboratory, and genital CDU examinations at both visits and completed different validated questionnaires, including the Female Sexual Function Index (FSFI).ResultsAt 6-month visit, T therapy significantly increased clitoral artery peak systolic velocity (PSV) when compared to both NH (p < 0.0001) and E (p < 0.0001) groups. A similar increase was found in the T + E group (p = 0.039 vs. E). In addition, T treatment was associated with significantly higher FSFI desire, pain, arousal, lubrication, orgasm, and total scores at 6-month visit vs. baseline. Similar findings were observed in the T + E group. No significant differences in the variations of total and high-density lipoprotein-cholesterol, triglycerides, fasting glycemia, insulin and glycated hemoglobin levels were found among the four groups. No adverse events were observed.ConclusionIn women complaining for FSD, systemic T administration, either alone or combined with local estrogens, was associated with a positive effect on clitoral blood flow and a clinical improvement in sexual function, showing a good safety profile.Trial registration numberNCT04336891; date of registration: April 7, 2020.

Validation of a Sagittal Section Technique for Measuring Clitoral Blood Flow. Volume Flow: A New Parameter in Clitoral Artery Doppler

BackgroundClitoral artery Doppler has been used as an objective technique to measure changes in genital women response. However, the technique has not been fully validated, and arterial volume flow has never been used as an outcome measure. AimsTo validate the technique clitoral artery Doppler measured in a sagittal section and explore arterial volume flow as a new parameter in clitoral Doppler. MethodsWe examined 90 healthy volunteers by clitoral artery Doppler using the sagittal section approach described by Battaglia et al in 2008. We calculated intraobserver, interobserver, and intraobserver intersession variability and reliability for all Doppler parameters and described and validated arterial volume flow as a new parameter in clitoral artery Doppler. OutcomesWe calculated peak systolic velocity (PSV), time-averaged maximum velocity, time-averaged mean velocity, end-diastolic velocity, pulsatility index, resistance index, and volume flow (v-flow) in all groups. We conducted reliability analyses using the intraclass correlation coefficient for agreement. We explored differences between and within observers and calculated agreement limits using the Bland-Altman test. ResultsThe intraclass correlation coefficient analysis showed correlation values higher than 0.75 (good reliability) for most of the variables and higher than 0.60 (moderate reliability) for the remaining ones. There were statistically significant differences between PSV and time-averaged maximum velocity in the intraobserver intersession measurements. For the remaining groups and variables, no statistically significant differences were observed. Bland-Altman analyses showed that the limits of agreement were acceptable and the regressions were not significant. The v-flow parameter also showed good reliability and low variability between groups. Clinical ImplicationsWe found that PSV was not a good outcome measure because of its high intraobserver and intersession variability. Moreover, it is possible to measure v-flow in the clitoral artery using the sagittal technique described by Battaglia et al, and it seems that this measure is reliable and reproducible. This could be the best parameter to assess clinical changes. Strengths & LimitationsThis study provided full validation of the sagittal section approach and of a new parameter, v-flow, which could beuseful for assessing clitoral blood flow. The main limitation of the study is its retrospective nature for validating v-flow. ConclusionWe found that clitoral artery Doppler measured using a sagittal approach is a valid and reliable technique for studying clitoral blood flow in women. The v-flow variable is a promising and reliable parameter for measuring changes in clitoral blood flow.Pérez MF, Agís IF, La Calle Marcos P, et al. Validation of a Sagittal Section Technique for Measuring Clitoral Blood Flow: Volume Flow – A New Parameter in Clitoral Artery Doppler. J Sex Med 2020;17:1109–1117.

Ultrastructural Study of Clitoral Cavernous Tissue and Clitoral Blood Flow From Type 1 Diabetic Premenopausal Women on Phosphodiesterase-5 Inhibitor

BackgroundThe effects of phosphodiesterase-type 5 (PDE5) inhibitors on the in vivo clitoral structure of women with diabetes have never been investigated. AimTo study the in vivo structural and hemodynamic changes of the clitoris in premenopausal women with type 1 diabetes on PDE5 inhibitors. Methods38 premenopausal women with type 1 diabetes aged 36 -46 years. A randomized 1:1 study design was used: Study Group (group A) on Tadalafil 5 mg daily, and control group (group B). Blood samples were taken from each woman to measure HbA1c, testosterone, and Free Androgen Index. The women underwent microbiopsy of the clitoral body by means of semiautomatic gun during total anesthesia for surgery therapy of a benign gynecological pathology. The tissue removed was processed for electron microscopy. Translabial color Doppler ultrasound was used to measure the peak systolic velocity (PSV), the end diastolic velocity (EDV), and the pulsatility index (PI) of clitoral arteries. Main Outcome MeasuresMicro-ultrastructure observation of clitoral tissue and color Doppler sonography of clitoral blood flow. ResultsOf the 38 women, 13 (68.4%) of group A and 15 (78.9%) of group B completed the study. Group A showed a mean PSV and EDV increase, and a mean PI decrease with respect to baseline (P < .001). Group B did not show any change in both the parameters (P = NS). By a quantitative study in both groups a variable degree of ultrastructural abnormalities of smooth muscle cells (SMCs) was observed, consisting in increased glycogen and lipoic deposits, cytoplasmic vacuoles, and focal increase of electron density of SMCs. Moreover, the mean SMC thickness of group A (1.83 ± 0.68 µm) was larger than that of group B (1.3 ± 0.41 µm) (P = .02). Clinical ImplicationsPDE5 inhibitors could be used to treat diabetic women with genital arousal disorder. Strengths & LimitationsThe study shows a clear effect of PDE5 inhibitors on clitoral SMCs. However, a limit was to not have investigated the sexual function/behavior of women of both groups, this was because of the short time of the study. ConclusionThis study could help to understand in what way PDE5 inhibitors act on the ultrastructural pathophysiological clitoral cavernous tissue of women with diabetes. It could support PDE5 inhibitor usage in women with genital sexual arousal disorder due to metabolic diseases.Caruso S, Cianci A, Cianci S, et al. Ultrastructural Study of Clitoral Cavernous Tissue and Clitoral Blood Flow From Type 1 Diabetic Premenopausal Women on Phosphodiesterase-5 Inhibitor. J Sex Med 2019;16:375–382.

Clitoral Blood Flow Changes after Surgery with Tension-Free Vaginal Mesh for Pelvic Organ Prolapse.

We measured basal clitoral blood flow by Doppler sonography to determine whether tension-free vaginal mesh(TVM) affects the clitoral blood flow and sexual function in women with pelvic organ prolapse (POP). We performed a prospective study of 22 patients who underwent TVM for POP. Clitoral blood flow was measured by Doppler ultrasound. The resistance index (RI), pulsatility index (PI), peak systolic velocity (PSV), and end-diastolic velocity (EDV) of the clitoral arteries were measured preoperatively and at 1, 3, and 6 months postoperatively. Female sexual function was also investigated with the Female Sexual Function Index (FSFI). The mean PI and RI were increased at 1 month and significantly decreased at 6 months postoperatively (p<0.05). In contrast, the mean PSV and EDV decreased at 1 month postoperatively and increased at 6 months postoperatively. These four parameters recovered to baseline levels at 6 months following surgery. Total FSFI scores improved significantly from 10.2±7.9 at baseline to 18.2±8.9 at 6 months postoperatively. Color Doppler ultrasonography is potentially useful in measuring clitoral blood flow in patients treated with TVM for POP. Prospective long-term studies are needed to evaluate the utility of this modality as a diagnostic and prognostic tool for female sexual dysfunction.

Test-retest reliability of clitoral blood flow measurements using color Doppler ultrasonography at rest and after a pelvic floor contraction task in healthy adult women.

Test-retest reliability assessment of the dorsal clitoral artery's blood flow at rest and after muscle activation has never been documented. If this outcome measure is to be used in conditions impeding vascularity, it requires a psychometric evaluation. The aim of this study was to assess the inter-session test-retest reliability of clitoral blood flow in healthy women using color Doppler ultrasonography at rest and after a pelvic floor muscle (PFM) contraction task. Two assessment sessions were conducted using a clinical ultrasound system. Clitoral blood flow measurements were repeated at rest and after a PFM contraction task. Measurements of the peak systolic velocity (PSV), time-averaged maximum velocity (TAMX), end-diastolic velocity (EDV), pulsatility index (PI), and resistance index (RI) were taken. The test-retest reliability was assessed using paired t-test, intraclass correlation coefficient (ICC), and Bland-Altman plots. For reliability at rest, ICC values were 0.95 for PSV, 0.87 for TAMX, and 0.67 for both PI and RI. The variability between measurements, as per Bland-Altman plots, was small for PSV, TAMX, and RI and acceptable for PI. For reliability after the PFM contractions task, ICC values were 0.85 for PSV, 0.77 for TAMX, 0.79 for PI, and 0.81 for RI. The variability between measurements was small for PSV and RI and acceptable for TAMX and PI. EDV parameter did not perform as well in both conditions. Assessment of the clitoral blood flow with color Doppler ultrasound is reliable at rest and after a PFM contraction task.

Female sexual dysfunction in systemic sclerosis: The role of endothelial growth factor and endostatin

Since female sexual dysfunction in systemic sclerosis women is multifactorial, we can assume that vascular damage may play a role in pathogenesis. The aim of the study was to evaluate the clitoral blood flow, by Echo color Doppler, and to correlate it whit serum levels of vascular endothelial growth factor and endostatin. A total of 15 systemic sclerosis women and 10 healthy controls matched for sex and age were enrolled in this study. Serum VEGF165 and endostatin levels were determined in systemic sclerosis patients by commercial enzyme-linked immunosorbent assay kit. Clitoral blood flow was measured by Doppler indices of clitoral artery: pulsatile index, resistive index, and systolic/diastolic ratio were measured. Sexual dysfunction was assessed by Female Sexual Function Index. Vascular endothelial growth factor (pg/mL) and endostatin (ng/mL) median values were significantly higher in systemic sclerosis women than healthy controls. Resistive index and systolic/diastolic ratio median values were significantly higher in systemic sclerosis women than healthy controls. Negative correlation exists between serum levels of vascular endothelial growth factor and resistive index (r = -0.55, p < 0.05). Positive correlation was observed between serum levels of endostatin and resistive index (r = 0.70, p < 0.01) and systolic/diastolic ratio (r = 0.77, p < 0.01). We can suppose that clitoral blood flow in systemic sclerosis women is reduced not only for macro- and microvascular damage but also for impaired angiogenesis.

Randomized crossover study investigating daily versus on-demand vulvar Visnadine spray in women affected by female sexual arousal disorder

The aim of the study was to verify the efficacy of vulvar Visnadine spray in premenopausal women affected by female sexual arousal disorder (FSAD). Thirty-eight women aged 25–40 years affected by FSAD were enrolled in the randomized crossover study, by two possible sequences: on-demand, washout, daily (A sequence); and daily, washout, on-demand (B sequence). The Female Sexual Function Index (FSFI) and the Female Sexual Distress Scale (FSDS) were used to assess sexual function and sexual distress, respectively. Color Doppler ultrasonography was used to measure clitoral blood flow. The study had two follow-ups at 30 (T1) and 60 days (T2). Thirty-one women completed the study. Mean (SD) sexual activity and vulvar Visnadine spray usage was 1 ± 0.9 weekly during on-demand administration for both the sequences (Vs T0, p = NS). The mean sexual activity during daily usage was 2 ± 0.9 (Vs T0, p < .004) and 2 ± 0.8 (Vs T0, p < .001) for A and B sequences, respectively. FSFI total score, particularly genital arousal, improved more during the daily than during on-demand phases of both sequences (p < .001). Finally, clitoral blood flow improved significantly during daily usage of both the sequences (p < .001). Our study suggests that vulvar Visnadine spray could improve sexual performance of women affected by FSAD, producing changes in subjective and objective sexual aspects.

Biocompatible porcine dermis graft to treat severe cystocele: impact on quality of life and sexuality.

To study the quality of life (QoL) and sexual function changes of women affected by severe cystocele treated using biocompatible porcine dermis graft. 20 women (ranging in age from 47 to 71 years, mean age 58.7) with third- and fourth-degree cystocele (according to Baden and Walker classification) were enrolled. The Short Form-36 questionnaire to assess QoL was administrated at baseline and 12 months after surgical treatment. The Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12) to measure the changes of sexual behavior was used at baseline and 12 months after surgical treatment. Each woman underwent translabial color Doppler ultrasonography to measure the clitoral blood flow before and 12 months after surgical treatment. Women reported QoL improvement (P < 0.001). By PISQ-12, improvement of the behavioral emotive factor score, the physical factor score, the partner-related factor score and of the total score during the 12-month follow-up with respect to baseline experience was observed (P < 0.001). Color Doppler measurement showed that the mean pulsatility index, peak systolic velocity, resistance index and end-diastolic velocity of clitoral arteries did not significantly change (P = NS). Biocompatible porcine dermis graft to treat severe cystocele considerably improves QoL and sexual function, and does not influence clitoral blood flow. Our data could add new information about sexual behavior after prolapse treatment using this kind of graft, particularly about the impact on clitoral blood flow changes.

The role of regulatory proteins and S-nitrosylation of endothelial nitric oxide synthase in the human clitoris: implications for female sexual function.

During female sexual arousal, clitoral blood flow is controlled by endothelial nitric oxide synthase (eNOS) and its product, nitric oxide (NO). The mechanisms regulating eNOS activity and NO bioavailability in the clitoris are largely unknown. To identify proteins involved in regulation of eNOS activity within the clitoris and to evaluate the effects of S-nitrosoglutathione reductase (GSNO-R) and eNOS nitrosylation/denitrosylation on clitoral blood flow. Immunohistochemistry for eNOS, caveolin-1 (Cav1), heat shock protein-90 (Hsp90), phosphodiesterase type 5 (PDE5), GSNO-R, and soluble guanylate cyclase (sGC) was performed on human and murine clitoral tissue. Western blot analysis was performed for eNOS, phosphorylated eNOS (phospho-eNOS, Ser1177), Cav1, Hsp90, sGC, PDE5, phosphoinositide 3-kinase (PI3K), Akt (protein kinase B), and GSNO-R on protein from human clitoral tissue. A biotin switch assay was used to analyze the S-nitrosylation of eNOS, nNOS, and GSNO-R. Clitoral blood flow was measured in wild-type and GSNO-R(-/-) mice at baseline and during cavernous nerve electrical stimulation (CNES). Localization of eNOS regulatory proteins and clitoral blood flow. eNOS and GSNO-R co-localized to the vascular endothelium and sinusoids of human clitoral tissue. Immunohistochemistry also localized Cav1 and Hsp90 to the endothelium and PDE5 and sGC to the trabecular smooth muscle. Expression of S-nitrosylated (SNO)-eNOS and SNO-GSNO-R was detected by biotin switch assays. Wild-type control mice exhibited increased clitoral blood flow with CNES whereas GSNO-R(-/-) animals failed to show an increase in blood flow. Several key eNOS regulatory proteins are present in the clitoral tissue in a cellular specific pattern. S-nitrosylation of eNOS may also represent a key regulatory mechanism governing eNOS activation/deactivation since mice deficient in GSNO-R failed to increase clitoral blood flow. Additional studies are necessary to define the role of S-nitrosylation in the genital vascular response and its subsequent impact on female sexual function.

Inhibition of Phosphodiesterase 4 Enhances Clitoral and Vaginal Blood Flow Responses to Dorsal Clitoral Nerve Stimulation or PGE1 in Anesthetized Female Rats

Inhibition of Phosphodiesterase 4 Enhances Clitoral and Vaginal Blood Flow Responses to Dorsal Clitoral Nerve Stimulation or PGE1 in Anesthetized Female Rats

Clitoral blood flow in systemic sclerosis women: correlation with disease clinical variables and female sexual dysfunction

The objectives of this study were to investigate clitoral blood flow in SSc women compared with healthy controls and to correlate it with microvascular damage and disease clinical variables. We also evaluated the correlation between clitoral blood flow and sexual dysfunction. Twenty-two SSc women and 20 healthy controls matched for sex and age were enrolled in this study. Baseline Doppler indices of the clitoral artery were measured. Peak systolic velocity, end diastolic velocity, resistive index (RI), pulsatile index (PI) and systolic/diastolic (S/D) ratio were measured. The female sexual function index (FSFI) was used to assess sexual function. The RI and S/D ratio were higher (P < 0.0001) in SSc women compared with healthy controls. The PI, RI and S/D ratio increased with progression of capillaroscopic damage. The RI and S/D ratio were higher (P < 0.01) in women with digital ulcers than in women without digital ulcers. No correlation exists between Doppler indices of the clitoral artery and age or clinical variables of disease. The FSFI was reduced in 7 (32%) of 22 SSc women. A negative correlation was observed between both the FSFI and RI (R = -0.74, P < 0.0001) and the S/D ratio (R = -0.68, P < 0.0001). A negative correlation exists between the RI and all domains of the FSFI score except for desire. Clitoral blood flow was reduced in SSc women compared with healthy controls. Clitoral blood flow was reduced in SSc women with digital ulcers and it correlated with capillaroscopic damage progression. A negative correlation exists between the RI and S/D ratio and all domains of the FSFI score except for desire.

Inhibition of Phosphodiesterase 4 Enhances Clitoral and Vaginal Blood Flow Responses to Dorsal Clitoral Nerve Stimulation or PGE1 in Anesthetized Female Rats

INTRODUCTION.: Cyclic adenosine 3'5' monophosphate (cAMP) is produced by adenylate cyclase after activation by, e.g., vasoactive intestinal polypeptide or prostaglandin E1 (PGE1). The cAMP-degrading phosphodiesterase 4 (PDE4) is expressed in the vagina and clitoris, but no information is available on the functional role for PDE4-related signals in the female neurovascular genital response. AIM.: The aim of this study is to study the effect of inhibition of PDE4 with rolipram on nerve- and PGE1-induced vaginal and clitoral blood flow responses of rat. METHODS.: Measure of clitoral and vaginal blood flow and blood pressure in anesthetized rats during activation of the dorsal clitoral nerve (DCN) before and after intraperitoneal administration of rolipram or sildenafil (phosphodiesterase type 5 inhibitors [PDE5]) and nitro-L-arginine (L-NNA) (nitric oxide synthase inhibitor). Effect by topical administration of PGE1 on genital blood flow was also evaluated. MAIN OUTCOME MEASURE.: Blood flow was recorded as tissue perfusion units (TPU) by a Laser Doppler Flowmeter. Mean arterial blood pressure (MAP) was recorded (cmH2 O) in the carotid artery. Blood flow responses are expressed as TPU/MAP. Unpaired t-test and an analysis of variance were used. RESULTS.: Compared with control stimulations, rolipram (0.3 mg/kg) caused a twofold increase in peak blood flow (P < 0.05) and fourfold increase of the rate of clitoral blood flow during activation of the DCN (P < 0.05). Simultaneously, a twofold increase in peak blood flow and threefold increase in rate of blood flow were noted in the vagina (P < 0.05). Similar effects were noted for sildenafil (0.2 mg/kg) (P < 0.05). Inhibitory effects by L-NNA (60 mg/kg) on blood flow responses to DCN activation were significantly lower for rats treated with rolipram than with sildenafil (P < 0.05). PGE1-induced (10 μg) blood flow responses were significantly higher (P < 0.05) in rats treated with rolipram than with sildenafil. CONCLUSIONS.: These findings suggest that the cAMP/PDE4 system may be of similar functional importance as the nitric oxide/cyclic guanosine monophosphate/PDE5 pathway for neurovascular genital responses of the female rat.