Neurovascular anatomy of the developing human fetal penis and clitoris.

The human penile and clitoral development begins from a morphologically indifferent genital tubercle. Under the influence of androgen, the genital tubercle forms the penis by forming a tubular urethra within the penile shaft. Without the effect of the androgen, the genital tubercle differentiates into the clitoris, and a lack of formation of the urethra within the clitoris is observed. Even though there are similarities during the development of the glans penis and glans clitoris, the complex canalization occurring along the penile shaft eventually leads to a morphological difference between the penis and clitoris. Based on the morphological differences, the main goal of this study was to define the vascular and neuronal anatomy of the developing penis and clitoris between 8 and 12 weeks of gestation using laser scanning confocal microscopy. Our results demonstrated there is a co-expression of CD31, which is an endothelial cell marker, and PGP9.5, which is a neuronal marker in the penis where the fusion is actively occurring at the ventral shaft. We also identified a unique anatomical structure for the first time, the clitoral ridge, which is a fetal structure running along the clitoral shaft in the vestibular groove. Contrary to previous anatomical findings which indicate that the neurovascular distribution in the developing penis and clitoris is similar, in this study, laser scanning confocal microscopy enabled us to demonstrate finer differences in the neurovascular anatomy between the penis and clitoris.

Increased clitoral artery pulsatility index and decreased sexual desire level in women with polycystic ovary syndrome.

OBJECTIVES: Polycystic ovary syndrome (PCOS) is claimed to effect the sexual desire, and recently, blood flow in the clitoral artery (CA) was measured by Doppler ultrasound (USG) examination and the level of sexual desire was objectively demonstrated by determining the pulsatility index (PI). In the present study, it was aimed to quantitatively determine the sexual desire levels in women with PCOS using Doppler USG and to compare the data with healthy women. MATERIAL AND METHODS: The study included 71 patients diagnosed with PCOS and 78 healthy women who applied to our tertiary hospital gynecology clinics and for control purposes. Pulsatility indices were determined by measuring blood flows in the clitoral artery, uterine artery, ovarian artery and labial artery using Doppler USG in all participants. The clitoral artery pulsatility index was found to be increased significantly in women with PCOS. RESULTS: The mean age was 28.5 ± 3.7 in the polycystic ovary syndrome group and 30.0 ± 5.2 in the control group. The mean clitoral artery pulsatility index (1.4 ± 0.5 cm/sec) in the PCOS group was significantly higher than the control group (1.2 ± 0.4 cm/sec) (p = 0.033 cm/sec).The mean ovarian artery pulsatility index (0.8 ± 0.2 cm/sec) in the PCOS group was also significantly higher than the control group (0.7 ± 0.2 cm/sec) (p = 0.015 cm/sec). PCOS is showed to influence sexual desire with an objective measurement. Since trying to obtain objective data about the level of sexual desire, questionnaires were not applied to the participants and no questions were asked. CONCLUSIONS: In our study, it was found that the clitoral artery pulsatility index, that is, the rate of resistance in the blood flow to the clitoral region, increased significantly in women with PCOS. This finding shows that the level of sexual desire in women with PCOS has decreased compared to healthy women.

Cardiometabolic risk is unraveled by color Doppler ultrasound of the clitoral and uterine arteries in women consulting for sexual symptoms.

Female sexual dysfunction (FSD) may be a mirror of a poor cardiometabolic state. In a small pilot study enrolling 71 women with FSD, we previously demonstrated that clitoral Pulsatility Index (PI) evaluated by using color Doppler ultrasound (CDU), reflecting vascular resistance, was associated with cardiometabolic risk factors. Data on uterine CDU in this context are lacking. First, to confirm previously reported data on the direct association between clitoral PI and cardiometabolic risk factors on a larger study population of women consulting for sexual symptoms; second, to investigate eventual similar correlations between cardiometabolic risk factors and CDU parameters of the uterine artery. We also ascertained whether uterine artery PI, similarly to what had previously been observed for clitoral artery PI, was directly related to body image uneasiness and psychopathological symptoms, assessed by validated questionnaires. N = 230 women consulting our clinic for sexual symptoms were examined with clitoral CDU and blood sampling and were asked to fill out the Female Sexual Function Index, the Middlesex Hospital Questionnaire (MHQ) and the Body Uneasiness Test (BUT). In a subgroup of women (n = 164), we also performed transvaginal CDU with measurement of uterine artery parameters. At multivariate analysis, we found a direct association between clitoral PI and body mass index (BMI) (p = 0.004), waist circumference (WC) (p = 0.004), triglycerides (p = 0.006), insulin (p = 0.029) and HOMA-IR (p = 0.009). Furthermore, a correlation between obesity and Metabolic Syndrome (MetS) and a higher clitoral PI was observed (p = 0.003 and p = 0.012, respectively). Clitoral PI was also correlated with MHQ-S (p = 0.010), a scale exploring somatized anxiety symptoms, and BUT-B Positive Symptom Distress Index (p = 0.010), a measure of body image concerns. Similarly, when investigating the uterine artery, we were able to demonstrate an association between its PI and BMI (p < 0.0001), WC (p = 0.001), insulin (p = 0.006), glycated haemoglobin (p = < 0.0001), and HOMA-IR (p = 0.009). Women diagnosed with obesity and MetS showed significantly higher uterine PI values vs. those without obesity or MetS (p = 0.001 and p = 0.004, respectively). Finally, uterine PI was associated with BUT-A Global Severity Index (p < 0.0001) and with several other BUT-A subdomains. Vascular resistance of clitoral and uterine arteries is associated with cardiometabolic risk factors and body image concerns in women consulting for sexual symptoms. If further confirmed in different populations, our data could suggest CDU, a common examination method, as a useful tool for an identification-and possible correction-of cardiometabolic risk factors.

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

PURPOSE: To explore the effects of 6-month systemic testosterone (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). 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. CONCLUSION: 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. TRIAL REGISTRATION NUMBER: NCT04336891; date of registration: April 7, 2020.

Association between clitoral tissue perfusion and female sexual dysfunction in healthy women of reproductive age: a pilot study.

The impact of abnormalities in the vascular bed of the external genitalia and vagina on female sexuality is not well defined because of some methodological difficulties in correctly assessing vascular changes of genitalia in women. Transmucosal oxygen tension (TmPO2) represents a precise measure of oxygen partial pressure at the clitoris surface and is expression of clitoral tissue perfusion. Aim of the study was to correlate TmPO2 with female sexual dysfunction (FSD) in healthy women in order to evaluate the impact of clitoral vascularization on female sexual health. Twenty-seven healthy, heterosexual, and sexually active women of reproductive age (mean age: 31.18 ± 4.71) were enrolled in the study. TmPO2 was assessed in every woman. In addition, all the women filled out the Female sexual function index (FSFI). After adjustment for some covariates (age, BMI, and smoking), TmPO2 significantly correlated with FSFI total score (r = 0.4261; p = 0.0379) and with arousal (r = 0.3239; p = 0.0390), lubrication (r = 0.4345; p = 0.0339), orgasm (r = 0.4092; p = 0.0471), and satisfaction (r = 0.4456; p = 0.0291) scores. In addition, TmPO2 was significantly lower in the FSD than in the NO FSD group (28.4 ± 14.5 versus 48.1 ± 25.1 mmHg; p = 0.0416). This study first shows that in healthy women of reproductive age clitoral tissue perfusion, as assessed by TmPO2, correlates very well with FSD and in particular with arousal, lubrication, orgasm, and satisfaction. Further studies should confirm our data and test TmPO2 as potential predictor for cardiovascular disease and metabolic conditions in women.

Nomegestrol acetate/17beta-estradiol does not negatively alter the vascular resistance of clitoral arteries: a prospective, exploratory study.

The effect of nomegestrol acetate/estradiol (NOMAC/E2) on clitoral and uterine vascularization has never been evaluated. We aimed to investigate, in women consulting for contraceptive needs, the possible changes in clitoral and uterine arteries hemodynamic parameters after 6 months treatment with NOMAC/E2 as compared with other hormonal contraceptives (HCs). In this observational, prospective pilot study, ten women were enrolled. Color Doppler ultrasound was performed on the clitoral and uterine arteries at baseline and after 6 months treatment with NOMAC/E2 (n = 5) or other HCs (n = 5). NOMAC/E2 did not exert any significant effect on clitoral vascular resistance expressed by the pulsatility index (PI); conversely, treatment with other HCs significantly increased this parameter (p = 0.04). The change in clitoral PI between the two groups retained a statistically significant difference even after adjusting for age. In the NOMAC/E2 group, at follow-up, uterine artery PI and acceleration were significantly reduced (p = 0.04), whereas no significant differences were observed in the HCs group; however, the change in uterine artery parameters did not differ significantly between the two groups. NOMAC/E2, differently from other COCs, does not negatively alter the vascular resistance of clitoral arteries and appears as a good contraceptive choice to protect both cardiovascular and sexual health.

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.

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

BACKGROUND: The effects of phosphodiesterase-type 5 (PDE5) inhibitors on the in vivo clitoral structure of women with diabetes have never been investigated. AIM: To study the in vivo structural and hemodynamic changes of the clitoris in premenopausal women with type 1 diabetes on PDE5 inhibitors. METHODS: 38 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 MEASURES: Micro-ultrastructure observation of clitoral tissue and color Doppler sonography of clitoral blood flow. RESULTS: Of 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 IMPLICATIONS: PDE5 inhibitors could be used to treat diabetic women with genital arousal disorder. STRENGTHS & LIMITATIONS: The 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. CONCLUSION: This 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.

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.

AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Assessment of the clitoral blood flow with color Doppler ultrasound is reliable at rest and after a PFM contraction task.

Morphometric and Vascular Modifications of the Clitoris During Pregnancy: A Longitudinal, Pilot Study.

During pregnancy, women go through a series of physical and emotional changes that may have an impact on their sexuality. The aim of the study was to examine modifications in sexual function during pregnancy by means of translabial ultrasonography and administration of questionnaires on sexual activity. Eighteen healthy and adult (25-35 years) pregnant women without sexual dysfunction and with a stable heterosexual relationship were examined at 10-12, 18-20, and 30-32 weeks of gestation. Patients underwent ultrasonographic translabial clitoral volume and labia minora thickness measurements and color Doppler assessment of the dorsal clitoral and posterior labial arteries. On the same day, each patient completed the two-factor Italian McCoy Female Questionnaire (MFSQ) and the Female Sexual Function Index (FSFI). The mean clitoral body volume progressively increased during pregnancy, and color Doppler analysis of the dorsal clitoral artery showed a significant decrease in the pulsatility index from the first to the third trimester. Similarly, the labia minora thickness increased and the posterior labial artery pulsatility index progressively decreased throughout gestation. The MFSQ score for sexuality and partnership and the number of intercourses/week did not significantly change during the study period. However, the MFSQ score for partnership reached the lowest value in the third trimester of pregnancy. Analysis of the FSFI data showed no significant differences throughout pregnancy for the majority of the domains (sexual desire, arousal, orgasm, lubrication, and pain), with the exception of the satisfaction item, which decreased during the third trimester. A significant proportion of women are concerned that changes in their body during pregnancy may have a detrimental effect on sexuality. Despite significant changes in genital morphology and vascularity throughout gestation, these modifications do not seem to have an impact on sexual function in pregnancy.

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.

Does ligation of internal iliac artery for postpartum hemorrhage affect clitoral artery blood flow and postpartum sexual functions?

OBJECTIVE: To investigate whether internal iliac artery ligation (IIAL) for postpartum hemorrhage (PPH) affects the sexual life in the postpartum period or significantly reduces the clitoral artery blood flow. STUDY DESIGN: The women who underwent IIAL due to PPH during cesarean section (CS) were compared with healthy postpartum women delivered by CS between October 2014 and February 2016 in the Gaziantep Women's Health and Maternity Hospital, Gaziantep, Turkey. Clitoral Doppler flow measurements and the Female Sexual Function Index questionnaire (FSFIQ) were performed in all women in the 3rd and 6th postpartum months. This study was registered at ClinicalTrials.gov with the identification number NCT02409602. RESULTS: Mean age, gravidity and parity, body mass index (BMI), first sexual intercourse after childbirth, and education years were similar in both groups. There was no statistically significant difference in the measurements of RI, PI, PSV, EDV, and S/D between the study and control groups in the 3rd month. Lack of statistical significance was also noted between the study and control groups values in the 6th month, as well as between the 3rd and 6th month's values within both the study group and the control group. Additionally, there were no statistically significant differences in the total FSFI scores including sexual desire, sexual arousal, lubrication, orgasm, sexual satisfaction, and pain domain scores between the study and control groups in the 3rd month; between the study and control groups 6th months; whereas all scores were higher in the 6th month compared to the 3rd month within each group. CONCLUSION: IIAL does not affect the blood flow of the dorsal clitoral artery between the 3rd and 6th months postpartum and between the women who underwent IIAL due to PPH and healthy postpartum women. The sexual function scores were significantly higher in the 6th month compared to the 3rd month in both groups.

The sexuological impact of hormonal contraceptives based on their route of administration.

Evidence on the effects of hormonal contraceptives on female sexuality is conflicting. We enrolled 556 women, divided into six groups: two composed of subjects using a combined hormonal contraceptive (COC) containing 0.020 ("COC20") and 0.030 ("COC30") mg of ethynyl estradiol (EE), "natural", using COC containing 1.5 mg of estradiol (E2), "ring", using a vaginal ring releasing each day 0.015 mg of EE + 0.120 of etonogestrel, "subcutaneous", using a progestin only subcutaneous contraceptive implant releasing etonogestrel and "controls", using no hormonal contraceptive methods. The subjects were required to answer to the McCoy female sexuality questionnaire and were subjected to a blood test for hormonal evaluation. An ultrasound evaluation of the dorsal clitoral artery was also performed. The higher McCoy sexological value were recorded in the subdermal group; significant differences were recorded among the groups in terms of hormone distribution, with the higher levels of androstenedione in subdermal and control groups. The ultrasound evaluation of dorsal clitoral artery shows a significative correlation between pulsatility and resistance indices and orgasm parameters of McCoy questionnaire. The recorded difference in the sexual and hormonal parameters among the studied hormonal contraceptives may guide toward the personalization of contraceptive choice.

The Impact of a Topical Sexual Enhancement Cream on the Female Sexual Response and Its Relationship to Clitoral Blood Flow.

OBJECTIVE: The aim of this investigation was to determine, through two Investigational Review Board (IRB)-approved studies, if a new topical vasodilating cream (NTVC; Life Science Enhancement Corporation, Pittsburgh PA) could improve female sexual response. Study I subjectively evaluated sexual female response as accessed by a modification of the Female Intervention Efficacy Index (FIEI). FIEI was developed at the University of California as an immediate outcome measure of medical intervention to treat female sexual dysfunction.1 In Study II, 10 randomly selected positive responders from Study I were subsequently analyzed objectively with clitoral plethysmography in order to determine the effect of the NTVC and placebo on blood flow.2 RESULTS: In the subjective Study I (81 patients ranging in age from 18 to 63), a positive response trend for the NTVC was demonstrated compared to the placebo. In the objective Study II, 10 randomly selected patients who responded positive in Study I were objectively evaluated for response of increased blood flow in the clitoris after application of both the NTVC and placebo. The clitoral blood flow was shown to have increased with statistical significance for the NTVC in all 10 patients compared to the placebo, with the NTVC exhibiting an average 69% increase in clitoral blood flow. CONCLUSIONS: The female sexual response is complex. In the subjective Study I, the NTVC demonstrated positive trends for enhanced lubrication, genital sensation, intercourse, and overall sexual experience. In the objective Study II, 10 of the positive subjective responders from Study I were randomly selected to evaluate their response to the NTVC compared to the placebo. This was done via Doppler plethysmography (DP). All 10 patients demonstrated a statistically significant response rate for increase in clitoral blood flow using the NTVC compared to the placebo, with an average blood flow increase of 69%. This portion of the investigation demonstrates a significant positive end organ response to the NTVC. The positive subjective trends combined with the significant and substantial increase in clitoral blood flow may result in enhanced female sexual satisfaction.

Cardiometabolic Risk and Female Sexuality: Focus on Clitoral Vascular Resistance.

INTRODUCTION: The relation between sexual and cardiovascular health in women is not well defined. Clitoral color Doppler ultrasound (CDU) with assessment of the pulsatility index (PI), reflecting resistance to blood flow, has been proposed as an objective measurement of sexual functioning. AIM: To investigate associations between clitoral PI and cardiometabolic risk factors, sexual and intrapsychic parameters, and self-perception of body image. METHODS: Seventy-one adult heterosexual women in a stable relationship attending our clinic for sexual dysfunction were consecutively recruited. MAIN OUTCOME MEASURES: Patients underwent physical, laboratory, and clitoral color Doppler ultrasound examinations and completed the Female Sexual Function Index, the Middlesex Hospital Questionnaire, and the Body Uneasiness Test (BUT). RESULTS: Clitoral PI was positively correlated with body mass index (r = 0.441, P < .0001), waist circumference (r = 0.474, P < .0001), glycemia (r = 0.300, P = .029), insulin (r = 0.628, P = .002), homeostatic model assessment index (r = 0.605, P = .005), triglycerides (r = 0.340, P = .011), total cholesterol (r = 0.346, P = .010), and low-density lipoprotein cholesterol (r = 0.334, P = .016). All relations, with the exception of glycemia, retained statistical significance after adjusting for age, smoking habit, and years since menopause (P < .0001 for body mass index, waist circumference, and triglycerides; P < .05 for all other associations). Analysis of covariance, after adjusting for confounders, showed that women with obesity or metabolic syndrome (MetS) showed significantly higher PI values (obesity: F = 17.79, P = .001; MetS: F = 7.37, P = .019). In particular, a stepwise increase of PI was found as a function of increasing MetS components (ß = 0.434, P = .007). Clitoral PI was negatively associated with Female Sexual Function Index arousal (ß = -0.321, P = .014) and satisfaction (ß = -0.289, P = .026) scores and positively associated with Middlesex Hospital Questionnaire somatized anxiety symptoms, even after adjusting for age, smoking habit, years since menopause, and current use of psychiatric medication (ß = 0.354, P = .011). A positive association also was observed between PI and the BUT positive symptom distress index (ß = 0.322, P = .039) and BUT for dislike of the womb, genitals, and breast (ß = 0.538, P < .0001; ß = 0.642, P < .0001; ß = 0.549, P < .0001, respectively). After introducing waist circumference as another covariate, the associations between clitoral PI and the BUT positive symptom distress index and BUT dislike of the womb, genitals, and breast retained statistical significance (P = .038 for positive symptom distress index; P < .0001 for dislike of womb, genitals, and breast). CONCLUSION: Clitoral vascular resistance is positively associated with MetS (in particular insulin resistance), decreased sexual arousal, body image concerns, and increased somatized anxiety symptoms. Further studies are needed to establish whether treatment of metabolic abnormalities might improve clitoral color Doppler ultrasound indices and sexual outcomes.

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

PURPOSE: To study the quality of life (QoL) and sexual function changes of women affected by severe cystocele treated using biocompatible porcine dermis graft. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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 Clitoral Photoplethysmograph: A Pilot Study Examining Discriminant and Convergent Validity.

INTRODUCTION: The clitoral photoplethysmograph (CPP) is a relatively new device used to measure changes in clitoral blood volume (CBV); however, its construct validity has not yet been evaluated. AIM: To evaluate the discriminant and convergent validity of the CPP. For discriminant validity, CBV responses should differ between sexual and nonsexual emotional films if the CPP accurately assesses clitoral vasocongestion associated with sexual arousal; for convergent validity, CBV responses should significantly correlate with subjective reports of sexual arousal. METHODS: Twenty women (M age = 21.2 years, SD = 3.4) watched neutral, anxiety-inducing, exhilarating, and sexual (female-male sex) audiovisual stimuli while their genital responses were measured simultaneously using vaginal and clitoral photoplethysmographs and CPPs. Most of these participants continuously reported sexual arousal throughout each stimulus (n = 16), and all reported their sexual and nonsexual affect before and after each stimulus; subjective responses were recorded via button presses using a keypad. MAIN OUTCOME MEASURES: Vaginal pulse amplitude (VPA), CBV, and self-reported sexual arousal and nonsexual affect were used as main outcome measures. RESULTS: CBV demonstrated both discriminant and convergent validity. CBV responses were similar to VPA responses and self-reported sexual arousal; all responses differed significantly as a function of stimulus content, with the sexual stimulus eliciting greater relative changes than nonsexual stimuli. CBV, but not VPA, was significantly (negatively) correlated with continuous self-reported sexual arousal during the shorter sexual stimulus. CBV was significantly negatively correlated with VPA for the shorter sexual stimulus. CONCLUSION: CBV may be a valid measure of women's genital sexual arousal that provides complementary information to VPA and correlates with self-reported sexual arousal. Given our relatively small sample size, and that this is among the first research to use the CPP, the current findings must be replicated. More research using the CPP and other devices is required for a more comprehensive description of women's physiological sexual arousal.

Hair-thread tourniquet syndrome of the hypertrophic clitoris in a 6-year-old girl.

Hair-thread tourniquet syndrome is defined as the ischemic strangulation of hair resulting in edema and severe pain and may cause amputation of organs. Strangulation of the external genitalia (clitoris, labia minora) has rarely been described in girls. Here, we present a case of hypertrophic clitoris injury secondary to hair strangulation in a 6-year-old girl.

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

INTRODUCTION: 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. AIM: 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. METHODS: 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). MAIN OUTCOME MEASURES: Localization of eNOS regulatory proteins and clitoral blood flow. RESULTS: 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. CONCLUSIONS: 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.