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.

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.

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.

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.

Body imaging and sexual behavior in lean women with polycystic ovary syndrome.

INTRODUCTION: In women with polycystic ovary syndrome (PCOS), changes in body appearance may influence the feminine identity of the patients with possible consequent depression and sexual dysfunction. AIM: The study aims to examine the differences in mood, perceived body image, sexual behavior, and clitoral vascularization between lean PCOS patients and healthy eumenorrheic controls. METHODS: Thirty-three lean PCOS women (Group I) and 22 healthy nonhirsute volunteers (Group II) were submitted, on day 3-5 of the cycle, to ultrasonographic (US) and Doppler analyses, to clinical, hormonal, and biochemical evaluations, and to psychometric tests. MAIN OUTCOMES MEASURES: Main outcome measures are Ferriman-Gallwey score (FG), clitoral volume, clitoral artery Pulsatility Index, the two-factor Italian McCoy female questionnaire (MFSQ), the Stunkard Figure Rating Scale (FRS), and the Beck Depression Inventory (BDI) questionnaire. RESULTS: The FG score and the androgens resulted, as expected, more elevated in PCOS patients than in controls. However, the US assessment of the clitoral body volume and the resistances registered at the level of the dorsal clitoral artery did not show any difference between Group I and Group II patients. Moreover, the two-factor Italian MFSQ, the FRS, and the BDI were similar in both groups. CONCLUSIONS: It seems that in lean PCOS women, the moderate hirsutism and hyperandrogenism do not have any important influence on body image and self-esteem and, as a consequence, on sexual function.

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.

Urethral sphincter innervation and clitoral blood flow after the transobturator (TOT) approach.

INTRODUCTION AND HYPOTHESIS: The aim of the study was to exclude neurovascular damage due to prosthetic mini-invasive surgery using transobturator tape (TOT) by pre- and postoperative electromyography (EMG) of the striated urethral sphincter and a color Doppler ultrasonography evaluation of clitoral blood flow. METHODS: A total of 25 women affected by clinical stress urinary incontinence (SUI) were enrolled. After undergoing urodynamic assessment, pelvic organ prolapse quantification, urine culture, Q-tip test, and stress test, each subject underwent color Doppler ultrasonography to record clitoral blood flow and EMG of the urethral sphincter with a needle electrode inserted through the mucosa into the muscle tissue before surgery. A single urogynecologist performed the TOT surgical technique for the treatment of all patients. Urogynecologic examination, EMG, and color Doppler ultrasound follow-up were performed at 1 and 6 months after surgery. RESULTS: At the urogynecologic examination performed 1 and 6 months after the TOT approach the stress test was negative, urethral hypermobility was reduced, and sling exposure was not observed for each patient. There was no statistically significant difference in electromyographic values (p > 0.05) in both the follow-ups with regard to baseline values. Pulsatility index (PI), resistance index (RI), and peak systolic velocity (PSV) values increased during the first follow-up (p < 0.01); PI and RI values increased during the second follow-up with respect to baseline values (p < 0.01) CONCLUSIONS: TOT prosthesis surgery, avoiding denervation and devascularization of pelvic structures, does not damage the urethral sphincter.

Vascular hamartoma: an unusual cause of clitoromegaly in an 18-year-old patient.

OBJECTIVE: Clitoromegaly encountered in clinical practice is more commonly due to endocrinopathies either congenital or acquired. However, acquired clitoromegaly due to a nonhormonal cause is quite rare. The authors report a case of nonhormonal-acquired clitoromegaly in a woman. MATERIALS AND METHODS: This is a case report of an 18-year-old patient with slowly increasing swelling in the vulval area for the past 6 months. Clinical examination revealed an enlarged, soft, nontender clitoris (4 × 2.5 cm), with a lobulated surface. RESULTS: Frozen section from clitoral mass showed a benign tumor. Surgical excision of the mass was carried out, preserving the glans. Histopathologic examination of the excised mass showed congested blood vessels and fibromuscular tissue with free nerve endings suggestive of vascular hamartoma of clitoris. CONCLUSIONS: The correct diagnosis of clitoromegaly is essential so that suitable therapy is instituted. Thus, management of such cases needs a good clinical judgment and a judicious individualization of management protocols.

Preservation of genital innervation in women during total mesorectal excision: which anterior plane?

BACKGROUND: Erectile dysfunction, principally related to injury of the autonomic nerve fibers in men, is a major cause of postoperative morbidity after anterolateral dissection during total mesorectal excision (TME) for rectal adenocarcinoma. However, the autonomic innervation of erectile bodies is less known in women, and the anterolateral plane of dissection during TME remains unclear. The existence of the rectovaginal septum(RVS) is controversial. The purpose of the present study was to identify the RVS in the human fetus and adult female by dissection, immunohistochemistry, and three-dimensional reconstruction, and to define its relationship with erectile nerve fibers so as to determine the anterolateral plane of dissection during TME, which could reduce postoperative sexual dysfunction in women. METHOD: Macroscopic dissection, histologic studies, and immunohistochemistry examination with 3D reconstruction were performed in six fresh female adult cadavers and six female fetuses. RESULTS: The RVS was clearly definable in all adult specimens. It was composed of multiple connective tissue, with smooth muscle fibers originating from the uterus and the vagina. It is closely applied to the vagina and has a relationship with the neurovascular bundles (NVBs) that contain erectile fibers intended for the clitoris. The NVBs are situated anteriorly to the posterior extension of rectovaginal septum. This posterior extension protects the NVBs during the anterior and anterolateral dissection for removal of rectal cancer. CONCLUSIONS: To reduce the risk of postoperative sexual dysfunction in women undergoing TME for rectal cancer, we recommend careful dissection to the anterior mesorectum to develop a plane of dissection behind the posterior extension of the RVS if oncologically reasonable.

Cigarette smoking decreases the genital vascularization in young healthy, eumenorrheic women.

INTRODUCTION: Cigarette smoking is a major health hazard and may impair the normal sexual response. AIM: To evaluate (in the early follicular phase, and independently from sexual stimulation) in young, eumenorrheic, healthy, lean women the general and genital vascular effects of the smoking habit. METHODS: One hundred thirty-seven patients undertook, in the early follicular phase of the menstrual cycle (day 3-5): the administration of the two-factor Italian McCoy Female Sexuality Questionnaire (MFSQ); two-dimensional (2-D) color Doppler evaluation of the ophthalmic, carotid, uterine, clitoral, and labia minora arteries; three-dimensional (3-D) analysis of clitoral and labia minora vascularization; and blood pressure evaluation. Fasting blood samples were drawn to test plasma estradiol, androstenedione, and testosterone circulating levels. MAIN OUTCOME MEASURES: The two-factor Italian MFSQ; the pulsatility index (PI) of internal carotid, ophthalmic, uterine, clitoral, and labia minora arteries; the vascularization index (VI), the flow index (FI), and the vascularization flow index (VFI) of clitoral body and labia minora, blood pressure measurement, and hormonal assay. RESULTS: The subjects were divided in: nonsmokers (Group I; N=72); current (>2 years) light smokers-1 to 10 cigarettes/day-(Group II; N=35); and current heavy smokers->10 cigarettes/day-(Group III; N=30). The 2-D Doppler analysis of the ophthalmic and internal carotid arteries showed significant increased resistance in Group III compared with Group II and Group I. The genital vessels (uterine, clitoral, and labium minus arteries) showed the lowest PIs in the nonsmokers. The 3-D power Doppler histogram analysis of clitoral and labium minus blood flow showed the worst vascular indices (VI, FI, VFI) in the heavy smokers. CONCLUSIONS: Cigarette smoking may favor a reduced central and peripheral tissue perfusion with consequent increased risk of cerebrovascular and cardiovascular diseases and with genital vessels stiffness and impaired sexual performances.

Ultrastructural and quantitative study of clitoral cavernous tissue from living subjects.

INTRODUCTION: There has never been an investigation about the in vivo clitoral structure. AIM: To study the "in vivo" age-related structural changes of the clitoris in healthy women and in those affected by metabolic disorders. METHODS: Forty-three women subgrouping in (i) five teenagers, aged 14-18; (ii) eight young premenopausal women, aged 23-32; (iii) 10 premenopausal women, aged 38-47; (iv) nine diabetic premenopausal women, aged 27-43; and (v) 11 naturally postmenopausal women aged 51-55. Each woman underwent microbiopsy of the clitoral body by means of an 18G needle, length 100 mm, using a semiautomatic gun during total anesthesia for a benign gynecological pathology. The tissue removed was processed for electron microscopy. A morphometric procedure was used on electron micrographs. MAIN OUTCOME MEASURE: Micro ultrastructure observation of clitoral tissue. RESULTS: The cavernous tissue from the teenagers and young women showed large amounts of smooth muscle cells (SMCs). The intercellular connective tissue showed scanty, small isometric collagen fibers and amorphous extracellular matrix. In the premenopausal diabetic women, ultrastructural abnormalities of SMCs were observed, consisting of increase of glycogen deposits, infolding cell borders, and cytoplasmic vacuoles. Moreover, the intercellular connective tissue was increased by densely packed collagen fibers. Finally, in the healthy, natural postmenopausal women, the SMCs were moderately reduced in number. We observed age-related structural changes of the vascular spaces and of the vascular lacunae. The SMC mean thickness was reduced with age; vascular abnormalities appeared to be correlated with the presence of metabolic diseases, such as diabetes. CONCLUSION: Our "in vivo" study could help to understand some aspects of the physiology of the clitoris and its role in sexual response. Apart from data obtained by studying healthy women and women affected by diabetes, other investigations are needed to study subgroups of otherwise healthy sexually dysfunctional women.

The effect of topical synthetic prostaglandin E1 (misoprostol) on clitoral hemodynamics.

INTRODUCTION: Genital blood flow plays an important role on female sexual function. Measures that increase genital blood flow may be a therapeutic approach for female sexual dysfunction. AIM: This study aims to show the effect of topical misoprostol, a synthetic prostaglandin, on clitoral blood flow. METHODS: Seventeen volunteers with female sexual dysfunction on the basis of female sexual function index scores were included in the study. All women were premenopausal and within their sexually active ages. Hormonal profiles were also normal. Those with suspected pregnancy, history of pelvic or vaginal surgery or radiotherapy, and diabetes or hypertension were excluded. Female sexual function index scores were determined. Clitoral peak systolic velocity (PSV) and clitoral artery diameter of all women were measured by using Doppler ultrasound. The measurements were done on two occasions as before and after placebo in one session and before and after 100 µg of misoprostol in another. This is a double-blind study where the patient and the ultrasonographist were unaware of either placebo or active drug has been applied before measurements. MAIN OUTCOME MEASURES: Clitoral artery diameter and peak systolic velocity. RESULTS: Misoprostol caused a significant increase in clitoral artery PSV compared to basal level (P = 0.0001), while changes in clitoral artery PSV with placebo remained insignificant. Remarkably, misoprostol caused 118.3% increase in clitoral artery PSV and 47.5% increase in clitoral artery diameter when compared to basal levels. No side effects were observed. CONCLUSION: Topical misoprostol can significantly increase clitoral blood flow without any unwanted effects and this finding may be promising for future investigations with relevance to female sexual dysfunction.

Quality of life and sexual changes after double transobturator tension-free approach to treat severe cystocele.

OBJECTIVES: To study the quality of life and sexual function changes of women affected by severe cystocele and treated with the double transobturator tension-free approach. STUDY DESIGN: 23 women (mean age 60.6) with third and fourth degree cystocele (according to Baden and Walker classification) were monitored by Short Form-36 (SF-36) and Pelvic Organ Prolapse/Urinary Incontinenece Sexual Questionnaire (PISQ-12) before and 12 months after surgical treatment. Each woman also underwent translabial color Doppler ultrasonography to measure the Resistance Index (RI), Pulsatility Index (PI), Peak Systolic Velocity (PSV), and End-Diastolic Velocity (EDV) of the clitoral arteries, before surgery and 12 months postoperatively. RESULTS: SF-36 showed a considerable increase in all of the categories (physical functioning, physical role functioning, bodily pain, general health, vitality, social functioning, emotional role functioning, and mental health) compared to those obtained at baseline (P<0.05). PISQ-12 also showed a considerable increase in the behavioural emotive factor score, in the physical factor score, in the partner-related factor score and, consequently, in the total score compared to that obtained at baseline (P<0.05). Color Doppler measurement showed that the mean Pulsatility Index, Peak Systolic Velocity, Resistance Index and End-Diastolic Velocity were not significantly lower to those obtained at baseline (P=NS). CONCLUSIONS: Double transobturator tension-free approach to treat severe cystocele considerably improves quality of life and sexual function, and does not significantly influence clitoral blood flow. Our data could add new information about sexual behaviour after prolapse treatment, particularly about the impact on clitoral blood flow changes.

UK-414,495, a selective inhibitor of neutral endopeptidase, potentiates pelvic nerve-stimulated increases in female genital blood flow in the anaesthetized rabbit.

BACKGROUND AND PURPOSE: Female sexual arousal consists of a number of physiological responses resulting from increased genital blood. Vasoactive intestinal peptide (VIP), neuropeptide Y and to a lesser extent nitric oxide are neurotransmitters found in the vasculature of the genitalia. Neutral endopeptidase (NEP) modulates the activity of neuropeptides including VIP. The aim of this study was to investigate the control of genital blood flow by VIP and endogenous neuropeptides using a selective NEP inhibitor [UK-414,495, ((R)-2-({1-[(5-ethyl-1,3,4-thiadiazol-2-yl) carbamoyl]cyclopentyl}methyl) valeric acid)]. EXPERIMENTAL APPROACH: Vaginal and clitoral blood flow (VBF and CBF) were monitored using laser Doppler in terminally anaesthetized New Zealand rabbits. Increases in VBF and CBF were induced by either electrical stimulation of the pelvic nerve or by i.v. infusion of VIP. KEY RESULTS: Stimulation of the pelvic nerve increased VBF and CBF, compared with basal flow. Increases were mimicked by infusion of exogenous VIP. UK-414,495 dose-dependently potentiated pelvic nerve-stimulated increases in VBF (EC(50)= 37 +/- 9 nM; 3.6 x IC(50) rabbit NEP). Nerve-stimulated increases in VBF and CBF were both enhanced after UK-414,495. UK-414,495 increased the amplitude and duration of VIP-induced increases in VBF. UK-414,495 had no effect on basal VBF or cardiovascular parameters. CONCLUSIONS AND IMPLICATIONS: Inhibition of NEP potentiates pelvic nerve-stimulated increases in genital blood flow. This suggests that the endogenous neurotransmitter mediating genital blood flow is a substrate for NEP (most likely VIP). NEP inhibitors may restore sexual arousal in women adversely affected by female sexual arousal disorder.

PCOS and urethrovaginal space: 3-D volumetric and vascular analysis.

INTRODUCTION: The vaginal orgasm seems to be evocated by the stimulation of the G-spot: a highly sensitive area on the anterior wall of the human vagina. However, the existence of such a spot is controversial. AIM: To evaluate, by the use of three-dimensional (3-D) ultrasonography, the anatomic structures of the urethrovaginal space both in polycystic ovarian syndrome (PCOS) patients and eumenorrheic non-hirsute controls. METHODS: Twenty-three (Group I) PCOS patients and 25 eumenorrheic young women (Group II) were submitted to two-dimensional (2-D) and 3-D ultrasonography and color Doppler analysis of the urethrovaginal space and of the clitoris. MAIN OUTCOME MEASURES: 2-D ultrasonographic evaluation of the ovaries and of the urethrovaginal space; color Doppler evaluation of the ovarian stromal arteries, urethrovaginal main feeding artery, and dorsal clitoral arteries; 3-D volume calculation of the urethrovaginal space, and 3-D power Doppler analysis of the vascularization index; flow index; and vascularization flow index; hormonal evaluation. RESULTS: The vaginal orgasm was present in 13/23 (56%) patients in PCOS Group and in 13/25 (52%) in the controls. The 3-D reconstruction of the urethrovaginal space demonstrated a gland-like aspect with small feeding vessels: "female prostate." The 3-D mean volume of the "female prostate" was significantly higher in Group I (0.48 ± 0.21 mL) than in Group II (0.39 ± 0.19 mL; P = 0.044). The Virtual Organ Computer-aided AnaLys (VOCAL) built mean volume of the "female prostate" was positively correlated with the time since intercourse (r = 0.486; P = 0.032), with the total length of the urethrovaginal space (r = 0.616; P = 0.025) and with the testosterone (r = 0.424; P = 0.048) circulating values. CONCLUSIONS: The presence of the G-spot and its role in vaginal orgasm remains controversial. In Italians, and normal weight PCOS patients the hyperandrogenism seems to result in ovarian stromal and "female prostate" hyperplasia.