Vaginal Blood Flow Research Articles

Preclinical Female Model of Urogenital Dysfunction and Pathophysiological Changes After Pelvic Radiation Therapy.

Introduction Radiation therapy (RT) is the gold standard for many pelvic cancers and improves overall patient survival. However, pelvic RT is associated with increased sexual dysfunction and urinary incontinence. Although the side effects of pelvic RT are well-documented, the pathological mechanisms leading to pelvic organ dysfunction are unknown, and a preclinical model has not been established. This study characterized the impact of pelvic RT at early and late timepoints on female rat bladder, vaginal, and urethral physiology and morphology. Methods Adult female Sprague-Dawley rats were divided into three groups (n = 8/group): (I) Sham, (II) four weeks RT (4wk RT), and (III) nine weeks RT (9wk RT). The RT groups received a single dose of 20 Gy external beam radiation, and experiments were conducted at 4wk and 9wk post-RT. Nerve-mediated vaginal blood flow was measured via laser Doppler. Tissue bath studies assessed vaginal contractility to electric field stimulation (EFS), adrenergic and cholinergic agonists, and relaxation to a nitric oxide donor. Bladder and urethral sphincters were evaluated for cholinergic, caffeine, and EFS-mediated contractility. Quantitative polymerase chain reaction (qPCR) measured gene expression of markers of oxidative stress. Vaginal, bladder, and urethral fibrosis were assessed with Masson's trichrome staining. Results At 4wk post-RT, total vaginal blood flow decreased, and at 9wk post-RT, returned to baseline levels. At 9wk post-RT, vaginal neurogenic and adrenergic-mediated contractile responses increased significantly. Vaginal epithelial thickness decreased post-RT and correlated with an acute rise in vaginal inflammatory gene expression. At 4wk post-RT, bladder neurogenic contractions decreased and remained lowered. Internal urethral contractions increased at 4wk post-RT and returned to Sham levels after 9wk post-RT. Pelvic RT increased external urethral neurogenic contractions, which remained elevated. Conclusion This novel preclinical model provides valuable insights into the temporal pathophysiology of pelvic RT-induced sexual and urinary dysfunction. The establishment of this model is crucial for understanding the underlying mechanisms involved in RT-induced pelvic injury. A reliable, clinically relevant model will allow for the testing of therapeutic strategies to prevent adverse effects with RT in pelvic cancer survivors.

Effects of natural mating, artificial insemination and intravaginal deposition of raw semen or seminal plasma on vaginal and uterine blood flow in German Holstein cows

AimThe present study was performed to characterize and compare the perfusion of vaginal and uterine arteries after challenging the reproductive tract of dairy cows via natural mating, artificial insemination (AI), or intravaginal deposition (vaginal fundus) of different biological fluids or a placebo.Materials and methodsIn a double-blind study, six German Holstein cows were administered PGF2α during dioestrus and 48 h later treated with GnRH. Intravaginal or intrauterine treatments were carried out 12 h after GnRH was administered. Animals served as their controls, using a cross-over design with an interval of 14 days between experiments. The experimental animals were allocated to receive the following treatments: natural mating (N), intrauterine artificial insemination (A), intravaginal deposition (vaginal fundus) of 6 mL raw semen (R) or 6 mL seminal plasma (S), and compared to their controls [control 1: 6 mL placebo (P: physiological saline); control 2: no treatment (C)). Corresponding time intervals were chosen for the untreated control oestrus. Blood flow volume (BFV) in the uterine (u) and vaginal (v) arteries ipsilateral to the ovary bearing the preovulatory follicle was determined using transrectal Doppler sonography.ResultsAll animals exhibited oestrus and ovulated between 30 and 36 h after GnRH. Transient increases (P < 0.05) in vaginal blood flow occurred between 3 and 12 h following mating as well as 3 to 9 h after deposition of raw semen and seminal plasma, respectively. The most distinct increases (199%) in vBFV occurred 6 h after mating compared to values immediately before mating (= time 0 h). Neither AI nor deposition of a placebo into the vagina affected vBFV (P > 0.05). Only mating and deposition of either raw semen, seminal plasma or AI increased uBFV (P < 0.003). The greatest rise in uBFV occurred after natural mating. Maximum uBFV values were detected 9 h after mating when values were 79% greater (P < 0.05) than at 0 h.ConclusionsThe natural mating, deposition of raw semen or seminal plasma and conventional AI affect vaginal and/or uterine blood flow to different degrees. The factors responsible for these alterations in blood flow and their effects on fertility remain to be clarified in future studies.

Sexual effects of commonly used recreational psychostimulants in women and the female rat model.

Recreational psychostimulants have been associated with increased sexual activity or changes in sexual function in women, but every drug in this class has not shown consistent sexual effects in scientific studies. Further, some studies in female animal models may recapitulate the effects observed in humans, while others produce conflicting results. Overall, though, published studies on the sexual effects of recreational stimulants in women are lacking. The objective of this manuscript was to review the published sexual effects of prominent recreational psychostimulants in women and in the female rat model. Literature searches for "any years" were performed through PubMed and Google Scholar. Keywords for the searches included "amphetamine," "methamphetamine," "MDMA," "ecstasy," "3,4-methylenedioxymethamphetamine," "cocaine," "caffeine," "sex," "sexual," "female," and "women." Studies in humans and using animal models were included. Older studies have shown that amphetamine produces a positive sexual effect in women, but often the sample size was too small to draw generalizable conclusions. Methamphetamine also has a positive effect on several sexual domains in women, as well as on vaginal lubrication. 3,4-Methylenedioxymethamphetamine may have a negative or positive effect on sexual activity, but often enhances the sensual aspects of sex. Though low doses of cocaine may heighten the sexual experience, most women who use cocaine experience negative sexual effects. Caffeine has been shown to enhance a physiological measure of arousal, vaginal blood flow, but based on our searches, no studies have investigated the subjective sexual effects of the drug. Different recreational psychostimulants produce varying effects on sexual behavior and responses in women and female animal models, but more research is needed to understand these effects better.

Reduction in genital sexual arousal varies by type of oral contraceptive pill.

Although oral contraceptive pills (OCPs) have been associated with decrements in self-reported genital arousal and vaginal lubrication, 1,2 little is known about how these outcomes vary across types of OCPs. The present study examined differences in physiological lubrication and vaginal blood flow, as well as rates of self-reported vulvovaginal atrophy and female sexual arousal disorder, among women using OCPs with varying androgenic properties. Participants in this study were 130 women: 59 naturally cycling control women, 50 women taking androgenic OCPs, and 21 women taking antiandrogenic OCPs. Participants watched sexual films while their sexual arousal responses were measured, completed questionnaires, and participated in a clinical interview. Vaginal blood flow, vaginal lubrication, self-reported vulvovaginal atrophy, and female sexual arousal disorder were assessed. Results indicated deficits in vaginal pulse amplitude and lubrication for women taking either form of OCP, with marked inhibitory effects found in women taking antiandrogenic OCPs. Rates of self-reported vulvovaginal atrophy and female sexual arousal disorder were also significantly greater in the antiandrogenic group compared with the control group. It is recommended that prescribing clinicians consult patients on such physiological effects of OCPs. To our knowledge, this was the first study to compare multiple measures of physiological sexual arousal across groups of women taking OCPs with varying hormonal profiles. Because all OCPs included in this study contained low doses of ethinylestradiol, we were able to identify the specific effects of the androgenic properties on women's sexual arousal responses. However, the self-administered lubrication test strip was subject to user error. Additionally, the generalizability of findings is limited by the largely heterosexual and college-aged sample. Compared with naturally cycling women, women taking OCPs that contain antiandrogenic progestins experienced decreased vaginal blood flow and lubrication as well as higher rates of self-reported vaginal bleeding and female sexual arousal disorder.

(058) Acute Dorsal Genital Neuromodulation can Improve Subjective Arousal: A Pilot Study in Women With and Without Spinal Cord Injury

Abstract Introduction Female sexual dysfunction (FSD) is a potentially life altering condition that impacts an estimated 40% of women. Unfortunately, the few treatment options available have limited success due to adverse events and an inability to improve subjective arousal. One potential treatment option, neuromodulation, has improved female sexual function index (FSFI) scores in small studies. The underlying mechanisms of how neuromodulation may improve FSD are not understood. We hypothesize that neuromodulation provides benefits by increasing genital blood flow. Objective Our primary objective is to determine if a single period of dorsal genital nerve stimulation (DGNS) or tibial nerve stimulation (TNS) directly causes a change in vaginal blood flow (VBF). Our secondary objective is to assess if subjective arousal increases during a single period of DGNS or TNS. These interventions will be compared among three cohorts of women: women with C6–T10 spinal cord injury (SCI), women with FSD (FSFI lubrication sub-score &amp;lt; 4), and able-bodied women without FSD. Methods Participants attended two separate visits, one for each nerve target, randomly ordered and separated by 1–5 months. We are testing two experimental paradigms: without and with erotic audio-visual materials. The first experiments measured vaginal pulse amplitude (VPA) using a vaginal photoplethysmography transducer (VPP) before, during, and after 20 minutes of nerve stimulation. After data processing, we calculated average peak to peak (p2p) amplitudes for each time period and performed an ANOVA and post-hoc pairwise comparisons within each participant. For the second experiment we measured VPA during neutral and erotic videos both without stimulation and with stimulation. In both experiments we measured subjective arousal via a Likert-type scale at 4 timepoints and made comparisons across participants with a paired t-test. The first experiments are complete and data collection for the second experiments is ongoing. Results We recruited three participants in each cohort in the first experiments, with five participants completing both sessions. All participants saw significant changes in their p2p amplitude from before stimulation to after stimulation in DGNS trials (n = 3 increased, n = 4 decreased). Three of five participants had significant p2p increases in TNS trials and one participant had significant decreases. DGNS subject arousal scores increased significantly after stimulation, but TNS scores did not (Figure 1). Most participants reported genital sensations during DGNS (7 of 8) and TNS (3 of 6) sessions. Three participants have completed both visits in the second set of experiments, with similar trends. Conclusions Acute DGNS, but not TNS, increased subjective arousal across all participants. VPA responses to stimulation were heterogeneous and although most changes were significant, there may not be physiological or clinical relevance. It is possible that repeated stimulation sessions over time may enhance changes in VPA. Disclosure No

(081) Comparing the Contributions of Nitric Oxide and Estrogen to Methamphetamine-Induced Alterations of Vaginal Blood Flow in Rats

Abstract Introduction Vaginal dryness is a frequent complaint, especially in post-menopausal women. The physiology underlying the production of vaginal lubrication in response to arousing stimuli is established; however, no current pharmacological agents successfully target mechanisms utilizing this physiology. Previous research from our lab has demonstrated that female methamphetamine (meth) users experience the production of excessive vaginal lubrication immediately following an intravenous injection of methamphetamine, and we have recapitulated this in an anesthetized rodent model. We have also found that this vaginal lubrication, as well as vaginal blood flow increased by meth, are heavily nitric oxide dependent. Objective The purpose of the current study is to determine if increased vaginal blood flow correlates with increased vaginal lubrication in response to meth, and to determine if alterations in this blood flow are dependent upon nitric oxide, estrogen, or both. Methods Adult female Wistar rats were implanted with chronic indwelling jugular catheters and allowed at least one week to recover from surgery. Rats anesthetized with isoflurane gas were intravenously infused with meth or saline via the implanted catheter. Vaginal blood flow, measured using a Periflux System 5000 and a small laser probe inserted 5-10 mm into the vaginal canal, was continuously recorded before and for at least twenty minutes following drug administration. After establishing meth-induced alterations in vaginal blood flow, rats were pre-treated with L-NG-Nitro arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor or fulvestrant, an estrogen receptor antagonist, followed by meth administration using the same procedure for measuring blood flow to determine the contribution of nitric oxide and estrogen. Results Meth immediately increases vaginal blood flow, followed by a decrease in perfusion, which is characteristic of a drug that induces such profound sympathetic activation. L-NAME reduced meth-induced increases in vaginal blood flow, and we predict that fulvestrant will be less effective. Conclusions Nitric oxide and estrogen are molecules critical to the production of vaginal lubrication. Nitric oxide, important for the vasodilation cascade leading to the production of vaginal transudate, contributes to meth-induced increases in vaginal blood flow and vaginal lubrication. Estrogen signaling likely contributes to meth-induced increases in vaginal blood flow, and thus, vaginal lubrication, but not as substantially as nitric oxide, making nitric oxide a better potential target for those suffering from vaginal dryness. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Embera NeuroTherapeutics &amp; JanOne, both affiliations unrelated to current research

(550) Sexual Arousal in Premenopausal Breast Cancer Patients on Antihormonal Treatment

Abstract Introduction Breast Cancer is the most common cancer in women and is associated with a severe impairment of general life quality, body-related self-esteem and sexual function and satisfaction. Sexual satisfaction has been shown to have a significant impact on general health and well-being. Nevertheless, research aiming at understanding sexual function in breast cancer patients is very scarce, no vaginal plethysmography data measuring vaginal blood flow on breast cancer patients currently exists. A better understanding of the interplay of the physiological sexual response and subjective sexual arousal in breast cancer survivors could help develop new strategies for treating this specific target group and contributing to improve their health and life quality. Objective The aim of this study is to collect preliminary data on psychophysiological aspects of the sex.al function of premenopausal breast cancer patients on antihormonal therapy and compare them with healthy controls. Specifically, we hypothesized that (1) genital arousal following visual stimuli is less in breast cancer patients than in healthy controls, (2) genital arousal following tactile stimuli is the same in breast cancer patients and healthy controls, (3) genital arousal following tactile stimuli is greater than following visual stimuli in both breast cancer patients and healthy controls. Serum sex hormone levels and self-reported sexual function are analyzed as moderators. Methods Breast cancer survivors (n=60) treated with antihormonal therapy for breast cancer, who are in complete remission for at least one year and healthy controls (n=20), undergo vaginal plethysmography while sexual stimuli (visual, tactile, visual + tactile) are presented. Subjective arousal and genital arousal are recorded continuously. Hormone serum levels, self-reported sexual function, sexual self-esteem, and quality of life measures are analyzed as potential moderators. Results Intraindividual differences (subjective and genital arousal) and interindividual differences (breast cancer patients, healthy controls) are analyzed based on a 2-level mixed effect models for each outcome variable. Pearson correlations are calculated to assess the relationships between subjective arousal and genital arousal for each group. Conclusions This study is the first to provide data on genital and subjective arousal in premenopausal women with breast cancer on antihormonal treatment compared to healthy controls and explore the data in connection with serum hormone levels. Overall, it will give a further insight in sexual function of breast cancer survivors to reveal targets to improve sexual function in this target group. Disclosure Yes, this is sponsored by industry/sponsor: WOW Tech™ Group. Clarification Industry funding only - investigator initiated and executed study.

Montelukast, a LRRC8A inhibitor, decreases the contractile response to Endothelin-1 in the vaginal smooth muscle of aged mice

Introduction: Vaginal smooth muscle (VaSM) is an important contributor to female sexual function, desire, and arousal. Increased vaginal blood flow via vasodilation of the vaginal blood vessels is key to the of lubrication and creating an enjoyable sexual experience. Female sexual dysfunction (FSD) is common in hypertensive and diabetic women, as well as many who suffer from hormonal imbalances, including menopause. Despite the substantial population that suffers from FSD, research into the mechanisms and non-hormonal treatments are limited. Leucine rich repeat containing channel 8A (LRRC8A) is a volume regulated anion channel (VRAC) that regulates Nox1 and can modulate the extracellular production of superoxide (O2∙-). In aged tissues, there are increased in extracellular ROS production as well as vascular and smooth muscle dysfunction. The objective of these experiments is to elucidate the mechanisms behind female sexual dysfunction that present with vascular and smooth muscle dysfunction and determine if the LRRC8A inhibitor, Montelukast, can alleviate some of the symptoms of FSD and improve quality of life. In this study, we hypothesize that the inhibition of LRRC8A in will decrease the contraction to Endothelin-1 in the vaginal smooth muscle of the aged mice. Methods: Aged (16 mo and 20 mo old) female lean mice underwent distal vaginal dissection. Vaginal tissue was cleaned and mounted on a strip myograph in Krebs solution and the contraction elicited by Endothelin-1 was performed in the absence and repeated in the presence of the LRRC8A inhibitor, Montelukast (1uM) after a 30-minute incubation. Data was analyzed using Prism. The maximal contraction in the absence of the inhibitor was taken as 100%, and the contraction in the presence of the inhibitor was calculated as a percentage of the maximal contraction attained in the absence of the inhibitor. Results: Contraction induced by Endothelin-1 (10-12 M to 3✕10 -8 M) alone compared to in the presence of Montelukast (1 uM) showed that Montelukast decreased both the potency and the maximum force of contraction in the aged VaSM. After incubation with 1 mM Montelukast, the EC50 and Emax were significantly different (0.0430 and &lt;0.0001, respectively). Conclusion: This is the first study investigating the vaginal smooth muscle from the perspective of ROS production and the influence of LRRC8A in aged animals. The change in the contractile response in the treated animals may be due to the modulation of the production of O2∙-. Patients that suffer from FSD are a large and overlooked community in need of new therapeutic approaches. Treatment with LRRC8A offers a potential novel approach to treat FSD and should be further researched to observe its overall impact in FSD. 1R01DK132948-01, SMSNA Student Grant This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

MP27-13 PERIPHERAL NEUROMODULATION OF VAGINAL BLOOD FLOW: A POTENTIAL TREATMENT FOR FEMALE SEXUAL DYSFUNCTION

You have accessJournal of UrologyCME1 Apr 2023MP27-13 PERIPHERAL NEUROMODULATION OF VAGINAL BLOOD FLOW: A POTENTIAL TREATMENT FOR FEMALE SEXUAL DYSFUNCTION Priyanka Gupta, Elizabeth Bottorff, Patricia Maymi-Castrodad, Mackenzie Moore, Giulia Lane, Gianna Rodriguez, and Tim Bruns Priyanka GuptaPriyanka Gupta More articles by this author , Elizabeth BottorffElizabeth Bottorff More articles by this author , Patricia Maymi-CastrodadPatricia Maymi-Castrodad More articles by this author , Mackenzie MooreMackenzie Moore More articles by this author , Giulia LaneGiulia Lane More articles by this author , Gianna RodriguezGianna Rodriguez More articles by this author , and Tim BrunsTim Bruns More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003255.13AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Female sexual dysfunction (FSD) is a potentially life altering condition that impacts an estimated 40% of women. Unfortunately, the few treatment options available have limited success due to their high incidence of adverse events and inability to improve subjective arousal. One potential treatment option, peripheral neuromodulation, has been successful in improving female sexual function index scores. However, the underlying mechanisms of how neuromodulation improves FSD are still largely unknown. We hypothesize that improvements in FSD symptoms are due to improvements in genital hemodynamics. METHODS: We developed a clinical study to investigate changes in vaginal blood flow (VBF) in response to dorsal genital nerve (DGN) and tibial nerve stimulation in three cohorts of women: healthy controls, women with FSD, and women with spinal cord injury (SCI). Incorporating women with SCI allows us to investigate which neural pathways contribute to genital sexual arousal. Each participant attends two study visits: one for each nerve target, randomly ordered. At each visit, a vaginal photoplethysmography (VPP) sensor is used to measure blood flow during a 5-minute baseline, 20 minutes of nerve stimulation, and a 5-minute washout period. The VPP signals are filtered in the neurogenic energy frequency spectrum (0.76 – 0.20 Hz) for analysis. RESULTS: Seven out of eight participants reported genital sensations due to nerve stimulation, three of whom have SCI. One participant with a complete SCI had increases in their VPP neurogenic energy during dorsal genital nerve stimulation (Figure 1). An animal study is being planned to investigate the VBF response observed in complete SCI. CONCLUSIONS: This work provides further support for neuromodulation as a treatment for neurogenic and non-neurogenic FSD. Source of Funding: Craig H. Neilsen Foundation and International Society for the Study of Women’s Sexual Health © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e367 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Priyanka Gupta More articles by this author Elizabeth Bottorff More articles by this author Patricia Maymi-Castrodad More articles by this author Mackenzie Moore More articles by this author Giulia Lane More articles by this author Gianna Rodriguez More articles by this author Tim Bruns More articles by this author Expand All Advertisement PDF downloadLoading ...

The vaginal and uterine blood flow changes during the ovsynch program and its impact on the pregnancy rates in Holstein dairy cows

AimOvSynch is a hormonal protocol for synchronization of estrus and use of artificial insemination (AI) at an optimal time without adverse effects on the ovaries or uterus. This study investigated the use of noninvasive color Doppler ultrasound to assess changes in uterine and vaginal blood flow during the Ovsynch program for synchronization of estrus and its relation to the pregnancy rates in Holstein cows.Materials and methodsThe experimental cows received an intramuscular dose of 10 μg of a GnRH analogue (G1), followed 7 days later with an intramuscular injection of synthetic prostaglandin F2α (P: PGF2α) analogue (500 μg cloprostenol sodium), and given a 10 μg, injection of the GnRH analogue (G2) i.m. 48 h after the PGF2α treatment, and the cows were bred 14-16 h after. Uterine and vaginal perfusion were investigated by performing transrectal Doppler ultrasonography of both the uterine and vaginal arteries in Holstein cows at different time points during the Ovsynch program to determine: peak systolic velocity (PSV), time-averaged maximum velocity (TAMV), the volume of blood flow (BFV), pulsatility index (PI), resistance index (RI), resistance impedance (S/D) and diameters of uterine (UA) and vaginal (VA) arteries. Steroid hormones were also assayed. Transrectal ultrasonography (TUS) was performed at 32 and 60 days to confirm the pregnancy per artificial insemination (P/AI).ResultsThe uterine PSV, TAMV, and PV were greater at the time of the cloprostenol sodium and second GnRH injections (p<0.05) than at the time of the first GnRH injection. The vaginal PSV, PV were greater at the time of the cloprostenol sodium than at the time of the first and second GnRH injections (p<0.05). The receiver operating characteristic curve (ROC curve) indicated a high correlation between the uterine and vaginal blood flow and the rate of the pregnancy (p<0.05). The area under the ROC curve was 0.920 and 0.87 (p<0.05) for vaginal and uterine arteries respectively at time of G2. The serum levels of progesterone, estrogen and cortisol were correlated with the P/AI (p<0.05). The P/AI significantly decreased from 43.9 % at 32 d to 35.37 % at 60 d.ConclusionThese results indicate that noninvasive Doppler ultrasonography is a valid method to evaluate changes in the characteristics of uterine and vaginal blood flow in cows during the Ovsynch protocol. Furthermore, vaginal and uterine blood flow are two determinant factors for the higher conception rates in Holstein dairy cows.

Methamphetamine-Induced Alterations of Vaginal Blood Flow in Rats

ABSTRACT Introduction Those suffering with vaginal dryness, whether experienced once or chronically, frequently experience painful and unpleasurable sexual experiences and diminished self-esteem as a result. Although the physiology of vaginal transudate production is long established, no pharmacological treatment other than estrogen has shown promise in attenuating vaginal dryness. Previously, our lab has shown that methamphetamine (meth) induced vaginal lubrication in adult women and anesthetized rats. The production of these vaginal secretions was shown to be dose-, as well as nitric oxide-dependent. As the secretion of vaginal lubrication is immensely dependent on local hemodynamics and the resulting increased blood flow to the genital tissues, determining meth-induced alterations in blood flow to these tissues is paramount. Objective The purpose of the current study is to determine if increased vaginal blood flow correlates with increased vaginal lubrication in response to meth, and to determine if alterations in this blood flow are nitric oxide-dependent. Methods Adult female Wistar rats were implanted with chronic indwelling jugular catheters and allowed at least one week to recover from surgery. Rats anesthetized with isoflurane gas were intravenously infused with meth (0.06-0.96 mg/kg) or saline via the implanted catheter. Vaginal blood flow, measured using a Periflux System 5000 and a small laser probe inserted 5-10 mm into the vaginal canal, was continuously recorded before and for at least twenty minutes following drug administration. After establishing meth-induced alterations in vaginal blood flow, pre-treatment with L-NG-Nitro arginine methyl ester (L-NAME), a non-specific nitric oxide synthase inhibitor, followed by meth administration following the same procedure for measuring blood flow allowed us to determine the contribution of nitric oxide to the observed changes in blood flow. Results Preliminary findings show that an IV infusion of meth induces an immediate increase in vaginal blood flow, followed by decreased blood flow due to vasoconstriction via increased sympathetic tone. We anticipate inhibition of nitric oxide production will reduce the increase in blood flow immediately after meth administration since this decreased vaginal lubrication in response to the same treatment. Conclusions These findings provide insight into the meth-induced vaginal lubrication we have previously reported, and that meth, whose sympathomimetic action traditionally induces vasoconstriction, produces increased blood flow in vaginal tissues, which is likely the driving force for the increased transudate produced. This advancement is critical for uncovering a mechanism that may serve as the optimal pharmacological target to treat vaginal dryness. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Embera NeuroTherapeutics &amp; JanOne

Efficacy of Yun-type pelvic floor optimal training therapy and PFMT on middle aged women with mild to moderate overactive bladder: a randomized controlled trial.

BackgroundThe symptoms of overactive bladder (OAB) are highly bothersome to patients. In behavioral therapy, traditional pelvic floor muscle training (PFMT) can be boring and monotonous, which can cause poor compliance. It’s important to establish a new safe and effective crotch-pelvic floor functional reconstruction training method [Yun-type pelvic floor optimal training (Yun-type training)] for OAB patients.MethodsThis randomized, double-blind, crossover trial recruited a total of 150 women with mild to moderate OAB. Patients were randomly assigned to receive Yun-type training (n=83) or PFMT (n=67). The intervention group was first given Yun-type training for 6 weeks, then switched to PFMT for 6 weeks after 2 weeks of elution. Patients in the control group were first treated with PFMT for 6 weeks, and changed to the use of Yun-type training for 6 weeks after 2 weeks of elution. The primary endpoint was overactive bladder symptom scores (OABSS) after 6 and 14 weeks of Yun-type training and PFMT.ResultsYun-type training could significantly improve OABSS compared with PFMT after 6 and 14 weeks (P<0.001). Yun-type training was associated with an improvement in urine, urgency, urge urinary incontinence (UUI), urogenital distress inventory-6 (UDI-6), patient’s perception of bladder condition (PPBC), voiding volume (VV), incontinence impact questionnaire-7 (IIQ-7), female sexual function index (FSFI), sexual desire, arousal, pain, satisfaction, pelvic floor muscle tone, type I muscle strength, type II muscle strength, and sex partner satisfaction as compared with PFMT after 6 and 14 weeks. Moreover, nocturia, maximum flow rate (Qmax), and climax in the Yun-type training group were significantly improved after 6 weeks, and the average flow rate (Qave) was improved after 14 weeks in the Yun-type training group.ConclusionsYun-type training could yield additional benefits on OAB symptoms, sexual function, and sex partner satisfaction as compared with PFMT. The superior sexual function resulting from Yun-type training can be explained by the fact that it can contract deep and superficial muscle layers, resulting in increased vaginal wall pressure and blood flow, which further improves FSFI and sex partner satisfaction. It could lead to a new non-invasive treatment for OAB patients.Trial RegistrationChinese Clinical Trial Registry ChiCTR-INR-17012192.

Establishment of Rat Model of Female Genital Sexual Arousal Disorder.

IntroductionFemale Genital Sexual Arousal Disorder (FGSAD) seriously affects women's quality of life and Sexual life, but it still lacks ideal FGSAD animal models for further study.AimTo establish a specific model of female genital sexual arousal disorder and explore the mechanisms resulting in FGSAD.MethodsAfter delivery, female rats were guided by expansions of the vagina and ovariectomy (VD+OVX, n = 10); in VD group female rats were just extended by the vagina (VD, n = 10), in OVX group female rats were treated with ovariectomy (OVX, n = 10);the remaining had 1 longitudinal incision as sham group(n = 10).OutcomesVaginal dilatation combined with ovariectomy in rats may reflect female genital sexual arousal disorder with high reproducibility and stability.ResultsVaginal tissue of female rats in OVX group and VD+OVX group showed an increase in blood flow, decrease in muscle content compared to the sham group. The proportion of collagen fiber I/III decreased and the elastic fiber showed significant rupture and fragmentation; Structural reticular integrity was also significantly separated and broken from the muscle fibers. However, there was no significant difference in vaginal blood flow, fibers and vascular between VD group and Sham group. The damage of vaginal tissue in VD+OVX group was more significant than that in OVX and VD groups.Clinical TranslationWe have constructed a specific animal model that can provide clinical insights into the mechanism of FGSAD and serves as a good avenue for further research of its treatment.Strengths and LimitationsVaginal dilatation combined with ovariectomy in rats is a specific animal model with high reproducibility and stability, but we do acknowledge the shortcomings and limitation present in our study. Since genital arousal disorder has many different etiologies that impact the vagina, the clitoris and surrounding tissues, there is no “gold standard” model that different models attempt to investigate different etiologies.ConclusionThe female genital sexual arousal disorder model established by vaginal dilatation combined with ovariectomy is a novel rat model with simple induction conditions, which pathogenic mechanism of female genital sexual arousal disorders maybe connected with the change of VEGF and MMP-9 in vaginal fibromuscular system and microvascular.Li G, Yu P, Hu Y, et al. Establishment of Rat Model of Female Genital Sexual Arousal Disorder. Sex Med 2022;10:100530.

Effects of Pueraria mirifica on vaginal artery vascularization in postmenopausal women with genitourinary syndrome of menopause

ObjectiveTo compare the effects of 6% Pueraria mirifica vaginal gel with those of placebo gel on vaginal blood flow, vaginal maturation index (VMI), vaginal health index (VHI), endometrial thickness and genitourinary symptoms in postmenopausal women. Study designIn a randomized, double-blinded, placebo-controlled study (TCTR20200624007), 72 postmenopausal women were randomized into the P. mirifica or the placebo gel group. Both groups were followed up at week 4 and week 12. Main outcome measureDoppler ultrasonography pulsatility index (PI) and resistance index (RI), VMI, VHI, endometrial thickness and genitourinary symptoms were evaluated at baseline, at week 4 and week 12 of treatment. ResultsSixty-three participants completed the study. After 4 and 12 weeks of treatment, PI and RI had significantly decreased in the P. mirifica group compared with the placebo group. At week 12, PI in the P. mirifica group and in the placebo group were 3.03 + 1.09 and 6.88 + 2.16, respectively (p = 0.002). Similar changes were also demonstrated in the resistance indices. The P. mirifica group demonstrated a markedly higher mean VMI at week 12 compared with the placebo group, 55.19 ± 18.53 and 20.29 ± 28.46 (p = 0.012). In addition, all parameters of VHI based on the vaginal physical findings at week 12 in the P. mirifica group were significantly higher than in the placebo group (p < 0.001). ConclusionIn this study, 6% P. mirifica vaginal gel for 12 weeks in postmenopausal women with GSM appeared to increase vaginal artery circulation and restore atrophic vaginal tissue. Clinical Trial Registration NumberTCTR20200624007.

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.

Uterine, vaginal and placental blood flows increase with dynamic changes in serum metabolic parameters and oxidative stress across gestation in buffaloes.

The aims of the present study were to determine uterine, vaginal and placental blood flows by Doppler ultrasound cross-buffalo gestation and to evaluate the relationships among reproductive Doppler parameters and serum metabolic parameters as well as oxidative stress. Uterine (UA) and vaginal (VA) arteries were scanned every month, and placentome was scanned from month 4 till 8 in gestation. Time-averaged maximum velocity (TAMV), pulsatility index (PI), resistance index (RI), systolic/diastolic ratio (SD) and arterial diameter (AD) were used for accessing UA and VA hemodynamics. Time-averaged maximum velocity positively correlated with and AD, and both negatively correlated with their PI, RI and SD in UA and VA. TAMV and AD increased constantly in pregnancy, with maximum increase in months 4 and 9. Pulsatility index, RI and AD of UA decreased between months 4 and 9, while PI, RI and AD of VA decreased between months 5 and 9 and then increased in month 10 in pregnancy. Time-averaged maximum velocity of placentome blood flow increased exponentially from months 4 to 8, but decreased at the last two months in pregnancy. Serum lipids were significantly higher in the first month compared to all other months, while glucose was significantly lower in months 9 and 10. Malondialdehyde increased from month 3 till term, but peaked in month 5 and 10. Glutathione and catalase were highest in the first month and remained after. Time-averaged maximum velocity and AD for both UA and VA negatively correlated with serum lipids, glucose, catalase and glutathione, while positively correlated with malondialdehyde and total protein. Thus, increases in uterine blood flow (UtBF), vaginal blood flow (VaBF) and placental blood flow (PaBF) are associated with increased metabolism and oxidative stress in buffalo pregnancy.

An Objective Measure of Vaginal Lubrication in Women With and Without Sexual Arousal Concerns

Changes in vaginal blood flow and lubrication are primary components of physiological sexual arousal in women. Despite the existence of well-established tools for measuring vaginal blood flow, there is not yet a consistently implemented measure of physiological lubrication. To address this methodological gap, researchers have begun examining the utility of litmus test strips, primarily in sexually healthy women. The present study builds on this work by examining the utility of an alternative tool, the Schirmer Tear Test strips, in women with (n = 32) and without (n = 32) sexual arousal concerns. Significant increases in physiological lubrication were found in response to a sexual film, and these changes were moderately correlated with self-reported genital arousal (r = .41) and lubrication (r = .30). No between-group differences in lubrication were observed. These results indicate the Schirmer Tear Test strips are sensitive enough to detect increases in lubrication and may be valuable in clinical and research assessments of female sexual arousal.

Effect of Tibial Nerve Stimulation on Menopause‐associated Symptoms in Ovariectomized Rats

Human menopause transition and post‐menopausal syndrome, driven by reduced ovarian activity which reduces estrogen levels, are associated with an increased risk for symptoms including but not limited to sexual dysfunction, osteoporosis, and metabolic disease. Current treatments (both hormonal and non‐hormonal) are limited in efficacy and may have adverse consequences, so investigation for additional treatment options are necessary. Previous studies have demonstrated that tibial nerve stimulation or electro‐acupuncture are minimally invasive treatments that increase vaginal blood flow and serum estrogen in the rat model. In this study we examined the effects of biweekly tibial nerve stimulation (0.2 ms pulse width, 20 Hz, 2× motor threshold) under ketamine‐xylazine anesthesia in female ovariectomized (OVX) Sprague Dawley rats on various measurements that can change in association with menopause (serum estradiol, resting blood glucose, vaginal blood perfusion, uterine weight/histology, and bone density) either at weekly time‐points or during a terminal necropsy. Rats were split into three groups (n = 10 per group): 1) intact + no stimulation, 2) OVX + no stimulation, and 3) OVX + stimulation. Although preliminary data has not shown significant differences between treatment groups, data collection is ongoing and trends are expected after weeks of stimulation. The results of this study will examine the effects of tibial nerve stimulation on various menopause associated symptoms, and help guide recommendations for future studies and treatments.

Effect of a Condom Cover on Vaginal Photoplethysmographic Responses

IntroductionThe vaginal photoplethysmograph (VPP) is a reusable intravaginal device often employed in sexual psychophysiology studies to assess changes in vaginal blood flow, an indicator of sexual arousal. AimTo test whether placing a disposable cover on the VPP probe impacts the acquired data. A condom cover would reduce risk of disease transmission and likely increase participant comfort but may negatively impact the VPP signal. MethodThe genital responses of 25 cisgender women (mean age = 21.3 years, standard deviation = 2.6) were assessed with VPP in a within-subjects design with 2 conditions—with and without a polyisoprene condom cover. Sexual responses were elicited by audiovisual film clips that varied in erotic intensity: nonsexual (nonsexual male-female interaction), low-intensity sexual (nude exercise), and high-intensity sexual (male-female intercourse). Women continuously rated their sexual arousal during stimulus presentations. Main Outcome MeasureChange in vaginal pulse amplitude and also self-reported sexual arousal. ResultsThe magnitude of sexual response to each stimulus category and the overall pattern of results were found to be highly similar in the cover-off and cover-on conditions. The high-intensity sexual stimulus category elicited a greater sexual response than all other categories. The low-intensity sexual category elicited a (small) genital response in only the cover-on condition, although we suspect this is a spurious finding. There was no difference in the average number of edited movement artifacts across conditions. Clinical ImplicationsPotential benefits of encasing the VPP probe with a protective cover include enhanced participant safety and comfort, especially if assessing genital responses of high-risk or immunocompromised samples. The use of a cover complies with current guidelines for reprocessing semi-critical medical devices (eg, vaginal ultrasound probes) in many regions. Strengths & LimitationsAlthough the idea of a VPP probe cover had been discussed among sexual psychophysiology researchers, this is the first study to empirically test whether a cover could jeopardize VPP data. Potential limitations include the use of a 10-Hz VPP sampling rate and a cover that was not tailored to the size of the VPP probe. ConclusionPlacing a protective cover on the VPP probe did not appear to meaningfully impact sexual arousal or the VPP data. Based on these results and the potential advantages of a protective cover, researchers may wish to integrate the use a condom cover in their experiment protocols and clinical applications.Sawatsky ML, Lalumière ML. Effect of a Condom Cover on Vaginal Photoplethysmographic Responses. J Sex Med 2020; 17:702–715.

The Clitoris-An Appraisal of its Reproductive Function During the Fertile Years: Why Was It, and Still Is, Overlooked in Accounts of Female Sexual Arousal.

Stimulating the clitoris activates the brain to instigate changes in the female genital tract, namely, the enhancement of vaginal blood flow that increases vaginal luminal pO2 , vaginal transudate (lubrication) facilitating painless penile penetration and partial neutralization of the basal luminal acidic pH, vaginal tenting, and ballooning delaying sperm transport and allowing semen de-coagulation and capacitation (sperm activation) factors to act until arousal ends (often by orgasm induction). All these genital changes taken together are of major importance in facilitating the possibility of reproductive success (and thus gene propagation) no matter how or when the clitoris is stimulated-they reveal its overlooked reproductive function. Of course, also commensurate with these changes, is its activation of sexual pleasure. The clitoris thus has both procreative (reproductive) and recreative (pleasure) functions of equal importance. Clitoridectomy creates not only sexual disability but also a reproductive disability. Clin. Anat. 32:136-145, 2019. © 2019 Wiley Periodicals, Inc.