Maureen Basha

The Effects of Hormonal Contraceptives on Female Sexuality: A Review

INTRODUCTION Hormonal contraceptives can influence female sexual function. AIM The goal of this article was to provide a comprehensive review of the effects that various hormonal contraceptives may have on female sexual function. METHODS A Medline search was conducted using several terms related to and including the terms contraception, oral contraceptive, female sexual function, dyspareunia, libido, and sexual desire. RESULTS A thorough review of the effects of hormonal contraceptives on female sexual function. CONCLUSIONS The sexual side effects of hormonal contraceptives are not well studied, particularly with regard to impact on libido. There appears to be mixed effects on libido, with a small percentage of women experiencing an increase or a decrease, and the majority being unaffected. Healthcare providers must be aware that hormonal contraceptive can have negative effects on female sexuality so they can counsel and care for their patients appropriately.

Contractile Response of Human Anterior Vaginal Muscularis in Women With and Without Pelvic Organ Prolapse

The aim of this study was to compare the contractility of the anterior vaginal muscularis (AVM) from women with and without pelvic organ prolapse (POP). In vitro experiments were performed to measure the peak force generated in response to potassium chloride (KCl; 125 mmol/L) and phenylephrine by AVM tissue from women with and without POP. Cross-sectional areas and co-localization of α1A adrenergic receptor protein with smooth muscle α-actin in AVM strips were determined by histology and immunofluorescence, respectively. There were no differences in the mean amplitude of force generated in response to KCl normalized to either wet weight or muscle cross-sectional area (mN/mm2) between women with and without POP (P > .30). However, AVM from women with prolapse produced a significantly higher mean force to KCl normalized to total cross-sectional area compared to controls (P = .007). While the control samples demonstrated a consistent response to phenylephrine, there was no response to this stimulant generated by AVM tissue from women with POP. The proportion of co-localized α1A adrenergic receptors with smooth muscle α actin in AVM tissue was significantly less in women with POP compared to normal controls (P < .0001). Although there was significantly greater tissue stress generated by AVM from women with prolapse compared to controls, there were no differences in muscle stress. Absent response to phenylephrine by AVM from women with prolapse may be related to a lower expression of α1A adrenergic receptors in vaginal smooth muscle.

Effect of Estrogen on Molecular and Functional Characteristics of the Rodent Vaginal Muscularis

INTRODUCTION Vaginal atrophy is a consequence of menopause; however, little is known concerning the effect of a decrease in systemic estrogen on vaginal smooth muscle structure and function. As the incidence of pelvic floor disorders increases with age, it is important to determine if estrogen regulates the molecular composition and contractility of the vaginal muscularis. AIM The goal of this study was to determine the effect of estrogen on molecular and functional characteristics of the vaginal muscularis utilizing a rodent model of surgical menopause. METHODS Three- to 4-month old Sprague-Dawley rats underwent sham laparotomy (Sham, N = 18) or ovariectomy (Ovx, N = 39). Two weeks following surgery, animals received a subcutaneous osmotic pump containing vehicle (Sham, Ovx) or 17β-estradiol (Ovx). Animals were euthanized 1 week later, and the proximal vagina was collected for analysis of contractile protein expression and in vitro studies of contractility. Measurements were analyzed using a one-way analysis of variance followed by Tukeys post hoc analysis (α = 0.05). MAIN OUTCOME MEASURES Protein and mRNA transcript expression levels of contractile proteins, in vitro measurements of vaginal contractility. RESULTS Ovariectomy decreased the expression of carboxyl-terminal myosin heavy chain isoform (SM1) and h-caldesmon and reduced the amplitude of contraction of the vaginal muscularis in response to KCl. Estradiol replacement reversed these changes. No differences were detected in the % vaginal muscularis, mRNA transcript expression of amino-terminal MHC isoforms, l-caldesmon expression, and maximal velocity of shortening. CONCLUSION Systemic estrogen replacement restores functional and molecular characteristics of the vaginal muscularis of ovariectomized rats. Our results indicate that menopause is associated with changes in the vaginal muscularis, which may contribute to the increased incidence of pelvic floor disorders with age.

Functional significance of muscarinic receptor expression within the proximal and distal rat vagina

Information regarding the role of cholinergic nerves in mediating vaginal smooth muscle contraction is sparse, and in vitro studies of the effects of muscarinic agonists on vaginal smooth muscle are discrepant. The goal of this study was to determine the expression of muscarinic receptors in the vaginal wall of the rat. In addition, we sought to determine the effect of the muscarinic receptor agonist carbachol on contractility and inositol phosphate production of the proximal and distal rat vaginal muscularis. RT-PCR analysis indicated that both M(2) and M(3) receptor transcripts were expressed within the proximal and distal rat vagina. Carbachol dose-dependently (10(-7)-10(-4) M) contracted the rat vaginal muscularis with a greater maximal contractile response in the proximal vagina (P < 0.01) compared with the distal vagina. The contractile responses of the rat vaginal muscularis to carbachol were dose dependently inhibited by the M(3) antagonist para-fluoro-hexahydrosiladefenidol, and a pK(B) of 7.78 and 7.95 was calculated for the proximal and distal vagina, respectively. Inositol phosphate production was significantly increased in both regions of the vagina following 20-min exposure to 50 muM carbachol with higher levels detected in the proximal vagina compared with the distal (P < 0.05). Preliminary experiments indicated the presence of M(2) and M(3) receptors in the human vaginal muscularis as well as contraction of human vaginal muscularis to carbachol, indicating that our animal studies are relevant to human tissue. Our results provide strong evidence for the functional significance of M(3) receptor expression in the vaginal muscularis.

Effects of Rho-kinase inhibition on myosin light chain phosphorylation and obstruction-induced detrusor overactivity.

To study the relationship between myosin light chain phosphorylation of the detrusor muscle and spontaneous smooth muscle contractions in a rabbit model of partial outlet obstruction.

MP81-13 EFFECT OF VAGINAL ESTROGEN DELIVERY ON THE VAGINAL MUSCULARIS IN A RODENT MODEL OF VULVOVAGINAL ATROPHY WITH MENOPAUSE.

Score >7) [OR 1.68], diabetes mellitus [OR 1.38], hypertension [OR 1.22].Risk factors: Poor general health status (first question of SF12) [OR 1.72], waist circumference (>1⁄4102cm) [OR 1.31], physical activity (<2 days a week minimum 30 minutes per day mild exercise) [OR 1.27], smoking regularly [OR 1.15]. The only factor eliminated during variable selection was BMI even though this factor showed a crude OR of 1.42. ED-prevalence increased with the number of risk factors (0 factors: 21.9%; 3 factors: 33.4%) and number of comorbidities (0 comorbidities: 22.4%; 3-4 comorbidities: 64.3%). CONCLUSIONS: ED was found in every fourth 45-year-old German man. Prevalence increased significantly with the number of risk factors and comorbidities.

Sex-dependent expression of TRPV1 in bladder arterioles

Transient receptor potential vanilloid type 1 (TRPV1) is a major nociceptive ion channel implicated in bladder physiology and/or pathophysiology. However, the precise expression of TRPV1 in neuronal vs. nonneuronal bladder cells is uncertain. Here we used reporter mouse lines (TRPV1-Cre:tdTomato and TRPV1PLAP-nlacZ) to map expression of TRPV1 in postnatal bladder. TRPV1 was not detected in the urothelium, however, we found marked expression of TRPV1 lineage in sensory nerves, and surprisingly, in arterial/arteriolar smooth muscle (ASM) cells. Tomato fluorescence was prominent in the vesical arteries and in small-diameter (15-40 μm) arterioles located in the suburothelial layer with a near equal distribution in bladder dome and base. Notably, arteriolar TRPV1 expression was greater in females than in males and increased in both sexes after 90 days of age, suggesting sex hormone and age dependency. Analysis of whole bladder and vesical artery TRPV1 mRNA revealed a similar sex and developmental dependence. Pharmacological experiments confirmed functional TRPV1 protein expression; capsaicin increased intracellular Ca2+ in ∼15% of ASM cells from wild-type female bladders, but we observed no responses to capsaicin in bladder arterioles isolated from TRPV1-null mice. Furthermore, capsaicin triggered arteriole constriction that was rapidly reversed by the TRPV1 antagonist, BCTC. These data show that predominantly in postpubertal female mice, bladder ASM cells express functional TRPV1 channels that may act to constrict arterioles. TRPV1 may therefore play an important role in regulating the microcirculation of the female bladder, and this effect may be of significance during inflammatory conditions.