Thermal and Mechanical Pain Thresholds of Women With Provoked Localized Vulvodynia: A Pilot Study.

CONTEXT: Vulvodynia is a chronic pain condition defined as vulvar pain lasting at least 3 months in the absence of gross anatomic or neurologic findings. Provoked, localized vulvodynia (PLV), a subtype of vulvodynia, is characterized by vestibular pain in response to light touch. The cause of PLV remains largely unknown, and triggering events have yet to be determined. OBJECTIVE: To evaluate vestibular and peripheral experimental pain thresholds in patients with PLV to further define the somatosensory profile of these patients. METHODS: After informed consent was provided, eligible participants completed a questionnaire and underwent quantitative sensory testing at the forearm and posterior vestibule. Detection and pain thresholds to thermal (cold and heat) and mechanical (pressure) stimuli were measured. RESULTS: Seventeen participants with PLV and 16 control participants were included. Participants in the PLV group scored lower on the patient health questionnaire 9 (PHQ-9) compared with those in the control group (P<.05) and had higher ratings of self-reported genital pain with sex (P<.001) and daily activity (P<.05). Forearm pain thresholds to cold (P<.01) and heat (P<.01) stimuli were also lower in the PLV group compared with those in the control group. Vestibular pain thresholds to cold (P<.05) and pressure (P<.01) stimuli were also lower in the PLV group. CONCLUSION: Lower scores on the PHQ-9 and higher self-reported genital pain ratings of patients with PLV highlight the significant impact of this poorly understood condition on quality of life. Quantitative sensory testing results demonstrated that vestibular cold allodynia may be a somatosensory feature of PLV. Reduced forearm pain thresholds in these patients suggest altered sensory processing at extrapelvic sites, although it is unclear whether these measurements are related to central sensitization.

The Evidence-based Vulvodynia Assessment Project. A National Registry for the Study of Vulvodynia.

OBJECTIVE: To create a national registry for the study of vulvodynia in order to enhance classification of vulvodynia based on multiple phenotypic domains such as pain characteristics, clinical examination, sexual function, psychological functioning, and distress. STUDY DESIGN: Methodology for this prospective cohort registry was institutional review board approved and implemented at 8 enrollment sites starting in 2009. Women underwent gynecologic evaluation and pressure sensory testing for assessment of pain sensitivity in the vaginal mucosa and vaginal muscles. Psychometric questionnaires were used to assess self-described pain, distress, sexual function, and quality of life. RESULTS: More than 300 women were enrolled and 176 charts were analyzed. This cohort had a median age of 29 years and median pain duration of 25.5 months. A total of 84% of participants were previously or currently sexually active in spite of pain. The most common pain comorbidities reported by the women were migraines (34%), chronic pelvic pain (22%), and irritable bowel syndrome (20%). Anxiety affected 41% of the cohort. More than 90% presented with localized vestibular pain, and 90% had muscular examination abnormalities. CONCLUSION: A national registry for the study of vulvodynia was established with successful enrollment of participants at 8 sites. In addition to the cotton swab evaluation for vulvar allodynia, women with vulvar chronic pain should also be routinely screened for musculoskeletal dysfunction, emotional distress with specific emphasis on anxiety, and comorbid pain conditions.

Polymorphisms of the androgen receptor gene and hormonal contraceptive induced provoked vestibulodynia.

AIM: Women who developed vestibulodynia (vulvar vestibulitis) while taking combined hormonal contraceptives (CHCs) and a control group of women were tested for polymorphisms of the gene coding for the androgen receptor (AR) that is located on the X chromosome. STUDY DESIGN: DNA from 30 women who developed vestibulodynia while taking CHCs and 17 control women were tested for the number of cytosine-adenine-guanine (CAG) trinucleotide repeats in the AR. In addition, serum-free testosterone was tested in both groups. RESULTS: The mean number of CAG repeats in the study group was significantly greater than the control group (22.05 ± 2.98 vs. 20.61 ± 2.19, respectively; P = 0.025). This significant difference persisted when analyzing the CAG repeats from the longer allele from each subject. Among those who were taking drospirenone-containing CHCs, the mean calculated free testosterone was 0.189 ± 0.115 ng/dL in the study group and 0.127 ± 0.054 ng/dL in the control group, all of whom were taking drospirenone-containing CHCs (P = 0.042). CONCLUSION: In the study cohort, women who developed vestibulodynia while taking CHCs are more likely to have longer CAG repeats in the AR than women who took the same type of CHC but did not develop vestibulodynia. We speculate that the risk of developing CHC-induced vestibulodynia may be due to lowered free testosterone combined with an inefficient AR that predisposes women to vestibular pain.

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 17ß-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 Tukey's 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.

The treatment of vestibulodynia with topical estradiol and testosterone.

INTRODUCTION: Combined hormonal contraceptives (CHCs) use is becoming an increasingly recognized causes of vestibulodynia. AIM: This study aims to describe pre- and posttreatment vestibular pain, sex hormone binding globulin (SHBG), and calculated free testosterone levels in women undergoing treatment for vestibulodynia. METHODS: This was a chart review of 50 premenopausal women who presented with vestibular pain while currently using CHCs. Pre- and posttreatment vestibular pain, SHBG, and calculated free testosterone levels were assessed. RESULTS: There was a statistically significant improvement in posttreatment vestibular pain scores (P = 0.001), SHBG (P = 0.001), and calculated free testosterone (P = 0.001) levels from baseline. CONCLUSION: Women with vestibulodynia that began while on CHC may effectively be treated by discontinuing the CHC combined with the application topical hormone therapy. Symptomatic improvement is accompanied by normalization of calculated free testosterone and SHBG values. Burrows LJ and Goldstein AT. The treatment of vestibulodynia with topical estradiol and testosterone. Sex Med 2013;1:30-33.

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.

A double-blind, randomized controlled trial of clobetasol versus pimecrolimus in patients with vulvar lichen sclerosus.

BACKGROUND: Lichen sclerosus (LS) is a lymphocyte-mediated chronic cutaneous disorder with a predilection for the vulva. The current gold standard treatment is topical ultrapotent corticosteroids such as clobetasol. OBJECTIVE: We sought to compare the safety and efficacy of clobetasol and pimecrolimus in the treatment of vulvar LS. METHODS: This double-blind, randomized trial enrolled 38 women with biopsy-proven vulvar LS. This study consisted of a 2-week screening period and a 12-week treatment period. The primary efficacy variable was the change in inflammation, as determined by a dermatopathologist, on the biopsy specimens obtained at screening and at the week 12 visit. Secondary efficacy variables included the change from baseline in pruritus and burning/pain as assessed by patients using a visual analog scale and a clinical evaluation by the investigator. RESULTS: Clobetasol was found to be superior in improving inflammation when compared with pimecrolimus (P = .015). Both groups showed improvement in pruritus and burning/pain but this difference was not statistically significant (P = .32 and .93, respectively). Both clobetasol and pimecrolimus were found to be effective in decreasing both the total score on the Investigator Global Assessment (P = .001) and all 3 subscales. Serum levels of pimecrolimus and clobetasol did not approach levels of concern during the study period. No adverse events were reported. LIMITATIONS: This study was limited by the relatively short study duration. CONCLUSION: Both clobetasol and pimecrolimus appear efficacious and well tolerated for the treatment of vulvar LS; however, clobetasol is more effective than pimecrolimus and should remain first-line therapy for LS.

The treatment of vulvar lichen sclerosus and female sexual dysfunction.

INTRODUCTION: Women with lichen sclerosus (LS) are more likely to have dyspareunia, decreased orgasm, and decreased coital frequency as compared to unaffected women. It is unknown whether standard medical therapy to treat LS results in improved sexual functioning. AIMS: To describe sexual function in women with LS and to assess if LS-associated sexual dysfunction decreases after appropriate medical therapy. METHODS: Women enrolled in a double-blind trial 12-week trial comparing clobetasol vs. pimecrolimus for the treatment of LS were administered the Female Sexual Distress Scale (FSDS) upon enrollment and at the end of the trial. The difference in the total score on the FSDS between the two groups before and after treatment was assessed with a paired t-test. MAIN OUTCOME MEASURES: The change in mean FSDS score from baseline to 12 weeks. RESULTS: A total of 31 out of 36 enrolled women had adequate treatment of LS as determined by a dermatopathologist's evaluation of pre and post-treatment biopsy specimens. The mean baseline FSDS score for the clobetasol group was 29 and, post-treatment, it was 15 (P=0.001). In the pimecrolimus group, the mean baseline FSDS score was 27 and, post-treatment, it was 21 (P=0.001). CONCLUSIONS: Despite adequate treatment, women with LS continue to have significant sexual dysfunction as assessed by the FSDS.

Parturition after vestibulectomy.

INTRODUCTION: Provoked vestibulodynia is the most common cause of sexual pain in premenopausal women. Vulvar vestibulectomy has been shown to be an effective treatment. AIM: To determine the optimum route of parturition in women who become pregnant after vulvar vestibulectomy. METHODS: All women who underwent a complete vulvar vestibulectomy by one of four surgeons were contacted between 12 and 72 months after surgery. For all women who had a term pregnancy and subsequent delivery, the research assistant abstracted data from the charts. Descriptive statistics were applied. MAIN OUTCOME MEASURES: The number of women who underwent a delivery after a vestibulectomy, mode of delivery, and rate of perineal lacerations. RESULTS: Of 109 women, 44 (40%) had undergone at least one term pregnancy and delivery; 23 (52%) were vaginal, and 21 (48%) were cesarean deliveries. Of the vaginal deliveries, 11 (48%) were over an intact perineum. Three (13%) women had a midline episiotomy, none of which extended into third or fourth degree lacerations and one woman (4.4%) sustained a spontaneous fourth degree perineal laceration. CONCLUSIONS: Vaginal delivery after vulvar vestibulectomy appears to be a safe option, with no increased perineal morbidity above the general population. Furthermore, it is not an indication for a cesarean delivery.

Etiology and treatment of overactive bladder in women.

Overactive bladder (OAB) is a condition that affects millions of women in the United States (US). Although the etiology is largely unknown, risk factors include Caucasian race, insulin-dependent diabetes mellitus, and history of depression. Patients present with urgency with or without urinary incontinence and often have urinary frequency and nocturia. Most patients can be evaluated in the office setting utilizing simple testing. Current treatments consist of behavioral/lifestyle modification, usually in combination with antimuscarinic drug therapy. Improvements in the adverse effect profiles of antimuscarinic drugs have positively impacted quality of life. When appropriately evaluated, most patients presenting to primary care providers can be effectively treated.

Prophylactic bilateral oophorectomy or removal of remaining ovary at the time of hysterectomy in the United States, 1979-2004.

OBJECTIVE: The purpose of this study was to describe national rates and trends of prophylactic bilateral oophorectomy or remaining oophorectomy (BO/RO) at hysterectomy in women without specific gynecologic disease. STUDY DESIGN: Data from the National Hospital Discharge Survey were analyzed for 1979-2004. Hysterectomies were divided into 2 groups: (1) hysterectomy with BO/RO and (2) hysterectomy alone (> or =1 ovary remaining). Age-adjusted rates (AARs) were calculated with 2000 US census data. RESULTS: Approximately 3,686,000 hysterectomies with BO/RO were performed from 1979-2004. AARs of hysterectomy with BO/RO decreased during this period; the AARs in women > or =50 years old increased. The number of hysterectomies alone was 5,461,100, and AARs of hysterectomy alone decreased significantly from 2.9 per 1000 women in from 1979-1981 to 1.1 per 1000 women in 2001 (P < .001). The proportion of women who underwent hysterectomy with BO/RO increased from 29% in 1979 to 45% in 2004. CONCLUSION: Although AARs of prophylactic BO/RO decreased from 1979-2004, the actual proportion of BO/RO at hysterectomy increased.

Lower urinary tract symptoms in women with pelvic organ prolapse.

INTRODUCTION AND HYPOTHESIS: The objective of this study was to describe lower urinary tract symptoms (LUTS) and urinary incontinence (UI) symptoms in women with prolapse. METHODS: LUTS were measured with the urinary distress inventory (UDI) and UI symptoms with UDI and the Medical, Epidemiological and Social Aspects of Aging (MESA) in women with POPQ stage >or=I support. UI symptoms were classified as stress- or urge-only, stress-predominant or urge-predominant mixed, or mixed. Bladder function was assessed by urodynamics. Bi- and multivariable analyses were performed. RESULTS: Three hundred thirty-six women aged 62 +/- 13 years were characterized by UDI scores as having mixed 72% (n = 242), urge-only 24% (n = 80), and stress-only <1% (n = 1) UI symptoms. Of subjects with mixed UI symptoms, 57% (n = 137) were stress-predominant and 43% (n = 105) were urge-predominant. In multivariable regression models, advancing age and prolapse were associated with less reported distress related to stress UI symptoms. Prior hysterectomy was associated with higher total UDI scores. Similar findings were noted with MESA. CONCLUSIONS: Mixed UI symptoms are the predominant symptom type in women with POP.

Umbilical hypersensitivity in women with primary vestibulodynia.

OBJECTIVE: To provide evidence that primary vestibulodynia (PV) is a congenital defect in tissue derived from the primitive urogenital sinus. STUDY DESIGN: Twenty-two women with PV, 16 with secondary vestibulodynia (SV) and 8 controls were included in this study. Subjects underwent a complete history and physical examination, including assessment with a vulvalgesiometer to measure the sensory and pain detection thresholds in the vulvar vestibule, deltoid and umbilicus. RESULTS: The median vestibular sensitivity was 5 g in the PV group and 10 g in the SV group (p= 0.77). The median umbilical pain thresholds for the PV, SV and control groups were 115, 675 and 500 g, respectively. Women with PV displayed a significantly higher level of umbilical sensitivity (a substantially lower pain threshold) compared with women with SV and the control group (p = 0.0001 and 0.002, respectively). There was no difference in umbilical sensitivity between the SV and control groups. CONCLUSION: Because both the umbilicus and vulvar vestibule are derived from primitive urogenital sinus, this suggests that women with PV may have a congenital abnormality in urogenital - sinus-derived epithelium.

The vulvar dermatoses.

INTRODUCTION: Dermatologic diseases of the vulva may cause dyspareunia. These disorders may be overlooked by gynecologists and urologists because of lack of residency training experience. Dermatologists who are most familiar with these diseases are infrequently trained in vulvovaginal examination. As such, these disorders are often improperly diagnosed and treated. AIM: To describe the presentation and management of the major vulvar dermatoses including irritant and allergic contact dermatitis, lichen sclerosus, lichen simplex chronicus, and lichen planus. MAIN OUTCOME MEASURE: Data from a peer review literature search on the topic of vulvar dermatoses. METHODS: The literature for this review article was obtained through a Medline search. Appropriate dermatology textbooks were utilized for additional information. RESULTS: A comprehensive survey of the vulvar dermatoses. CONCLUSION: Vulvar dermatoses must be considered a part of the differential diagnosis of any woman with a sexual pain disorder. As such, healthcare providers who evaluate and treat women with dyspareunia must become familiar with the most common dermatologic disorders of the vulva.

Pimecrolimus cream 1% for treatment of vulvar lichen simplex chronicus: an open-label, preliminary trial.

BACKGROUND: To evaluate efficacy and safety of pimecrolimus cream 1% twice daily for treatment of vulvar lichen simplex chronicus (LSC). METHODS: Patients in this 12-week, open-label study had biopsy-proven vulvar LSC. Inclusion criteria were patient-reported Visual Analog Scale for Pruritus Relief > or = 3 (VAS-PR, 0 cm = no itching to 10 cm = severe itching) and Investigator's Global Assessment > or = 2 (IGA, 0 = no disease to 3 = severe disease). Safety was evaluated by adverse event reports and pimecrolimus blood level measurements. RESULTS: Twelve women aged 25-53 years were enrolled. The median pruritus score (VAS-PR) decreased from 6 (min. 4.9, max. 9.0) at baseline to 0 cm at week 4 (max. 4.2), week 8 (max. 3.1) and week 12 (max. 2.1). Seven patients reported complete resolution of pruritus by week 4. Median IGA decreased from 2.5 (min. 2, max. 3) at baseline to 0 (min. 0, max. 2) at week 12. Erythema, excoriation, and lichenification improved for all patients. Pimecrolimus blood concentration for all samples was below the limit of quantification, 0.3 ng/ml. No adverse events were reported. CONCLUSIONS: In this exploratory study, signs and symptoms of vulvar LSC improved for all women and pimecrolimus cream showed a favorable safety profile. Larger prospective studies are needed to further evaluate pimecrolimus for treatment of vulvar LSC.

Risk factors for primary and subsequent anal sphincter lacerations: a comparison of cohorts by parity and prior mode of delivery.

OBJECTIVE: This study was performed to assess the effect of pregnancy, route of delivery, and parity on the risk of primary and subsequent anal sphincter laceration in women at first vaginal delivery (1st VD), vaginal birth after cesarean delivery (VBAC), or second vaginal delivery (2nd VD). METHODS: This retrospective cohort study used data from a perinatal database that included all deliveries at Magee-Womens Hospital from 1995 to 2002. Anal sphincter laceration was the primary outcome, defined as third- and fourth-degree perineal lacerations. The adjusted odds ratio (OR) for primary and subsequent anal sphincter laceration at delivery by risk group was estimated using logistic regression models and reported with 95% confidence intervals (CIs). RESULTS: We assessed 20,674 live, singleton, term deliveries at Magee-Womens Hospital from 1995 to 2002, including 13,183 with 1st VD, 6068 with 2nd VD, and 1423 with VBAC. Anal sphincter laceration occurred in 16% of women with 1st VD, 18% with VBAC, and 3% with 2nd VD. Multivariable logistic regression modeling for primary anal sphincter laceration showed that 1st VD had OR of 5.1 and 95% CI 4.4, 5.9, and VBAC had OR of 5.1, 95% CI 4.2, 6.2 when compared with the reference group with 2nd VD. Shown in order for 1st VD, VBAC, and 2nd VD, the following factors, adjusted for the other listed factors, were significantly related to anal sphincter laceration except as noted: forceps, ORs of 3.0, 2.6, 5.5; midline episiotomy, ORs of 2.7, 2.9, 2.9; infant birth weight 3500 g or more, ORs of 1.9, 1.9, 1.1, not significantly different from OR of 1.0; vacuum delivery, ORs of 1.7, 1.8, 1.5, not significantly different from OR of 1.0, and 2nd stage of labor 2 hours or longer, ORs of 1.8, 0.9, 0.9, last 2 not significantly different from OR of 1.0. Of women who had anal sphincter laceration in their first vaginal delivery, 7.2% (76 of 1054 women who had 2 pregnancies) had recurrent laceration in their second vaginal delivery, compared with 2.3% (123 of 5147) of women who had a primary anal sphincter laceration in their second vaginal delivery. Multivariable logistic regression modeling for recurrent anal sphincter laceration yielded the following significant factors: episiotomy, OR 8.5, 95% CI 4.1, 17.7; vertex malpresentation (primarily occiput posterior), OR 4.3, 95% CI 1.4, 12.6; shoulder dystocia, OR 2.7, 95% CI 1.2, 5.8; and infant birth weight 3500 g or greater, OR 1.7, 95% CI 1.1, 2.7. CONCLUSION: At this institution, women undergoing VBAC are at similarly high risk of anal sphincter laceration, compared with nulliparous women. Women with prior anal sphincter laceration are at 3 times increased risk for subsequent sphincter laceration, compared with women with prior vaginal delivery without sphincter laceration. Pregnancy by itself does not appear to be an important factor in decreasing the risk of anal sphincter laceration in subsequent deliveries.