Abstract
Although women with vulvodynia typically have increased vulvar sensitivity, data on characteristics associated with the degree of vulvar sensitivity are lacking. We measured vulvar sensitivity by cotton swab test and vulvodolorimeter among a subset of 335 women, ages <70 years, in the longitudinal Woman to Woman Health Study. Comparing the vulvodynia screening results from their online/paper survey to that at the time of the examination, 42 cases had ongoing vulvodynia, 66 cases had a recent remission, 22 controls now had a recent onset of vulvodynia, and 205 controls remained asymptomatic. Vulvar sensitivity was greater in each vulvodynia group compared to controls (P<0.001), and was associated with younger age at first onset of pain (p=0.025), pain after intercourse (p=0.008), describing the pain as a “pressure,” “burning,” or “irritating” (p=0.015, p=0.005, and p=0.006, respectively), with increased severity of pain ever (p=0.012), and with subsequent persistent or relapsing vulvodynia (p<0.001 for each). A score of >1 for the cotton swab summary score best differentiated cases from controls (sensitivity 71.9%; specificity 72.0%). Although 13.8% of women with vulvodynia had no increased sensitivity on cotton swab testing, they did not differ in most clinical characteristics or clinical course from those with increased vulvar sensitivity.
Perspective: This study demonstrated that women with vulvodynia have more vulvar sensitivity than controls, but the spectrum of sensitivity is broad. Furthermore, those with and without vulvar sensitivity did not differ in most vulvar pain characteristics or in prognosis, suggesting a positive swab test is not required to substantiate the diagnosis.
Keywords: Vulvodynia, vulvar sensitivity, vulvodolorimeter, cotton-swab test, diagnosis
Vulvodynia is a relatively common chronic pain disorder that is frequently misdiagnosed.20, 33 Vulvar hypersensitivity, as measured by exerting pressure with a cotton swab or quantitative vulvodolorimeter, has been documented to be increased among groups of women with vulvodynia, compared to those without.5, 19 However, the current consensus statement on vulvodynia describes vulvodynia (as opposed to vulvar pain caused by a specific disorder) as “vulvar pain of at least 3 months duration, without clear identifiable cause, which may have potential associated factors”.8 Yet, it remains unclear whether all women with symptoms of vulvodynia have vulvar sensitivity to pressure. Since most studies on vulvar sensitivity have been conducted at one point in time, it is unknown whether the presence or magnitude of the vulvar sensitivity predicts clinical course or other outcomes (treatment response, natural history, etc.). In addition, the relative benefits of using the cotton swab test versus a more quantitative vulvar pressure device are unclear.1
Risk characteristics for vulvar sensitivity were assessed in this study, with attention to characteristics associated with vulvar sensitivity in general and those associated with characteristics of pain with vulvodynia. In addition, we evaluated the relationship between results of cotton swab testing and the vulvodolorimeter to determine whether the clinically expedient, but less quantitative, cotton swab test is a reasonable tool for use in the office and in research. Lastly, we assessed whether the presence of vulvar sensitivity predicted the clinical course of vulvar symptoms, and whether the lack of enhanced vulvar sensitivity negates the vulvodynia diagnosis.
Methods
Study design
This study was approved by the University of Michigan Medical IRB (HUM17098), and informed consent was obtained. In 2008, 2542 women aged 18 and over, living in a four-county area in southeast Michigan, were enrolled via random-digit dialing for the Woman to Woman Health Study (a.k.a. the Longitudinal population-based study of vulvodynia). Of those enrolled, 2269 completed the initial 26-page survey which inquired about demographics, health status, and detailed information about past and present vulvar symptoms. It also included validated screening instruments for vulvodynia,31 for several comorbid pain conditions (fibromyalgia,9, 39 interstitial cystitis,4 and irritable bowel syndrome12, 37), and for depression and PTSD (post-traumatic stress disorder).24, 28 Follow-up surveys were sent every six months for three years to assess changes in symptoms and in risk factors.
Women who screened positive for vulvodynia and a random sample of those who screened negative were contacted by telephone and invited to have a clinical examination. Five attempts were made to reach each selected woman. Office visits were offered on weekdays and Saturday mornings and a payment of $40 to offset time and travel was provided.
Two research assistants conducted all the in-office examinations. At the beginning of the study, they worked together to assure they conducted the interviews and examinations in a consistent manner. At the visit, an in-office computer-assisted interview was conducted by one of two research assistants, asking about current symptoms, and re-screening with the previously verified vulvodynia criteria (pain at the opening to the vagina (introitus) for three or more months, that has not resolved), in order to document changes in screening outcome since the previous survey.31, 35 A standardized gynecologic examination was conducted that concentrated on the external genitalia, the vulvar region, and the vagina, including presence of erythema, swelling, discharge, and other dermatologic changes. Discharge from the lateral walls of the vagina was obtained and assessed for pH amine odor on application of KOH (whiff test), microscopic examination findings, and Candida culture. Any woman with a visible vulvar dermatosis or symptoms in the presence of vaginal Candida was excluded.
Two methods were utilized to assess vulvar sensitivity, including the semi-quantitative cotton swab test, and the vulvodolorimeter quantitative assessment. The cotton swab test consisted of exerting mild pressure (indentation of the skin/membrane gently to 1/3 centimeter depth) perpendicular to the tissue at seven sites – left and right posterior interlabial sulci; 5-, 6-, and 7-o’clock positions of the introitus; and 8- and 4- o’clock positions of the hymen. Participants rated each pressure as zero (no discomfort), 1 (mild discomfort), 2 (moderate discomfort), or 3 (severe discomfort). If discomfort was present, the participant was asked to describe the discomfort (i.e., burning, sharp, prickly, pressure, irritation, itch, etc.).
The vulvodolorimeter consisted of a calibrated hand-held pressure-based device used in our previous research,19 that consisted of two low-resistance 6-cc syringes, a three-way stopcock, and a disposable three-inch Dacron swab (Figure 1). A small hole had been drilled in the plunger of the syringe to allow the swab to be inserted. Pressure applied to the swab would allow the plunger to compress the air in the syringe (set at the beginning of each test to the maximum cc’s of the syringe), and the level of the plunger when the participant first felt discomfort, and the level at which the discomfort was moderately severe, were determined and recorded. The vulvodolorimeter was calibrated using a desktop scale to determine the grams of pressure exerted at each ½ cc of excursion of the plunger. The greatest pressure measurable with the vulvodolorimeter was 1500 g, and hence the data was right censored at this level. Vulvar sensitivity (minimal and maximal) as measured using the vulvodolorimeter was determined at 17 sites – 2 at the upper leg (R and L), 4 at the labia majora (right and left anterior and posterior), 4 at the interlabial sulci (right and left anterior and posterior), 5 at the introitus (10-, 2-, 5-, 7-, and 6-o’clock), and 2 at the hymen (5- and 7-o’clock), with scoring at each site varying from 31 grams (least pressure measurable) to 1500 grams (maximal pressure measurable).
Figure 1.
Vulvodolorimeter, consisting of 2 low-resistance 6-cc syringes, connected by a three-way stopcock. One syringe had a small hole bored in the piston for insertion of a 3” cotton-swab for use in applying pressure (designed by R. Gracely, PhD).
Statistical Analysis
Data entry from the surveys was performed by professional data entry organizations, and examination data was entered by the department data manager using double data entry verification.
Patient characteristics at the time of in-office examination and clinical case status were compared using analysis of variance and chi-square tests. The relationship between vulvar sensitivity using the cotton swab test categorized as negative (score=0) or positive (score>0) with that using the vulvodolorimeter (31 grams to censored at 1500 grams) was obtained using a log-rank test at each site. Several cotton-swab summary scores were constructed by summing individual site scores together: hymen sites, introitus sites, interlabial sites and hymen and introitus sites together. ROC curves were constructed for each score and equality tested between scores to find the optimal score and resulting cutoff that maximized sensitivity and specificity. A score based on the areas of most likely vulvar sensitivity (summation of three introital and two hymenal sites) was created and used to quantify vulvar sensitivity through the rest of the analysis.
Demographic characteristics and the presence of pain and psychological comorbidities were compared across the different clinical case groups using analysis of variance (ANOVA) and chi-square tests. The association of vulvar sensitivity with case status, demographics, and presence of comorbid pain conditions were assessed using Pearson correlations and ANOVA. Similar analysis was carried out to compare characteristics of vulvar pain with vulvar sensitivity among cases. Vulvar sensitivity was assessed across the four clinical case groups using ANOVA and pairwise comparisons with p-values adjusted for multiple comparisons. This association was further evaluated using linear regression models adjusting for age, ethnicity, difficulty paying for basics, or presence of one or more comorbid conditions. Characteristics of those with and without increased vulvar sensitivity who screened positive for vulvodynia were compared using chi-square and independent sample t-tests to assess whether presence of sensitivity distinguishes two groups of varying quality and clinical course.
We continued to follow all the women in the Woman to Woman Health Study throughout three years following their initial enrollment. Those women coming in for an in-office examination with sensory testing therefore often completed a number of surveys in the years after that examination. We determined the number of women who had at least four follow-up surveys (approximately two years) after their examination, and assessed their clinical course following their clinical examination as “remission without relapse,” “relapse following remission,” or “persistence.” We also assessed among controls whether they later screened positive for vulvodynia during the study. Average vulvar sensitivity across clinical courses and between cases that later screened positive for vulvodynia and those who remained controls was assessed using ANOVA.
Results
Participants
Over the course of the study, 443 out of 657 invited (67.4%) study participants presented for an initial in-office examination. Of these, 415 were ≤70 years of age and eligible for this analysis. Further excluded were 76 women who denied vulvar pain but who were not sexually active in the past six months. For many women the presence of vulvar pain is only present when provoked (often only by intercourse), hence making the history of no vulvar pain unclear for making the diagnosis of case or control in these women. In addition, 4 women had no vulvar sensitivity measures recorded. Hence, 335 women were included in the analysis – 108 who had screened positive for vulvodynia, and 227 controls. Although 5 women reported female partners and 1 reported both male and female partners (1.8% of those included), they were not excluded from the analysis since they were sexually active.
Categorization of Case Status
Our previous work suggested remission of vulvar symptoms, and new onset of symptoms, occurs fairly commonly among women.34, 35 Because the average number of days from completion of the online or paper survey to the day of the in-office examination was 66 +/−44 days, the vulvodynia screening test was repeated at the examination in order to subcategorize those with changing symptoms. Compared to the screening results on their most recent online or mailed survey, 247 (73.7%) of women had consistent screening results at the time of in-office examination including 42 (38.9%) of cases (ongoing case) and 205 (90.3%) of controls (ongoing controls). Changes in the screening results were noted in 88 (26.6%) of the women (Table 1; 66 (61.1%) of those recently screening positive now reported symptoms had abated (resolving cases) and 22 (9.7%) of those screening negative originally now screened positive (recent case). These four categories were therefore used in the analysis to clarify any differences in outcomes.
Table 1.
Clinical status of women examined, based on vulvodynia screening test online or on paper prior to the visit, and the results on the same test at the time of the visit.
| Vulvodynia screen results prior to in-office examination |
Vulvodynia screening results at the time of the in-office examination |
||
|---|---|---|---|
| Positive screen N (%) |
Negative screen N (%) |
Total N (%) |
|
| Positive (presumptive cases) | 42 (12.5%, Persistent cases) | 66 (19.7%, Resolving case) | 108 (32.2%) |
| Negative (presumptive controls) | 22 (6.6%, Recent case) | 205 (61.2%, Persistent control) | 227 (67.8%) |
| 64 (19.1%) | 271 (80.9%) | 335 (100%) | |
The relationships between the clinical case status with demographic characteristics and the presence of other comorbid conditions are shown in Table 2. The average age of participants was 44.3±13.2 years (range 18–70 years), and the average number of surveys completed during the Woman to Woman Health Study was 5.6±0.9 (range 1–6): neither differed significantly among the four subgroups (p=0.50 for age, and p=0.76 for numbers of survey completed, data not shown). Pairwise comparisons indicated controls had a higher proportion of Black individuals, had less difficulty paying for basics, had fewer comorbid pain conditions, and had fewer individuals screening positive for depression. No difference was noted between these four groups in marital status, education, or number of surveys ultimately completed in the longitudinal study.
Table 2.
Demographic, Comorbid Pain, and Psychological Characteristics of Women at Time of Their First in-office Examination (N=335)
| Characteristics | Clinical Case Categories | |||||
|---|---|---|---|---|---|---|
| Overall (N=335) % (N) |
Ongoing Case (N= 42) % (N) |
Resolving Case (N=66) % (N) |
Recent Case (N=22) % (N) |
Ongoing Control (N=205) % (N) |
P value |
|
| Married | 76.1 (255) | 78.6 (33) | 80.3 (53) | 81.8 (18) | 73.7 (151) | 0.604 |
| Ethnicity/race | 0.026 | |||||
| White | 77.0 (258) | 88.1 (37) | 86.4 (57) | 63.6 (14) | 73.2 (150) | |
| Black | 15.8 (53) | 4.8 (2) | 10.6 (7) | 13.6 (3) | 20.0 (41) | |
| Hispanic | 3.3 (11) | 4.8 (2) | 1.5 (1) | 9.1 (2) | 2.9 (6) | |
| Other | 3.9 (13) | 2.4 (1) | 1.5 (1) | 13.6 (3) | 3.9 (8) | |
| College graduate | 63.3 (212) | 57.1 (24) | 66.7 (44) | 54. (12) | 64.4 (132) | 0.607 |
| Household income >60K* | 62.8 (187) | 48.7 (19) | 58.2 (32) | 57.1(12) | 67.8(124) | 0.110 |
| Hard to pay for basics† | 32.8 (110) | 53.7 (22) | 31.3 (20) | 40.9 (9) | 29.8 (59) | 0.025 |
| Comorbid pain conditions present by screen at time of exam‡ | ||||||
| Fibromyalgia | 10.2 (34) | 26.2 (11) | 13.6 (9) | 18.2 (4) | 5.0 (10) | <0.001 |
| Interstitial cystitis | 11.1 (37) | 21.4 (9) | 19.7 (13) | 9.1 (2) | 6.4 (13) | 0.003 |
| Irritable bowel disorder | 16.3 (54) | 33.3 (14) | 25.8 (17) | 27.3 (6) | 8.4 (17) | <0.001 |
| Any of the 3 above | 25.7 (86) | 42.9 (24) | 42.4 (38) | 36.4 (14) | 15.6 (173) | <0.001 |
| Psychologic disorders present by screen at time of exam | ||||||
| PTSD | 11.7 (39) | 11.9 (5) | 15.2 (10) | 4.5 (1) | 11.3 (23) | 0.595 |
| Depression | 15.2 (51) | 14.3 (6) | 25.8 (17) | 36.4 (8) | 9.8 (20) | <0.001 |
Household income only reported by 298 (89.0%).
Hard to pay for basics reported by 325 (97.0%).
Comorbid pain conditions available for 332 (99.1%).
Vulvar Sensitivity
Scoring for the cotton swab testing ranged from 0 (no vulvar sensitivity) to 3 (severe vulvar sensitivity) at each of the 7 sites (introitus and hymen) tested. Vulvar sensitivity (minimal and maximal) as measured using the vulvodolorimeter was determined at 17 sites (see methods). The values for the vulvodolorimeter were right censored due to there being a maximum pressure of 1500 grams exerted – a level that did not cause discomfort in a substantial number of women. Using a log-rank test (with right censored data), we found that having a positive score (≥1) using the cotton-swab led to higher values on the vulvodolorimeter for each of the introital (5-, 6-, and 7-o’clock) and hymenal (5-, and 7-o’clock) pain threshold levels (p<0.001 for each site tested, Table 3) than when a negative (=0) cotton-swab score was observed. The proportion of values for the cotton-swab test that was greater than 0 (no discomfort) are shown for seven sites (five introital and two hymenal) among the three case groups (ongoing case, new onset and recent remitting cases) and the controls) (Figure 2). As shown, in all groups the most sensitive area was the hymenal remnants, followed by the posterior introitus, and least was the interlabial sulcus.
Table 3.
Relationship between Positive (>0) or Negative (=0) Cotton Swab Scores and Median Vulvodolorimeter Pressures (Minimal Discomfort, Censored at 1500 grams) at Similar Urogenital Sites (N=334, 1 Woman had Missing Values for Vulvodolorimeter Readings)
| Vulvar Site Testing Location | |||||||
|---|---|---|---|---|---|---|---|
| Interlabial sulcus | Introitus | Hymen | |||||
| 7 o’clock |
5 o’clock |
7 o’clock |
6 o’clock |
5 o’clock |
7 o’clock |
5 o’clock |
|
| Vulvodolorimeter (Median ± S.E grams of pressure)* | |||||||
| Negative cotton-swab score (=0) | 751±31 | 707±33 | 441±25 | 584±32 | 441±224 | 624±30 | 624±26 |
| Positive cotton-swab score (>0) | 260±289 | 88±176 | 182±50 | 182±64 | 182±92 | 158±31 | 88±27 |
| P value | 0.731 | 0.001 | <0.001 | <0.001 | <0.001 | <0.001 | <0.001 |
Vulvodolorimeter – lower score = greater vulvar sensitivity; Cotton swab – positive (>0) score = greater vulvar sensitivity.
Figure 2.
Proportion of participants having a positive cotton-swab test (score >0) at each introital and hymenal site, stratified by vulvodynia screening categories.
A summary score was calculated for the cotton swab test using the 0–3 score for each of the three sites in the posterior introitus and the two sites on the hymen (the five sites of maximal discomfort). The mean cotton swab (introitus/hymen) summary score was 1.39±2.54 (SD), with a range of 0 to 13. Among those current vulvodynia cases with tenderness at any of the introital and hymenal sites, the mean cotton swab score was 4.09 +/− 3.09, with an average of 2.83 +/− 1.34 of the 5 sites having at least mild tenderness. No summary score for the vulvodolorimeter was created due to the censored nature of the data.
We assessed the relationships of demographic characteristics, comorbid pain, and psychologic screens with vulvar sensitivity as measured by the cotton-swab summary score. Vulvar sensitivity based on this summary score had an inverse relationship with age (p=0.008) although the relationship was weak (r=−0.144). No relationship was noted between vulvar sensitivity and ethnicity, marital status, household income, difficulty paying for basics, education, comorbid PTSD, depression, irritable bowel disorder, interstitial cystitis, or fibromyalgia.
Vulvar Sensitivity in Vulvodynia Cases Versus Controls
Vulvar sensitivity as measured by the cotton-swab summary score (mean ± S.D.) was greater among those in any of the three case groups (ongoing cases 2.81±3.29, new cases 3.18±3.08, remitting cases 1.86±3.01) and least among controls (0.75±1.81, p=<0.001 overall and between controls and each of the case categories, Figure 3). After adjusting for age, ethnicity, difficulty paying for basics, or presence of one or more comorbid conditions, the association between vulvar sensitivity and case status remained similar.
Figure 3.
Mean and 95% confidence intervals of summary cotton-swab score (3 introitus and 2 hymenal measures), with significant difference between each of the vulvodynia case categories and the control category (p<0.001).
Factors Associated With Vulvar Sensitivity as Measured by Cotton Swab Testing
Urogenital sensitivity varied among women who screened positive for vulvodynia. We therefore assessed whether characteristics of women’s current or historical vulvar pain were associated with the level of vulvar sensitivity as measured by the cotton swab summary scores. The three case subgroups did not differ statistically (p<0.05) in the pain characteristics shown in Table 4. However, some characteristics were associated with the level of vulvar pain determined by the summary cotton-swab score (Table 5). These included increase vulvar sensitivity (introitus and hymen) in association with younger age at first vulvar pain, describing pain as burning or pressure and not as irritation, having provoked pain, pain after intercourse, and a higher rating of worst vulvar pain ever. Of note, vulvar sensitivity was not associated with whether pain had been present since first tampon use or first intercourse (measures of primary versus secondary vulvodynia), with the presence of spontaneous pain (with or without provoked pain), or with having other positive screens for comorbid pain conditions (IBS, IC, and/or fibromyalgia), or screening positive for depression or PTSD.
Table 4.
Prevalence of Pain Characteristics among the Various Case Categories (N=130)
| Characteristics | Case Status by Category (incident, persistent, remission) |
|||
|---|---|---|---|---|
|
| ||||
| Ongoing Case (N= 42) |
Recent Case (N=22) |
Resolving Case (N=66) |
P value | |
| Age first pain with intercourse (years, mean±SD) | 30.0±14.9 | 28.2±3.1 | 28.7±13.0 | 0.883 |
| Duration of pain (years, mean±SD) | 9.3±9.8 | NA | 11.3±11.6 | 0.469 |
| Worse pain ever (0 none to 10 severe, mean±SD) | 5.9±2.9 | 5.8±2.9 | 5.5±2.9 | 0.694 |
| Worse pain past 6 months (0 none to 10 severe, mean±SD) | 5.2±2.4 | 3.7±2.4 | 4.3±2.6 | 0.083 |
| Pain since | ||||
| 1st tampon use | 40.5% | 50.0% | 31.0% | 0.266 |
| 1st Intercourse | 42.9% | 63.6% | 39.3% | 0.138 |
| Characteristics of pain | ||||
| Burning | 61.9% | 44.4% | 43.9% | 0.168 |
| Pressure | 35.7% | 22.2% | 27.3% | 0.497 |
| Sharp | 26.2% | 27.8% | 24.2% | 0.944 |
| Stab | 9.5% | 16.7% | 9.1% | 0.631 |
| Itch | 31.0% | 22.2% | 24.2% | 0.681 |
| Irritated | 61.9% | 61.1% | 54.5% | 0.720 |
| Raw | 42.9% | 50.0% | 45.5% | 0.877 |
| Spontaneous pain | 43.9% | 25.0% | 32.3% | 0.313 |
| Provoked pain | 83.3% | 88.9% | 81.5% | 0.761 |
| Pain after intercourse | 88.1% | 100.0% | 89.2% | 0.321 |
| Screening positive for one or more comorbid pain conditions | 42.9% | 36.4% | 42.4% | 0.863 |
| Screening positive for depression | 14.3% | 36.4% | 25.8% | 0.126 |
| Screening positive for PTSD | 11.9% | 4.5% | 15.2% | 0.421 |
Table 5.
Association between Vulvar Sensitivity (Cotton-Swab Summary Score from Introitus and Hymen) and Pain Characteristics among Those Screening Positive for Vulvodynia (N=130)
| Characteristics | Association between pain characteristics and the cotton-swab summary score* |
|
|---|---|---|
| Beta† | P value | |
| Age first pain with intercourse | −0.204 | 0.025 |
| Duration of pain (years) | 0.18 | 0.587 |
| Pain since | ||
| 1st tampon use | −0.218 | 0.717 |
| 1st Intercourse | −0.118 | 0.838 |
| Characteristics of pain | ||
| Burning (126) | 1.365 | 0.015 |
| Pressure | 1.718 | 0.005 |
| Sharp | 0.830 | 0.204 |
| Stab | −1.025 | 0.273 |
| Itch | −0.023 | 0.971 |
| Irritated | −1.557 | 0.006 |
| Raw | 0.554 | 0.333 |
| Spontaneous pain | −0.983 | 0.115 |
| Provoked pain | 1.917 | 0.047 |
| Pain after intercourse | 1.558 | 0.008 |
| Worse pain ever (1 to 10) | −0.139 | 0.012 |
| Worse pain past 6 months (1 to 10) | −0.084 | 0.207 |
| Screening positive for one or more comorbid pain conditions | 0.184 | 0.743 |
| Screening positive for depression | −0.219 | 0.737 |
Linear regression using cotton swab summary score of three introitus and two hymen measures as outcome and listed variable as predictor.
Positive beta = greater vulvar sensitivity.
Relationship Between Vulvar Sensitivity and Prognosis
We assessed the ongoing clinical course as determined by surveys sent every 6–12 months over the 36 months of the data collection. As shown in Figure 4, those women who continued to screen negative for vulvodynia throughout the course of the Woman to Woman Health Study were more likely to have a lower cotton swab summary score (less sensitive) than were cases who recently remitted, those who had a relapse, and persistent cases who continued to have a positive vulvodynia screen (p=<0.001). Among 205 initial controls, the cotton swab summary score was greater in women who would subsequently screen positive for vulvodynia over the following four surveys (N=47) versus those who would never screen positive over the course of the three-year study (N=158) (1.53±2.95 vs, 0.53±1.26, p=0.03).
Figure 4.
Relationship between Clinical Course over The 36 Months of the Woman to Woman Health Study and Vulvar Sensitivity as Measured by the Cotton Swab Summary Score (Mean ± SD) at the Time of The In-Office Examination (N=268, p<0.001).
Vulvar Sensitivity Value Cut-off to Predict Positive Versus Negative Case Status
To assess the most accurate cut-off value for distinguishing vulvodynia cases from controls, ROC analyses were performed using the cotton swab summary score with the vulvodynia screening results at the time of the examination as the gold standard. The ROC curve for the cotton swab summary score determined an area under the curve of 0.728 (95% CI 0.657–0.800), and indicated that optimizing both sensitivity and specificity was reached at a cut-off score of 1 or greater for the sum of cotton swab scores in the introitus and hymen (sensitivity 71.9% and specificity 72.0%, Figure 5). This was repeated for summary scores of the hymen alone, introitus alone, interlabial sulcus alone, and hymen and introitus together, as shown in Table 6. Statistically comparing the AUC values across the scores found that the hymen and introitus score was significantly higher than all others (p-values=.036, .037 and <0.001 for hymen alone, introitus alone and interlabial alone, respectively).
Figure 5.
ROC curve assessing the cotton-swab summary score (3 introital and 2 hymenal sites) best predicting vulvodynia (AUC = 0.728).
Table 6.
Sensitivity and Specificity of Cotton Swab Summary Scores, Based on Differing Sites of Testing and Different Cut-off Scores
| Area under curve | Cotton-swab summary score Cut-off |
Sensitivity | Specificity | |
|---|---|---|---|---|
| Hymen alone | 0.692 (0.616, 0.768) | 1 | 0.63 | 0.75 |
| Introitus alone | 0.678 (0.598, 0.758) | 1 | 0.50 | 0.86 |
| Interlabial sulcus | 0.546 (0.463, 0.629) | 1 | 0.11 | 0.98 |
| Hymen and Introitus | 0.728 (0.657, 0.800) | 1 | 0.72 | 0.72 |
A similar ROC analysis was conducted using individual threshold pressures exerted by the vulvodolorimeter at the introitus (range 50 grams to 1500 grams). The best cut-off was found at the 6 o’clock position of the introitus (area under the curve of 0.643) at a pressure of 529 or less grams at which the sensitivity was 60.9% and specificity was 56.6%.
Characteristics of Women Screening Positive for Vulvodynia by Survey, Yet Having a Negative Cotton Swab Test
Of the 64 women screening positive for vulvodynia at the time of the in-office examination, 18 (28.1%) were negative on cotton swab testing at all five sites used for the summary score (three sites at the posterior introitus and two sites at the hymenal remnants).
Differences and similarities between vulvodynia cases who did have vulvar sensitivity (>=1 on cotton swab summary score) compared to those who did not are shown in Table 7. Those without altered vulvar sensitivity by the cotton swab test were likely to have had pain a shorter period of time (p=0.04) and to not have pain after intercourse (p=0.03). However, they were equally likely to have persistent pain over the subsequent 2 years, to have a remission, and to relapse after remission, as were those with more severe vulvar sensitivity.
Table 7.
Comparison of Vulvodynia Cases (by History) with and without Vulvar Sensitivity by Cotton Swab or Vulvodolorimeter Summary Scores with Demographic Variables, Vulvar Pain Characteristics, and Clinical Course
| Vulvar sensitivity by cotton swab* | |||
|---|---|---|---|
| Demographics | Score of 0 (Not sensitive) N=18 |
Score ≥1 (Sensitive) N=46 |
P value |
| Age (mean ± SD in years) | 47.9±12.9 | 41.9±14.0 | 0.12 |
| Caucasian | 94.4 (17) | 73.9 (34) | 0.07 |
| Vulvar pain characteristics | |||
| Duration (mean ± SD years)† | 3.9±4.1 | 12.2±10.8 | 0.04 |
| Age of onset (mean ± SD years) | 34.2±10.5 | 29.9±14.6 | 0.33 |
| Primary onset | |||
| Pain with first tampon use | 44.4 (8) | 43.5 (20) | 0.94 |
| Pain with first intercourse | 54.3 (25) | 38.9 (7) | 0.27 |
| Provokable | 83.3 (15) | 85.7 (36) | 0.81 |
| Spontaneous pain | 27.8 (5) | 35.9 (14) | 0.55 |
| Pain after intercourse | 55.6 (10) | 82.6 (38) | 0.03 |
| Severity | 0.47 | ||
| Discomfort | 70.6 (12) | 69.2 (27) | |
| Painful to have intercourse | 29.4 (5) | 23.1 (9) | |
| Impossible to have intercourse | 0.0 (0) | 7.7 (3) | |
| Worse vulvar pain ever (0–10) | 5.2±3.0 | 6.2±2.7 | 0.20 |
| Sensations | |||
| Burning | 50.0 (9) | 59.5 (25) | 0.50 |
| Pressure | 22.2 (4) | 35.7 (15) | 0.31 |
| Sharp | 16.7 (3) | 31.0 (13) | 0.25 |
| Stab | 11.1 (2) | 11.9 (5) | 0.93 |
| Itch | 33.3 (6) | 26.2 (11) | 0.57 |
| Irritated | 77.8 (14) | 54.8 (23) | 0.09 |
| Raw | 55.6 (10) | 40.5 (17) | 0.28 |
| Natural history of vulvodynia by screen (≥ 2 years) ‡ | 0.13 | ||
| Persistent | 0.0 (0) | 29.2 (7) | |
| Relapsing | 63.6 (7) | 41.7 (11) | |
| Remission without relapse | 36.4 (4) | 29.2 (7) | |
Sum introitus at 5-, 6- and 7-o’clock, and hymen at 4- and 8-o’clock, rated 0 (none) to 3 (severe pain).
Measure of trend (linear association).
N=35 due to shorter f/u after first positive for some participants diagnosed later in study
Discussion
Although the average level of vulvar sensitivity is increased in women with vulvodynia compared to controls without vulvar pain, the variability in that sensitivity is substantial, with a subset of those with vulvodynia symptoms having no increased sensitivity to vulvar testing, and a subset of asymptomatic control women exhibiting increased vulvar tenderness. We found that the level of vulvar sensitivity was often not associated with demographic characteristics, and only with a small subset of vulvar pain characteristics. The subset of women who did not demonstrate increased vulvar sensitivity to cotton-swab testing, while reporting vulvar pain of a shorter duration, and reporting less likelihood of pain after intercourse, did not differ from those with increased sensitivity in many pain characteristics and in clinical course over the following 2 years. Hence, the measure of vulvar sensitivity appears to be equivalent to other vulvar pain descriptors8 in further defining individual cases, without being necessary, or optimal, for diagnosis.
Vulvar Sensitivity not Currently Part of Vulvodynia Definition/Diagnosis
The role of vulvar sensitivity on examination in confirming the diagnosis and predicting the clinical outcome over time of women with vulvodynia has been controversial. Although early definitions of vulvodynia, such as that by proposed by Friedrich,18 suggested sensitivity to cotton-swab pressure confined to the vulva as one of three criteria for vulvodynia, more recent definitions of the disorder do not include this measure as a criteria for diagnosis.1, 8, 26 Nevertheless, in a survey of vulvodynia investigators, the majority indicated they considered testing for vulvar sensitivity an essential component of their evaluation.32 Similarly, criteria for inclusion in clinical trials often has included a measure of enhanced vulvar sensitivity,11, 15, 17, 31 despite findings that vulvar sensitivity as measured in the office and reports of clinical improvement in the level of pain with intercourse do not correlate well.7 Whether enhanced vulvar sensitivity is a necessary component for vulvodynia diagnosis, and whether level of sensitivity, or even any documented increased vulvar sensitivity in the office predicts severity/pathology/clinical outcomes have remained unclear. Our findings provide further evidence that vulvar sensitivity on examination is not a requisite criterion for the diagnosis of vulvodynia.
QST Can Help Characterize Pain within the Vulvodynia Diagnosis
Although quantitative sensory testing (QST) is not recommended as a stand-alone test for neuropathic pain,3 QST can be utilized to characterize specific attributes associated with, but quite variable within, neuropathic pain disorders (pain in the area of abnormal somatic sensation),2 and may clarify subgroups varying in pathophysiology, clinical course, and probability of symptomatic improvement over time.10, 38 The vulva is ordinarily not very sensitive to pressure testing via QST,14, 29 and pain sensitivity declines with age.14 In addition, vulvar sensitivity has been shown to vary considerably, with some controls quite sensitive to pressure testing at the vulva, and some vulvodynia cases being as insensitive as many controls.16 To further complicate the issue, the reproducibility and standardization of pressure testing at the vulva has varied substantially.41 Nevertheless, the study by Zolnoun41 as well as the current study suggest a substantial correlation between the magnitude of sensitivity at the vulva and the probability of meeting clinical criteria either for vulvodynia or for control status. The more modest sensitivity and specificity found in the current study (72% sensitivity and 72% specificity) compared to that obtained using similar criteria by Zolnoun (85.5% sensitivity and 82.4% specificity) is likely related to differences in the populations studied – with this analysis including a broader age range (<70 years of age versus 21 to 45 year of age) and including women with spontaneous pain and with a negative cotton-swab test who were excluded by Zolnoun and colleagues. Caution is thus advised when suggesting that pressure sensitivity can help diagnose, rather than help characterize, vulvodynia – since the diagnosis of pain disorders, as well as the response to QST testing, is a subjective measure, based on patient report.
Cotton-swab (Qualitative) Testing Versus Vulvodolorimeter (Quantitative)
Various studies have reported on the cotton-swab test and also on the use of devices that allow a more quantitative estimate of vulvar sensitivity.5, 6, 13, 19, 25, 27, 30, 41 Although average values of pain thresholds have differed between studies, and between examiners within a study, data are remarkably consistent that as a group, those with symptoms suggestive of vulvodynia have a lower threshold to pain with pressure than do controls.19, 23, 25, 29, 30, 41 with vulvar sensitivity in the posterior introitus being more pronounced than that anteriorly. 6, 13, 40, 41 The comparisons of the cotton-swab test and the vulvodolorimeter in the current study suggest vulvar sensitivity is well measured by either method, a finding that is consistent with using the more qualitative sensitivity estimate (of severity and pain quality) available with the cotton-swab test in the clinical setting, and using either or both tests in the research setting depending on the goals and requirements of the research question.
Although increased vulvar sensitivity is commonly seen in many studies of vulvodynia, the utility of using this measure as an indication of treatment response has been controversial. Also some have shown an association between intensity of intercourse pain and pain sensitivity by QST,25, 41 others have not,40 and a lack of correlation between changes in vulvar sensitivity as measured by QST with clinical outcomes have been reported by a number of studies on vulvodynia7, 22 as well as in other chronic pain disorders such as fibromyalgia.21
Variability in Vulvar Sensitivity Among Cases and Controls
The importance of the variability of pain sensitivity as measured with QST within both those with symptoms of vulvodynia and within the control groups has garnered little attention to date. Previous reports on vulvar sensitivity tended to list the mean values of pressure sensitivity – without clarification of differences among participants with more vulvar sensitivity versus less, or on the proportion with minimal, if any, alteration in vulvar sensitivity. We therefore assessed whether the level of vulvar sensitivity might provide other details regarding which factors impact the level of vulvar sensitivity noted, whether the vulvar sensitivity is associated with specific characteristics of the vulvar pain itself, and whether it might predict the clinical course (remission, relapse, or persistence) among cases, or new onset of disease among controls. We found level of vulvar sensitivity does differ by age (decreased with advancing age), and several characteristics of the pain (increased in those whose vulvar pain started at a younger age, those with an increase in worst pain ever, in those with provokable pain, those with pain after intercourse, and in those describing cotton-swab discomfort as “pressure” or “burning,” but less if described as “irritating”). Of note, vulvar sensitivity did not differ by ethnicity, marital status, duration of pain, whether pain was primary (with first intercourse or tampon use) or secondary, or whether they had spontaneous pain with or without provokable pain. This differs from the study by Sutton et al in which those with primary vulvodynia had lower pain thresholds than those with secondary vulvodynia.36 We found that if vulvodynia cases were followed over at least two years after first diagnosis in the study, increasing vulvar sensitivity at diagnosis was associated with increased likelihood of either having persistent vulvodynia symptoms, or of relapsing after a remission occurred. Those controls later becoming an incident case tended to have more vulvar sensitivity prior to developing clinical symptoms as well.
Subgroup of Vulvodynia Cases without Increased Vulvar Sensitivity Differ Little from Those with Greater Sensitivity
Assessment of those meeting criteria for vulvodynia for whom no altered cotton-swab sensitivity was found led to several critical findings. Those with minimal or no increased vulvar sensitivity were similar to those with greater sensitivity in the majority of characteristics we assessed. Most importantly, the clinical course over the following two years was very similar among those with a negative test for vulvar sensitivity (but a positive vulvodynia screen) compared to those with greater vulvar sensitivity. This evidence suggests that excluding those without vulvar sensitivity, who otherwise meet criteria for vulvodynia, from getting the diagnosis, or from participating in clinical trials, may be an arbitrary decision that may hinder effective treatment and appropriate assessment of these women.
Limitations
Limitations to this study exist. Not all women invited for an in-office examination were able to come for the visit, often due to time and travel difficulties, and hence some participation bias is possible. In addition, the use of medications that might impact pain sensitivity was not an exclusion for the study for either cases or controls. The analysis was limited to those 70 years of age and younger, and hence, cannot be extrapolated to older women.
Conclusions
These findings indicate that among women with symptoms of vulvodynia, qualitative or quantitative measurement of vulvar sensitivity is not a necessary component of the definition of vulvodynia. However, continued evaluation of the utility of such a measure in assessing subgroups that may have a different clinical course or response to specific treatments continues to be warranted. Further parallel measures of the more qualitative cotton-swab test with a more quantitative vulvar pressure device may be advisable in instances where this level of detail is deemed advantageous – but as cotton-swab tenderness did equally well in predicting vulvodynia in this study as did scores from the vulvodolorimeter, the simple cotton swab tool is of value in clinical diagnosis. Utilization of the five-site summary score (with hymenal as well as introital sites included) has a greater sensitivity and specificity than using any one site alone. Lastly, not all women with vulvodynia, as defined by diagnostic criteria and pain characteristics and clinical course, have increased vulvar sensitivity as measured by QST.
Highlights.
Women with vulvodynia average greater vulvar sensitivity than control women.
The spectrum of vulvar sensitivity among cases and controls is broad.
Presence or absence of vulvar sensitivity did not predict vulvar pain prognosis.
A negative cotton swab test is still consistent with the vulvodynia diagnosis.
Acknowledgments
This study was supported by a grant from National Institute of Child Health and Human Development of the NIH (HD054767). We thank Harriette Hartigan for in-office vulvar sensitivity testing, Yuhong Zhang for data entry and management, and Jill Bowdler for manuscript preparation.
Footnotes
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Disclosures: This study was supported by a grant from National Institute of Child Health and Human Development of the NIH (HD054767). The funder had no role in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the article for publication. The authors declare no conflicts of interest.
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