Topical treatment of vulvodynia, dyspareunia and pudendal neuralgia: A single clinic audit of amitriptyline and oestriol in organogel

Background Vulvodynia and pudendal neuralgia comprise significant contributors to vulvar‐related pain and its impact on daily life. Aim A retrospective clinical audit was conducted at the Women’s Health & Research Institute of Australia, Sydney, to determine the pattern of use and the efficacy of the application of topical amitriptyline 0.5% plus oestriol 0.03% in organogel (AOO), to the vulvar vestibule in reducing the impact of pain on daily life. Materials and Methods There were 1174 patients who received a script from May 2017 until February 2020: 1054 patients agreed to be contacted and had a valid email address. Results There were 376 (35.7%) patients who replied. Pain with intercourse was the main indication for use. Treatment was rated effective by 51.2% (95% CI: 35.4–66.8%) of patients less than 30 years of age, 66.7% (95% CI: 57.3–74.9%) of patients 30–50 years of age, and 58.3% (95% CI: 50.9–65.4%) in patients over 50. Stinging at the site of application was the most commonly reported side effect. Conclusion Topical AOO is an effective and well‐tolerated treatment for vulvar pain.


INTRODUCTION
The impact of vulvodynia and pudendal neuralgia can be significant on a woman's quality of life, affecting her mental health, intimacy, and activities of daily living both socially and occupationally.
Dyspareunia is a common and debilitating condition with a prevalence up to 39.5%. Vulvodynia has an estimated lifetime prevalence varying between 8% and 28%. [1][2][3] Typical symptoms include burning, stinging, itching or stabbing; with the diagnosis being one of exclusion. [2][3][4] Pudendal neuralgia, like vulvodynia, is a pain condition diagnosed clinically in the absence of other pathology. 5 Characteristic symptoms include urinary frequency and urgency, dysuria, dyschezia, vaginal burning, dyspareunia, rectal or vaginal foreign body sensation and sensitivity to touch in the perineum.  individuals (nine physicians, seven allied health practitioners, six lay people). All responses were anonymous to protect patient privacy and they could opt-out at any time via not completing the survey.

MATERIALS AND METHODS
The χ 2 test statistic was used to compare categorical data with statistical significance threshold of P < 0.05. Where the null hypothesis was rejected, post hoc comparisons were made by examining the standard residuals after adjusting the critical z-score value per the Bonferroni method. Logistic regression was performed on dichotomous outcome (ie modelling responses of 'Yes' compared to 'No', responses of 'Not sure' were excluded from regression analysis). Ordinal logistic regression was used to model the association of side effects and duration of use. 18 All regression analyses were adjusted for age and reason for use. All data wrangling and analysis were completed in the R programming language for statistical analysis. 19 Missing data were excluded from analysis.  Reversibility was noted in 53% of patients with resolution of side effects on cessation of AOO.

DISCUSSION
Within the limitations of a retrospective audit, the results indicate that AOO is beneficial in the treatment of pudendal neuralgia type symptoms related to a variety of aetiologies.
The lower response rate to the audit in the younger age group is a commonly observed phenomenon. In a study conducted by Eaker et al., 20 assessing response rates to mailed questionnaires, a marked reduction in response rate was noted in those aged under 35 years. This trend was also noted in another study by Mannetje et al. 21 where younger age was a strong predictor of non-response. In this study, those in the younger age groups were two times less likely to participate. With equivalences in the middle age group and incidence of mesh neuropathy, we believe that the audit sample is representative of the cohort.  There is no evidence (χ 2 test, P = 0.26) to reject the null hypothesis that the relative proportions of outcomes are different between topical amitriptyline 0.5% plus oestriol 0.03% in organogel reasons for use. Counts of responses to each group paring and row percentages of those that responded to this question. There is evidence (χ 2 , P = 0.030) to reject the null hypothesis in favour of the alternative that at least one of the relative proportions of topical amitriptyline 0.5% plus oestriol 0.03% in organogel reasons for use between durations is different than what is expected.
literature detailing adverse effects of topical amitriptyline specifically for treatment of vulvo-vaginal pain. A systematic review evaluating topical amitriptyline for neuropathic pain sited common adverse effects of skin irritation, itching, burning, sedation, dry mouth in addition to cardiac effects of rapid heart rate and palpitations. Of note, the topical preparations comprised of amitriptyline concentrations between 1% and 5%. 22 The majority of side effects reported by 24% of the respondents from this audit were minor and resolved with cessation of application.
Based on the results of this audit, a prospective randomised placebo-controlled study has been designed to further qualify the efficacy of AOO for the treatment of entry dyspareunia. Counts of responses to each group paring and column percentages. With a P-value of 1 (χ 2 test), there is no evidence to reject the null hypothesis that there is a difference to the relative proportions in the number of reported side effects between topical amitriptyline 0.5% plus oestriol 0.03% in organogel reasons for use.