Date Published: January 24, 2019
Publisher: Public Library of Science
Author(s): Dimitrios Chatsiproios, Iris M. Schmidts-Winkler, Lisa König, Clarissa Masur, Christoph Abels, Salomon M. Stemmer.
This open, prospective, multicenter, observational study was performed to investigate the efficacy and safety of a non-hormonal cream in women undergoing breast cancer treatment and experiencing vulvovaginal dryness symptoms. Overall, 128 patients from 22 study centers participated. The cream was applied to the vagina and vulva for 28 days. For the efficacy analysis, changes in subjective symptoms (feeling of dryness, itching, burning, pain independent of sexual intercourse, dyspareunia, urinary incontinence) were evaluated. Additionally, the following objective diagnostic findings were assessed by a physician: thinning of vaginal epithelium, redness, petechiae, and discharge. Safety and tolerability were assessed by evaluating type and frequency of adverse events, including adverse medical device-related effects. The frequency and intensity of all subjective symptoms significantly improved from baseline at 28 days (p<0.0001). Additionally, 21.4% of patients were completely free of symptoms (p<0.0001) and urinary incontinence was improved or eliminated in 30.8% of women. The overall sum score for all four objective findings was significantly improved from baseline at 28 days (p<0.0001). The frequency of petechial bleedings was significantly reduced (p<0.0001). Further, significant decreases in the severity of vaginal epithelium thinning, redness and petechiae were observed (p<0.0001). More than 88% of patients and investigators assessed the efficacy and tolerability as being good or very good. No serious adverse events were documented. This study demonstrates that the investigated cream is an effective and safe non-hormonal, topical option in the treatment of vulvovaginal dryness symptoms in patients undergoing breast cancer treatment for. However, the study duration and follow-up time of 4 weeks as well as the non-randomized trial design are limitations of the study.
Induction of premature menopause by chemotherapy and the increased use of aromatase inhibitors leading to estrogen deprivation have resulted in a high prevalence of severe side effects in breast cancer patients [1–5]. Vulvovaginal atrophy (VVA), also termed genitourinary syndrome of menopause (GSM), depicts in this context one of the long-term side effects . The main symptom vulvovaginal dryness (VVD) negatively affects the quality of life and leads to sexual problems and dysfunctions [3, 5].
SAS software (Version 9.1.3, Heidelberg, Germany) was used in this study for data collection, management and statistical analysis. A total number of at least 100 participants were needed for obtaining valid results regarding the change of subjective symptoms. A statistical analysis plan was defined prior to study start. Descriptive statistical methods like frequency counts and summary statistics, including arithmetic mean ± standard deviation (SD), median and range, were used. Frequency distributions for discrete variables were provided as percentage in relation to the total sample. Statistical significance was determined by using an alpha level of 0.05 and two-sided tests. Quantitative variables were compared using the chi-square test. Evaluation of parameter changes during the study course were performed by intra-individual difference analysis (V1 vs. V2) using the Wilcoxon signed-rank test.
The present study was an open, observational study performed over a period of 4 weeks in 117 patients, reflecting the everyday life of breast cancer patients with VVD symptoms and their individual needs regarding frequency of product application. Here, this non-hormonal cream significantly reduced subjective symptoms and even improved objective findings of VVD in women undergoing breast cancer treatment. The results confirm the findings in post-menopausal women, in which efficacy has already been demonstrated in a previous study . Notably, more than 20% of patients in this study reported being free of symptoms after the treatment period. In addition, about one third of women experienced improvement or full elimination of urinary incontinence after using this non-hormonal cream for 28 days. Moreover, application of the product resulted in a highly significant reduction regarding severity of objective findings of vaginal dryness, such as thinning of the vaginal epithelium, redness and petechial bleedings, and at day 28, all patients were free of petechial bleedings. Apart from transient sensations of burning and itching after product application there were no AMDEs. Physicians and patients assessed the efficacy and tolerability of the cream in the majority of cases as being “good” or “very good”. No serious adverse effects were reported.
In conclusion, Vagisan Moisturising Cream is an effective and safe non-hormonal option for the treatment of VVD symptoms, not only in postmenopausal women but also in women undergoing cancer treatment. Since long-term data on the safety of local estrogen treatment is still lacking it is important to have an effective and safe non-hormonal option, especially for breast cancer survivors with estrogen-dependent tumors. Further experiences regarding long-term use (> 4 weeks of follow up) of the investigated cream must be gathered in a randomized trial.