Hypothesis / aims of study
Genitourinary Syndrome of Menopause (GSM) is associated with sexual symptoms, genital symptoms and urinary symptoms. Breast cancer survivors (BCS) receiving aromatase inhibitors (AI) are one of the most likely groups to present severe GSM and sexual complaints.
Vulvovaginal health is a key factor for female sexual pleasure which may be affected by lack of lubrication and dyspareunia due to GSM. However, sexual health involves not only genitals but eroticism, intimacy, reproduction or body image. Most of these aspects may be affected in BCS and could impact in other dimensions of female sexuality as desire, arousal, orgasm and satisfaction.
The aim of the present preliminary study was to evaluate sexual health in BCS with GSM receiving AI, regarding sexual activity, global sexual function and dimensions (desire, arousal, lubrication, orgasm, satisfaction and pain).
Study design, materials and methods
This study represents a preliminary analysis of an ongoing prospective double-blind randomized controlled trial (RCT) with two parallel study arms: 1) Fractional CO2 laser therapy and 2) Sham laser therapy. The main goal of the RCT is to report an improvement in sexuality. Female Sexual Function Index (FSFI) to measure sexual function is the primary outcome. Herein, we present observational cross-sectional descriptive data from the RTC study focused on baseline sexual records of female BCS receiving AI with GSM, aimed to better understand the sexual life of the participants before any intervention.
We conduct the study in Breast Cancer Unit from a tertiary university hospital. The RCT began in October 2020 and the recruitment is planned to finish in December 2021.
The inclusion criteria are:1) BCS treated with AI ± GnRH analogues; 2) menopause, GSM signs / symptoms, dyspareunia, Vaginal pH ≥5; 3) negative Human Papillomavirus; 4) willingness to have sex. The exclusion criteria are: 1) vaginal hormonal treatment in the last 6 months; 2) vaginal moisturizers and / or lubricants in the last 30 days; 3) laser treatment, radiofrequency, hyaluronic acid, lipofilling in the vagina in the last 2 years; 4) ospemifene treatment; 5) being affected for: active genital tract infection; intraepithelial neoplasm of cervix, vagina, or vulva; have or have been treated for genital cancer; pelvic organ prolapse stage ≥II on pelvic examination.
Relevant methods for the present observational study are summarized, focused on the baseline assessment. We collect epidemiological variables, including age, menopause state and body mass index.
Vaginal health is assessed with the Vaginal Health Index (VHI), which subjectively assesses the vagina's elasticity, the amount of discharge, the integrity of the epithelium and humidity, along with pH as the only objective criteria.(score ≤15 indicates vulvovaginal atrophy, range 5-25).
Sexual health is assessed with self-reported FSFI questionnaire [1], a generic sexual questionnaire validated for cancer survivors. We used the 19-item Spanish validated questionnaire to assess 6 sexual dimensions (desire, arousal, lubrication, orgasm, satisfaction and pain) and the global sexual function (range 1.2-36, higher score indicating a better sexual function, cut-off ≤ 26.55 risk of female sexual dysfunction (FSD)). A specific Spanish cut-off of ≤21.7 is also proposed [2]. According to DSM 5, sexual disorder should be considered when there is a clinically significant disturbance. As FSFI did not report on disturbance, we also ask patients to fill in a visual analogue scale (VAS) 0-10 about disturbance by their sexual life, we classified disturbance as clinically significant when women scored >3. Dyspareunia intensity is also assessed in all patients (sexually active and inactive) at the baseline visit according to their last coital sexual activities. Moreover, a sexual interview to assess sexual activity/inactivity, sexual activity frequency (nº sexual activity/week) and sexual history is also performed.
Statistical Analysis
Considering FSFI score as the main variable of the study, we performed a calculation of the hypothesis contrast study sample with the comparison of two independent means. Accepting an alpha risk of 0.05 and a beta risk of less than 0.1 in a bilateral contrast, there are 44 subjects in the first group and 44 in the second. The common standard deviation is assumed to be 1. A follow-up loss rate of 15% has been estimated.
Statistical analyses were performed with the Software for Statistics and Data Science release 15.1 (STATA, College Station, Texas: StataCorp LLC). A descriptive analysis of all data was performed. Continuous variables were compared using the independent or paired-samples T-test and presented as mean ± standard deviation. P<0.05 was considered statistically significant.
Results
We included 67 women until May 2021. On average patients had been diagnosed of BC 5 years ago (between June 2007 and February 2020) and had been treated with surgery (98.5%), radiotherapy (70.1%), chemotherapy (76.1%) and hormonal therapy (100%). Sample characteristics are described in Table 1. FSD rate was 97% according to ≤26.55 cut off, whereas it was 79% according to ≤21,7 cut off.
Sexual activity rate was 61%. Comparing sexually active to inactive women, no statistically significant difference on subjective (VHI) and objective (Vaginal pH) assessment of GSM was found; however, more intense dyspareunia was reported by sexually inactive patients. Table 2 shows FSFI score among overall population, as well as according to sexual activity and sexual dysfunction. We found sexually inactive women were more affected than sexually active in both, global sexual function and all of its dimensions.
Interpretation of results
This preliminary data confirmed that BCS with AI and GSM presented a high prevalence of FSD not only based on dyspareunia.
Comparing our results to published studies on healthy women [1, 2], FSFI mean score was lower and the rate of sexual dysfunction was greater in BCS. According to FSFI cut-off ≤26.55, nearly all women were sexually affected, but that did not correlate with sexual disturbance referred by our patients. On the other hand, the rate of FSD was similar when comparing reported sexual disturbance with the Spanish cut-off of FSFI. These findings highlight how sociocultural differences may affect the interpretation of the results of validated questionnaires; therefore, for a better assessment of sexuality, it should be recommended to combine quantitative and qualitative measures
Our results showed dyspareunia was not the only dimension which affects sexual function and sexual activity in BCS, in addition, sexual desire, arousal, lubrication, orgasm and satisfaction were also impaired.
When comparing women with FSD to those without, in addition to the global score, all the dimensions were also affected considering the Spanish cut-off. The results between sexually active and sexually inactive subgroups seemed similar, except for pain domain which showed no differences in sexually inactive population. However, that result should be considered with caution as it could be explained by a selection bias related to our inclusion criteria.
The wide-ranging nature of the factors affecting the sexuality of those patients needs a comprehensive assessment to guarantee pleasurable sexual experiences. According to that, in the ongoing RCT, both study groups are receiving multidisciplinary approach including moisturizers, lubricants, pelvic floor muscle relaxation, dilators and sexual assessment using the PLISSIT Model according to usual care in our hospital and international recommendations, so we expect to extend this sexual preliminary data at the end of the RCT.