Qualitative cross-cultural exploration of vaginal bleeding/spotting symptoms and impacts associated with hormone therapy in post-menopausal women to inform the development of new patient-reported measurement tools
Introduction
It is estimated there are over 166 million postmenopausal women in the US, Japan and the European Union (EU) [1]. Due to decreasing levels of estrogens at menopause, women often experience bothersome vasomotor symptoms (VMS), vulvar and vaginal atrophy (VVA), and an increased risk of osteoporosis [2]. There appear to be cultural differences in the manner and degree to which menopausal symptoms are reported [3]. Hot flushes are recognized as a symptom directly associated with menopause within the Western biomedical health framework. However in other cultures, such as Japan, while thermoregulation problems are reported, these tend to be experienced as chills and shivers [4].
Estrogen plus progestin therapies (EPT) represent the current standard of care for the treatment of menopause symptoms in postmenopausal women with a uterus. While estrogens have shown success for treating climacteric symptoms, the presence of progestin is necessary to prevent endometrial proliferation [5]. However, progestins in EPT are associated with side effects such as breast pain/tenderness and vaginal spotting/bleeding [6]. Irregular bleeding and spotting is reported to occur in approximately 50% of women receiving continuous EPT [7]. These side effects can result in women permanently discontinuing EPT and have been associated with impairments in quality of life [8] and increased healthcare resource utilization (an estimated 32,000–42,000 postmenopausal women in the US were investigated for abnormal bleeding associated with EPT in 2010 [9]).
Clinical trials aimed at evaluating the clinical benefit of novel therapies relative to existing therapies require reliable and culturally valid measures that assess not only the efficacy of the treatment (in terms of reduction in symptoms), but also benefits in terms of tolerability. A literature review identified no suitable symptom measures, but the Postmenopausal Bleeding Questionnaire (PMBQ) was identified via personal communication as a potentially appropriate impact measure. However, while the PMBQ was well-developed based upon patient focus groups, further content validity testing was deemed necessary to establish the appropriateness of the measure for these particular patient populations, which seemingly has not occurred since there is no reference to the measure in the public domain, currently. This paper thus describes qualitative research to explore patients’ experiences of vaginal bleeding/spotting associated with EPT to inform the development of a symptom measure of vaginal bleeding/spotting and to evaluate the content validity of a vaginal bleeding/spotting impact measure.
Section snippets
Overview of study
This paper reports the qualitative research findings from a three-stage study (Fig. 1). Although the study explored the experiences and impacts of two common EPT side effects, namely vaginal bleeding/spotting and breast sensations, this paper focuses on the findings for vaginal bleeding and spotting only.
In Stage 1, concept elicitation interviews with women from culturally diverse backgrounds were used to understand how postmenopausal women describe the symptoms of bleeding and spotting
Demographic and clinical characteristics (Stages 1 and 3)
A diverse sample of postmenopausal women on EPT was recruited for both interview stages (Table 1). In total, 59 women participated in Stage 1 (n = 14 in the US, 15 in Italy, n = 15 in Mexico and n = 15 in China,) and 20 in Stage 3 (US only). Mean age was 50 years (range 40–63) in Stage 1 and 53.4 years (range 42–61) in Stage 3. In both Stages 1 and 3, the US sample included good representation of non-Caucasian ethnicities. In China and Italy it is considered culturally inappropriate to ask about
Discussion
The results of initial exploratory interviews in four countries provide evidence that bleeding/spotting is a commonly experienced side effect of EPT, reported and described in a consistent manner by women in a range of different cultures, as supported in the literature [8], [15]. Moreover, the results indicate that vaginal bleeding/spotting impact on postmenopausal women's HRQL including emotional wellbeing, choice of clothing, physical functioning, social functioning and sexual functioning.
Conclusions
This work highlights that vaginal bleeding is a significant and impactful side effect of EPT, which is relevant across cultures and affects women's HRQL. The qualitative research supported the development and refinement of two PRO instruments which were shown to have strong content validity in a sample of postmenopausal women.
Contributors
Steven Walmsley participated in the data analysis and approved the final version. Rob Arbuckle participated in the design, conduct and reporting of the project, highly involved in the writing of the manuscript and approved the final version. Louise Humphrey participated in the study design, data analysis and interpretation, manuscript development & review and approved the final version. Lucy Abraham participated in the design, analysis and reporting of the study, fully contributed to the
Competing interest
Steven Walmsley was employed by Adelphi Values at the time of the study. Rob Arbuckle is an employee of Adelphi Values, a health outcomes consultancy that was contracted by Pfizer to perform the research described in the manuscript. As an employee of Adelphi Values he has also performed research for many other pharmaceutical companies. Louise Humphrey was employed by Adelphi Values at the time of the study. Lucy Abraham is an employee of Pfizer Ltd. Lorraine Dennerstein received honorarium from
Funding
This work was sponsored by Pfizer Ltd.
Ethical approval
The study was conducted in accordance with the Declaration of Helsinki and was approved by an Independent Review Board (IRB) in the US for Stages 1 and 2. In Stage 1, ethical approval was also obtained in Italy and Mexico. Ethical approval for a study of this nature was not required in China. Written informed consent was obtained from all participants prior to data collection.
Acknowledgements
Linguists/interviewers: Bin Shi, Market Research and Consulting Director, Chinese interviewer. Daniela Carboni, Consultant Psychologist, Italian interviewer. Gaudalupe Riego, Mexican interviewer. Felicitas Colombo, Director of Datos and Estragias, Mexican interviewer.
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Evaluation of the impact, treatment patterns, and patient and physician perceptions of vasomotor symptoms associated with menopause in Europe and the United States
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- 1
Now with Abacus International, Portland Street, Manchester M1 3LF, UK.
- 2
Now with TherapeuticsMD, Boca Raton, FL 33487, USA.
- 3
Now with University of Western Sydney, Sydney, Australia.