Health Technology Assessment (Oct 2023)
Rates of medical or surgical treatment for women with heavy menstrual bleeding: the ECLIPSE trial 10-year observational follow-up study
Abstract
Background Heavy menstrual bleeding is a common problem that can significantly affect women’s lives until menopause. There is a lack of evidence on longer-term outcomes after seeking health care and treatment for heavy menstrual bleeding. Objectives To assess the continuation rates of medical treatments and the rates of ablative and surgical interventions among women who had participated in the ECLIPSE trial (ISRCTN86566246) 10 years after initial management for heavy menstrual bleeding in primary care. To explore experiences of heavy menstrual bleeding and influences on treatment for women. Design This was a prospective observational cohort study, with a parallel qualitative study. Setting Primary care. Participants A total of 206 women with heavy menstrual bleeding who had participated in the ECLIPSE trial consented to providing outcome data via a questionnaire approximately 10 years after original randomisation. Their mean age at follow-up was 54 years (standard deviation 5 years). A purposeful sample of 36 women also participated in semistructured qualitative interviews. Interventions The ECLIPSE trial randomised participants to either the levonorgestrel-releasing intrauterine system (52 mg) or the usual medical treatment (oral tranexamic acid, mefenamic acid, combined oestrogen–progestogen or progesterone alone, chosen as clinically appropriate by general practitioners and women). Women could subsequently swap or cease their allocated treatment. Main outcome measures The main outcome measures were rates of ablative and surgical treatments; the rate of continuation of medical treatments; and quality of life using the Short Form questionnaire-36 items and EuroQol-5 Dimensions; women’s experiences of heavy menstrual bleeding; and the influences on their decisions around treatment. Results Over the 10-year follow-up period, 60 out of 206 (29%) women had received a surgical intervention [hysterectomy, n = 34 (17%); endometrial ablation, n = 26 (13%)]. Between 5 and 10 years post trial intervention, 89 women (43%) had ceased all medical treatments and 88 (43%) were using the levonorgestrel-releasing intrauterine system alone or in combination with other oral treatments. More women in the usual medical treatment group had also used the levonorgestrel-releasing intrauterine system than women in the levonorgestrel-releasing intrauterine system group. Fifty-six women (28%) used the levonorgestrel-releasing intrauterine system at 10 years. There was no statistically significant difference in generic quality-of-life scores between the two original trial groups, although small improvements in the majority of domains were seen in both groups across time. Women reported wide-ranging impacts on their quality of life and normalisation of their heavy menstrual bleeding experience as a result of the taboo around menstruation. Women’s treatment decisions and experiences were influenced by the perceived quality of health-care interactions with clinicians and their climacteric status. Limitations Fewer than half of the original 571 participants participated; however, the cohort was clinically and demographically representative of the original trial population. Conclusions Medical treatments for women with heavy menstrual bleeding can be initiated in primary care, with low rates of surgical intervention and improvement in quality of life observed 10 years later. Clinicians should be aware of the considerable challenges that women with heavy menstrual bleeding experience at presentation and subsequently over time, and the importance and value to women of patient-centred communication in this context. Future work Any further evaluation of treatments for heavy menstrual bleeding should include long-term evaluation of outcomes and adherence. Trial registration The original ECLIPSE trial was registered as ISRCTN86566246. Funding This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 27, No. 17. See the NIHR Journals Library website for further project information. Plain language summary What is the problem? Heavy menstrual bleeding is a common problem that can significantly affect women’s lives, yet many women do not seek medical help. Medical treatments, such as tablets and a hormonal coil inserted in the womb, were shown to help women with heavy menstrual bleeding in a previous clinical trial that we conducted, called ECLIPSE. What did we plan to do? In the ECLIPSE trial, women provided information for 5 years after their treatment started. We planned to continue to ask these women about their periods, their symptoms and quality of life, and the treatments that they chose about 10 years after they first joined the trial. We did this using questionnaires and by interviewing women. What did we find? We received questionnaires from 206 out of the 490 women (42%) who had participated in the ECLIPSE trial 10 years earlier. Responders were, on average, 54 years old, and half reported that they had reached the menopause. About 3 in 10 women overall had either received a hysterectomy or undergone destruction of the womb lining. Just over one-quarter of women were using the hormonal coil. Quality of life remained improved and was generally higher than that before treatment. There was no big difference in quality of life or in the numbers of women having surgery between those who first used tablets and those who received the coil. Women described the wide-ranging impact of heavy bleeding on their lives and the taboo around periods. Women’s experience of good or poor communication with their doctors, and thoughts about fertility and menopause, influenced the treatment choices that they made. What does this mean? Women’s quality of life was improved by medical treatments for heavy menstrual bleeding, even as menopause approached, and this shows the importance of these treatments. This research can help doctors and women to make more informed decisions about medical and surgical treatments. Scientific summary Background Heavy menstrual bleeding (HMB) is a common problem that can significantly affect women’s lives until menopause. Despite its high incidence and burden, many women do not seek medical help. The Clinical effectiveness and cost-effectiveness of levonorgestrel releasing intrauterine system in primary care against standard treatment for menorrhagia trial (ECLIPSE) randomised 571 women presenting to primary care with HMB to treatment with the levonorgestrel-releasing intrauterine system (LNG-IUS) or usual medical treatment (oral tranexamic acid, mefenamic acid, combined oral contraceptive pill or progesterone alone). The primary outcome was a patient-reported score of the burden of HMB, which was assessed over a 2-year period. This score improved significantly in both groups across all time points compared with baseline scores. At follow-up after 2 years, women in the LNG-IUS group reported significantly greater improvements than women assigned to the usual medical treatment group. By the 5-year follow-up, this benefit was reduced. There is a lack of evidence on longer-term outcomes, beyond 5 years, after seeking health care and treatment for HMB. Objectives The primary objective of this study was to assess continuation rates of medical treatments, and rates of ablative and surgical interventions, in women 10 years after initial management for HMB in primary care. Additional secondary objectives were to develop a greater understanding of the natural history and treatment of HMB, in particular: an assessment of whether or not initial medical treatment (the LNG-IUS or usual medical treatments) influences women’s trajectories an assessment of quality of life and sexual function experienced, and an evaluation of whether or not these are influenced by initial medical treatment a qualitative exploration of women’s experiences of HMB, and decisions about treatments or surgical interventions, to provide insight into women’s choices and what influences them, over this time period. Design This was a prospective observational cohort study, with a parallel qualitative study. Participants A maximum of 490 women who had participated in the ECLIPSE trial (ISRCTN86566246) were available to be re-approached. Of these women, 206 consented to providing outcome data via a questionnaire approximately 10 years after their original randomisation. A purposeful sample of 36 women, who had a range of ages, social diversity (socioeconomic, ethnicity and educational background), educational backgrounds, treatment experiences and trajectories, also participated in semistructured qualitative interviews. Interventions The allocation method of the ECLIPSE trial interventions and the distribution of the treatments used have been previously reported. The ECLIPSE trial randomised participants to either the LNG-IUS or usual medical treatment [oral tranexamic acid, mefenamic acid, combined oestrogen–progestogen or progesterone alone, chosen as clinically appropriate by general practitioners (GPs) and women]. Women could subsequently swap or cease their allocated treatment. Main outcome measures Data were collected directly from women on the use of treatments for HMB and the surgical interventions of hysterectomy and endometrial ablation as the primary outcomes for this observational study. Changes in treatment or cessation of treatment were also recorded. Generic quality of life was assessed using the Short Form questionnaire-36 items (SF-36), the EuroQol-5 Dimensions (EQ-5D) descriptive system and the EQ-5D visual analogue scale. The Sexual Activity Questionnaire (SAQ) measured the pleasure, discomfort and frequency of sexual activity. The primary outcome measure in the original trial was the patient-reported, condition-specific Menorrhagia Multi-Attribute Scale (MMAS) at 2 years’ follow-up. As expected, few (n = 13) respondents completed the MMAS, so no data are reported for this outcome. All semistructured telephone and face-to-face interviews were conducted by a female researcher. Interviews were audio-recorded and transcribed verbatim. The coding of interview transcripts was aided by the application of NVivo (QSR International, Warrington, UK) software, with the field researcher and a senior researcher each identifying emerging themes from the data and then developing these together. Data generation and thematic analysis were iterative until no new themes emerged, suggesting data saturation. A process of member checking was also undertaken. Results The baseline (prior to randomisation) characteristics of the reconsented responding women and those who were not followed up were very similar. The mean age of the women at follow-up was 53.7 years (standard deviation 5.1 years). Over the 10-year follow-up period, 60 out of 206 (29%) women had received a surgical intervention [hysterectomy, n = 34 (16.5%); endometrial ablation, n = 26 (12.6%)]. Between 5 and 10 years, 89 women (43.2%) had ceased all medical treatments and 88 (42.7%) continued to use the LNG-IUS alone or in combination with other oral treatments. Fifty-six women (28%) were using the LNG-IUS at 10 years [35% (38/110) of women originally allocated to the LNG-IUS and 19% (18/96) of women originally allocated to usual medical treatments]. There were improvements over time in SF-36 scores in both women who were initially allocated to the LNG-IUS and women who were allocated to usual medical treatment, with small and statistically insignificant differences between the two original allocation groups. Changes over time in the EQ-5D scores were very small and, again, no differences were seen between the original allocation groups. There was a clear deterioration in the discomfort domain of the SAQ, with no evidence of a difference between the allocation groups, but no changes were seen in the pleasure domain. In the qualitative study, women reported wide-ranging debilitating impacts on their quality of life. Women had often normalised their HMB experience, reflecting wider societal and generational taboos around menstruation and low awareness that HMB is a treatable problem. Treatment decisions and experience were strongly positively or negatively influenced by the perceived quality of health-care interactions with clinicians. Other key influences on women’s decisions about treatment for HMB over time included considerations in their lives in transition (e.g. changing personal relationships, requirements for contraception or desire for children, and changes in work); the effects of treatment on fertility; their health concerns and knowledge, including that of family and peers; and their views about approaching menopause, or on avoiding premature menopause. Limitations Fewer than half of the original 571 participants contributed, but the cohort was demographically and clinically representative of the original trial population. A large proportion of women had, as expected, stopped having periods, owing to either the menopause or the surgical treatment, meaning that only a small number of women were able to report on the original primary outcome measure. Conclusions The study provides a helpful new indication of the expected proportions of women continuing to use or not use treatments for HMB, or progressing to surgical intervention, and of the significant proportion of women using the LNG-IUS, after a decade. Medical treatments for women with HMB can be initiated in primary care, with low rates of surgical intervention and improvement in quality of life observed 10 years later and with high likelihood of avoiding surgery. Clinicians should be aware of the considerable challenges that women with HMB experience over time, and the importance and value of patient-centred communication about treatment in this context. Future work Any further evaluation of treatments for HMB should include the long-term evaluation of outcomes and adherence. Further qualitative research might investigate the perspectives of health professionals, in particular GPs and nurse practitioners in primary care, alongside gynaecologists, to understand the challenges that they may experience seeing women with HMB and to elicit their perceptions of how care may be enhanced. Trial registration The original ECLIPSE trial was registered as ISRCTN86566246. Funding This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 27, No. 17. See the NIHR Journals Library website for further project information.
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