Improving outcomes for women with endometriosis
Background “Endometriosis is a chronic hormone-dependent inflammatory disorder that affects 6- 10% of women of reproductive age. It is defined by the presence of endometrial-like tissue (lesions) found outside the uterine cavity, usually within the pelvis. The most widely reported symptoms of endometriosis are chronic pelvic pain and infertility. Endometriosis-associated pain can have a significant and debilitating impact on quality of life. In the United Kingdom, the impact on society of endometriosis is estimated at £8.2 billion in healthcare/treatment costs coupled with lost productivity. The exact aetiology of endometriosis is unknown. Standard treatments such as analgesic regimens, drugs that induce hormone suppression or invasive surgery can be associated with unacceptable side effects or complications. Notably many medical treatments are contraceptive, and endometriosis-associated symptoms typically recur after women stop taking drug treatments or after surgery. New therapies are therefore needed that: (i) can reduce painful symptoms associated with the condition (ii) are disease modifying (reduce lesion size) (iii) preserve the patients’ ability to conceive whilst on medication (iv) have no, or limited, side effects and (v) are acceptable to women with endometriosis.” Objectives “The two aims of my thesis were (a) to identify research priorities for endometriosis and (b) to determine the feasibility of a future multi-centre, large randomised controlled trial (RCT) to evaluate the effectiveness of Omega-3 purified fatty acids (PUFA) for endometriosis-associated pain. To achieve these objectives, I have (a) engaged with experts in the management of endometriosis, women with endometriosis and prepared a report of the research uncertainties, using a template provided by the James Lind Alliance (JLA) and (b) undertaken a two-arm, double-blind pilot randomised controlled clinical trial.” (a) Identifying research priorities for endometriosis “The JLA brings patients, carers and clinicians together in Priority Setting Partnerships (PSPs) to identify and prioritise the ‘top 10’ uncertainties, or unanswered questions, about the effects of treatments. An endometriosis PSP was launched in 2016 with the formation of a steering group, I prepared a survey where research questions were invited from members of the public (this included women with endometriosis and their families) and health care professionals (HCPs). Priority setting was carried out using data from (a) online survey complemented by clinical guidelines and systematic reviews (b) online voting and (c) a facilitated workshop of equal numbers of women with endometriosis and HCPs. In the first online survey, 4767 research questions were submitted by 1237 UK and Ireland respondents (67.7% women with endometriosis and 15.8% HCPs). A further 111 research uncertainties were identified from literature searches. After removing questions already addressed by systematic reviews or ongoing research and merging similar questions, 72 were listed in a second survey allowing participants to vote and rank the questions, 1380 participants from the UK and Ireland voted. From the 30 uncertainties which received most votes, 10 research priorities were agreed during a final face to face workshop comprising of equal numbers of women with endometriosis and HCPs.” (b) A pilot trial to evaluate the feasibility of performing a future RCT of the effectiveness of Omega-3 PUFA for endometriosis-associated pain (PurFECT) “In human trials on painful inflammatory conditions, other than endometriosis, Omega-3 PUFA have been shown to have minimal side effects with no obvious effects on fertility and may therefore be an acceptable treatment for endometriosis-associated symptoms. I performed a pilot two-armed double-blind RCT in NHS Lothian, comparing Omega-3 PUFA to a comparator (olive oil), to assess the feasibility of a future large-scale RCT for treatment of women with endometriosis-associated pain. The primary objectives were to determine recruitment and retention rates. The secondary objectives were to evaluate the acceptability of the methods of recruitment, randomisation, interventions and assessment tools and any signals of effectiveness of the interventions. The analyses by treatment group were by intention-to-treat. Between June 2016 and June 2017, of the 92 women who were referred to the study, 73 (79.3%) were eligible, 42 (57.5%) recruited and 33 (81.8%) women randomised. These 33 women all of whom had endometriosis-associated pain were randomised double-blindly and given either Omega-3 PUFA or the comparator. The effects of the interventions were assessed by validated pain scores and physical/emotional functioning questionnaires, completed at baseline and at the end of the study. The acceptability of the questionnaires was recorded as data completion and the absence of missing values. The majority of participants described their trial experience favourably. The recruitment rate was 57.5% (i.e. > 50%), the retention rate was 81.8% (considered a satisfactory rate), and the primary outcome was achieved. For most of the assessment tools, it appeared that there is no evidence that the treatment is better than control.” Conclusions The top 10 priorities identified by the PSP provide a platform for researchers, funding bodies and the pharmaceutical industry to ensure that future research activities focus on questions that are important to both women with endometriosis and HCPs. The PurFECT trial shows that a future RCT is feasible, but also highlights the need for a larger appropriately powered trial to assess the effectiveness of Omega-3 PUFA as treatment for endometriosis-associated pain.
endometriosis, Omega-3 fatty acids, endometriosis-associated pain, potential treatment, double-blind
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