Worth waiting for?

Abstract

The article by Ellis and Wood ‘A decade to wait’¹ has added to the focus of energies on identifying and reducing the delay in diagnosis of endometriosis for those suffering pelvic pain. Such anonymous, retrospective, self-report surveys have recognised limitations.² These endeavours also have an a priori assumption that a shorter time to diagnosis of endometriosis improves outcomes and does not pose risks. Women's health has an unfortunate history of harms caused by assumptions based on ‘first principles’ without rigorous research.^{3, 4}

The recently formed Endometriosis Initiative Group comprises experts from across the globe with the aim of considering ‘alternatives to the commonly accepted hypotheses … and common sense propositions’, noting that to do so ‘we may need to move away from our “comfort zone” and not become complacent’.⁵

In this spirit we propose alternative viewpoints on the effects of reducing delays to diagnosis of endometriosis for women living with pelvic pain, which could be uncomfortable reading for some.

The Webster dictionary defines diagnosis as ‘the art or act of identifying a disease from its signs and symptoms’, yet it is well recognised that endometriosis – the presence of ectopic endometrial glands and stroma – cannot be reliably identified from clinical signs and symptoms.

Endometriosis lesions are neither necessary nor sufficient for pelvic pain. Women with extensive lesion burden can be completely pain free, yet many others who suffer severe pain have very minimal (or no) visible abnormalities. A drive to reduce delay in diagnosis of endometriosis could be extended to include making the diagnosis in those without symptoms.

Lesions have been demonstrated in up to 45% of pain-free women; it is possible that with wide peritoneal excision microscopic lesions could be found in most, if not all, women.⁶ Identification of such asymptomatic lesions moves from early diagnosis to screening.

Calls for an earlier diagnosis or screening for a condition are grounded in the presumption of disease progression over time and that the outcome of the disease process could be improved by earlier intervention. This approach is the cornerstone for many cancers. The early detection of cervical dysplasia, and intervention to treat this (and now even prevent this with vaccination) is an excellent example.

However, unlike cervical cancer, endometriosis does not fulfil the World Health Organization/Wilson & Jungner criteria for screening. The natural history is poorly understood, not predictably progressive or with a recognised latent stage, there are no predictors of which asymptomatic lesions will progress to a symptomatic state, and there are no treatments proven to prevent such progression to nervous system upregulation and development of persistent pain.⁶

Available data suggest that without active treatment lesions remain stable, or spontaneously regress, in more than two-thirds of women and that asymptomatic women with endometriosis lesions are unlikely to subsequently develop pain.⁶

The 11th revision of the International Classification of Diseases, the global standard for recording health information, recognises chronic pain as a diagnostic entity.⁷ Persistent pelvic pain (PPP) is diagnosed by history of pain symptoms perceived to originate from pelvic structures typically lasting more than three months.⁸

Definitively diagnosing endometriosis, classically defined as the presence of endometrial glands and stroma in ectopic locations outside the uterine cavity, usually requires surgery. Pain suffered by those with (or assumed to have) such lesions is often labelled ‘endometriosis-associated pain’; however, it has been proposed this label be removed from the classification system for PPP ‘because the endometriosis may be irrelevant’.⁸

Most women with pelvic pain have multiple contributors to their symptoms. A focus on early diagnosis of endometriosis prioritises the search for lesions; however, the finding of ectopic endometrial glands and stroma does not protect against other conditions, and such an approach risks a tunnel vision of care that misses other treatment targets or sinister pathology.

The Choosing Wisely campaign identifies ‘tests, treatments and procedures healthcare providers and consumers should question’: What are the benefits of this test? What are the risks? What are the alternatives? What if I don't have any tests?

If an accurate non-invasive test for endometriosis lesions were to be available tomorrow, how would this stand up to these questions? How would the result change management of a woman with PPP (who is not currently trying for pregnancy) when compared to making a diagnosis of PPP without this test? Given the likelihood that such a test would also be applied to some asymptomatic people keen to simply know if they have endometriosis or not, what would we then do with this result noting that guidelines currently recommend against treatment for asymptomatic lesions?

It has been proposed that instead of requiring any tests, endometriosis should be diagnosed clinically⁹ with attempts to determine predictive symptoms. The pursuit of tests or clinical prediction models for lesion status in those suffering pelvic pain, however, ignores the reality that currently the mainstay of management for women with PPP – with or without endometriosis lesions – is the same. Women with PPP, regardless of lesion status, require an individualised symptom and priority-based multimodal approach. This commonly includes hormonal suppression with contraceptives or gonadotropin hormone-releasing hormone agonists, which is as effective for reducing pelvic pain in those with and without endometriosis lesions.^{10, 11}

Hormonal manipulation along with analgesia, recommendations for movement, dietary interventions and pain science education can be instigated in primary care after a clinical diagnosis of PPP. Early initiation of treatment reduces suffering, loss of schooling and the risks of worsening of nervous system sensitisation.¹²

The only treatment currently appropriate to consider in women with PPP and endometriosis lesions, but not in those with PPP and no lesions, is lesion-directed surgery. Available evidence raises concerns of high rates of return of symptoms even in expert hands,¹³ and deterioration in pain for some women, questioning the benefits for this approach and providing sufficient equipoise for placebo-controlled trials.^14-16 Further, Australasian data demonstrate equivalent outcomes between higher and lower surgical intervention rate services and that a primarily empiric medication management of PPP does not result in adverse long-term outcomes.^{17, 18}

The validation of suffering by an assumption or confirmation of lesions has many troubling consequences. That a woman's symptoms are (more) valid once attributed to lesions implies they were less valid prior to this – elevating the validity of lesions (or the clinician's proclamation of likelihood of lesions) over the lived experience and reported suffering. It is impossible to argue that a diagnosis of endometriosis validates someone's pain and suffering, without conversely and simultaneously implying the opposite – that someone who does not have endometriosis lesions has less valid pain and suffering. These consequences of this ‘hierarchy of validity’¹⁹ are reflected in our clinics and in the literature.^{20, 21}

The doctor–patient relationship is inherently imbalanced. The use of diagnosis for validation further shifts the power balance from the person who has the lived experience of suffering to the diagnostician. Whether this diagnosis is made by surgery, by advanced imaging or by clinical acumen alone, the clinician holds the power as the bestower of their validating diagnostic powers.

The argument that ‘a rising tide lifts all boats’ fails to recognise this requires all to have equal access to a boat. Clinical resourcing and research funding allocated to endometriosis fail to benefit those suffering from pelvic pain without a diagnosis of endometriosis.

In Aotearoa until 2019 Pharmac funding for the levonorgestrel intrauterine system was available for those with endometriosis but not for women suffering from pelvic pain without an endometriosis diagnosis. Currently Australian women with ‘visually proven’ endometriosis can access pharmaceutical benefits scheme funding for six months of goserelin or nafarelin, but those with PPP and no endometriosis are not afforded this benefit.

Research that recruits those with a label of endometriosis limits the generalisability of the outcomes to women with PPP without endometriosis. The inconsistent use of the term ‘endometriosis’ in research further hampers progress. The term is variably used to indicate self-reported symptoms or clinically, radiologically or surgically diagnosed lesions. Control groups are often pain-free women who have not had a laparoscopy to confirm the absence of asymptomatic lesions, which invalidates conclusions drawn. It is impossible to establish which, if any, of the findings result from the presence of lesions and which are consequences of living with pain symptoms. Analysing outcomes by pain status versus by lesion status may result in different conclusions.²²

We call for all future research using the term ‘endometriosis’ to state the lesion and symptom status of both the active and control groups, and to clearly identify if recurrence refers to return of lesions, symptoms or both.

Unintended harms from diagnosis labelling are increasingly being recognised, including over-treatment with associated financial burden, increased worry and lower quality of life.

People with back, hip or shoulder pain assigned structural pathology–based labels rather than pain-based diagnoses experience increased psychological distress, preference for invasive treatments, greater disability and poorer long-term outcomes.²³ Young people assigned a mental health diagnosis had higher rates of hospitalisation, work absence and unemployment and lower expectations of relationship success than their peers experiencing the same symptoms managed without being assigned a diagnostic label.²⁴

Receiving the diagnosis of endometriosis, a chronic disease with no definitive cure and often associated with worry about infertility, increases anxiety²⁵ and creates new uncertainties about future well-being and treatment costs.²⁶ Risk factors for increased disability in those living with pelvic pain include anxiety, fear and worry. A cohort study identified that receiving a surgically confirmed endometriosis diagnosis was associated with a higher rate of ceasing employment compared to those with a suspected but unconfirmed diagnosis.²⁶

Lowering the threshold of diagnosis of polycystic ovarian syndrome has failed to bring the intended benefits of improving health behaviour and has resulted in increased anxiety about long-term consequences and worry about fertility for many women with subsequent reduction in contraception use and increase in unplanned pregnancies.²⁷ The potential impacts of introducing a non-invasive test or clinical prediction tool for endometriosis lesions are unknown.

At present, definitive diagnosis of endometriosis can be made only via surgery, and a drive towards earlier diagnosis will reduce the age at which interventional laparoscopic surgery is undertaken. Younger age at surgical treatment of endometriosis lesions is the most significant risk factor for subsequently undergoing further surgeries in the future.²⁸ The current drive for earlier diagnosis may thus be one of the contributors to the number of women undergoing multiple repeated operations.²⁹

A management approach that includes pursuing a diagnosis of endmoetriosis prior to symptom management will inherently carry higher cost and risk than one that prioritises symptom management of PPP. Such a symptom-based approach to dysmenorrhoea has demonstrated improvement for over 90% of young women.³⁰ Until or unless higher-cost approaches are demonstrated to be superior, such low-cost management models permit more women to be treated within the limited healthcare budget.

We call for the efforts of clinicians, researchers, funders and guidelines to be focused on improving the quality of life for all those suffering from pelvic pain. In the absence of convincing evidence that a label or diagnosis of endometriosis for women with PPP brings more benefits than harms, the focus on its delay is unnecessary and may be detrimental. Women deserve better than assumptions and ‘common sense’ medicine even if this moves us out of our comfort zone.

There is no reason to wait.