'A Decade to Diagnose: a review of research into the pathology and treatment of endometriosis' by Tallulah Flint (they/she)

The current average time between onset of symptoms and receiving diagnosis for endometriosis in the UK is 9 years and 4 months (Endometriosis UK, 2026). Lack of research, funding and understanding of the disease leaves millions of people assigned female at birth (AFAB) ignored and medically neglected. Endometriosis affects 190 million women and AFAB people, accounting for 1 in 10 people of reproductive age (World Health Organization, 2023), and this number is likely an underestimate, given the length of wait time for diagnosis. The following review will outline recent and current research into the aetiology, pathology, diagnosis and treatment of endometriosis, with an aim to spread much needed awareness of the disease which leaves so many struggling to be listened to.  

What is endometriosis?

Endometriosis is a chronic inflammatory disorder where lesions of endometrial-like tissue grow outside of the uterine cavity (Chauhan et al., 2022). These lesions most commonly appear in the peritoneum, the thin lining covering the organs in the pelvis and abdomen. Lesions may also appear on the ovaries, or can invade pelvic, or even extra-pelvic organs such as the heart or lungs (Saunders & Horne, 2025). These lesions cause high levels of inflammation, leading to a range of symptoms that negatively impact quality of life - notably, severe chronic pain, dysfunction of the organs of the pelvic cavity, infertility and secondary mental health issues(Lamceva et al., 2023). 

Aetiology and pathology

Multiple theories have been suggested when it comes to the aetiology of endometriosis. The most widely recognised explanation for the cause of endometriosis is Sampson’s theory of retrograde menstruation. This is where sloughed endometrial cells and debris from menstruation travel retrogradely up the fallopian tubes and enter the pelvic cavity (Sampson, 1927). The main limitation of this theory is that 76%-90% of AFAB people experience retrograde menstruation, and 90% of those individuals do not develop endometriosis. Additionally, while this theory might explain superficial peritoneal, and ovarian endometriosis, it fails to explain lesions outside the peritoneal cavity (Lamceva et al., 2023).  To encompass these lesions, Sampson proposed the metastatic theory, by which endometrial cells exit the peritoneum via the uterine-draining lymph vessels during menstruation, and much like cancer cells, travel via lymphatic capillaries to organs around the body (Sampson, 1927). While both of Sampson’s theories may be able to explain the development of some cases of endometriosis, neither provide explanation for cases in pre-pubescent and menopausal AFAB individuals, those with an absent or underdeveloped uterus, or those assigned male at birth (AMAB). 

Very rarely, endometriosis has been found in the lower genitourinary tract of AMAB individuals who receive high dose oestrogen therapy for prostate carcinoma. This occurrence has led to the proposition of the coelomic metaplasia theory (Matsuura et al., 1999). Coelomic epithelium is the developmental precursor to the Müllerian ducts, which give rise to the female reproductive organs during embryo development. Progenitors of coelomic epithelial cells persist in both male and female adults as the mesothelium - the lining of the peritoneal cavity and organs. Under the stimulation of high levels of oestrogen, mesothelium cells are capable of undergoing metaplasia, the process by which a specialised cell undergoes abnormal differentiation into another type of mature cell. In this case, coelomic epithelial cells transform into endometrial cells, leading to the development of endometriosis in those without an endometrium. 

These are just a few of the many proposed mechanisms by which endometrial-like cells locate outside of the uterine cavity. It may be that there isn’t one single process by which endometriosis occurs, and multiple mechanisms explain its aetiology. The pathology of the disease is also a poorly understood phenomenon, with multiple proposed pathways leading to the disease’s debilitating symptoms. 

Upon implantation of endometrial-like cells, high levels of inflammation occur, leading to the most common symptom of endometriosis - debilitating pain. The cause of this inflammation is likely down to numerous interacting processes. Firstly, the development and growth of lesions is dependent on neuroangiogenesis, by which new nerve fibres and blood vessels form, supplying oxygen and nutrients needed for cell proliferation. Neuroangiogenesis requires the increase in growth factors, which recruit innate immune cells and pro-inflammatory cytokines. These mediators are able to activate and sensitise (reduce the threshold for excitability) nociceptors, sensory nerve endings that initiate the sensation of pain (Maddern et al., 2020). In addition to neuroangiogenesis, immune cells and cytokines are recruited due to the hormonal changes responsible for menstruation. During menstruation, high levels of oestrogen signalling, and low levels of progesterone signalling lead to the release of pro-inflammatory cytokines by endometrial cells. These recruit and activate innate immune cells such as macrophages and natural killer cells, which provide cyclical breakdown and clearing of endometrial cells and debris. The inflammation is so great that at its peak, one in every three cells in the uterus is an inflammatory cell (Gibson, 2025). Endometrial-like cells that form endometriosis lesions maintain these hormone receptors, leading to the same inflammatory response that occurs during the menstrual phase in the cells of the endometrium (Maybin & Critchley, 2015), contributing to a highly inflammatory microenvironment leading to the pathology of the disease. 

Endometriosis-associated pain is often poorly correlated with lesion size and is persistent outside of times of initial lesion formation, and the menstrual phase, with 80% patients with endometriosis suffering from chronic pelvic pain (Saunders & Horne, 2025). Additionally, pain persists after surgical lesion removal, indicating that mechanisms beyond acute inflammation at the site of the lesion alone drive pain severity and persistence. The most widely understood cause for the chronic pain associated with endometriosis is central sensitisation, a systematic change in pain signalling.

The current understood pathway of pain signalling is as follows. Noxious stimuli damage cells, leading to the release of inflammatory factors. These factors bind to nociceptors on sensory afferent nerves. The nociceptive signal is transferred to the nerve root of the dorsal horn of the spinal cord, which transfers the signal to the thalamus, the brain stem, and finally the cerebral cortex, where emotional and behavioural response to pain is coordinated. Upon persistent stimulation of nociceptors by inflammatory factors, as seen in endometriosis, peripheral synapses are remodelled, lowering the activation threshold of peripheral afferent nerves. This magnifies future pain, and forms more intense memories of pain in the cerebral cortex. This process is known as central sensitisation, and evokes long term changes to pain sensation, as seen in most cases of endometriosis (Zheng et al., 2019). Additionally, this pathway explains the overlap in symptoms, and comorbidity with diseases of the gut, bowel and bladder such as IBS. The uterus, bladder, and colon share convergent neural pathways in the spinal cord, therefore sensitisation of these pathways by endometriosis can lead to worsened bladder or bowel discomfort in IBS or painful bladder syndrome, and vice versa.

Diagnosis and treatment

The current standard method for diagnosis and treatment of endometriosis is laparoscopy, an invasive surgery by which, under general anaesthesia, a laparoscope (narrow viewing tube) is inserted into the abdomen through an incision. Upon identification of lesions, further incisions are made in the abdomen for the insert of surgical instruments to cauterise or excise them. (Chauhan et al., 2022). 

Given the invasive nature of the procedure, the fact that lesion removal often does not eliminate chronic pain, and that recurrence is estimated at 20-50% within 5 years of surgery (Guo, 2009), it is common practice for symptom control by hormonal contraceptives to be implemented before surgery is considered. Many patients also trial at-home remedies to control symptoms, such as diet alterations and supplementation. One notable field of research driving the popularity of these at home remedies is the link between the gut-microbiome and inflammatory disease. The gut-microbiota-brain axis communicates closely with the immune system, impacting neuronal pathways involved in pain signalling (O’Riordan et al., 2025), so many patients take probiotics in order to help control symptoms. This remains an understudied field with no clear evidence yet to support the effectiveness of such remedies. Likewise, hormonal contraceptives vary in their efficacy of symptom control, risking adverse side effects, without being a treatment for the underlying disease. 

The reality for those suffering from endometriosis

The lack of non-invasive techniques for diagnosis or effective treatment, in combination with wait times for diagnosis, potential medical neglect, and societal stigma surrounding the disease, makes living with the disease debilitating. That such a lack of scientific and social understanding persists in affecting AFAB individuals specifically, should not be understated. 

There is severe disproportion in the dispersal of funding, and scientific research into diseases that are sex-linked.  Shockingly, a 2021 report calculating funding by the U.S National Institutes of Health shows that 3/4 of the cases where a disease afflicts primarily one gender, the funding pattern favours males (Mirin, 2021). An example of such gender bias in medical research is that there is five times more research into erectile dysfunction, which affects 20-50% AMAB people worldwide (Sarnoski et al., 2026), than into premenstrual syndrome, which affects 90% of women (Chumpalova et al., 2020) (England, 2016).

In addition to funding disparity, patient-level medical negligence is astonishingly prevalent.  Endometriosis UK (2026) conducted a survey of 4371 people with a diagnosis and found that “47% had visited their GP 10 or more times with symptoms prior to receiving a diagnosis”.  Additionally, it is a common experience for the severity of symptoms to be doubted, and invalidated by healthcare professionals, with “78% of people who later went on to receive a diagnosis of endometriosis [experiencing] one or more doctors telling them they were making a ‘fuss about nothing’ or similar comments”. It is a given that the pain of women and AFAB people has historically been belittled, leaving millions suffering with little to no support. This needs to be addressed and it is for this reason that raising awareness for, and reducing stigma towards gynaecological health, and associated chronic pain conditions, is vital. 

The future of endometriosis diagnosis and treatment

While the current state of endometriosis understanding and care is lacking, the field of research is growing. A promising study in the search for a non-invasive diagnostic tool is being conducted at the University of Oxford by Dr Tatjana Gibbons. Successful phase one and two studies have been achieved using intravenous imaging agent ^99mTc-maraciclatide (DETECT), a gamma emitting radiotracer that binds to avB3 integrins, which are upregulated in some endometrial lesions during angiogenesis. A non-invasive scan produces SPECT-CT images, from which endometriosis lesions can be identified.  During phase two, the tool was able to identify all three subtypes of endometriosis, with images concordant with presence or absence of endometriosis in 16/19 participants. Phase three has been planned, to validate these findings in a larger group of participants(Gibbons et al., 2026). 

Another non-invasive diagnostic tool showing similar promise is EndoTect, developed at the University of Hull by Dr Barbara Guinn. EndoTect is an ELISA urine test for PGAM1, an enzyme involved in glycolysis, and a proposed biomarker for deep endometriosis. In a trial of 190 participants, EndoTect was able to correctly identify deep endometriosis with 70-90% accuracy, and larger clinical trials are set to follow (Draper et al., 2025).

To summarise, endometriosis is a poorly understood disease, leaving hundreds of millions of (mostly AFAB) people facing debilitating physical and mental symptoms. Rooted in misogyny, there is undeniable lack of funding for female sex-related diseases, and a harmful, dismissive attitude towards pain in AFAB people by many healthcare workers, and society as a whole. These realities contribute to the wait times for diagnosis being extensive and limit the progress that can be made in the understanding of the disease, and therefore the development of non-invasive diagnostic tools and effective treatments. While progress is being made in the identification of biomarkers, and development of diagnostic tools, wider scale societal change in the attitude towards AFAB people experiencing chronic- pain and reduction in the stigma of gynaecological health is of upmost importance to support the understanding and treatment of endometriosis.

By Tallulah Flint (they/she)

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