We need to talk about Endometriosis
In the United Kingdom (UK), 1 in 10 women of reproductive age suffers from endometriosis[1]. This amounts to approximately 1.5 million women, which is similar to the number of women with diabetes[2]. Endometriosis can affect women of any age and is the second most common gynaecological condition in the UK (after fibroids)[3], however, it is often not diagnosed until women are over 25[4]. This is because symptoms vary between women and are similar to other conditions such as inflammatory bowel disease, fibromyalgia, polycystic ovary syndrome, and urinary tract infections, to name only a few[5]. There is also an assumption that it “is just a heavy period”, which needs to be overcome. Understanding of the disease and the impact it has on women’s day-to-day lives needs to be improved to prevent this blasé attitude from continuing to delay treatment for women.
What is Endometriosis?
It is where endometrium tissue, which normally lines the uterus and womb, grows elsewhere, such as in the ovaries and fallopian tubes[6]. This tissue responds to monthly hormonal changes leading to inflammation, pain, and eventually scar tissue which may need to be surgically removed[7].
Although the mechanism by which this tissue ends up there is not yet fully understood, retrograde menstruation (where blood flows backwards into the pelvis instead of out of the vagina during menstruation) is generally accepted to be the cause. However, it does not fully explain the occurrence of endometriosis in extra-pelvic locations[6], meaning further research is required to truly understand this disease.
What are the symptoms of Endometriosis
Endometriosis is characterised by symptoms of chronic abdominal pain, fatigue, pain during sex and urination, nausea, heavy periods, constipation or diarrhoea, and infertility[8], which can affect a women’s attendance at work, sex life and relationships, and have an impact on mental health, with women often reporting feelings of depression and isolation[8].
Currently, there is no cure for endometriosis, and it is difficult to diagnose due to the similarity of symptoms to other conditions such as inflammatory bowel disease, fibromyalgia, polycystic ovary syndrome, and urinary tract infections. Additionally, because of a lack of awareness from both front-line healthcare professionals (HCPs), and the general public, there is often a delay between symptom onset and diagnosis, with women waiting on average 8 years for a diagnosis[9]. Therefore, there is a need for more research and awareness to ensure effective prevention, early diagnosis, and improved management of the disease.
What is already in place?
The World Health Organisation (WHO) has pledged to stimulate and support the adoption of effective policies and interventions to address endometriosis globally, especially in low and middle-income countries, and plan to partner with stakeholders to identify effective models of endometriosis prevention, diagnosis, treatment, and care[10].
Additionally, the Priority Setting Partnership (PSP) was formed in 2017 with the objective of identifying the key questions about endometriosis that were most important to both women with endometriosis and HCPs involved in their care. The top 3 questions to be answered were identified as[11]:
- Can a cure be developed?
- What causes endometriosis?
- What are the most effective ways of educating HCPs throughout the healthcare system resulting in reduced time to diagnosis and improved treatment and care of women with endometriosis?
This shows that there is an awareness of the lack of attention towards endometriosis and has provided a direction for researchers to focus on. However, more commitment and funding for research is required to understand the disease and develop effective treatments.
Currently, treatments include over-the-counter painkillers, hormone-based medications and contraceptives, and surgery to cut away patches of endometrial tissue[8]. However, these come with major drawbacks including bone-density loss, headaches, depression, anxiety and weight gain with hormonal medications[12], and risk of infections, excess bleeding, and scarring with surgery[13]. Additionally, women who are trying to conceive have limited options.
Is there anything in the pipeline to help women with Endometriosis?
It is not all negative. In recent years, more clinical trials have been initiated, with 12 companies conducting trials in 2019, compared to only 3 in 2010. Although this sounds small, this amounts to a 300% increase over a 10-year period[14], which is a small but important step in the right direction.
Currently, there is one trial that is investigating dichloroacetate (DCA), a treatment normally used to treat metabolic disorders in children, as a non-contraceptive treatment for endometriosis. Women with endometriosis have high levels of lactate present in their pelvis. DCA reduces lactate production and could potentially reduce the survival rate and growth of endometriosis growths[15].
There is also early-stage research ongoing into targeted therapies, with the goal of damaging endometriotic tissue whilst leaving healthy tissue unharmed[16]. Additionally, following a 2019 study, there are investigations into macrophage reduction therapies that demonstrated reversal of pain behaviours in mice with endometriosis[17].
A recently published study has also identified specific deoxyribose nucleic acid (DNA) methylation present only in women with endometriosis, which could provide insights that may help with diagnosis in the future[18].
This all sounds like it is on track, so why should endometriosis receive more attention and funding from Big Pharma?
Endometriosis has a significant social, public health, and economic burden – currently costing the UK economy £8.2 billion a year in treatment, loss of work, and healthcare costs. Some studies highlighted that the economic burden of endometriosis is similar to other chronic diseases such as diabetes, Crohn’s disease, and rheumatoid arthritis[19]. Yet, there are no accurate non-invasive diagnostic tests or biomarkers, and current treatment options are inadequate.
Women with endometriosis experience debilitating pain that often prevents them from going to work or school. By addressing endometriosis, absences can be reduced, and women’s education and career prospects can be improved.
Presently, we do not know how to prevent endometriosis, nor do we have a cure, and although enhanced awareness, followed by early diagnosis and management, may slow or halt the natural progression of the disease and reduce the long-term burden of its symptoms, more needs to be done to understand the disease and develop a treatment, which not only focuses on treating the symptoms but treats the root of the problem.
What can I do to help?
Talk about it. Talk to your doctor if you think you have symptoms. Talk about endometriosis with your friends and colleagues and help improve awareness of the disease. The more the disease is talked about, and the burden is understood, hopefully, the quicker it will be diagnosed, and eventually, pharmaceutical companies will be forced into committing to drug development and research.
Endometriosis UK has resources offering valuable information to help you understand more about the disease with a support network that has already reached 25,000 women with endometriosis.
If we all do our bit to understand diseases that only, or disproportionately, affect women, then hopefully Pharma will follow suit and start funding more research in this arena.
Look out for our next blog in our Women’s Health series on the 4 November 2021!
References:
[1] P. A. W. Rogers et al., ‘Priorities for endometriosis research: recommendations from an international consensus workshop’, Reprod Sci, vol. 16, no. 4, pp. 335–346, Apr. 2009, doi: 10.1177/1933719108330568.
[2] ‘Diabetes in the UK 2012 (April 2012)’, Diabetes UK. https://www.diabetes.org.uk/professionals/position-statements-reports/statistics/diabetes-in-the-uk-2012 (accessed Oct. 18, 2021).
[3] ‘Endometriosis | Womens health | Royal College of Nursing’, The Royal College of Nursing. https://www.rcn.org.uk/clinical-topics/womens-health/endometriosis (accessed Oct. 18, 2021).
[4] S. Gunawardena, U. P. Dior, C. Cheng, and M. Healey, ‘New Diagnosis of Endometriosis is Less Common in Women over Age Forty Presenting with Pelvic Pain’, Journal of Minimally Invasive Gynecology, vol. 28, no. 4, pp. 891-898.e1, Apr. 2021, doi: 10.1016/j.jmig.2020.08.012.
[5] E. T. June 22 and 2018, ‘Health Conditions with Similar Symptoms to Endometriosis’, Endometriosis.net. https://endometriosis.net/diagnosis/exclusion (accessed Oct. 21, 2021).
[6] C. Mehedintu, M. Plotogea, S. Ionescu, and M. Antonovici, ‘Endometriosis still a challenge’, J Med Life, vol. 7, no. 3, pp. 349–357, Sep. 2014.
[7] T. Tanbo and P. Fedorcsak, ‘Endometriosis-associated infertility: aspects of pathophysiological mechanisms and treatment options’, Acta Obstetricia et Gynecologica Scandinavica, vol. 96, no. 6, pp. 659–667, 2017, doi: 10.1111/aogs.13082.
[8] ‘Endometriosis’, nhs.uk, Oct. 20, 2017. https://www.nhs.uk/conditions/endometriosis/ (accessed Oct. 18, 2021).
[9] S. K. Agarwal et al., ‘Clinical diagnosis of endometriosis: a call to action’, Am J Obstet Gynecol, vol. 220, no. 4, p. 354.e1-354.e12, Apr. 2019, doi: 10.1016/j.ajog.2018.12.039.
[10] ‘Endometriosis’, WHO. https://www.who.int/news-room/fact-sheets/detail/endometriosis (accessed Oct. 18, 2021).
[11] A. W. Horne, P. T. K. Saunders, I. M. Abokhrais, and L. Hogg, ‘Top ten endometriosis research priorities in the UK and Ireland’, The Lancet, vol. 389, no. 10085, pp. 2191–2192, Jun. 2017, doi: 10.1016/S0140-6736(17)31344-2.
[12] ‘Your contraception guide’, nhs.uk, Dec. 21, 2017. https://www.nhs.uk/conditions/contraception/ (accessed Oct. 18, 2021).
[13] ‘Endometriosis – Complications’, nhs.uk, Oct. 20, 2017. https://www.nhs.uk/conditions/endometriosis/complications/ (accessed Oct. 18, 2021).
[14] ‘Endometriosis Awareness Month 2021: 300% increase in endometriosis clinical trials – Clinical Trials Arena’. https://www.clinicaltrialsarena.com/comment/endometriosis-companies-trials/ (accessed Oct. 18, 2021).
[15] University of Edinburgh, ‘A Single-arm Open Label Exploratory Clinical Trial to Evaluate Dichloroacetate (DCA) as a Possible Treatment for Endometriosis-associated Pain’, clinicaltrials.gov, Clinical trial registration NCT04046081, Dec. 2019. Accessed: Oct. 17, 2021. [Online]. Available: https://clinicaltrials.gov/ct2/show/NCT04046081
[16] K. Sugihara et al., ‘Development of pro-apoptotic peptides as potential therapy for peritoneal endometriosis’, Nat Commun, vol. 5, no. 1, p. 4478, Jul. 2014, doi: 10.1038/ncomms5478.
[17] R. Forster et al., ‘Macrophage-derived insulin-like growth factor-1 is a key neurotrophic and nerve-sensitizing factor in pain associated with endometriosis’, The FASEB Journal, vol. 33, no. 10, pp. 11210–11222, 2019, doi: 10.1096/fj.201900797R.
[18] S. Houshdaran, A. B. Oke, J. C. Fung, K. C. Vo, C. Nezhat, and L. C. Giudice, ‘Steroid hormones regulate genome-wide epigenetic programming and gene transcription in human endometrial cells with marked aberrancies in endometriosis’, PLOS Genetics, vol. 16, no. 6, p. e1008601, Jun. 2020, doi: 10.1371/journal.pgen.1008601.
[19] S. Simoens et al., ‘The burden of endometriosis: costs and quality of life of women with endometriosis and treated in referral centres’, Hum Reprod, vol. 27, no. 5, pp. 1292–1299, May 2012, doi: 10.1093/humrep/des073.