Endometriosis
Endometriosis is a common disease in which tissue like the lining of the uterus is found outside it and causes lesions and pain; its cause is unknown, its diagnosis is invasive and often delayed by years, and its treatment eases symptoms and limits its spread without curing it.
What endometriosis is
Endometriosis takes its name from the Greek endos (inside), metra (womb or uterus) and -osis (disease), so it can be translated as "disease of the uterus"; clinically, it is defined by the presence of endometrium-like tissue outside the uterus. The endometrium is the lining of the uterus, made of epithelium and connective tissue, and during each menstrual cycle it thickens and sheds under the influence of the two main female hormones, oestrogen and progesterone; its shedding is commonly known as a period. In endometriosis, endometrial cells are found outside the uterus, in places such as the fallopian tubes or the ovaries, and sometimes they escape the female reproductive system and attach to nearby organs such as the bladder or the colon. When a period occurs, these cells also break down, and their shedding outside the uterus ultimately causes lesions, alters the function of the organs they have colonised, or both, and pain accompanies the process as it does any wound.
Its burden
Endometriosis is estimated to affect about 10% of women of reproductive age, the equivalent of 190 million women worldwide. It impairs the physical, mental, sexual and social well-being of affected women. Its burden on society includes lost productivity, lower study activity and grades, and an estimated cost to the healthcare system equivalent to that of other chronic diseases such as type 2 diabetes or Crohn's disease. Although it is common, in 2022 its aetiology was still unknown, its diagnosis was still difficult and its treatment was still palliative, so that it remained a complex challenge for patients, clinicians and researchers and, for millions of women, a diagnosis like an obstacle course with limited treatment options.
Its possible causes
The origin of endometriosis is still unknown. One hypothesis suggests that retrograde menstruation, the reflux of menstrual debris through the fallopian tubes, could carry viable endometrial cells outside the uterus. Because 90% of women experience retrograde menstruation, other factors are likely to be involved in the development of the disease, and genetic predisposition, prenatal exposure to endocrine-disrupting chemicals, the intestinal and female-tract microbiome, the immune system and sex hormones are possible factors.
Symptoms and presentations
Endometriosis is a spectrum disease: it includes a wide range of signs and symptoms and a variety of subtypes and clinical presentations. The symptoms most commonly observed include painful periods, pain during or after intercourse, painful bowel movements or urination, fatigue and infertility. Some women show no sign of the disease or experience no symptoms, while others experience painful symptoms, infertility or both, and present with an endometrioma (endometrial tissue forming a cyst on the ovary), an extra-pelvic lesion or both.
Diagnosis
Given the broad range of symptoms, biomarkers detected by non-invasive methods such as a blood sample could help clinicians quickly and easily detect or rule out endometriosis. In 2022, however, the gold standard for diagnosis combined surgical examination by laparoscopy, a surgical procedure to access the inside of the abdomen, with histological examination of the specimens collected during it, an invasive procedure that requires specialised materials, trained practitioners and time. Diagnosis is made harder still by a lack of awareness of the disease among both patients and general practitioners. Expecting painful periods is strongly ingrained in society, and stigma prevents affected women from seeking help and delays their diagnosis by 5 to 9 years, and a delayed diagnosis means further damage to the affected tissues and organs.
Treatment
In 2022 there was no cure for endometriosis, but palliative treatments eased its symptoms and limited its spread. The first line of treatment was to relieve the pain during periods with analgesics such as ibuprofen or paracetamol. Two options were available to tackle the lesions and limit their spread: hormonal treatment and surgery. Endometriosis is an oestrogen-dominant condition, so controlling the secretion and circulation of oestrogen could limit its development. The most widely used hormonal treatment was the contraceptive pill, which, besides limiting the disease, also limits dysmenorrhoea (severe and frequent menstrual cramps and pain during the period) or chronic pelvic pain. Other hormonal treatments, such as gonadotropin-releasing hormone (GnRH) agonists and aromatase inhibitors, have a similar mechanism of action, although the evidence for their effectiveness is limited. In hormone-resistant endometriosis, surgery can be considered to remove lesions and endometriotic adhesions, but lesions reappear after surgery and progress in approximately 30% of cases.
Research leads
In 2022, promising candidate biomarkers had emerged for non-invasive, accurate and sensitive diagnosis: patients with endometriosis had higher levels of VEGF-A and lower levels of miR-135a than patients without it. Both biomarkers could be analysed from a simple blood sample, a cheaper, faster and less invasive procedure than surgery. Fifteen clinical trials were then testing non-hormonal therapies as alternatives to analgesics and hormonal treatments for endometriosis-related pain.
The microbiota of the gut and of the female genital tract were emerging topics in both the diagnosis and the treatment of endometriosis. The genital microbiome of women with endometriosis had been observed to differ from that of controls and could be associated with the severity of the disease. Women with endometriosis also showed reduced microbiome diversity and a greater proportion of potentially pathogenic microbes in both the gut and the genital tract than healthy women. Two clinical trials showed a decrease in endometriosis-related pain after oral administration of a pool of Lactobacillus strains. These studies call for further analysis of the relationship between the microbiome and endometriosis, which would allow diagnostic options and potential treatment or prevention with prebiotics, probiotics or both.
Raising awareness
Everyone, even someone not directly affected, can do at least one thing to fight endometriosis: raise awareness of it. Fighting the stigma of painful periods will help ensure early diagnosis, improve the management of the disease and promote research and clinical trials, which are key to providing new therapeutic options.