Endometriosis: a silent and chronic disease

Original article: Endometriosi – il dolore cronico a silenzioso, by Priscilla Caputi

Description

Endometriosis is an inflammatory and chronic pathology that involved the female reproductive system. Advanced conditions can extend to other organs. In this case, it is called extragenital or extrapelvic endometriosis, affecting mainly the caecum, the small intestine, the navel, and rarely, the lungs and the diaphragm. In this pathology, the endometrium is outside the uterus, while usually, this tissue is located inside. As a result, this abnormality is responsible for a progressive, chronic and harmful inflammation for the female organism, giving extreme soreness since the first menstruation. The pain is debilitating and produces persisting physical tiredness and intestinal disorders both during the menstrual and premenstrual periods.

Above all, this pathology is responsible for physical and psychological repercussions in affected women, both for the insufficient information and the subject’s comprehension. It is a commonplace that interpersonal and professional relationships are compromised because of it.

March: month of endometriosis consciousness

March is the month chosen to raise awareness about this pathology; for this reason, on an international level (EndoMarch Global Movement), every year since 2004, world marches are organized to share the experiences, fears, and most of all, the importance of fighting to change, face and comprehend the needs, very often dissatisfied and not listened, of all women who suffer for this pathology.

The yellow color represents this movement (and reminds of this pathology), so every year, some Italian towns chose to light a specific zone with this color, like a monument or center, to contribute to the cause. Unfortunately, due to the SARS CoV-2 pandemic, from 2020, the march has been replaced by webinars and online discussions with some experts, waiting to reunite all together in favor of the fighting for this cause (Fig.1).

*Figure 1- Team Italy of Endomarch [Bibliography: ilfattoquotidiano]*

Epidemiology

Endometriosis is a widespread pathology worldwide, and it affects one woman out of ten. It is estimated that the females involved are nearly 200 million between woman and teenagers. As a result, this disease has been recognized as a severe medical condition and included in the list of chronic and disabling pathologies, mainly for the third and fourth study, recognizing exemptions and specialist performances.

Pathogenesis and risk factors

The risk factors of endometriosis are the condition of being nulliparous, menorrhea, oligomenorrhea with an overstimulation of the endometrium. Moreover, studies of other risk factors show the hypothesis that it could be a hereditary disease. For instance, it has been discovered that in first-degree relatives, there is a risk of 6 times higher to develop endometriosis.

The best theory about pathogenesis is that the migration of some fragments of endometrial tissue can cause the illness (Fig. 2) during menstruation. They go from the uterus to the ovaries passing through the tubes until they arrive at the abdomen, implanting themselves on the perineum. Moreover, sometimes this tissue can migrate to the liver, diaphragm, and the thorax, involving the pleura and lungs (retrograde menstruation).

A fascinating theory has been studied and claims that endometriosis can result from a reduced peritoneal clearance. Some fragments of endometrial tissue result from the retrograde menstrual flow for an alteration of the mediated cell immunity. There is a functional deficit of the natural killer cells and a reduced mediated cell cytotoxicity against endometrial cells and production of inflammatory cytokines.

Figure 2- *Anatomy of the female reproductive system and localization of the endometrium (inner layer)* [Bibliography: Fecondazione.org]

Clinical characteristics and complications

Endometriosis often concerns unknown clinical implications. The symptoms can be present since the menarche, with a deep pelvic pain (dysmenorrhea), physical and mental chronic tiredness, dyspareunia, intestinal disorder alternated with constipation, diarrhea, and rectal tenesmus; moreover, the menstrual cycles are abundant and prolonged, lumbar pain and in some cases haematuria.

The ovary is the most affected organ by endometriosis; in 50% of the cases, in pelvic and/or transvaginal ultrasound, it appears more prominent in volume for the presence of endometrioma or chocolate cysts (Fig.3), which can get up to 10 cm. They can have a wall coated with an endometrium that contains material formed by very dark blood and histiocytes charged with haemosiderin, a compound of iron deposit tough to metabolize that remains “stuck” in the cyst. For this reason, it is called “chocolate.”

*Figure 3 – Endometrioma ultrasound [Bibliography: wikipedia.org]*

Another frequent symptom is the development of adenomyosis, characterized by the presence of endometrial tissue in the myometrium, which is a muscular wall of the uterus (interim layer). The extra pelvic localizations go from the rectum-vaginal septum to the uterus-sacral ligaments, bladder, intestines. In more rare cases, the presence of endometrial fragments has been shown in the lungs, brain, and liver (Fig.4).

Anatomy of some of the extraperlvic localization of the endometriosis — *Figure 4 – Anatomy of some of the extrapelvic localization of the endometriosis [everydayhealth.com]*

The complications of endometriosis are based on the localization; the most frequent is infertility. For example, in the presence of intestinal endometriosis, there can also be its resection as surgical treatment.

In 1985 the American Fertility Society established the severity of the disease in its revision. Practically basing on the state of the endometriosis (mild, moderate, profound), it is possible to determine the precise stage by taking into account the outbreaks, the endometriosis plants, the adhesions, and the districts concerned. A brief description of the events as follows.

minimal disease, a few superficial outbreaks;
a mild illness, with more profound episodes;
some deep and infiltrative episodes, presence of endometriomas;
massive endometriomas on one or both the ovaries, involvement of the rectum that adheres to the back of the uterus, adhesions, many outbreaks of endometrial tissue.

Diagnosis

Diagnosis is often tricky and tortuous; it can be necessary to use different exams and medical advice to understand the prognosis. At the base of the diagnosis, there is the anamnesis, the patient’s medical history, followed by a gynecological examination combined with medical tests and laboratory exams.

Medical tests are considered the pelvic and/or transvaginal ultrasound, and they determine the presence of endometriosis. Besides, it is also used the color doppler to have a confirmation of their existence. Ultrasound is also employed as a follow-up during the disease. Moreover, also M.R.I. helps in the diagnosis of endometriosis.

Laboratory exams include the enzyme assay of the tumor marker called CA-125. In endometriosis, the values can be altered and be over the threshold; it is essential to remember that it is a specific marker.

Laparoscopy is performed, both for the diagnosis and the surgical treatment, followed by a histological exam of the biopsy. It helps establish and confirm the nature of the lesions (endometriosis cysts, extrapelvic lesions, etc.).

Treatment and prevention

Treatments depend on the stage of the disease. In moderate or severe, the gold standard is the surgical treatment (laparoscopy), which aims to remove all the outbreaks present, preserving as much as possible all the anatomic structures and the ovarian reserve.

In the cases where the endometriosis is minimal or mild, in which the pelvic pain is still present, and it is chronic and disabling, the hormonal therapy is the one suggested, mainly of progestin type. Recent studies have shown that in some groups of women treated with Dienogest, the pain and endometrioma size were lowered, improving their condition. During the treatments with oral contraception, it is essential to monitor the patients’ coagulation because this therapy increases the risk of a thrombotic event. The non-steroidal anti-inflammatory (FANS) represents the first choice for the symptomatic treatment for controlling the pain. Unfortunately, they are not effective in preventing the disease and its progression.

In conclusion, endometriosis cannot be prevented since it is a chronic inflammatory disease and probably congenital. A cure doesn’t exist, but by adopting a healthy diet, it is, at least, possible to keep the symptoms under control. The only possible thing is to trust science and all the studies about endometriosis and inform the population to make them aware of this disease that is often underestimated.

Martina Calderato

Bibliography

Parola M., Patologia generale ed elementi di fisiopatologia. Edises, 2020.
Taylor, H. S., Kotlyar, A. M., & Flores, V. A. (2021). Endometriosis is a chronic systemic disease: clinical challenges and novel innovations. The Lancet, 397(10276), 839-852.
Andrews, W., Buttram Jr, V., Weed, J., Hammond B., & Thomas, H. H. (1985). Revised American fertility society classification of endometriosis: 1985. Fertility and sterility, 43(3), 351-352.
DeAngelo, C., Tarasiewicz, M. B., Strother, A., Taggart, H., Gray, C., Shanahan, M., … & Farias-Eisner, R. (2020). Endometriosis: A Malignant Fingerprint. Journal of cancer research and therapeutic oncology, 8(2).
Namazi, M., Behboodi Moghadam, Z., Zareiyan, A., & Jafarabadi, M. (2020). Impact of endometriosis on reproductive health: an integrative review. Journal of Obstetrics and Gynaecology, 1-20.
Uludag, S. Z., Demirtas, E., Sahin, Y., & Aygen, E. M. (2020). Dienogest reduces endometrioma volume and endometriosis-related pain symptoms. Journal of Obstetrics and Gynaecology, 1-10.
Azizad-Pinto, P., & Clarke, D. (2014). Thoracic endometriosis syndrome: case report and review of the literature. The Permanente Journal, 18(3), 61.