Clinical FeaturesWomen’s Health

Management of Endometriosis

Endometriosis is a word that 1 in 10 women hear from their gynaecologist, relating to their ongoing pain or as an explanation for their fertility problems. It is one of the most commonly seen gynaecological diseases, yet is poorly understood and not commonly talked about.

We recently spoke to Theresa Lowry Lehnen, RGN, RNP, BSc, MSc, PG. Dip. Ed (QTS), M. Ed, PhD, Clinical Nurse Specialist and Associate Lecturer South East Technological University to gain a further understanding of this common, chronic condition.

Endometriosis is a chronic gynaecological condition characterised by the presence of endometrial-like tissue in anatomical positions and organs outside of the uterine cavity. “Establishment and growth of such endometriotic tissue is oestrogendependent,” Theresa told us.

The exact prevalence of endometriosis is unknown, but estimates range from 2 to 10% within the general female population, and up to 50% in infertile women. It is estimated that at least 190 million women and adolescent girls worldwide are currently affected by the disease during reproductive age, although some women are affected beyond menopause.

“Most endometriotic disease is located on the pelvic peritoneum including the ovaries, fallopian tubes, the bowel, and the areas in front, on the back, and to the sides of the uterus while a smaller percentage involves the ureters, bladder, urethra and the upper abdomen,” she explains.

“The condition is not limited to the pelvis, and occasionally can cause damage to extra pelvic structures such as the pleura and the pericardium, however, it rarely extends beyond the peritoneal cavity.”

Pathophysiology

Theresa adds, “The pathophysiology of endometriosis is strongly influenced by factors such as genetic predisposition and hormonal factors such as resistance to progesterone, oestrogen dependence; inflammation, angiogenesis, and vascularisation processes. Oxidative stress, resistance to apoptosis and immunological factors are also involved to various degrees in lesion development. Several predisposing factors have been linked with the risk of developing endometriosis. Early age at menarche (below 11 years old), shorter duration of menstrual periods of less than 27 days, menorrhagia, and nulliparity increase the risk for endometriosis, indicating that it is closely linked with the female hormonal.

“On the contrary, there are protective factors against endometriosis, mainly acting via lowering the inflammatory process, or by decreasing the levels of oestrogen in the body. Protracted breastfeeding, current oral contraceptive use, tubal ligation, and smoking are related to a decreased risk for endometriosis. Although the mechanism is still not clear, women who smoke have lower levels of oestrogen in the body.”

The clinical presentation of endometrial disease differs not only in presentation but also in duration, Theresa notes adding, “Symptoms of endometriosis can begin prior to the first menstrual period, and for many it can persist into menopause and throughout their lives. It has been found in cis males, Tran’s males, pre-menarche girls and postmenopausal women. Endometriosis triggers a chronic inflammatory reaction resulting in pain and adhesions, and can have a profound effect on an individual’s quality of life. Adhesions develop when scar tissue attaches separate structures or organs together. Pain and symptoms due to endometriosis may vary during the menstrual cycle as hormone levels fluctuate.

“Symptoms may be worse at certain times in the menstrual cycle, with ovulation and prior to and during menstruation being the most severe for many. While some experience severe pelvic, bladder and/or bowel pain, others may have few or no symptoms or regard the symptoms as simply period pain or cramps.”

Diagnosis

Diagnosis is often delayed on average of 4 to 11 years from the onset of symptoms,” Theresa told us. “According to the endometriosis association of Ireland, the average delay in Ireland is 9 years. This phenomenon is attributed to the non-existence of a pathognomonic test or biomarker to detect the disease; to the diversity of symptoms being considered physiologic responses during menstruation, and to the wide range of reported symptoms that overlap with other gastrointestinal or gynaecological conditions.

“The European Society of Human Reproduction and Embryology (ESHRE) Guidelines on Endometriosis were updated in 2022, and offer best practice advice on the care of women with endometriosis, including recommendations on the diagnostic approach and treatments for endometriosis for both the relief of painful symptoms and infertility due to endometriosis

“Laparoscopy is no longer the diagnostic gold standard, and is now only recommended in patients with negative imaging results and / or where empirical treatment was unsuccessful or inappropriate. The ESHRE guideline development group (GDG) recommends that clinicians should consider the diagnosis of endometriosis in individuals presenting with cyclical and non-cyclical signs and symptoms; dysmenorrhea, deep dyspareunia, dysuria, dyschezia, painful rectal bleeding or haematuria, shoulder tip pain, catamenial pneumothorax, cyclical cough/haemoptysis/ chest pain, cyclical scar swelling and pain, fatigue, and infertility.”

The American Society of Reproductive Medicine (ASRM) developed a staging system, to stage endometriosis and adhesions due to endometriosis.

• Stage 1 and 2 (Minimal to mild disease): Superficial peritoneal endometriosis. Possible presence of small deep lesions. No endometrioma. Mild filmy adhesions, if present. 4

• Stages 3 and 4 (Moderate to severe disease): The presence of superficial peritoneal endometriosis, deeply invasive endometriosis with moderate to extensive adhesions between the uterus and bowels and/ or endometrioma cysts with moderate to extensive adhesions involving the ovaries and tubes.

Theresa adds, “The classification was originally developed to predict impairment to fertility, and is therefore focused on ovarian disease and adhesions. Patients with the same ‘stage’ of disease may have different disease presentations and types, and some forms of severe disease such as invasive disease of the bowel, bladder and diaphragm are not included.

“Apart from the classification system, 3 subtypes of endometriosis can be distinguished according to localisation: superficial peritoneal endometriosis, cystic ovarian endometriosis (endometrioma or ‘chocolate cysts’) and deep endometriosis also referred to as deeply infiltrating endometriosis.

“The different types of disease may co-occur.

• Superficial peritoneal endometriosis is the most common type. Lesions involve the peritoneum, are flat, shallow, and do not invade the space underlying the peritoneum.

• Cystic ovarian endometriosis (ovarian endometrioma) occurs less commonly. The cyst is filled with old blood, and because

of the colour are referred to as ‘chocolate cysts’. Most people with endometrioma cysts will also have superficial and/or deep disease present elsewhere in the pelvis.

• Deep endometriosis is the least common subtype. An endometriosis lesion is defined as deep if it has invaded at least 5mm beyond the surface of the peritoneum. Deep lesions involve tissue underlying the retroperitoneal space.”

Treatment

There is no cure for endometriosis, and treatment is broadly divided into two main categories; pharmacological and surgical, says Theresa. Currently, there is no specific drug that can inhibit the progress of the disease, other than hormonal and non-hormonal agents used to alleviate the symptoms and increase fertility rates.

“Treatment of endometriosis depends on the severity of symptoms, reproductive plans, patient’s age, medical history and side effects of both surgical and medical treatments. Regarding treatment of symptoms in postmenopausal women, the potential increased risk of underlying malignancy in this population should be keep in mind and the uncertainty of the diagnosis, as pain symptoms may present differently in this group compared to premenopausal women.

“NSAIDs or other analgesics, either alone or in combination with other treatments, can be used to reduce endometriosis-associated pain. ESHRE guidelines recommend offering women hormone treatment; combined hormonal contraceptives, progestogens, GnRH agonists or GnRH antagonists, as one of the options to reduce endometriosisassociated pain.

“Ovarian suppression can reduce disease activity and pain. Systematic review has confirmed the efficacy of combined hormonal contraceptives and continuous progestogens, including medroxyprogesterone acetate, norethisterone, cyproterone acetate, or dienogest, for pain associated with endometriosis. Second line medical treatments include GnRH agonists and the levonorgestrel releasing intrauterine device (IUD). Danazol and the antiprogesterone gestrinone should not be used, as androgenic side effects outweigh benefits.

“Ovarian suppression with GnRH agonists improves symptoms but induces vasomotor symptoms in most women, and prolonged use of more than six months can lead to bone demineralisation. Prospective studies have shown that this bone loss is reversible and that concurrent treatment with a low dose oestrogen and progestogen hormone replacement therapy (HRT) regimen or tibolone can extend use without reducing treatment efficacy.

“There is limited evidence from randomised trials to show superior efficacy of one ovulation suppression treatment for pain over another, and, in clinical practice, choice of treatment is commonly guided by the tolerability of available treatments. GnRH agonists are sometimes used to “trial” how a patient might respond to surgical menopause, but the predictive value of this approach is not known,” she adds.

“In women with endometriosis associated pain refractory to other medical or surgical treatment, it is recommended to prescribe aromatase inhibitors, as they reduce endometriosis-associated pain. Aromatase inhibitors may be prescribed in combination with oral contraceptives, progestogens, GnRH agonists or GnRH antagonists.

“Surgical treatment to eliminate endometriotic lesions and divide adhesions has long been an important part of the management of endometriosis. Historically, surgical approaches were achieved at open surgery, but in recent decades, laparoscopy has dominated. Elimination of endometriosis may be achieved by excision, diathermy, or ablation/ vaporisation. Division of adhesions aims to restore pelvic anatomy. Some clinicians use interruption of pelvic nerve pathways with the intention of improving pain control.

Surgery

“Surgery is recommended as one of the options to reduce endometriosis associated pain. When surgery is performed, clinicians may consider excision instead of ablation to reduce endometriosis associated pain. Clinicians can consider hysterectomy with or without removal of the ovaries, with removal of all visible endometriosis lesions in women who no longer wish to conceive, and who failed to respond to more conservative treatments.

“Oestrogen as HRT is advised for those aged under 45 and/ or symptomatic women after oophorectomy for endometriosis, but HRT or tibolone can potentially lead to recurrence. There is, however, no indication to use combined HRT after hysterectomy for endometriosis.

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