Endometriosis : management

Management of endometriosis involves medical therapy and surgical therapy. Endometriosis should only be treated when there is either pain or infertility. Medical therapy for endometriosis may include COCPs (combined oral contraceptive pills), POPs (progestin only pills), DMPA (Depot progestin therapy), LNG-IUS (intrauterine progestin releasing system), GnRH agonists and Danazol. Surgical intervention might be needed when there is indication which include; 1) Endometriosis-related pain not well respond to medical therapy. 2) Endometriosis-related infertility. 3) Pain with ovarian endometrioma.

Under medical therapy COCP,s POPs or DMPA should be considered as the 1st line treatment for managing endometriosis while GnRH agonist with HT(hormone therapy) addback, or LNG-IUS should be considered as the second line therapy.

Each therapy take time to become effective. Analgesia, ranging from NSAIDs (non-steroidal anti-inflammatory drugs) to opioids is commonly prescribed while awaiting resolution of symptoms from the primary medical therapy or surgical therapy. This is to ensure that the patient is more comfortable until the primary treatment becomes effective.

COCPs may be administered as a continuous or cyclic therapy. However continuous therapy is preferred than cyclic therapy since withdrawal bleeding, which occurs with cyclic therapy, usually associated with retrograde menstruation causing the pain symptoms.

POPs may be more effective compared to COCPs in managing endometriosis related pain. However, it may cause breakthrough bleeding and also may lead to systemic effects of progestin such as metabolism and cholesterol abnormalities.

DMPA is effective in relieving pain associated with endometriosis and it gives more long term effect. However, because its progestin effect could not be reversed immediately, there will be a prolonged delay in resumption of ovulation, which is not suitable for women who want pregnancy in the near future, and it may cause prolonged and heavy breakthrough bleeding as well. It is an ideal choice for those with residual endometriosis after hysterectomy done, in which future conception and irregular uterine bleed are not an issue.

One LNG-IUS can provide continuous therapy for 5 years, but the effect can be reversed just by removal of the device. It provides high concentration of progestin in the pelvis and less progestin secreted in to the systemic circulation so that the risk of systemic side effects is reduced. Few risks associated with LNG-IUS include risk of expulsion – 5%, risk of pelvic infection 1.5% and risk of ovarian endometrioma since ovulation is not inhibited.

GnRH agonists is indicated in patient who do not well respond to COCPs or progestins. It induces hypoestrogenism thus effective in managing the pelvic lesions and resolving the pain. GnRH agonists should be used with HT addback in managing endometriosis to avoid the side effects of hypoestrogenism which include hot flashes, insomnia, vaginal dryness ,loss of libido and etc.

Endometriosis : diagnosis

Clinical features	Symptoms	Pain
	Pelvic examination	Tenderness
		Nodularities
		Fixed retroverted uterus
		Adnexal masses
Investigation	Ultrasound	Ovarian endometrioma / chocolate cyst
	Diagnostic laparoscopy	Endometrial implant
		Biopsy

Women with endometriosis commonly presented with pain symptoms (dysmenorrhea, dyspareunia, dysuria, dyschezia, abdominal pain, back pain) eventhough some of them may be asymptomatic and only found out incidentally during surgery for other condition.

Pelvic examination may elicit tenderness which can be ill-localized or focal tenderness for example over the posterior fornix or anterior vaginal wall. Nodularities may be appreciated during pelvic examination upon palpation of the uterosacral ligament or upon rectovaginal examination, which may suggest endometrial lesions over the uterosacral ligament and the rectovaginal septum respectively. Adnexal masses found during pelvic examination of a woman with suspected endometriosis may suggest presence of ovarian endometrioma (chocolate cyst). Bimanual examination may revealed fixed retroverted uterus which suggest significant degree of adhesion has occurs.

Pelvic examination - bimanual examination

Pelvic examination - rectovaginal examination

Ultrasound imaging in endometriosis may revealed ovarian endometrioma / chocolate cyst which can be described as homogenous hypoechoic grain-like lesion surrounding by well defined thickened cyst wall.

Ultrasound

Diagnostic laparoscopic examination is the gold standard investigation in diagnosing endometriosis, which allows direct visualization of the endometriotic lesions. During the laparoscopy, usually the discovered endometriotic lesions are removed and biopsy taken and sent for histopathological examination to confirm the diagnosis.

Laparoscopic examination

Laparoscopic examination

Endometriosis

Endometriosis : pathophysiology

The survival and persistence of endometrial implants is maintained by the presence of estrogen hormones. These estrogen-dependent lesions, grow and regress as the estrogen level fluctuating up and down respectively. As it regresses, inflammation occurs and leads to release of various inflammatory mediators which responsible for the pain symptoms in endometriosis. These mediators lead to damage of the surrounding tissues and when healing process take places later, there will be scarring and adhesion which increase the severity and complication of the disease.

Depending on the location of the endometrial implants, the pain symptoms may vary in term of presentation, commonly such as: 1) dysmenorrhea 2) dyspareunia 3) dyschezia 4) dysuria 5) lower abdominal / back pain. Some women may presented with more atypical presentation which may suggest more invasive disease such as hematuria (bladder invasion), hematochezia (bowel invasion), sciatica (nerve invasion), or dyspnea (catamenial pneumothorax).

Endometriosis is a chronic relapsing progressive disorder. as the disease progresses, patient may develop chronic pelvic pain due to the chronic inflammatory process. Besides,patient may suffer from subfertility with all the adhesion which may cause mechanical obstruction of the reproductive route preventing fertilization or implantation to occur properly.

Endometriosis

Endometriosis: pathogenesis

Pathogenesis

There are many theories describing the pathogenesis of endometriosis. These theories can be classified into: 1) in-situ development 2) transplantation / implantation 3) combination of in-situ development and transplantation / implantation.

In-situ development -The cells of that site itself undergo differentiation and become endometrial cells	a)       Germinal epithelium of the ovary
	b)       Embryonic cell
	c)        Coelomic metaplasia
	d)       Metaplasia by inflammation
	e)       Metaplasia by hormonal stimulation
	f)        Metaplasia by induction
	g)       Secondary mullerian system
Transplantation / implantation -The endometrial cells from the uterus lining migrate to other sites	a)       Retrograde menstruation
	b)       Mechanical transplantation
	c)        Benign lymphogenous metastasis
Combination of in-situ development and transplantation/implantation

Among the most widely accepted theories include: 1) retrograde menstruation 2) coelomic metaplasia 3) benign lymphogenous metastasis.

In retrograde menstruation theory, it is said that the menstrual blood contain some viable endometrial tissues, which retrogradely shed into the peritoneal cavity and get attach to the peritoneal cavity, proliferate and produce endometriosis implant.

Coelomic metaplasia theory claims that formation of endometriosis implant is caused by metaplasia of the coelomic epithelium, perhaps induced by environmental factor.

Another theory suggests that shedding menstrual tissue travels from the endometrial cavity through lymphatic channels and veins to distant sites, for example outside the pelvic cavity.

Endometriosis

Endometriosis

Definition

Endometriosis can be defined as presence of endometrial tissue outside the uterus. These tissues are also called endometrial implants or ectopic endometrial tissues.

Commonly, endometriosis / ectopic endometrial tissues are found in the following places: 1)Peritoneum, 2)Ovaries, 3)Fallopian tubes, 4)Outer surface of uterus, bladder, ureters, intestine and rectum, 5)Pouch of Douglas (rectouterine pouch).

Pathogenesis

There are few theories that has been suggested as the underlying mechanism on how endometriosis can occur, including 1)theory of retrograde menstruation, 2)coelomic-metaplasia theory, 3)circulation and implantation theory.

Endometriosis : pathogenesis

Pathophysiology

Ectopic endometrial tissues have similar features with the endometrial tissue lining the uterus. Just like the endometrial lining of the uterus, ectopic endometrial tissues also undergo cyclical changes of the menstrual cycle and respond to changes of the estrogen level. As we know, menstruation is associated with inflammatory process. These repetitive inflammatory events eventually lead to scarring and adhesion. All these inflammation, scarring and adhesion lead to the clinical signs and symptoms of endometriosis and its complications, depending on where is the location of the ectopic endometrial tissues.

Woman with endometriosis may be presented with symptoms of abdominal/back pain, dysmenorrhea, dyspareunia, dysuria, or dyschezia. Some women may be presented with the complications such as chronic pelvic pain and subfertility.

 Endometriosis : pathophysiology

Diagnosis

Endometriosis should be suspected when a woman in her reproductive age presented with severe dysmenorrhea, which is not improved with NSAIDs. On physical examination in women with endometriosis, there may be pelvic tenderness, or nodularity of the uterosacral ligaments and rectovaginal septum, and ultrasound may reveal ovarian cyst and endometrioma. Laparoscopic examination, which is the gold standard procedure to confirm the diagnosis, might be done and the suspected lesions are removed and sent for biopsy. However, laparoscopy for diagnosis is not necessary to be done before starting treatment with medications. Laparoscopy should generally be performed only when the surgeon plan to remove the lesions if endometriosis is discovered during the procedure.

Endometrial : diagnosis

Treatment

Treatment modalities in the management of endometriosis can be divided into medical treatment and surgical treatment. A woman with endometriosis may be treated medically or surgically or both. The aim of the treatment should be directed to improve patient’s symptoms and quality of life, and should be tailored based on the severity of the disease and patient’s fertility desire.