Endometriosis - Subrat

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Endometriosis

Subrat Behera

06.13.2012


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Chronic condition

Defined as the presence of endometrial glands

and stroma outside the endometrial cavity

and musculature

Severe pain, but it is most often silent

Introduction


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Epidemiology

Endometriosis

Majorgynecologicsurgery 1%

Sterilization1-7%

Women of reproductiveage undergoing

laparoscopy to diagnosepelvic pain 12-32%

Women undergoinglaparoscopy forinfertility 9-50%

Teenagers undergoinglaparascopy for pelvic

pain or dysmenorrhea50%


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Growth of endometriotic implants is dependent upon ovarian

steroid production.

Typically occurs in the reproductive years and is rare in pre-

pubertal girls and post menopausal women.

Delayed pregnancy is believed to increase the risk ofendometriosis Higher socio-economic strata.

Also, have access to better health care increasing incidence in

the group.

Caucasians = Afro-americans.


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Pathogenesis

Endometrial tissue shed from the uterus during menstruation enters the pelvisthrough the fallopian tubes and implants on pelvic structures

Implantation theory

Explains the development of endometriosis at episiotomy, laparotomy, andother surgical sites

Direct transplantationtheory

Endometriosis at extrapelvic sitesHematogenous orlymphatic spread

Coelomic or peritoneal cavity contains undifferentiated cells or cells capable oftransforming into endometrial tissue

Coelomic metaplasiatheory

Reflux of menstrual blood through the fimbriated end of the fallopian tubes,

this blood carrying viable endometrial cells that could thereby attach to andproliferate on peritoneal surfaces

Retrogrademenstruation

Deficient CMI and reduced NK cell activity may permit the growth of autologousendometrium in abnormal locations Also secrete cytokines (including IL-1, 6, and 8;tumor necrosis factor, RANTES) and growth factors promoting implants.

Altered immunitytheory

7 times more common in first-degree relatives than in the general population.

Twin concordance has also been observedGenetic factors


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Most common site of endometriosis is the ovary; 50% cases bilateral

Other sites - Posterior and anterior cul-de-sac, posterior broad ligament,

uterosacral ligaments, uterus, fallopian tubes, sigmoid colon and appendix,

and round ligaments

Myometrium involvement is termed adenomyosis

Less commonly, vagina, cervix, rectovaginal septum, small intestine, inguinal

canals, abdominal and perineal scars, ureters, bladder mucosa, andumbilicus.

Has been reported to occur in the breast, pancreas, liver, gallbladder,

kidney, urethra, arm, leg, vertebrae, bone, diaphragm, lung, and peripheral

and central nervous systems.

Pathology and surgical findings


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Implants -> Classic dark blue or brown "powder burn" lesions, white

or red opacifications, yellow-brown discolorations, clear vesicles, ora scarred or puckered area of peritoneum.

Ovary -> superficial implants or as pelvic masses containing cysts

(endometriomas) filled with thick chocolate syrup-like material.

Microscopically -> Endometrial glands and stroma. May also contain

fibrous tissue, blood, and cysts.

Decidual reaction or a "naked nuclei" cellular pattern surrounded by

a delicate reticulum or spiral arterioles with adjacent predecidua,

with or without hemorrhage.

Malignancy is rare.


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Cyclic pelvic pain (more severe during menses), dysmenorrhea,dyspareunia, abnormal menses, and infertility. Sometimesdysuria and painful defecation.

Many are completely asymptomatic.

Pain attributed to bleeding, production of cytokines, andirritation of pelvic nerves.

Related more to peritoneal inflammatory reaction than to thevolume of implants.

Clinical features - symptoms


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The most common physical finding is tenderness on palpating theposterior fornix

Localized tenderness and nodularity in the cul-de-sac, utero-sacral

ligaments, or recto-vaginal septum

Pain on uterine movement

Tender and enlarged adnexal masses

Deviation of the cervix

Fixation of the adnexa or uterus in a retroverted position

Clinical features - signs


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Gold standard is by direct visualization - Laparoscopy (the preferredless invasive technique) or laparotomy w or w/o biopsy andhistologic analysis.

Staging by site and severity of pelvic involvement : minimal, mild,moderate, or severe : American Society of Reproductive Medicinein 1979, revised in 1996.

Pelvic ultrasonography and MRI to differentiate from other adnexalmasses, but cannot detect implants.

Elevated serum CA125 or CA19-9 level : Not very sensitive : Alsoelevated with ovarian tumors and other disorders.

Diagnosis


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Dependent on the severity of symptoms, the extent and location of disease, the ageof the patient, and the patient's desire for pregnancy.

Medical management - considered for women with very little disease or forperimenopausal women

Medical management - Expectant management, analgesia with non-steroidal anti-inflammatory drugs (NSAIDs), oral contraceptives, other medical therapies includingprogestins, danazol, or gonadotropin-releasing hormone (GnRH) analogs

Surgical therapy with laparoscopy or laparotomy (conservative or definitive)

Combination of medical and surgical therapy

Endometriosis detected incidentally on physical examination or at surgery may alsobenefit from cyclic oral contraceptives to retard disease progression

Treatment


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Types of treatment:

Minimal pelvic pain - NSAIDs, other analgesics, and cyclic oral contraceptives

(OCs).

Refractory pain - Progestins, danazol, and GnRH agonists.

MoA:

Progestins alone or in combination with estrogen (as in continuous OCs) mimic

the hormonal state of pregnancy.

Danazol and GnRH analogs induce pseudomenopause.

When not suitable:

Advanced endometriosis with adhesions or for women desiring pregnancy.

Medical treatment


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Administered cyclically or continuously

Induce decidualization and subsequent atrophy of endometrial

tissue

Good choice for women with minimal or mild symptoms

Low rate of side effects and provide contraception

Randomized trial gave significant relief of pain with both, goserelin,

a GnRH analog, and OC pills, but goserelin was superior for treating

dyspareunia

Oral Contraceptives


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Cause initial decidualization, then atrophy

Also inhibit gonadotropin secretion and ovarian hormone

production

Excellent pain relief : Effective in 80% women

Oral medroxyprogesterone acetate (10 mg three times OD) or

norethindrone acetate (5 mg OD) x 6 months.

Depot medroxyprogesterone acetate as monthly injection (100 to150 mg)

Side effects include irregular bleeding, nausea, breast tenderness,

fluid retention, and depression.

Progestins


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Inhibit pituitary gonadotropin secretion -> Near-complete suppression of ovarian

hormone production Side effects -> Hypoestrogenic state (hot flushing, vaginal dryness, transient

menstruation, decreased libido, insomnia, breast tenderness, depression, and

headaches).

Loss of bone density when administered for 6 months or longer

Due to these significant side effects, usually administered only after a definitivediagnosis is made at surgery.

Usual dose is

400 to 800 mg daily for nafarelin nasal spray

3.6 mg subcutaneous goserelin monthly

3.75 mg monthly intramuscular leuprolide

Duration of therapy : 3-6 months usually.

Extended therapy of 12 months requires add-back low dose estrogen therapy to

protect the bone. Add-back therapy -> Estrogen and/or progestins -> Decrease loss

in bone mineral density and vasomotor symptoms with GnRH agonists withoutreducing their effect on pain.

GnRH analogs


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19-nortestosterone derivative with progestin-like effects.

Mechanisms of action ->

Inhibition of pituitary gonadotropin secretion

Suppression of endometriotic implant growth

Direct inhibition of ovarian enzymes used in estrogen production

Mild to moderate disease

Orally in divided doses ranging from 400 to 800 mg daily, generally for six

months.

Side effects are dose-dependent -> weight gain, edema, decreased breast

size, acne, oily skin, hirsutism, voice deepening, headache, hot flushes, and

muscle cramps. HDL levels decrease.

Pregnancy should be avoided due to pseudohermaphroditism in female

offsprings.

Danazol


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Indicated :

When the symptoms of endometriosis are severe, incapacitating, or acute

When symptoms have failed to improve with medical therapy

When the disease is advanced

Conservative surgery preserves the uterus and the maximal amount of

ovarian tissue possible

Definitive surgery involves hysterectomy with or without oophorectomy.

Surgical treatment


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Laparoscopy (Implants are excised, fulgurated, or vaporized with

laser ; adhesions are lysed)

Extensive and invasive disease may require laparotomy

Pain relief is obtained in 80 to 90 percent of patients

However risk of recurrence is estimated to be as high as 40 percentat 10 years.

Surgical treatment - Conservative


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When significant disease is present and childbearing is completed

When incapacitating symptoms persist after medical therapy or

conservative surgery.

Bilateral oophorectomy only when the ovaries are extensively

damaged by endometriosis or when the woman is approaching

menopause.

Risk of symptom recurrence with hormone replacement therapy is loweven with residual implants, except if there is bowel involvement.

Surgical treatment - Definitive


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Pre-operative medical therapy : To reduce the amount of surgical

resection required.

Post-operative medical therapy : To treat residual implants or pain.

Combination medical and surgicaltreatment


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Common cause of female infertility

Mechanisms :

Anatomic distortion from pelvic adhesions

Endometriomas

Secretion of cytokines etc. that interfere with normal

ovulation, fertilization, and implantation

When pregnancy does occur, regression or complete resolution of

endometriosis is common

Endometriosis and Infertility


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Endometriosis - Subrat

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