Endometriosis

ENDOMETRIOSIS

A benign but progressive condition, characterized by endometrial glands and stroma found in locations other than the endometrium.

Prevalence

Five to fifteen percent of women 20% of gynecologic laparotomies *e.g. If you open up patient with myoma, youll find 20% of them have endometriosis 30-50% of infertility patients *If a couple didnt have a child on their first year of marriage and they have to undergo already an infertility work-up.

Predominant Age

Often seen in the third and forth decades of life 5% diagnosed after menopause(no more estrogen).

Genetics

Familial predisposition (polygenic or multifactorial inheritance pattern)

Etiology and Pathogenesis

Causes: Endometriosis may arise by one of several proposed mechanisms:1. Lymphatic spread the endometrial glands and stroma spreads to the lymphatics2. Metaplasia of celomic epithelium or Mllerian rests3. Seeding by retrograde menstruation4. Direct hematogenous spread

Note: The most common cause of endometriosis is transtubal regurgitation of menstrual blood. Not all of the menstrual blood comes out; some of it goes back and gets out of the tube to involve the pelvic cavity(seeding by retrograde menstruation). Sometimes the patient will complain of severe dysmenorrhea which is not normal. Needs consultation

Risk factors

Obstructive anomalies such as an unrecognized double uterus or a cervical and or vaginal outflow tract obstruction.*In the event that something is blocking the menstrual flow, then some of it goes back and gets out of the tube and implants in to the pelvic cavity.

Note:Most common site of endrometriosisare the ovaries followed by your other pelvic organs which can metastasize up to lungs, umbilicus, and vaginal canal.

Clinical Characteristics

Signs and symptoms: Asymptomatic (up to 30%) Cyclic pelvic pain or dysmenorrhea(both worst 36-48 hours before menses) most common In post-menopausal, it is dyspareunia Premenstrual and menstrual pain, dyschezia, mid-cycle (ovulatory) pain.Note: if there is monthly progression of dysmenorrhea then you should consider endometriosis Often the pain reported by patients seems inversely proportional to the amount of disease; small implants maybe exquisitely painful and large endometrioma maybe asymptomatic. Other Complaints of Patients with Endometriosis

Infertility Intermenstrual bleeding (15-20%) Anovulation (15%) Intermittent constipation or diarrhea (implants are found in large intestines; if this occurs in the post menopausal, may be mistaken for coelomic CA) Adnexal masses Uterine retroversion, scarring and nodularity of the posterior cul-de sac.Note: when pelvic exam is done may find scarring and nodularity looks like a hardened wood-like structure in the posterior cul-de sac. Even without other adjuntive diagnostic procedure, based only on the history and the PE, you can label them as having endometriosis.

Differential Diagnosis

Pelvic adhesive disease secondary to pelvic infection or surgery Uterine fibroids(myomas) Gastrointestinal, urologic, or musculoskeletal problems Corpus luteum cysts(when follicle ruptures and extrudes the egg, you produce your corpus luteum cyst and often presents with hemorrhage which may mimic endometrioma) Ovarian neoplasm Adenocarcinoma of the large bowel

Associated Conditions

Adenomyosis in 20% of cases(endometrial glands and stroma traverses the myometrium and lodges there and grows even bigger than the endometriomas that are found in the ovaries) Infertility and nulliparity(more than about 30% of patients not having children will have endometriosis) Pelvic pain Dyspareunia(painful coitus) Intermenstrual bleeding(bleeding between menses)

Workup and Evaluation

Laboratory: no evaluation indicated (CA-125 is not useful for screening or follow up; only useful for epithelial tumors of the ovary; although it may be elevated in endometriosis but this is not still specific for this disease.) Pelvic ultrasound or MRI may demonstrate endometriomas(tumors of the ovaries which contain hemorrhages and paste-like tissues)or signs of scarring. Diagnostic procedure: the ultimate diagnosis of endometriosis rests on direct visualization of endometrial implants by laparoscopy or laparotomy, supported by histologic confirmation.Note: Not all implants seen by laparascopy may mean to be endometriosis; you still have to send it for histologic confirmation.

Management and therapy (dependent on future fertility plans)

A. Pharmacologic1. Analgesics nonsteroidal anti-inflammatory drugs Diminishes inflammatory reaction produced by endometriosis2. Oral contraceptives modification of periods to diminish pain during menses. Continuous administration of monophasic OCs (low estrogen-high progestin potency) induces amenorrhea and endometrial decidualization, suppressing endometriosis and enhancing apoptosis of eutopic endometrial tissues3. Gonadotropin releasing hormones(suppresses menses) Danazol Attenuated androgen (ethisterone)which is active when given orally Eliminates midcycle surge of FSH and LH resulting to amenorrhea Produces hypoestrogenic and hyperandrogenic effects on steroid sensitive end-organs producing atrophy Hypoestrogenic: flushes, decreasein breast size, changes in libido, atrophic vaginitis, vaginal dryness, deepened voice, decreased HDL and increased LDL and cholesterol Androgenic: acne, weight gain Affects modulation of immunologic functions of macrophages or T-lymphocytesi. Progestins for suppression of periods Medroxyprogesterone acetate (MPA) and 19-Nortestosterone derivatives (e.g. Levonorgestrel-releasing intrauterine system LNG-IUS) Effect is decidualization leading to endometrial attenuation over time then ovulation inhibition and amenorrhea. Hypogonadal state lead to spinal bone mineral depletion LNG-IUS(levonorgestrel intrauterine system) Steady, local release 20 g/day LNG; which falls to 11g/dayat the end of 5 years Rapid absorption of locally- relseased LNG from the uterine cavity via capillary network in the basal layer of the endometrium into the systemic circulation Detected in the circulation within 15 minutes from insertion and reaching maximum plasma levels within a few hours Plasma concentration plateaus in 1 month (0.4-0.6 nmol/L) which is by far, lower than most hormonal contraceptives

B. Surgical Endometriomas>5cm require surgical therapy (oophorocystectomy)or definitive treatment of pelvic endometriosis(hysterectomy) Selection of therapy depends on many factors: Reliability of diagnosis Extent of disease and symptoms Patients desire for fertility Degree of involvement with other organs

**Example from maam: she had a patient complaining of bleeding in the umbilicus, this was concomitant to her menstrual cycle, examination was done and endometrial implant, excision was done and was confirmed that it was endometriotic thus causing the bleeding. This just indicated that endometriosis could lodge in different areas of our body.

Drug of Choice GnRH agonist for 6 months leuprolide acetate (Lupron) 3.75 mg IM/month goserelin acetate (Zoladex) 3.6 mg implant monthly. Contraindication: known or suspected pregnancy, breastfeeding, undiagnosed vaginal bleeding. *if given for more than 6 months, may decrease bone mineral density (reversible but may become irreversible if not treated) Should give Add-Back Therapy: Progestins or low dose estrogen or both maybe used to suppress this effect. Danazol 200 mg orally QID for 6-9 months (80% of patients experience side effects causing 10-20% discontinue treatment) Sideeffects: hoarseness of the voice, hirsutism, hyperandrogenism Continuous combined oral contraceptives (monophasic formulation)taken daily for 6-9 months (if breakthrough bleeding occurs, the dose is doubled for 5 days) Taken continuously and is usually within 6-9months Breakthrough bleeding is due to the increase in the growth of the endometrium Medroxyprogesterone acetate 30mg orally daily or 150 mg daily IM every 3 months for 6-9 months. Like a contraception (no menstruation) If given less than 3 months, it will have to effect

**Give GnRH agonist for >6 months suppression of menstrual flow, no growth of endometrium glands cannot get out of endometrial cavity

Adenomyosis

Endometrial glands and stroma found in the uterine wall or myometrium. Endometrial glands and stroma have traversed the myometrium

Prevalence

10-15% of women; 60% inwomen 40-50 years old. Genetics: familial predisposition (polygenic or multifactorial inheritance pattern) **if patient came in with complaints of pain centered in the uterine wall even without menstruation, think of adenomysosis

Causes

Adenomyosis is derived from aberrant glands of the basalis layer of the endometrium. These grow by direct extension into the myometrium.

Risk Factors

High levels of estrogen High parity Postpartumendometritis

Clinical Characteristics

Asymptomatic in 40% Menorrhagia (now called abnormal uterine bleeding) (40-50%) often increasing in severity. Dysmenorrhea Symmetric woody enlargement of the uterus (up to 2-3 times normal). Uterine tenderness that varies with the cycle (worst just before menstruation) Pain is main problem; Infertility if still with no children

Diagnosis

The characteristic history of painful, heavy periods accompanied by a symmetrical, firm woody uterus suggest adenomyosis. Only histologic examination can confirm the diagnosis. Identification of endometrial glands and stroma > 2.5mm below the basalis layer of the endometrium (histopath diagnosis).

Management

There is no satisfactory medical treatment for adenomyosis. All medical therapy is aimed at ameliorating the symptoms or delaying the progression of the condition. Symptoms generally resolve with the loss of ovarian function. Hysterectomy is the definitive treatment for adenomyosis

**Patients diagnosed with adenomyosis should be counseled to let go of their uterus and their ovaries. The ovaries are the ones that produces estrogen and progesterone which stimulates the endometrium to grow those lining and expel the lining. No ovaries, no growth, no development of glands and stroma.

**Even if without ovaries but with uterus, may still have adenomyosis since there is still circulating estrogen (estriol, passive estrogen) from adrenals and fat cells through peripheral conversion-----------END----------

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