AUTHOR INFORMATION

Section 1 of 11

Authored by Turandot Saul, MD, Staff Physician, Department of Emergency Medicine, Bellevue Hospital Center/New York University Medical Center

Coauthored by Ami K Davé, MD, Assistant Professor, Department of Emergency Medicine, New York University School of Medicine; Assistant Residency Director, Department of Emergency Medicine, New York University/Bellevue Hospital Center; Kyle Hsu, MD, Consulting Staff, Department of Emergency Medicine, Mike O'Callahan Federal Hospital, Nellis Air Force Base

Turandot Saul, MD, is a member of the following medical societies: Alpha Omega Alpha, American Medical Association, Emergency Medicine Residents' Association, and Society for Academic Emergency Medicine

Edited by Robert M McNamara, MD, FAAEM, Professor of Emergency Medicine, Temple University; Chief, Department of Internal Medicine, Section of Emergency Medicine, Temple University Hospital; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Mark Zwanger, MD, MBA, Assistant Professor, Department of Emergency Medicine, Thomas Jefferson University; John Halamka, MD, Chief Information Officer, CareGroup Healthcare System, Assistant Professor of Medicine, Department of Emergency Medicine, Beth Israel Deaconess Medical Center; Assistant Professor of Medicine, Harvard Medical School; and Pamela Dyne, MD, Program Director, Associate Professor, Department of Medicine, Division of Emergency Medicine, University of California at Los Angeles School of Medicine

Author's Email:	Turandot Saul, MD
Editor's Email:	Robert M McNamara, MD, FAAEM

eMedicine Journal, May 22 2006, VOLUME 7, Number 5

INTRODUCTION

Section 2 of 11

Background: Endometriosis is the presence of endometrial-like tissue outside the uterine cavity, which induces a chronic inflammatory reaction. It can occur in various pelvic sites such as on the ovaries, fallopian tubes, vagina, cervix, or uterosacral ligaments or in the rectovaginal septum. It can also occur in distant sites including laparotomy scars, pleura, lung, diaphragm, kidney, spleen, gallbladder, nasal mucosa, spinal canal, stomach, and breast.

This condition is often associated with pelvic pain and infertility but can be asymptomatic. It is a frequently encountered gynecologic disorder in the emergency department (ED) as well as in the outpatient setting. Because it is enigmatic, endometriosis can present as a diagnostic and therapeutic challenge for emergency physicians in their approach to the female patient with pelvic pain.

Pathophysiology: The exact cause and pathogenesis of endometriosis is unclear. Several theories exist that attempt to explain this disease though none have been entirely proven.

Previous theories suggest that endometriosis results from the transport of viable endometrial cells through retrograde menstruation. Cells flow backwards through the fallopian tubes and deposit on the pelvic organs where they seed and grow. A population of cells reside in the endometrium, which retain stem cell properties. It may be these properties that allow these cells to survive in ectopic locations.

Retrograde menstruation is a common physiologic event. Diagnostic laparoscopy during the perimenstrual period has shown that as many as 90% of women with patent fallopian tubes have bloody peritoneal fluid. Since most women do not have endometriosis, perhaps immunologic or hormonal dysfunction leaves some women predisposed.

Recent research has suggested involvement of the immune system in the pathogenesis of endometriosis. Women with this disorder appear to exhibit increased humoral immune responsiveness and macrophage activation while showing diminished cell-mediated immunity with decreased T-cell and natural killer cell responsiveness.

Transtubal dissemination is the most common route, although other routes have been observed. These include lymphatic and vascular channels. This may explain how endometrial tissue can be found at distant locations in the body.

Metaplasia, or the changing from one normal type of tissue to another normal type of tissue, is another theory. The endometrium and the peritoneum are derivatives of the same coelomic wall epithelium. Peritoneal mesothelium has been postulated to retain its embryologic ability to transform into reproductive tissue. Such transformation may occur spontaneously, or it may be facilitated by exposure to chronic irritation by retrograde menstrual fluid.

Another theory states that remnant mullerian cells may remain in the pelvic tissues during development of the mullerian system. Under situations of estrogen stimulation, they may be induced to differentiate into functioning endometrial glands and stroma.

Finally, iatrogenic deposition of endometrial tissue has been found in some cases following gynecologic procedures and cesarean sections.

Some women may have a genetic predisposition to endometriosis. Studies have shown that first-degree relatives of women with this disease are more likely to develop it as well. The search for an endometriosis gene is currently underway.

Many theories exist as to why endometriosis occurs, and it is likely a combination of these factors that cause and determine severity of disease.

Frequency:

• In the US: The incidence of endometriosis has not increased in the last 30 years. The prevalence is approximately 6-8% but estimates vary. It is usually diagnosed during laparoscopic surgery for evaluation of pelvic pain. Most prevalence studies are based on a surgical population in which the likelihood of disease is greater. Of the surgical population, endometriosis was diagnosed in 25% of women who had a laparoscopy for pelvic pain and in 20% of women who underwent surgery for infertility. No large-scale laparoscopic evaluation of asymptomatic women has been undertaken.

Age: Pelvic endometriosis typically occurs in women aged 25-30 years. Extrapelvic manifestations of this disorder occur in woman aged 35-40 years. Women younger than 20 years with this disease often have anomalies of the reproductive system. Endometriomas and symptoms related to them regress significantly after menopause.

CLINICAL

Section 3 of 11

History:

• Patients with endometriosis present with a variety of symptoms including the following:

• Dysmenorrhea

• Heavy or irregular bleeding

• Pelvic pain

• Lower abdominal or back pain

• Dyspareunia

• Dyschezia (pain on defecation) often with cycles of diarrhea and constipation

• Bloating, nausea, and vomiting

• Inguinal pain

• Pain on micturition and/or urinary frequency

• Pain during exercise

• The most common symptom is dysmenorrhea, which may precede the onset of menstruation. In addition to pain, patients present with nonspecific symptoms of fatigue, generalized malaise, and sleep disturbances.

• Intensity of pain and discomfort does not correlate with extent of disease because the location and depth of endometrial implants affect the symptomatology. Associated intrapelvic/intra-abdominal adhesions are also important determinants of the degree of pain experienced.

• Ureteral obstruction and hydronephrosis can result from endometrial implants on the ureter or mass effect from an endometrioma.

• Extra-abdominal manifestations can include cyclical hemoptysis and pneumothorax (catamenial).

• Symptoms usually improve during pregnancy and after menopause. They can recur postpartum or with postmenopausal hormone replacement therapy.

• In 15% of cases of pelvic pain, endometriosis is the underlying cause.

• One third of women with endometriosis are asymptomatic.

Physical: The physical examination usually correlates with the extent of disease.

• The most common finding is nonspecific pelvic tenderness. In one study, 22% of adolescents had abnormal physical findings consistent with anatomic lesions found during surgery.

• The hallmark finding on examination is the presence of tender nodular masses along thickened uterosacral ligaments, the posterior uterus, or the posterior cul-de-sac.

• Ovarian involvement may present with adnexal tenderness or masses.

• Obliteration of the cul-de-sac in conjunction with fixed uterine retroversion implies extensive disease.

• Rupture of an ovarian endometrioma may present as an acute abdomen.

• Extensive involvement of the rectum and other areas of the GI tract may cause adhesions and obstruction.

• Examination should include evaluation for cervicitis, abnormal discharge, and sexually transmitted diseases (STDs).

Causes: Refer to Pathophysiology for more detail.

• Retrograde menstruation

• Lymphatic/vascular metastases

• Coelomic metaplasia

• Remnant mullerian cells induced by estrogen

• Direct implantation

• Genetic predisposition

• Risk factors

• Family history of endometriosis

• Early age of menarche

• Short menstrual cycles (<27 d)

• Long duration of menstrual flow (>7 d)

• Heavy bleeding during menses

• Inverse relationship to parity

• Delayed childbearing

• Defects in the uterus or fallopian tubes

• Hypoxia and iron deficiency may contribute to the early onset of endometriosis

DIFFERENTIALS

Section 4 of 11

Appendicitis, Acute
Diverticular Disease
Ovarian Cysts
Ovarian Torsion
Pelvic Inflammatory Disease
Pregnancy, Ectopic
Urinary Tract Infection, Female

Other Problems to be Considered:

Adenomyosis
Colon cancer
Ovarian cancer

WORKUP

Section 5 of 11

Lab Studies:

• In the ED setting, few laboratory tests prove to be valuable in the diagnosis of endometriosis.

• CBC with differential may help differentiate pelvic infection from endometriosis as well as assess the degree of blood loss.

• Urinalysis and urine culture should be sent if urinary tract infection (UTI) is in the differential.

• Cervical Gram stain and cultures should be considered because STDs can also cause pelvic pain and infertility.

• Beta human chorionic gonadotropin (HCG) can rule out complications of pregnancy.

Imaging Studies:

• Routine radiographs are not recommended unless other disease entities requiring these studies are in the differential diagnosis.

• Endometriosis can be assessed by either transvaginal ultrasonography or endorectal ultrasonography.

• Magnetic resonance imaging (MRI) offers a superior combination of 3D imaging with high-resolution special and temporal resolution, low observer dependency, no radiation exposure, and none of the risks associated with iodinated contrast agents.

• With dynamic contrast-enhanced MRI, dynamic changes in MR signal intensity in selected tissues can be detected. Some of the newer generation contrast agents can be loaded with specific antibodies that allow for targeted imaging.

• MRI has a higher sensitivity for detecting pelvic masses than ultrasonography but is limited in identifying diffuse pelvic endometriosis.

• Using CT, endometriomas may appear as cystic masses, but their appearance is nonspecific and CT should not be relied on for diagnosis. Complications of endometriosis, including bowel obstruction and hydronephrosis, may be seen on CT.

• Hysterosalpingography may reveal tubal occlusion or periadnexal adhesions.

Other Tests:

• A new diagnostic test has been based on the detection of autoantibodies against Thomsen-Friedenreich (T) antigen (Gal beta1-3GalNAc) bearing proteins. The sensitivity and specificity of the test are 80%. This test may prove useful in the outpatient setting.

• CA 125 is a marker that may also be useful in the outpatient setting but is not a useful tool for an initial screening.

• Another office test is the marker CCR1. The expression of the blood-borne marker CCR1 mRNA in peripheral blood leukocytes is significantly higher in women with endometriosis compared with unaffected women.

Procedures:

• Laparoscopy with biopsy is the only definitive way to diagnose endometriosis. It is an invasive procedure with an overall sensitivity of 97% and a specificity of only 77%. Hallmark findings are the classic powder burn, blue-black lesions.

• The most common sites of involvement found during laparoscopy are the following, in descending order:

• Ovaries

• Posterior cul-de-sac

• Broad ligament

• Uterosacral ligament

• Rectosigmoid colon

• Bladder

• Distal ureter

TREATMENT

Section 6 of 11

Prehospital Care: Follow established protocols of resuscitation for unstable female patients of reproductive age with acute abdominal/pelvic pain.

Emergency Department Care: The goal of the emergency physician is to provide pain relief and exclude life-threatening causes of pelvic/abdominal pain.

• Unstable patients require resuscitation and possibly urgent surgical consult.

• Medical management in the ED generally is restricted to pain control. Long-term medical therapy usually is suppressive and rarely curative.

• Medical treatments for endometriosis act in a variety of ways to abolish the trophic effect of estradiol on both the eutopic and ectopic endometrium. Therefore, the patient develops amenorrhea because all endometrial tissue becomes inactive.

• Medical treatment can relieve symptoms, but the recurrence rate is high after cessation of medications.

• All medical treatments are equally effective in managing endometriosis; about 80-85% of patients note improvement in their symptoms.

• The main difference between medical treatments is their side effect profile.

• Medical treatments include nonsteroidal anti-inflammatory drugs (NSAIDs), progestins (ie, medroxyprogesterone), combination estrogens and progestins, synthetic androgens (ie, danazol), and gonadotropin-releasing hormone analogues with or without hormone replacement therapy.

• Surgical management can be either conservative (ie, laparoscopy with lysis of adhesions) or definitive (ie, total abdominal hysterectomy with bilateral salpingo-oophorectomy [TAH/BSO]).

• The fact that TAH/BSO relieves the symptoms of endometriosis is well established. In some cases, however, not all of the endometrial tissue implanted outside the uterus can be removed and symptoms may persist.

• Patients may require surgery involving dissection of the urinary tract, bowel, and/or rectovaginal septum.

• Stable patients with the presumptive diagnosis of endometriosis require gynecologic referral for long-term management.

Consultations:

• Obstetrician/gynecologist

MEDICATION

Section 7 of 11

Medication management beyond pain control is outside the scope of emergency medicine. Patients should have their pain controlled and be referred to a gynecologist for further management.

Medical therapy for treating endometriosis involves hormonal therapy. Progestins, combination estrogens/progestins, danazol, and gonadotropin-releasing hormone (GnRH) agonists are some of the medications used. Patients should not begin a regimen of danazol or GnRH agonists unless they are monitored by a gynecologist and have a laparoscopically confirmed diagnosis of endometriosis.

Suppression of ovulation and menses often occurs with medical management.

Drug Category: Hormones -- These agents can make endometrial tissue become inactive and atrophic.

Drug Name	Medroxyprogesterone acetate (Cycrin, Provera) -- Progestins stop endometrial cell proliferation, allowing organized sloughing of cells after withdrawal. Typically does not stop acute bleeding episode but produces normal bleeding episode following withdrawal.
Adult Dose	10-20 mg PO qd continuously
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; cerebral apoplexy; undiagnosed vaginal bleeding; thrombophlebitis; liver dysfunction
Interactions	Aminoglutethimide may decrease effects by increasing hepatic metabolism of medroxyprogesterone
Pregnancy	X - Contraindicated in pregnancy
Precautions	Caution in asthma, depression, renal or cardiac dysfunction, or thromboembolic disorders

Drug Name	Ethinyl estradiol and norgestimate (Ortho Tri-Cyclen, Ortho-Cyclen) -- Reduces the secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the pituitary by decreasing amount of gonadotropin-releasing hormone.
Adult Dose	28-tab package: Begin dose on first Sunday after onset of menstruation; start that Sunday if menstrual period starts on Sunday 21-tab package: 1 tab qd for 21 d followed by 7 d off medication; new course begins on 8th d after taking last tab Continue dosing cycle if 1 period missed; pregnancy test required if 2 periods missed
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; endometrial or hepatic cancer; thromboembolic disorders; undiagnosed vaginal bleeding; smokers >35 y; cardiovascular disease
Interactions	Phenobarbital, phenytoin, paramethadione, carbamazepine, troglitazone, rifampicin, and griseofulvin induce enzymes that decrease levels of contraceptive steroids; oral anticoagulants may increase thromboembolic potential; antibiotics may alter GI flora and cause a reduction in absorption of oral contraceptives, which may reduce efficacy
Pregnancy	X - Contraindicated in pregnancy
Precautions	Caution in patients with hepatic impairment, migraine, seizure disorders, cerebrovascular disorders, breast cancer, or thromboembolic disease

Drug Name	Danazol (Danocrine) -- Synthetic steroid analog, derived from ethisterone, with strong antigonadotropic activity (inhibits LH and FSH) and weak androgenic action without adverse virilizing and masculinizing effects. Use of androgens might stimulate erythropoiesis and clotting efficiency. Androgens alter endometrial tissue so that it becomes inactive and atrophic.
Adult Dose	400-600 mg/d PO divided bid/tid
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; seizure disorders; renal or hepatic insufficiency; cardiac disease; lactation; conditions influenced by edema; undiagnosed genital bleeding; porphyria
Interactions	Decreases insulin requirements and increases effects of anticoagulants; may increase carbamazepine and cyclosporine levels
Pregnancy	X - Contraindicated in pregnancy
Precautions	Caution in renal, hepatic, or cardiac insufficiency, and seizure disorders

Drug Name	Leuprolide acetate (Lupron, Eligard) -- Suppresses ovarian steroidogenesis by decreasing LH and FSH levels
Adult Dose	3.5-7.5 mg/mo IM; not to exceed 6 mo without adding low-dose estrogen and progestin therapy
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; undiagnosed vaginal bleeding, and spinal cord compression
Interactions	None reported
Pregnancy	X - Contraindicated in pregnancy
Precautions	Caution in patients with urinary tract obstruction; tumor flare and bone pain may occur; monitor patients for weakness and paresthesias

FOLLOW-UP

Section 8 of 11

Further Outpatient Care:

• Disease is progressive and can result in chronic pain and infertility. Gynecologic follow-up is advised.

In/Out Patient Meds:

• If the presumptive diagnosis is endometriosis and follow up is arranged, pain management can include the use of NSAIDs or narcotic analgesics.

Complications:

• Infertility/subfertility

• Chronic pelvic pain

• Adhesions

• Ruptured cysts

Prognosis:

• Medical management (suppression of ovulation) is effective for decreasing pelvic pain but ineffective for treatment of endometriosis-associated infertility. It does, however, preserve the potential for conception.

• Combination estrogens/progestins relieve pain in as many as 80-85% of patients with endometriosis-related pelvic pain.

• After 6 months of danazol therapy, as many as 90% of patients with moderate endometriosis experience adequate pain relief.

• Total abdominal hysterectomy and bilateral salpingo-oophorectomy is reported to be up to 90% effective in relieving pain.

• Pregnancy is possible but depends on the severity of disease.

• Signs and symptoms generally regress with the onset of menopause and during pregnancy.

Patient Education:

• The National Institute of Health (NIH) is currently conducting a clinical trial to research new treatments for endometriosis. Patients who are interested in participating in this study may visit their Web site for more information.

• For excellent patient education resources, visit eMedicine’s Women's Health Center. Also, see eMedicine’s patient education article Endometriosis.

• For patients interested in more information or support groups The Endometriosis Association and Endometriosis.org are valuable resources.

MISCELLANEOUS

Section 9 of 11

Medical/Legal Pitfalls:

• Prior to ascribing a patient's abdominal or pelvic pain to endometriosis, the clinician should consider other important causes of such pain, including ectopic pregnancy, pelvic infection, and ovarian torsion.

TEST QUESTIONS

Section 10 of 11

CME Question 1: Which of the following symptoms is not consistent with the clinical diagnosis of endometriosis?

A: Vaginal bleeding between periods
B: Dyspareunia
C: Intermittent fevers
D: Painful bowel movements
E: Cyclic pelvic pain

The correct answer is C: Fever is associated with pelvic infection. It is not found in endometriosis and should arouse suspicion that an alternative diagnosis is likely.

CME Question 2: In what age group is endometriosis most likely to be diagnosed?

A: Prepubertal ( <12 y)
B: Adolescent (13-17 y)
C: 20-35 years
D: Perimenopausal (45-52 y)
E: Postmenopausal (>52 y)

The correct answer is C: Endometriosis usually is diagnosed in women aged 20-35 years. Extrapelvic manifestations of this disorder occur in woman aged 35-40 years. Women younger than 20 years with this disease often have anomalies of the reproductive system. Endometriomas and symptoms related to them regress significantly after menopause.

Pearl Question 1 (T/F): Medical management is superior to surgery in correcting endometriosis-related infertility.

The correct answer is False: Medical management (ovulation suppression) is effective for decreasing pelvic pain but ineffective for treatment of endometriosis-associated infertility. It does, however, preserve the potential for conception.

Pearl Question 2 (T/F): Endometriosis is the presence of endometrial glands and stroma within the wall of the uterus.

The correct answer is False: Endometrial glands and stroma in the wall of the uterus is adenomyosis. Endometriosis is the presence of endometrial tissue outside the uterine cavity.

Pearl Question 3 (T/F): Endometriosis may present as an acute abdomen.

The correct answer is True: Rupture of an ovarian endometrioma may present as an acute abdomen.

Pearl Question 4 (T/F): The most common site endometriosis is found is the ovary.

The correct answer is True: Common sites of involvement in decreasing frequency are ovary, posterior cul-de-sac, broad ligament, uterosacral ligament, rectosigmoid colon, bladder, and distal ureter.

BIBLIOGRAPHY

Section 11 of 11

• Adamson, GD, Nelson, HP: Surgical treatment of endometriosis. Obstet Gynecol Clin North Am 1997; 24: 375-409[Medline].
• Brosens IA: New principles in the management of endometriosis. Acta Obstet Gynecol Scand Suppl 1994; 159: 18-21[Medline].
• Buchweitz O, Poel T, Diedrich K, Malik E: The diagnostic dilemma of minimal and mild endometriosis under routine conditions. J Am Assoc Gynecol Laparosc 2003 Feb; 10(1): 85-9[Medline].
• Carlson KJ, Nichols DH, Schiff I: Indications for hysterectomy. N Engl J Med 1993 Mar 25; 328(12): 856-60[Medline].
• Eskenazi, B, Warner, ML: Epidemiology of Endometriosis. Obstet Gynecol Clin North Am 1997; 24: 235-258[Medline].
• Hummelshoj L, Prentice A, Groothuis P: Update on endometriosis. Women's Health 2006; 2(1): 53-56.
• Jubanyik KJ, Comite F: Extrapelvic Endometriosis. Obstet Gynecol Clin North Am 1997; 24: 411-440[Medline].
• Kennedy S, Bergqvist A, Chapron C, et al: ESHRE guideline for the diagnosis and treatment of endometriosis. Hum Reprod 2005 Oct; 20(10): 2698-704[Medline].
• Lu PY, Ory SJ: Endometriosis: Current Management. Mayo Clin Proc 1995; 170: 453-463[Medline].
• Mahmood TA, Templeton A: Prevalence and genesis of endometriosis. Hum Reprod 1991 Apr; 6(4): 544-9[Medline].
• Markham SM, Carpenter SE, Rock JA: Extrapelvic Endometriosis. Obstet Gynecol Clin North Am 1989; 16: 193[Medline].
• Prentice A: Regular review: Endometriosis. BMJ 2001 Jul 14; 323(7304): 93-5[Medline].
• Shepard MK, Mancini MC, Campbell GD: Right-sided hemothorax and recurrent abdominal pain in a 34 year-old woman. Chest 1993; 103: 1239[Medline].
• Wilson AL: Endometriosis. A common cause of infertility and pelvic pain. JAAPA 2003 Dec; 16(12): 20-3[Medline].

eMedicine Journals > Emergency Medicine > Obstetrics And Gynecology > Endometriosis

Please email us with any comments you have on our new chapter format.

Author Information | Introduction | Clinical | Differentials | Workup | Treatment | Medication | Follow-up | Miscellaneous | Test Questions | Bibliography