Endometriosis

Overview

Definition

Endometriosis is a condition in which endometrial glands and stroma implant outside of the uterus Uterus The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The uterus has a thick wall made of smooth muscle (the myometrium) and an inner mucosal layer (the endometrium). The most inferior portion of the uterus is the cervix, which connects the uterine cavity to the vagina. Uterus, Cervix, and Fallopian Tubes: Anatomy. These implants can be highly inflammatory but are generally not malignant.

Epidemiology

• Incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency in general female population: approximately 10%
  • Estimates vary widely based on the population studied.
  • Many cases are asymptomatic.
• Incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency in infertile patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship: up to 50%
• Incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with pelvic pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways: 70%–80%
• Average age at diagnosis: 27 years
• Cases are uncommon, but also possible in: 
  • Premenarcheal girls 
  • Postmenopausal women (2%–5% of cases)

Risk factors

• Prolonged endogenous estrogen Estrogen Compounds that interact with estrogen receptors in target tissues to bring about the effects similar to those of estradiol. Estrogens stimulate the female reproductive organs, and the development of secondary female sex characteristics. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds. Ovaries: Anatomy exposure:
  • Nulliparity
  • Early age at menarche Menarche The first menstrual cycle marked by the initiation of menstruation. Menstrual Cycle
  • Late menopause Menopause Menopause is a physiologic process in women characterized by the permanent cessation of menstruation that occurs after the loss of ovarian activity. Menopause can only be diagnosed retrospectively, after 12 months without menstrual bleeding. Menopause
  • Shorter menstrual cycles
• Heavy menstrual bleeding Heavy menstrual bleeding Excessive menstrual blood loss (objectively defined as > 80 mL blood loss/cycle). Can be based on heavy flow, as determined by the patient Abnormal Uterine Bleeding
• History of infertility Infertility Infertility is the inability to conceive in the context of regular intercourse. The most common causes of infertility in women are related to ovulatory dysfunction or tubal obstruction, whereas, in men, abnormal sperm is a common cause. Infertility
• History of obstructed outflow (e.g., Müllerian anomalies)
• Low body mass index Body mass index An indicator of body density as determined by the relationship of body weight to body height. Bmi=weight (kg)/height squared (m2). Bmi correlates with body fat (adipose tissue). Their relationship varies with age and gender. For adults, bmi falls into these categories: below 18. 5 (underweight); 18. 5-24. 9 (normal); 25. 0-29. 9 (overweight); 30. 0 and above (obese). Obesity ( BMI BMI An indicator of body density as determined by the relationship of body weight to body height. Bmi=weight (kg)/height squared (m2). Bmi correlates with body fat (adipose tissue). Their relationship varies with age and gender. For adults, bmi falls into these categories: below 18. 5 (underweight); 18. 5-24. 9 (normal); 25. 0-29. 9 (overweight); 30. 0 and above (obese). Obesity)
• Family history Family History Adult Health Maintenance of endometriosis

Pathophysiology

Contributing factors

• Genetic factors
• Abnormal endocrine signaling:
  • Estrogen Estrogen Compounds that interact with estrogen receptors in target tissues to bring about the effects similar to those of estradiol. Estrogens stimulate the female reproductive organs, and the development of secondary female sex characteristics. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds. Ovaries: Anatomy stimulates endometrial proliferation.
  • Unlike normal endometrium Endometrium The mucous membrane lining of the uterine cavity that is hormonally responsive during the menstrual cycle and pregnancy. The endometrium undergoes cyclic changes that characterize menstruation. After successful fertilization, it serves to sustain the developing embryo. Embryoblast and Trophoblast Development, endometriosis implants express enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes that: 
    • Convert androgens Androgens Androgens are naturally occurring steroid hormones responsible for development and maintenance of the male sex characteristics, including penile, scrotal, and clitoral growth, development of sexual hair, deepening of the voice, and musculoskeletal growth. Androgens and Antiandrogens to estrogens
    • Inhibit estrogen Estrogen Compounds that interact with estrogen receptors in target tissues to bring about the effects similar to those of estradiol. Estrogens stimulate the female reproductive organs, and the development of secondary female sex characteristics. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds. Ovaries: Anatomy deactivation
  • Results in ↑ estrogen Estrogen Compounds that interact with estrogen receptors in target tissues to bring about the effects similar to those of estradiol. Estrogens stimulate the female reproductive organs, and the development of secondary female sex characteristics. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds. Ovaries: Anatomy stimulation within endometriosis implants compared with normal endometrium Endometrium The mucous membrane lining of the uterine cavity that is hormonally responsive during the menstrual cycle and pregnancy. The endometrium undergoes cyclic changes that characterize menstruation. After successful fertilization, it serves to sustain the developing embryo. Embryoblast and Trophoblast Development
• Altered immunity:
  • ↑ Inflammatory response
  • Thought to contribute to the implantation Implantation Endometrial implantation of embryo, mammalian at the blastocyst stage. Fertilization and First Week process
• Abnormalities in cell proliferation and apoptosis Apoptosis A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, I.e., DNA fragmentation. It is genetically-programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. Ischemic Cell Damage
• Obstruction of the reproductive outflow tract

Theories about the establishment of implants

• Retrograde menstruation Menstruation The periodic shedding of the endometrium and associated menstrual bleeding in the menstrual cycle of humans and primates. Menstruation is due to the decline in circulating progesterone, and occurs at the late luteal phase when luteolysis of the corpus luteum takes place. Menstrual Cycle (Sampson’s theory):
  • Menstrual efflux of endometrial cells into the peritoneal cavity Peritoneal Cavity The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs are connected by the foramen of winslow, or epiploic foramen. Peritoneum: Anatomy through the fallopian tubes Fallopian tubes The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The fallopian tubes receive an ovum after ovulation and help move it and/or a fertilized embryo toward the uterus via ciliated cells lining the tubes and peristaltic movements of its smooth muscle. Uterus, Cervix, and Fallopian Tubes: Anatomy
  • Does not explain implants outside the abdominopelvic cavity or cases in premenstrual girls
• Coelomic metaplasia Metaplasia A condition in which there is a change of one adult cell type to another similar adult cell type. Cellular Adaptation: 
  • Coelomic epithelium Epithelium The epithelium is a complex of specialized cellular organizations arranged into sheets and lining cavities and covering the surfaces of the body. The cells exhibit polarity, having an apical and a basal pole. Structures important for the epithelial integrity and function involve the basement membrane, the semipermeable sheet on which the cells rest, and interdigitations, as well as cellular junctions. Surface Epithelium: Histology transforms into endometrium-like glands.
  • Coelomic epithelium Epithelium The epithelium is a complex of specialized cellular organizations arranged into sheets and lining cavities and covering the surfaces of the body. The cells exhibit polarity, having an apical and a basal pole. Structures important for the epithelial integrity and function involve the basement membrane, the semipermeable sheet on which the cells rest, and interdigitations, as well as cellular junctions. Surface Epithelium: Histology normally becomes:
    • Endometrium Endometrium The mucous membrane lining of the uterine cavity that is hormonally responsive during the menstrual cycle and pregnancy. The endometrium undergoes cyclic changes that characterize menstruation. After successful fertilization, it serves to sustain the developing embryo. Embryoblast and Trophoblast Development
    • Ovary
    • Peritoneum Peritoneum The peritoneum is a serous membrane lining the abdominopelvic cavity. This lining is formed by connective tissue and originates from the mesoderm. The membrane lines both the abdominal walls (as parietal peritoneum) and all of the visceral organs (as visceral peritoneum). Peritoneum: Anatomy
    • Pleura Pleura The pleura is a serous membrane that lines the walls of the thoracic cavity and the surface of the lungs. This structure of mesodermal origin covers both lungs, the mediastinum, the thoracic surface of the diaphragm, and the inner part of the thoracic cage. The pleura is divided into a visceral pleura and parietal pleura. Pleura: Anatomy
• Vascular or lymphatic dissemination:
  • Similar mechanisms to how cancer spreads via the blood and lymph Lymph The interstitial fluid that is in the lymphatic system. Secondary Lymphatic Organs system
  • Explains cases of endometriosis lesions outside the abdominopelvic cavity

Sites of ectopic implantation Implantation Endometrial implantation of embryo, mammalian at the blastocyst stage. Fertilization and First Week

• Ovary (most common site)
• Pelvic peritoneum Peritoneum The peritoneum is a serous membrane lining the abdominopelvic cavity. This lining is formed by connective tissue and originates from the mesoderm. The membrane lines both the abdominal walls (as parietal peritoneum) and all of the visceral organs (as visceral peritoneum). Peritoneum: Anatomy (2nd-most common)
• Uterine ligaments (broad, uterosacral)
• Within the uterine myometrium → adenomyosis Adenomyosis Adenomyosis is a benign uterine condition characterized by the presence of ectopic endometrial glands and stroma within the myometrium. Adenomyosis is a common condition, affecting 20%-35% of women, and typically presents with heavy menstrual bleeding and dysmenorrhea. Adenomyosis
• Rectovaginal septum
• Fallopian tubes Fallopian tubes The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The fallopian tubes receive an ovum after ovulation and help move it and/or a fertilized embryo toward the uterus via ciliated cells lining the tubes and peristaltic movements of its smooth muscle. Uterus, Cervix, and Fallopian Tubes: Anatomy
• Colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy, rectum Rectum The rectum and anal canal are the most terminal parts of the lower GI tract/large intestine that form a functional unit and control defecation. Fecal continence is maintained by several important anatomic structures including rectal folds, anal valves, the sling-like puborectalis muscle, and internal and external anal sphincters. Rectum and Anal Canal: Anatomy, and appendix Appendix A worm-like blind tube extension from the cecum. Colon, Cecum, and Appendix: Anatomy
• Bladder Bladder A musculomembranous sac along the urinary tract. Urine flows from the kidneys into the bladder via the ureters, and is held there until urination. Pyelonephritis and Perinephric Abscess and ureters Ureters One of a pair of thick-walled tubes that transports urine from the kidney pelvis to the urinary bladder. Urinary Tract: Anatomy
• Prior surgical incision Surgical Incision Surgical Site Infections sites
• Distant organs (rare):
  • Lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs: Anatomy
  • Breast
  • Bones
  • Liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy, gallbladder Gallbladder The gallbladder is a pear-shaped sac, located directly beneath the liver, that sits on top of the superior part of the duodenum. The primary functions of the gallbladder include concentrating and storing up to 50 mL of bile. Gallbladder and Biliary Tract: Anatomy, pancreas Pancreas The pancreas lies mostly posterior to the stomach and extends across the posterior abdominal wall from the duodenum on the right to the spleen on the left. This organ has both exocrine and endocrine tissue. Pancreas: Anatomy, and spleen Spleen The spleen is the largest lymphoid organ in the body, located in the LUQ of the abdomen, superior to the left kidney and posterior to the stomach at the level of the 9th-11th ribs just below the diaphragm. The spleen is highly vascular and acts as an important blood filter, cleansing the blood of pathogens and damaged erythrocytes. Spleen: Anatomy

Causes of pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways

• Cyclic hormone fluctuations → bleeding from implants → ↑ production of inflammatory mediators
• Chronic inflammation Chronic Inflammation Inflammation → fibrin Fibrin A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. Rapidly Progressive Glomerulonephritis deposition → pelvic adhesions and scarring Scarring Inflammation → distortion Distortion Defense Mechanisms of peritoneal surfaces → pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways
• Nerve sensitization near implants, potentially caused by:
  • Chronic inflammation Chronic Inflammation Inflammation
  • Estrogen Estrogen Compounds that interact with estrogen receptors in target tissues to bring about the effects similar to those of estradiol. Estrogens stimulate the female reproductive organs, and the development of secondary female sex characteristics. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds. Ovaries: Anatomy acting as a neuromodulator
  • Direct neuronal invasion of endometrial implants
• The severity of pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways is not directly related to the extent of disease.

Clinical Presentation

General considerations

• The location of implants determines the clinical presentation.
• Symptoms may be cyclic or chronic.
• Some patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship are asymptomatic.
• Symptoms often improve during pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care.

Pelvic pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways

• Presenting symptom in 80% of cases
• Severe dysmenorrhea
  • Dull or crampy pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways
  • Cyclic, often beginning a few days before the onset of bleeding
• Noncyclic pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways:
  • Pelvic or abdominal
  • May be focal or generalized
  • Dull, throbbing, sharp, or pressure
• Dyspareunia Dyspareunia Recurrent genital pain occurring during, before, or after sexual intercourse in either the male or the female. Primary Ovarian Insufficiency

Infertility Infertility Infertility is the inability to conceive in the context of regular intercourse. The most common causes of infertility in women are related to ovulatory dysfunction or tubal obstruction, whereas, in men, abnormal sperm is a common cause. Infertility

• Presenting symptom in 25% of cases
• Due to:
  • Pelvic adhesions in fallopian tubes Fallopian tubes The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The fallopian tubes receive an ovum after ovulation and help move it and/or a fertilized embryo toward the uterus via ciliated cells lining the tubes and peristaltic movements of its smooth muscle. Uterus, Cervix, and Fallopian Tubes: Anatomy
  • Inflammatory and/or hormonal milieu affecting folliculogenesis Folliculogenesis Ovaries: Anatomy

Ovarian mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast

• Presenting symptom in 20% of cases
• Called an endometrioma:
  • Benign ovarian cyst with endometrial tissue
  • Also called “chocolate cysts“

Less common symptoms

• Heavy or irregular menstrual bleeding
• Low back pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways
• Fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia
• Bladder Bladder A musculomembranous sac along the urinary tract. Urine flows from the kidneys into the bladder via the ureters, and is held there until urination. Pyelonephritis and Perinephric Abscess symptoms:
  • Dysuria Dysuria Painful urination. It is often associated with infections of the lower urinary tract. Urinary tract infections (UTIs)
  • Frequency
  • Hematuria Hematuria Presence of blood in the urine. Renal Cell Carcinoma
• Bowel symptoms:
  • Constipation Constipation Constipation is common and may be due to a variety of causes. Constipation is generally defined as bowel movement frequency < 3 times per week. Patients who are constipated often strain to pass hard stools. The condition is classified as primary (also known as idiopathic or functional constipation) or secondary, and as acute or chronic. Constipation
  • Diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea
  • Dyschezia ( pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways with defecation Defecation The normal process of elimination of fecal material from the rectum. Gastrointestinal Motility)
  • Hematochezia Hematochezia Gastrointestinal Bleeding

Diagnosis

Definitive diagnosis can only be made on histologic examination of a surgical biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma. The diagnosis is therefore often made clinically based on history and exam findings alone, unless imaging suggests an endometrioma.

Physical exam

Findings suggestive of endometriosis:

• Tenderness on vaginal exam
• Visible vaginal endometrial implants
• Palpable nodules in the posterior fornix Fornix Vagina, Vulva, and Pelvic Floor: Anatomy or rectovaginal septum
• Adnexal mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast
• “Frozen pelvis Pelvis The pelvis consists of the bony pelvic girdle, the muscular and ligamentous pelvic floor, and the pelvic cavity, which contains viscera, vessels, and multiple nerves and muscles. The pelvic girdle, composed of 2 “hip” bones and the sacrum, is a ring-like bony structure of the axial skeleton that links the vertebral column with the lower extremities. Pelvis: Anatomy”:
  • Immobility of the cervix Cervix The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The most inferior portion of the uterus is the cervix, which connects the uterine cavity to the vagina. Externally, the cervix is lined by stratified squamous cells; however, the cervical canal is lined by columnar epithelium. Uterus, Cervix, and Fallopian Tubes: Anatomy and/or uterus Uterus The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The uterus has a thick wall made of smooth muscle (the myometrium) and an inner mucosal layer (the endometrium). The most inferior portion of the uterus is the cervix, which connects the uterine cavity to the vagina. Uterus, Cervix, and Fallopian Tubes: Anatomy on bimanual exam
  • Due to adhesions and scarring Scarring Inflammation

Laboratory

• Lab tests are not clinically useful.
• Test for gonorrhea Gonorrhea Gonorrhea is a sexually transmitted infection (STI) caused by the gram-negative bacteria Neisseria gonorrhoeae (N. gonorrhoeae). Gonorrhea may be asymptomatic but commonly manifests as cervicitis or urethritis with less common presentations such as proctitis, conjunctivitis, or pharyngitis. Gonorrhea and chlamydia Chlamydia Chlamydiae are obligate intracellular gram-negative bacteria. They lack a peptidoglycan layer and are best visualized using Giemsa stain. The family of Chlamydiaceae comprises 3 pathogens that can infect humans: Chlamydia trachomatis, Chlamydia psittaci, and Chlamydia pneumoniae. Chlamydia if considering pelvic inflammatory disease Pelvic inflammatory disease Pelvic inflammatory disease (PID) is defined as a polymicrobial infection of the upper female reproductive system. The disease can affect the uterus, fallopian tubes, ovaries, and adjacent structures. Pelvic inflammatory disease is closely linked with sexually transmitted diseases, most commonly caused by Chlamydia trachomatis, Neisseria gonorrhoeae, and Gardnerella vaginalis. Pelvic Inflammatory Disease ( PID PID Pelvic inflammatory disease (PID) is defined as a polymicrobial infection of the upper female reproductive system. The disease can affect the uterus, fallopian tubes, ovaries, and adjacent structures. Pelvic inflammatory disease is closely linked with sexually transmitted diseases, most commonly caused by Chlamydia trachomatis, Neisseria gonorrhoeae, and gardnerella vaginalis. Pelvic Inflammatory Disease)
• Cancer antigen 125 Cancer antigen 125 A carbohydrate antigen that occurs in tumors of the ovary as well as in breast, kidney, and gastrointestinal tract tumors and normal tissue. While it is tumor-associated, it is not tumor-specific and may have a protective function against particles and infectious agents at mucosal surfaces. Serum Tumor Markers ( CA CA Condylomata acuminata are a clinical manifestation of genital HPV infection. Condylomata acuminata are described as raised, pearly, flesh-colored, papular, cauliflower-like lesions seen in the anogenital region that may cause itching, pain, or bleeding. Condylomata Acuminata (Genital Warts) 125) may be ↑ in endometriosis
  • ↑ CA CA Condylomata acuminata are a clinical manifestation of genital HPV infection. Condylomata acuminata are described as raised, pearly, flesh-colored, papular, cauliflower-like lesions seen in the anogenital region that may cause itching, pain, or bleeding. Condylomata Acuminata (Genital Warts) 125 is more commonly associated with ovarian carcinoma. 
  • Should be ordered in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with an ovarian mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast suspicious for cancer

Imaging

• Transvaginal ultrasound Transvaginal Ultrasound Obstetric Imaging:
  • Endometrioma (chocolate cysts Cysts Any fluid-filled closed cavity or sac that is lined by an epithelium. Cysts can be of normal, abnormal, non-neoplastic, or neoplastic tissues. Fibrocystic Change)
  • Nodules on the rectovaginal septum, abdominal wall Abdominal wall The outer margins of the abdomen, extending from the osteocartilaginous thoracic cage to the pelvis. Though its major part is muscular, the abdominal wall consists of at least seven layers: the skin, subcutaneous fat, deep fascia; abdominal muscles, transversalis fascia, extraperitoneal fat, and the parietal peritoneum. Surgical Anatomy of the Abdomen, or bladder Bladder A musculomembranous sac along the urinary tract. Urine flows from the kidneys into the bladder via the ureters, and is held there until urination. Pyelonephritis and Perinephric Abscess
  • Normal-size uterus Uterus The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The uterus has a thick wall made of smooth muscle (the myometrium) and an inner mucosal layer (the endometrium). The most inferior portion of the uterus is the cervix, which connects the uterine cavity to the vagina. Uterus, Cervix, and Fallopian Tubes: Anatomy (compared with an enlarged uterus Uterus The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The uterus has a thick wall made of smooth muscle (the myometrium) and an inner mucosal layer (the endometrium). The most inferior portion of the uterus is the cervix, which connects the uterine cavity to the vagina. Uterus, Cervix, and Fallopian Tubes: Anatomy with adenomyosis Adenomyosis Adenomyosis is a benign uterine condition characterized by the presence of ectopic endometrial glands and stroma within the myometrium. Adenomyosis is a common condition, affecting 20%-35% of women, and typically presents with heavy menstrual bleeding and dysmenorrhea. Adenomyosis)
• Magnetic resonance imaging (MRI):
  • More sensitive than ultrasound for detection of localized disease
  • Not useful in cases of diffuse endometriosis

Laparoscopy Laparoscopy Laparoscopy is surgical exploration and interventions performed through small incisions with a camera and long instruments. Laparotomy and Laparoscopy

• The gold standard for diagnosis
• Implant appearance:
  • Lesions may be red, white, clear, or black-purple.
  • Powder-burn lesions: superficial implants with the appearance of sprinkled powder
• Biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma is used for definitive histologic confirmation.
• Other findings:
  • Peritoneal defects or holes
  • Endometriomas
  • Pelvic adhesions

Management and Complications

General considerations

• Therapy can be initiated based on a clinical (rather than surgical) diagnosis.
• Requires a chronic management plan in order to ↓ repeated surgeries
• Goals of treatment:
  • Improve pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways.
  • Suppress endometrial growth.
  • Treat infertility Infertility Infertility is the inability to conceive in the context of regular intercourse. The most common causes of infertility in women are related to ovulatory dysfunction or tubal obstruction, whereas, in men, abnormal sperm is a common cause. Infertility:
    • Standard treatment until patient is ready to conceive
    • Refer to a reproductive endocrinology specialist.

First-line medical management

• Non-steroidal anti-inflammatory drugs ( NSAIDs NSAIDS Primary vs Secondary Headaches)
• Hormonal contraceptives Hormonal contraceptives Hormonal contraceptives (HCs) contain synthetic analogs of the reproductive hormones estrogen and progesterone, which may be used either in combination or in progestin-only formulations for contraception. Hormonal Contraceptives:
  • Primary initial treatment
  • Often given continuously (without placebo Placebo Any dummy medication or treatment. Although placebos originally were medicinal preparations having no specific pharmacological activity against a targeted condition, the concept has been extended to include treatments or procedures, especially those administered to control groups in clinical trials in order to provide baseline measurements for the experimental protocol. Epidemiological Studies days) to completely suppress menstruation Menstruation The periodic shedding of the endometrium and associated menstrual bleeding in the menstrual cycle of humans and primates. Menstruation is due to the decline in circulating progesterone, and occurs at the late luteal phase when luteolysis of the corpus luteum takes place. Menstrual Cycle
  • Progestins Progestins Compounds that interact with progesterone receptors in target tissues to bring about the effects similar to those of progesterone. Primary actions of progestins, including natural and synthetic steroids, are on the uterus and the mammary gland in preparation for and in maintenance of pregnancy. Hormonal Contraceptives suppress endometrial growth.
  • Options include:
    • Combined oral contraceptive pills Combined oral contraceptive pills Fixed drug combinations administered orally for contraceptive purposes. Hormonal Contraceptives (OCPs)
    • Progesterone-only contraceptive pills ( POPs POPs Hormonal Contraceptives)
    • Contraceptive patch Patch Nonpalpable lesion > 1 cm in diameter Generalized and Localized Rashes 
    • Contraceptive vaginal ring Vaginal Ring Hormonal Contraceptives
    • Levonorgestrel-containing intrauterine devices Intrauterine devices Contraceptive devices placed high in the uterine fundus. Hormonal Contraceptives (IUDs)
    • Etonogestrel Etonogestrel Hormonal Contraceptives contraceptive implant
    • Medroxyprogesterone acetate Medroxyprogesterone acetate A synthetic progestin that is derived from 17-hydroxyprogesterone. It is a long-acting contraceptive that is effective both orally or by intramuscular injection and has also been used to treat breast and endometrial neoplasms. Hormonal Contraceptives injections

Second-line medical management

The following are used in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship who cannot take or derive no benefit from 1st-line management:

• Gonadotropin-releasing hormone Gonadotropin-releasing hormone A decapeptide that stimulates the synthesis and secretion of both pituitary gonadotropins, luteinizing hormone and follicle stimulating hormone. Gnrh is produced by neurons in the septum preoptic area of the hypothalamus and released into the pituitary portal blood, leading to stimulation of gonadotrophs in the anterior pituitary gland. Puberty (GnRH) agonists and antagonists:
  • Suppress the hypothalamic-pituitary-ovarian (HPO) axis by eliminating the GnRH pulse
  • Results in ↓ estrogen Estrogen Compounds that interact with estrogen receptors in target tissues to bring about the effects similar to those of estradiol. Estrogens stimulate the female reproductive organs, and the development of secondary female sex characteristics. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds. Ovaries: Anatomy → endometrial atrophy Atrophy Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. Cellular Adaptation
  • Used to treat severe pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways
  • Should only be used for 6–12 months in order to prevent osteoporosis Osteoporosis Osteoporosis refers to a decrease in bone mass and density leading to an increased number of fractures. There are 2 forms of osteoporosis: primary, which is commonly postmenopausal or senile; and secondary, which is a manifestation of immobilization, underlying medical disorders, or long-term use of certain medications. Osteoporosis
  • Options: 
    • Leuprolide Leuprolide A potent synthetic long-acting agonist of gonadotropin-releasing hormone that regulates the synthesis and release of pituitary gonadotropins, luteinizing hormone and follicle stimulating hormone. Antiestrogens (agonist)
    • Elagolix Elagolix Antiestrogens (antagonist)
• Androgens Androgens Androgens are naturally occurring steroid hormones responsible for development and maintenance of the male sex characteristics, including penile, scrotal, and clitoral growth, development of sexual hair, deepening of the voice, and musculoskeletal growth. Androgens and Antiandrogens
  • Danazol Danazol A synthetic steroid with antigonadotropic and anti-estrogenic activities that acts as an anterior pituitary suppressant by inhibiting the pituitary output of gonadotropins. It possesses some androgenic properties. Danazol has been used in the treatment of endometriosis and some benign breast disorders. Antiestrogens
  • Effective at treating pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways
  • Not commonly used due to androgenic side effects
• Neuropathic agents
  • To treat pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, especially when nerve sensitization is suspected
  • Options:
    • Tricyclic antidepressants Tricyclic antidepressants Tricyclic antidepressants (TCAs) are a class of medications used in the management of mood disorders, primarily depression. These agents, named after their 3-ring chemical structure, act via reuptake inhibition of neurotransmitters (particularly norepinephrine and serotonin) in the brain. Tricyclic Antidepressants ( TCAs TCAs Tricyclic antidepressants (TCAs) are a class of medications used in the management of mood disorders, primarily depression. These agents, named after their 3-ring chemical structure, act via reuptake inhibition of neurotransmitters (particularly norepinephrine and serotonin) in the brain. Tricyclic Antidepressants)
    • Serotonin-norepinephrine reuptake inhibitors Serotonin-Norepinephrine Reuptake Inhibitors Serotonin Reuptake Inhibitors and Similar Antidepressants ( SNRIs SNRIs Serotonin Reuptake Inhibitors and Similar Antidepressants)
    • Antiepileptic drugs (e.g., gabapentin Gabapentin A cyclohexane-gamma-aminobutyric acid derivative that is used for the treatment of partial seizures; neuralgia; and restless legs syndrome. Second-Generation Anticonvulsant Drugs)

Surgical management

The goal is to provide a definitive histologic diagnosis and resect any visible lesions to treat pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways.

• Ovarian cystectomy for endometriomas
• Resection or ablation of the endometrial lesions
• Lysis of adhesions
• Hysterectomy with or without salpingo-oophorectomy:
  • Reserved for patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with moderate-to-severe pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways
  • Definitive procedure
  • If ovaries Ovaries Ovaries are the paired gonads of the female reproductive system that contain haploid gametes known as oocytes. The ovaries are located intraperitoneally in the pelvis, just posterior to the broad ligament, and are connected to the pelvic sidewall and to the uterus by ligaments. These organs function to secrete hormones (estrogen and progesterone) and to produce the female germ cells (oocytes). Ovaries: Anatomy remain → persistent estrogen Estrogen Compounds that interact with estrogen receptors in target tissues to bring about the effects similar to those of estradiol. Estrogens stimulate the female reproductive organs, and the development of secondary female sex characteristics. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds. Ovaries: Anatomy production → stimulates any remaining implants → possible to have persistent pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways
  • Supplemental hormone therapy may be considered if ovaries Ovaries Ovaries are the paired gonads of the female reproductive system that contain haploid gametes known as oocytes. The ovaries are located intraperitoneally in the pelvis, just posterior to the broad ligament, and are connected to the pelvic sidewall and to the uterus by ligaments. These organs function to secrete hormones (estrogen and progesterone) and to produce the female germ cells (oocytes). Ovaries: Anatomy are removed.
• Nerve ablation or transection to treat refractory pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways.

Complications

• Pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care implications:
  • ↑ Risk of preterm birth Preterm birth Preterm labor refers to regular uterine contractions leading to cervical change prior to 37 weeks of gestation; preterm birth refers to birth prior to 37 weeks of gestation. Preterm birth may be spontaneous due to preterm labor, preterm prelabor rupture of membranes (PPROM), or cervical insufficiency. Preterm Labor and Birth
  • Infertility Infertility Infertility is the inability to conceive in the context of regular intercourse. The most common causes of infertility in women are related to ovulatory dysfunction or tubal obstruction, whereas, in men, abnormal sperm is a common cause. Infertility
  • Ectopic pregnancy Ectopic pregnancy Ectopic pregnancy refers to the implantation of a fertilized egg (embryo) outside the uterine cavity. The main cause is disruption of the normal anatomy of the fallopian tube. Ectopic Pregnancy
• ↑ risk of clear cell epithelial ovarian cancer Ovarian cancer Ovarian cancer is a malignant tumor arising from the ovarian tissue and is classified according to the type of tissue from which it originates. The 3 major types of ovarian cancer are epithelial ovarian carcinomas (EOCs), ovarian germ cell tumors (OGCTs), and sex cord-stromal tumors (SCSTs). Ovarian Cancer
• Intestinal obstruction Intestinal obstruction Any impairment, arrest, or reversal of the normal flow of intestinal contents toward the anal canal. Ascaris/Ascariasis from adhesions
• Possible ↑ risk of cardiovascular disease due to chronic systemic inflammation Systemic Inflammation Surgical Site Infections

Differential Diagnosis

• Adenomyosis Adenomyosis Adenomyosis is a benign uterine condition characterized by the presence of ectopic endometrial glands and stroma within the myometrium. Adenomyosis is a common condition, affecting 20%-35% of women, and typically presents with heavy menstrual bleeding and dysmenorrhea. Adenomyosis: similar to endometriosis; however, endometrial implants are confined specifically to the uterine myometrium, resulting in painful and heavy menstrual bleeding Heavy menstrual bleeding Excessive menstrual blood loss (objectively defined as > 80 mL blood loss/cycle). Can be based on heavy flow, as determined by the patient Abnormal Uterine Bleeding. On ultrasound, the uterus Uterus The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The uterus has a thick wall made of smooth muscle (the myometrium) and an inner mucosal layer (the endometrium). The most inferior portion of the uterus is the cervix, which connects the uterine cavity to the vagina. Uterus, Cervix, and Fallopian Tubes: Anatomy is often enlarged and may show myometrial cysts Cysts Any fluid-filled closed cavity or sac that is lined by an epithelium. Cysts can be of normal, abnormal, non-neoplastic, or neoplastic tissues. Fibrocystic Change or heterogeneity. Management involves suppression Suppression Defense Mechanisms of the endometrium Endometrium The mucous membrane lining of the uterine cavity that is hormonally responsive during the menstrual cycle and pregnancy. The endometrium undergoes cyclic changes that characterize menstruation. After successful fertilization, it serves to sustain the developing embryo. Embryoblast and Trophoblast Development, usually with progestins Progestins Compounds that interact with progesterone receptors in target tissues to bring about the effects similar to those of progesterone. Primary actions of progestins, including natural and synthetic steroids, are on the uterus and the mammary gland in preparation for and in maintenance of pregnancy. Hormonal Contraceptives, or definitive treatment with hysterectomy. Adenomyosis Adenomyosis Adenomyosis is a benign uterine condition characterized by the presence of ectopic endometrial glands and stroma within the myometrium. Adenomyosis is a common condition, affecting 20%-35% of women, and typically presents with heavy menstrual bleeding and dysmenorrhea. Adenomyosis often coexists with endometriosis. 
• Leiomyoma Leiomyoma A benign tumor derived from smooth muscle tissue, also known as a fibroid tumor. They rarely occur outside of the uterus and the gastrointestinal tract but can occur in the skin and subcutaneous tissue, probably arising from the smooth muscle of small blood vessels in these tissues. Infertility ( fibroids Fibroids A benign tumor derived from smooth muscle tissue, also known as a fibroid tumor. They rarely occur outside of the uterus and the gastrointestinal tract but can occur in the skin and subcutaneous tissue, probably arising from the smooth muscle of small blood vessels in these tissues. Infertility): benign Benign Fibroadenoma fibrous Fibrous Fibrocystic Change tumors of myometrial origin. Leiomyomas are more common in Black women than Caucasian women, and typically present with heavy menstrual bleeding Heavy menstrual bleeding Excessive menstrual blood loss (objectively defined as > 80 mL blood loss/cycle). Can be based on heavy flow, as determined by the patient Abnormal Uterine Bleeding, dysmenorrhea, or pelvic pressure. Leiomyomas are typically easily identified on ultrasound. Management involves hormonal suppression Suppression Defense Mechanisms with OCPs for smaller fibroids Fibroids A benign tumor derived from smooth muscle tissue, also known as a fibroid tumor. They rarely occur outside of the uterus and the gastrointestinal tract but can occur in the skin and subcutaneous tissue, probably arising from the smooth muscle of small blood vessels in these tissues. Infertility or if a woman wants to retain her uterus Uterus The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The uterus has a thick wall made of smooth muscle (the myometrium) and an inner mucosal layer (the endometrium). The most inferior portion of the uterus is the cervix, which connects the uterine cavity to the vagina. Uterus, Cervix, and Fallopian Tubes: Anatomy. Surgical resection is the definitive treatment.
• PID PID Pelvic inflammatory disease (PID) is defined as a polymicrobial infection of the upper female reproductive system. The disease can affect the uterus, fallopian tubes, ovaries, and adjacent structures. Pelvic inflammatory disease is closely linked with sexually transmitted diseases, most commonly caused by Chlamydia trachomatis, Neisseria gonorrhoeae, and gardnerella vaginalis. Pelvic Inflammatory Disease: an ascending infectious process involving the uterus Uterus The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The uterus has a thick wall made of smooth muscle (the myometrium) and an inner mucosal layer (the endometrium). The most inferior portion of the uterus is the cervix, which connects the uterine cavity to the vagina. Uterus, Cervix, and Fallopian Tubes: Anatomy, fallopian tubes Fallopian tubes The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The fallopian tubes receive an ovum after ovulation and help move it and/or a fertilized embryo toward the uterus via ciliated cells lining the tubes and peristaltic movements of its smooth muscle. Uterus, Cervix, and Fallopian Tubes: Anatomy, and ovaries Ovaries Ovaries are the paired gonads of the female reproductive system that contain haploid gametes known as oocytes. The ovaries are located intraperitoneally in the pelvis, just posterior to the broad ligament, and are connected to the pelvic sidewall and to the uterus by ligaments. These organs function to secrete hormones (estrogen and progesterone) and to produce the female germ cells (oocytes). Ovaries: Anatomy. Pelvic inflammatory disease Pelvic inflammatory disease Pelvic inflammatory disease (PID) is defined as a polymicrobial infection of the upper female reproductive system. The disease can affect the uterus, fallopian tubes, ovaries, and adjacent structures. Pelvic inflammatory disease is closely linked with sexually transmitted diseases, most commonly caused by Chlamydia trachomatis, Neisseria gonorrhoeae, and Gardnerella vaginalis. Pelvic Inflammatory Disease is closely linked with sexually transmitted diseases (especially Chlamydia trachomatis Chlamydia trachomatis Type species of Chlamydia causing a variety of ocular and urogenital diseases. Chlamydia and Neisseria gonorrhoeae Neisseria gonorrhoeae A species of gram-negative, aerobic bacteria primarily found in purulent venereal discharges. It is the causative agent of gonorrhea. Neisseria) and bacterial vaginosis Bacterial vaginosis Polymicrobial, nonspecific vaginitis associated with positive cultures of gardnerella vaginalis and other anaerobic organisms and a decrease in lactobacilli. It remains unclear whether the initial pathogenic event is caused by the growth of anaerobes or a primary decrease in lactobacilli. Vulvovaginitis. Unlike endometriosis, which is chronic, PID PID Pelvic inflammatory disease (PID) is defined as a polymicrobial infection of the upper female reproductive system. The disease can affect the uterus, fallopian tubes, ovaries, and adjacent structures. Pelvic inflammatory disease is closely linked with sexually transmitted diseases, most commonly caused by Chlamydia trachomatis, Neisseria gonorrhoeae, and gardnerella vaginalis. Pelvic Inflammatory Disease is an acute process and causes extreme tenderness on pelvic exam, and fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever. Diagnosis involves identification Identification Defense Mechanisms of the causative organism. Treatment is with antibiotics.
• Hemorrhagic ovarian cyst: a functional cyst arising from a normal ovarian follicle that has bled into itself. These cysts Cysts Any fluid-filled closed cavity or sac that is lined by an epithelium. Cysts can be of normal, abnormal, non-neoplastic, or neoplastic tissues. Fibrocystic Change are often painful, usually with more of an acute onset of pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways. Hemorrhagic cysts Cysts Any fluid-filled closed cavity or sac that is lined by an epithelium. Cysts can be of normal, abnormal, non-neoplastic, or neoplastic tissues. Fibrocystic Change can appear clinically indistinguishable from endometriomas. However, hemorrhagic cysts Cysts Any fluid-filled closed cavity or sac that is lined by an epithelium. Cysts can be of normal, abnormal, non-neoplastic, or neoplastic tissues. Fibrocystic Change will resolve spontaneously (usually within 1–2 menstrual cycles) while endometriomas will not. Repeating pelvic ultrasound is important to confirm resolution.
• Interstitial cystitis Cystitis Inflammation of the urinary bladder, either from bacterial or non-bacterial causes. Cystitis is usually associated with painful urination (dysuria), increased frequency, urgency, and suprapubic pain. Urinary tract infections (UTIs)/ bladder Bladder A musculomembranous sac along the urinary tract. Urine flows from the kidneys into the bladder via the ureters, and is held there until urination. Pyelonephritis and Perinephric Abscess pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways syndrome: a noninfectious, inflammatory condition involving chronic bladder Bladder A musculomembranous sac along the urinary tract. Urine flows from the kidneys into the bladder via the ureters, and is held there until urination. Pyelonephritis and Perinephric Abscess pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways that can be severe. The cause is unknown. Pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways is typically worse when the bladder Bladder A musculomembranous sac along the urinary tract. Urine flows from the kidneys into the bladder via the ureters, and is held there until urination. Pyelonephritis and Perinephric Abscess is distended, with pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways relief after voiding, and is unrelated to the menstrual cycle Cycle The type of signal that ends the inspiratory phase delivered by the ventilator Invasive Mechanical Ventilation. Urinalysis Urinalysis Examination of urine by chemical, physical, or microscopic means. Routine urinalysis usually includes performing chemical screening tests, determining specific gravity, observing any unusual color or odor, screening for bacteriuria, and examining the sediment microscopically. Urinary Tract Infections (UTIs) in Children is normal, and the diagnosis is one of exclusion. Treatment is complex and can include lifestyle modifications, medical therapy, and surgical procedures.
• Irritable bowel syndrome Irritable bowel syndrome Irritable bowel syndrome (IBS) is a functional bowel disease characterized by chronic abdominal pain and altered bowel habits without an identifiable organic cause. The etiology and pathophysiology of this disease are not well understood, and there are many factors that may contribute. Irritable Bowel Syndrome ( IBS IBS Irritable bowel syndrome (IBS) is a functional bowel disease characterized by chronic abdominal pain and altered bowel habits without an identifiable organic cause. The etiology and pathophysiology of this disease are not well understood, and there are many factors that may contribute. Irritable Bowel Syndrome): a functional disorder of the gastrointestinal tract that typically presents with chronic abdominal pain Abdominal Pain Acute Abdomen and altered bowel habits. Endometriosis may present similarly if there is bowel involvement. In endometriosis, symptoms will often have a cyclic component to them. This is also a diagnosis of exclusion. Management for IBS IBS Irritable bowel syndrome (IBS) is a functional bowel disease characterized by chronic abdominal pain and altered bowel habits without an identifiable organic cause. The etiology and pathophysiology of this disease are not well understood, and there are many factors that may contribute. Irritable Bowel Syndrome involves dietary modification and symptom-control measures.