
Am Fam Physician. 2022;106(4):397-404
Patient information: See related handout on endometriosis, written by the authors of this article.
Author disclosure: No relevant financial relationships.
Endometriosis is an inflammatory condition caused by the presence of endometrial tissue in extra-uterine locations and can involve bowel, bladder, and all peritoneal structures. It is one of the most common gynecologic disorders, affecting up to 10% of people of reproductive age. Presentation of endometriosis can vary widely, from infertility in asymptomatic people to debilitating pelvic pain, dysmenorrhea, and period-related gastrointestinal or urinary symptoms. Diagnosis of endometriosis in the primary care setting is clinical and often challenging, frequently resulting in delayed diagnosis and treatment. Although transvaginal ultrasonography is used to evaluate endometriosis of deep pelvic sites to rule out other causes of pelvic pain, magnetic resonance imaging is preferred if deep infiltrating endometriosis is suspected. Laparoscopy with biopsy remains the definitive method for diagnosis, although several gynecologic organizations recommend empiric therapy without immediate surgical diagnosis. Combined hormonal contraceptives with or without nonsteroidal anti-inflammatory drugs are first-line options in managing symptoms and have a tolerable adverse effect profile. Second-line treatments include gonadotropin-releasing hormone (GnRH) receptor agonists with add-back therapy, GnRH receptor antagonists, and danazol. Aromatase inhibitors are reserved for severe disease. All of these treatments are effective but may cause additional adverse effects. Referral to gynecology for surgical management is indicated if empiric therapy is ineffective, immediate diagnosis and treatment are necessary, or patients desire pregnancy. Alternative treatments have limited benefit in alleviating pain symptoms but may warrant further investigation.
Endometriosis is one of the most common gynecologic disorders, affecting up to 10% of patients of reproductive age,1 or approximately 5 million to 10 million people in the United States.2,3 The prevalence of endometriosis may be higher because definitive diagnosis requires surgical visualization, which all patients might not pursue.4 The prevalence ranges from 2% to 11% among asymptomatic patients and increases to 5% to 50% among patients presenting with infertility. Among symptomatic adolescents with dysmenorrhea, the prevalence of endometriosis is estimated at 50% to 70% for those with chronic pelvic pain and up to 75% for those with pain unresponsive to medical treatment.1 Data for population distributions, disease manifestations, and risk factors are limited to patients who are successfully diagnosed, which may introduce bias related to access to care.1
Etiology
Endometriosis is defined by the presence of endometrial glands and stroma in extrauterine locations. It is an inflammatory, estrogen-dependent condition associated with pelvic pain and infertility.5 Endometriosis involves a complex interaction between various endocrine, immunologic, inflammatory, and proangiogenic processes.4 Additional molecular mechanisms allow endometrial cells to adhere to peritoneal surfaces, proliferate, and develop into endometriotic lesions.4 Estrogen promotes implantation of endometrial tissue through proliferative and antiapoptotic effects in endometrial cells and stimulates local and systemic inflammation.6 Pain from endometriosis is elicited by localized immune and inflammatory responses. Neurogenesis, which is indicated by high levels of nerve growth factors that alter and increase sensory and sympathetic nerve fibers, is observed in endometriotic tissue.7,8 Nerve fiber entrapment within endometriotic lesions may explain associated sacral radiculopathy. Finally, central sensitization may cause endometriosis-induced neuropathic changes that decrease inhibition pathways.8,9
Risk Factors
Endometriosis is influenced by genetic and environmental factors (Table 1).1,4 There is a strong familial component to endometriosis shown by genetic studies that indicate increased frequency of disease in close relatives.10–12 Twin studies have estimated heritability of endometriosis at approximately 50%.12 Increased burden with common genetic variants is associated with more severe disease.11,12 Environmental factors such as diet, environmental contamination, and in utero hormonal exposures that may affect genetic expression are thought to explain more than one-half of disease liability.12 These risk factor associations suggest critical periods of exposure in utero and in early childhood that affect later development of endometriosis. Childhood and adolescent risk factors include early menarche and lower body mass index. In adulthood, risk factors include shorter menstrual cycles and nulliparity. There is inconsistent evidence for any relationship between physical activity, alcohol use, caffeine intake, or skin sensitivity and endometriosis.1

Category | Probable risk factors |
---|---|
Adult | Increased menstrual flow, low body mass index, nulliparity, short menstrual cycles |
Childhood and adolescence | Early menarche, low body mass index |
Genetic | First-degree relative with endometriosis |
In utero/early childhood | Diethylstilbestrol exposure, low birth weight, prematurity |
Diagnosis
HISTORY AND PHYSICAL EXAMINATION
The diagnosis of endometriosis in primary care is clinical and should be based on history and physical examination findings. Patients with endometriosis typically present during their reproductive years with pelvic pain, infertility, or an ovarian mass (Table 2).13 The peak prevalence of endometriosis occurs in people 25 to 35 years of age. Endometriosis can be a diagnostic and clinical challenge, with many patients experiencing delays in diagnosis of up to four to 10 years.14 This delay can lead to disease progression and decreased quality of life15 and reinforces the importance of having a high clinical suspicion based on history. The diagnosis should also be considered in transgender and nonbinary patients or any persons with a uterus (Table 3).16,17
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