Version October 2024
INTRODUCTION — Uterine cancer is the second most common gynecologic cancer worldwide when both resource-abundant and resource-limited countries are considered (cervical cancer is more common in worldwide statistics) [1]. Over 90 percent of uterine cancers are endometrial, originating in the epithelium; most of the remainder are mesenchymal, originating in the myometrial muscle or, less commonly, the endometrial stroma [2].
The major risk factor for endometrial carcinoma (EC) is the presence of a clinical scenario associated with an excess of endogenous or exogenous estrogen without adequate opposition by a progestin. Lynch syndrome (hereditary nonpolyposis colon cancer) is a genetic risk factor; the pathogenesis in these cases is a germline mutation in one of the DNA mismatch repair genes.
This topic will discuss the epidemiology, risk factors, and prevention of EC. Related topics are reviewed separately, including the following:
●Histopathology, genomic subtypes, and pathogenesis (see "Endometrial cancer: Pathology and classification")
●Clinical features, diagnosis, and screening for high-risk patients (see "Endometrial carcinoma: Clinical features, diagnosis, prognosis, and screening")
●Staging and surgical treatment (see "Endometrial carcinoma: Staging and surgical treatment")
●Adjuvant therapy (see "Overview of resectable endometrial carcinoma", section on 'Role of adjuvant therapy')
Issues related to Lynch syndrome are also reviewed separately. (See "Lynch syndrome (hereditary nonpolyposis colorectal cancer): Clinical manifestations and diagnosis", section on 'Genetics' and "Lynch syndrome (hereditary nonpolyposis colorectal cancer): Screening and prevention of endometrial and ovarian cancer".)
EPIDEMIOLOGY — EC develops in approximately 3 percent of females in the United States [3] and is the fourth most common cancer among females in the United States after cancer of the breast, lung/bronchus, and colon/rectum [4,5]. The incidence peaks between ages 60 and 70 years, but 2 to 5 percent of cases occur before age 40 years [6]. Patients under age 50 who develop EC are often at risk because of chronic anovulation and/or obesity [7-9].
The incidence of EC has been increasing [5,10], potentially due to a variety of factors, including the increasing prevalence of obesity [11], decreasing use of menopausal hormone therapy with progestins, increasing prevalence of diabetes, and changes in reproductive behaviors (eg, increasing prevalence of nulliparity) [12].
In United States Surveillance, Epidemiology, and End Results (SEER) data (2015 to 2019), the age-adjusted incidence of EC was highest in Black females (29.3 per 100,000) compared with White females (28 per 100,000), Hispanic females (26 per 100,000), and Asian American females (22.6 per 100,000) [13,14]. However, there was no adjustment for prevalence of hysterectomy; thus, these data likely underestimate the incidence of EC among females with an intact uterus. When hysterectomy prevalence is considered, Black females compared with White females continue to have a higher incidence of EC [15], a higher incidence of aggressive endometrial cancers (clear cell, serous, high-grade endometrioid, malignant mixed Müllerian tumors), and a higher five-year mortality for nearly every stage and subtype of EC [13]. The etiology of these differences is unknown and cannot be fully explained by known factors that vary by race [16].
RISK FACTORS — ECs are broadly classified into two major types that have different clinicopathologic characteristics and risk factors [17,18]. This section will review risk factors for grade 1 and 2 endometrioid tumors, which comprise the majority (80 percent) of ECs. Such tumors, termed "nonaggressive" in the 2023 International Federation of Gynecology and Obstetrics (FIGO) staging system [19], and which largely overlap with "type I" EC in older classification systems, is stimulated by estrogen, typically preceded by endometrial hyperplasia (also referred to as endometrial intraepithelial neoplasia [EIN]), usually presents at an early stage, and has a good prognosis. Although most experts focus on estrogen as a key in the pathogenetic pathway of endometrioid neoplasms, lack of exposure to progesterone is likely to be equally important. In menopausal patients, progesterone is secreted mostly by the adrenal glands, levels are very low (<0.05 ng/mL), and levels decrease as patients age because of waning adrenal secretion. The increasing prevalence of obesity, decreasing use of menopausal hormone therapy with progestins, and changes in reproductive behaviors probably explain the increasing prevalence of these tumors.
Risk factors for the less common histologies, which include FIGO grade 3 endometrioid histology and nonendometrioid histologies (eg, serous, clear cell, mixed cell, undifferentiated, carcinosarcoma), include lower body mass index [BMI], older age at diagnosis, parity, Black race, and a personal history of breast cancer; this is discussed in detail separately. These neoplasms (termed "aggressive" in the 2023 FIGO staging [19], and largely overlapping with "type II" tumors in older classification systems) are not estrogen-sensitive, often occur in an atrophic endometrium, and have a poor prognosis. The reason for the increasing incidence of these neoplasms is unknown. (See "Endometrial carcinoma: Serous and clear cell histologies", section on 'Epidemiology and risk factors'.)
Chronically increased estrogen levels or estrogenic activity — The primary risk factor for endometrioid EC is long-term exposure to increased estrogen levels from an exogenous or endogenous source without adequate opposition by a progestin [20-26].
Exogenous sources
Unopposed estrogen therapy — In a patient with a uterus, systemic estrogen therapy from any route (oral, transdermal patch, vaginal ring) without concurrent administration of a progestin results in a markedly increased risk of developing EC precursors (EIN or hyperplasia with atypia) and EC. In a meta-analysis of randomized trials of hormone therapy in postmenopausal patients, the increased risk of developing endometrial hyperplasia (any type) was statistically significant after one year of use of moderate- or high-dose unopposed estrogen (odds ratios [OR] 8.4 and 10.7, respectively) and after 18 to 24 months of low-dose therapy (OR 2.4) [27]. In addition, multiple case-control and prospective studies have reported an increased risk of EC in patients who used estrogen alone, with the increase in relative risk ranging from 1.5- to 10-fold, depending on the dose and duration of use [28-32]. It has been estimated that the absolute risk of EC in postmenopausal patients is approximately 1 in 1000; thus, the absolute risk in patients taking unopposed estrogen increases to as high as 1 in 100 [28]. (See "Menopausal hormone therapy: Benefits and risks", section on 'Endometrial hyperplasia and carcinoma'.)
Low-dose vaginal estrogen therapy is a common treatment for symptoms related to vulvovaginal atrophy. The systemic absorption of these preparations is small; thus, most do not have adverse effects on the endometrium, but some may require use of an opposing progestin because of high systemic estrogen levels. (See "Genitourinary syndrome of menopause (vulvovaginal atrophy): Treatment", section on 'Use of an opposing progestogen'.)
Tamoxifen — Tamoxifen is a selective estrogen receptor modulator (SERM) with both agonist and antagonist properties, depending upon the individual target organ and circulating levels of serum estrogen [33-35]. In endometrial tissue, it acts as an estrogen agonist in postmenopausal patients (who have low estrogen levels), whereas it acts as an estrogen antagonist in premenopausal patients (who have high estrogen levels). As a result, use of tamoxifen increases the risk of EC in postmenopausal patients. The risk of EC in premenopausal patients on tamoxifen has not been as well established. (See "Abnormal uterine bleeding and uterine pathology in patients on tamoxifen therapy", section on 'Endometrial effects' and "Abnormal uterine bleeding and uterine pathology in patients on tamoxifen therapy", section on 'Endometrial carcinoma'.)
The effect of concurrent administration of a progestin on the risk of EC in patients on tamoxifen has not been well studied because many patients have progesterone receptor-positive breast cancer and the safety of progestins in such patients is uncertain. (See "Abnormal uterine bleeding and uterine pathology in patients on tamoxifen therapy", section on 'Management'.)
The American College of Obstetricians and Gynecologists does not recommend routine screening for EC in patients on tamoxifen but advises counseling them about the risks associated with tamoxifen, monitoring them closely for symptoms of endometrial hyperplasia or EC, and evaluating them if symptoms of EC occur [36]. These issues are discussed in detail separately. (See "Endometrial carcinoma: Clinical features, diagnosis, prognosis, and screening", section on 'Screening'.)
Clomiphene is a nonsteroidal triphenylethylene derivative; while it acts as a SERM (similar to tamoxifen), its primary action is its antiestrogen effect on the uterus. Data are inconsistent regarding whether ovulation induction for treatment of infertility, particularly with clomiphene citrate, is associated with an increased risk of EC. (See "Ovulation induction with clomiphene citrate" and "Ovulation induction with clomiphene citrate", section on 'Pharmacology/mechanisms of action' and "Ovulation induction with clomiphene citrate", section on 'Cancer risks'.)
Endogenous sources
Chronic anovulation — Chronically anovulatory patients continue to produce sex steroid hormones but not cyclically. As a result, normal endometrial turnover does not occur, and chronic estrogen production unopposed by adequate progesterone production allows continued proliferation of the endometrium, which can lead to endometrial hyperplasia and EC. The menopausal transition and polycystic ovary syndrome (PCOS) are two common clinical settings associated with anovulation with endogenous production of unopposed estrogen. In both of these settings, the risk for development of endometrial hyperplasia and EC is increased. (See "Clinical manifestations and diagnosis of menopause", section on 'Menopausal transition' and "Clinical manifestations of polycystic ovary syndrome in adults", section on 'Endometrial cancer risk'.)
Nulliparity and infertility have been associated with EC but do not appear to be independent risk factors; instead, the association is probably related to the high frequency of anovulatory cycles in infertile patients.
Obesity — Patients with obesity have high levels of endogenous estrogen due to the conversion of androstenedione to estrone and the aromatization of androgens to estradiol, both of which occur in peripheral adipose tissue [37]. Patients with obesity may also have lower circulating levels of sex hormone-binding globulin (leading to increased steroid hormone activity), alterations in the concentration of insulin-like growth factor and its binding proteins, and insulin resistance, all of which may contribute to the increased risk of EC in these patients [38,39]. Patients without these metabolic abnormalities (ie, metabolically healthy patients with obesity) also appear to have an increased risk of EC [40].
In a pooled analysis of individual patient data from 10 cohort and 14 case-control studies including over 14,000 EC cases and over 35,000 controls, the odds of type I EC (defined in the study as endometrioid adenocarcinoma, adenocarcinoma not otherwise specified, and adenocarcinoma with squamous differentiation) by body mass index (BMI) were: OR 1.5 for overweight (BMI 25.0 to <30.0 kg/m2), OR 2.5 for class 1 obesity (30.0 to <35.0 kg/m2), OR 4.5 for class 2 obesity (35.0 to 39.9 kg/m2), and OR 7.1 for class 3 obesity (≥40.0 kg/m2) [41]. For type II EC, the ORs were 1.2 for overweight, 1.7 for class 1 obesity, 2.2 for class 2 obesity, and 3.1 for class 3 obesity. A limitation of this study was that the definition of type I EC varied from the standard definition; type I is usually defined as endometrioid grades 1 and 2, and type II is all other grades and histologies.
Others have reported the following: higher BMI is associated with the development of EC at a young age (<45 years old) [42]; the distribution of adipose tissue does not appear to be a factor in EC risk [43-45]; obesity appears to play a similar role as a risk factor for EC in Black, Hispanic, and White patients [46]; and patients with a BMI ≥40 kg/m2 who develop EC are more likely to have a less aggressive histologic subtype (endometrioid 87 percent versus serous or clear cell 75 percent) compared with patients with a BMI <30 kg/m2 [47]. Accordingly, patients with class 3 obesity are more likely to present with stage I disease (77 versus 61 percent) or low-grade histology (44 versus 24 percent). Despite a propensity to low-stage and low-grade carcinoma, class 3 obesity is paradoxically associated with an increased risk of death in patients with EC [48,49]. The reason is unclear but may be due to continued stimulation of metastatic cells by endogenous estrogen or may result from obesity-associated conditions, such as diabetes or cardiovascular disease [50,51].
Estrogen-secreting tumors — Granulosa cell tumors of the ovary are the tumor type most likely to be associated with endometrial hyperplasia and EC. In patients with these tumors, endometrial hyperplasia is detected in 25 to 50 percent and EC in 5 to 10 percent [52-54]. The ECs are usually early stage and well-differentiated [55]. (See "Sex cord-stromal tumors of the ovary: Epidemiology, clinical features, and diagnosis in adults".)
Early menarche and late menopause — Early age at menarche is a risk factor for EC in some studies; late menopause is less consistently associated with an increased risk of the disease [20,56-60]. The underlying mechanism may be a prolonged duration of exposure to estrogen stimulation.
Hereditary factors
Lynch syndrome — Lynch syndrome (hereditary nonpolyposis colorectal cancer) is an autosomal dominant disorder caused by a germline mutation in one of several DNA mismatch repair genes. Patients with Lynch syndrome have up to a 71 percent lifetime risk of developing EC compared with 2.7 percent in the general population (table 1), and they account for 2 to 5 percent of all patients with EC [61]. The mean age at EC diagnosis in patients with Lynch syndrome is 46 to 54 years compared with a mean age of 61 years in other patients. The majority of Lynch syndrome-associated EC is endometrioid histology and presents at an early stage, similar to sporadic EC.
Lynch syndrome, including EC screening, EC cancer prevention strategies, and other cancers that occur with increased frequency in this population, is discussed in detail separately. (See "Lynch syndrome (hereditary nonpolyposis colorectal cancer): Clinical manifestations and diagnosis" and "Lynch syndrome (hereditary nonpolyposis colorectal cancer): Screening and prevention of endometrial and ovarian cancer", section on 'Endometrial cancer surveillance'.)
Other potential heritable factors
●Cowden syndrome (also known as Cowden disease or multiple hamartoma syndrome) – Patients with Cowden syndrome, an autosomal dominant disorder in which there is a mutation in the PTEN tumor suppressor gene, exhibit characteristic mucocutaneous lesions; have a high prevalence of uterine leiomyomas; and have an increased risk of endometrial, breast, thyroid, colorectal, and renal cancers. There are few data regarding this rare syndrome; a 13 to 19 percent lifetime risk of EC has been described [62-64]. (See "PTEN hamartoma tumor syndromes, including Cowden syndrome", section on 'Cowden syndrome'.)
●First-degree relative with EC – In a meta-analysis of 16 comparative studies, patients with a first-degree relative with a history of EC were at increased risk of EC (relative risk 1.82, 95% CI 1.65-1.98) [65]. The cumulative risk of EC to age 70 years in patients with an affected first-degree relative was estimated to be 3.1 percent compared with <2 percent in the general population. However, only three of the studies excluded patients with Lynch syndrome.
●BRCA carriers – The risk of uterine cancer in BRCA1 carriers, and consequently its role as part of the BRCA mutated syndrome, is debated [66], and whether there is a small increase in risk of EC associated with pathogenic BRCA variants is unclear. Most or all of the observed increase may be attributable to use of tamoxifen for prevention or treatment of breast cancer. (See "Cancer risks and management of BRCA1/2 carriers without cancer", section on 'Other gynecologic malignancies' and "Abnormal uterine bleeding and uterine pathology in patients on tamoxifen therapy", section on 'Endometrial carcinoma'.)
Other germline mutations have also been described [67].
Uncertain risk factors
●Phytoestrogens – Phytoestrogens are nonsteroidal compounds that occur naturally in many plants, fruits, and vegetables and have both estrogenic and antiestrogenic properties.
The effect of phytoestrogens on EC risk is unclear [68,69]. The body of data from observational studies suggests no increased risk of endometrial hyperplasia or EC with phytoestrogen supplements or dietary intake and actually a decreased risk. In a meta-analysis of seven case-control and cohort studies including over 3500 patients with EC, high compared with low soy intake was associated with a 30 percent decrease in EC risk (OR 0.70, 95% CI 0.57-0.86) [70].
Most randomized trials that have addressed this issue have had only 6 to 12 months of follow-up [69]. In the only trial with longer follow-up, postmenopausal patients assigned to soy isoflavone supplements (150 mg/day) for five years had a higher rate of endometrial hyperplasia (detected by endometrial biopsy) compared with the placebo group (3.8 versus 0 percent) [71]. However, the quality of this trial was limited since the total number of events was small (six cases endometrial hyperplasia: five simple and one complex) and the hyperplasias that developed were of generally low malignant potential. Endometrial hyperplasia with atypia and, less consistently, hyperplasia without atypia are the precursor lesions for EC. (See "Endometrial hyperplasia: Clinical features, diagnosis, and differential diagnosis", section on 'Risk factors'.)
●A history of breast cancer is a risk factor for developing EC, at least in part because of breast cancer treatment factors (eg, tamoxifen use), shared behavioral factors (eg, obesity), and shared genetic susceptibility (eg, Cowden syndrome).
●A history of pelvic radiation for treatment of primary rectal carcinoma may increase the risk for developing uterine cancer, although the overall incidence is small. In one cohort study including over 20,000 female patients with rectal cancer, treatment with radiotherapy plus surgery compared with surgery alone was associated with an increase in uterine corpus cancer (2.8 versus 1.0 percent, adjusted hazard ratio 3.06, 95% CI 2.1-4.4) after a five-year latency period [72]. One limitation of this study is that it did not differentiate between types of uterine corpus cancers (eg, endometrial, uterine sarcoma). (See "Approach to the care of colorectal cancer survivors", section on 'Second malignancies'.)
●Patients with diabetes mellitus and hypertension are at increased risk for developing EC [73-75]. Comorbid factors, primarily obesity, account for much of this risk [45,76], but some studies have found independent effects as well [20,77-85]. In patients with diabetes, insulin resistance, chronic inflammation, and high free ovarian steroid hormone levels are possible mechanisms for the association [86].
●The body of evidence suggests that menopausal hormone therapy with combined estrogen-progestin preparations does not increase the risk of endometrial hyperplasia, with one notable exception. An analysis of unpublished data from the Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial showed a statistically significant increase in endometrial hyperplasia after two years of cyclic combined therapy (3.3 versus 0 percent in the placebo group) [27,87,88]. The regimen used in this trial was conjugated equine estrogen 0.625 mg daily plus medroxyprogesterone acetate 10 mg for 12 days/month. The reporting of summary data for all histologic types of endometrial hyperplasia was a limitation of this analysis since hyperplasia with atypia is most likely to be associated with carcinoma. A further limitation of this study was inclusion of only oral therapy; thus, it is uncertain whether the results can be generalized to nonoral hormone therapy (patches or vaginal rings). Summary data for the risk of EC were not reported for most interventions in this analysis because there were too few events. (See "Menopausal hormone therapy: Benefits and risks", section on 'Protective effect of progestins'.)
●Certain chemicals, such as those found in hair straighteners, may be associated with increased rates of EC [89], but evidence is limited and further study is needed.
PROTECTIVE FACTORS
Use of hormonal contraception — The use of estrogen-progestin oral contraceptives (OCs) decreased the risk of EC by 30 to 40 percent in large epidemiologic studies, and the risk reduction persisted for years after discontinuation [90,91]. This benefit, which likely applies to nonoral estrogen-progestin contraceptives as well, is attributed to the progestin component, which suppresses endometrial proliferation. Progestin-only contraceptives (eg, depot medroxyprogesterone acetate, progestin implants, progestin-releasing intrauterine devices [IUD]) appear to provide even greater protection against development of EC in epidemiologic studies [92-94]. However, in older studies, OCs contained higher estrogen doses than contemporary preparations, which are progestin-dominant and thus may have protective effects comparable to progestin-only contraceptives. (See "Combined estrogen-progestin contraception: Side effects and health concerns", section on 'Noncontraceptive benefits'.)
Because of their strong antagonistic effects on endometrial proliferation, progestins have also been used to treat endometrial hyperplasia and early EC. (See "Endometrial hyperplasia: Management and prognosis", section on 'Progestin therapy' and "Fertility preservation in patients with endometrial carcinoma", section on 'Progestin therapy'.)
Other potential protective factors
●Increasing gravidity and parity – The risk of EC is inversely related to gravidity and parity [56,95-97]. As an example, a nationwide, register-based cohort study from Denmark observed that a first pregnancy was associated with a reduced risk of EC, and the reduction was observed whether it ended in induced abortion (adjusted relative risk [aRR] 0.53, 95% CI 0.45-0.64) or childbirth (aRR 0.66, 95% CI 0.61-0.72) [97]. In addition, each subsequent pregnancy was associated with additional reductions in risk, possibly because of the role of progesterone activity throughout pregnancy. A limitation of this study was that information on lifetime use of OCs was not available.
●Older age at last birth – Childbearing at an older age, independent of parity and other factors, was associated with a decreased risk of EC in a meta-analysis of individual data from 17 studies that included over 8000 cases of EC [98]. A significant decrease in risk was found per five years of increasing age at last birth (odds ratio [OR] 0.87, 95% CI 0.85-0.90); rate of EC in patients with last birth at age <25 years was used as the reference standard. As an example, patients who last gave birth at ages 35 to 39 years had a 32 percent decrease in risk (95% CI 0.61-0.76). The reason older age is protective is not known; we speculate that high progesterone levels during pregnancy may be an important protective factor as patients age.
●Breastfeeding – In a meta-analysis of 17 studies including nearly 9000 patients with EC from several countries, ever-breastfeeding was associated with an 11 percent reduction (OR 0.89, 95% CI 0.81-0.98) in EC compared with parous patients who did not breastfeed [99]. In terms of average duration of breastfeeding per child, it appeared that at least three months were required to be associated with decreased EC risk, and the degree of risk did not continue to decrease after six to nine months. The association with ever-breastfeeding was not impacted by greater parity, body mass index, or histologic subtype. The reason breastfeeding is protective is not known; we speculate that low estrogen levels during breastfeeding may have a protective role. (See "Maternal and economic benefits of breastfeeding".)
●Smoking – Cigarette smoking is associated with a decreased risk of developing EC in postmenopausal, but not premenopausal, patients [100]. Obviously, the major health risks associated with tobacco use far outweigh this benefit. The mechanism suggested for this effect is that smoking stimulates hepatic metabolism of estrogens, leading to a reduced incidence of endometrial abnormalities.
●Physical activity and diet – Meta-analyses have observed a decreased risk of EC with increased physical activity [101,102]. Several plausible biological mechanisms have been proposed to explain a possible association between high levels of physical activity and reduced cancer risk; these include decreased obesity and central adiposity and favorable changes in immune function and in endogenous sexual and metabolic hormone levels and growth factors [103].
A meta-analysis of comparative studies noted a decreased risk of EC proportional to the quantity of coffee consumed [104]. Another noted a decreased risk of EC proportional to the quantity of tea consumed and suggested that consumption of green tea was more protective than consumption of black tea [105,106].
●Copper IUD – As with hormonal contraception, the copper IUD may also be associated with lower rates of endometrial carcinoma [107]. Copper induces a cytotoxic inflammatory response within the endometrium which may reduce rates of endometrial hyperplasia. (See "Intrauterine contraception: Background and device types", section on 'Copper IUD'.)
STRATEGIES FOR PREVENTION
Patients at highest risk
●Patients with Lynch syndrome – Preventive strategies include chemoprevention with oral contraceptive pills (estimated 50 to 60 percent reduction in EC); progestin-only contraceptives (including intrauterine systems) are also likely to be effective. When childbearing is complete, risk-reducing total hysterectomy is recommended. (See "Lynch syndrome (hereditary nonpolyposis colorectal cancer): Screening and prevention of endometrial and ovarian cancer".)
●Patients taking tamoxifen – Use of the levonorgestrel-releasing intrauterine system has been proposed for prevention and treatment of uterine pathology in patients on tamoxifen. However, the safety of this treatment in patients with progesterone receptor-positive breast cancer has not been established. Use must be individualized and discussed with the patient's oncologist. (See "Abnormal uterine bleeding and uterine pathology in patients on tamoxifen therapy", section on 'Management'.)
●Patients with polycystic ovary syndrome – Combined estrogen-progestin oral contraceptives are the first-line therapy for endometrial protection as they also treat hyperandrogenism and menstrual dysfunction and provide contraception. (See "Treatment of polycystic ovary syndrome in adults", section on 'Endometrial protection'.)
●Patients with obesity – Weight reduction through lifestyle modifications (diet and physical activity) or bariatric surgery can reduce obesity. Bariatric surgery has been associated with 50 to 80 percent reductions in occurrence of EC in large studies and a meta-analysis of controlled studies [108-110]. Progestin-dominant contraceptives are also likely to be protective. (See "Outcomes of bariatric surgery", section on 'Cancer risk and mortality'.)
Patients at average risk — Patients at average risk for developing EC can minimize this risk by achieving and maintaining a normal body mass index, engaging in regular physical activity, breastfeeding rather than formula feeding, and using hormonal rather than nonhormonal contraceptives. All of these behaviors have health benefits beyond protection of the endometrium.
●(See "Overweight and obesity in adults: Health consequences" and "Obesity in adults: Overview of management".)
●(See "The benefits and risks of aerobic exercise", section on 'Cancer prevention and treatment'.)
●(See "Maternal and economic benefits of breastfeeding", section on 'Cancer'.)
●(See "Combined estrogen-progestin oral contraceptives: Patient selection, counseling, and use", section on 'Noncontraceptive uses' and "Intrauterine contraception: Candidates and device selection", section on 'Endometrial protection' and "Intrauterine contraception: Background and device types", section on 'Noncontraceptive benefits'.)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Uterine cancer".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topics (see "Patient education: Uterine cancer (The Basics)")
●Beyond the Basics topics (see "Patient education: Endometrial cancer diagnosis, staging, and surgical treatment (Beyond the Basics)" and "Patient education: Endometrial cancer treatment after surgery (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Epidemiology – Endometrial carcinoma (EC) develops in approximately 3 percent of females in the United States and is the fourth most common cancer among females in the United States after cancer of the breast, lung/bronchus, and colon/rectum. The incidence peaks between ages 60 and 70 years, but 2 to 5 percent of cases occur before age 40 years. Patients under age 50 who develop EC are often at risk because of chronic anovulation and/or obesity or genetic predisposition (eg, Lynch syndrome). (See 'Epidemiology' above.)
●Types – ECs are broadly classified by the International Federation of Gynecology and Obstetrics (FIGO) staging system into two major types that have different clinicopathologic characteristics and risk factors:
•Nonaggressive – These neoplasms have low-grade (FIGO grades 1 and 2) endometrioid histology and comprise the majority (80 percent) of ECs; this category largely overlaps with "type I" EC in older classification systems. (See 'Risk factors' above.)
•Aggressive – These neoplasms (FIGO grade 3 endometrioid histology and nonendometrioid histologies: serous, clear cell, mixed cell, undifferentiated, carcinosarcoma) are less common and are typically not estrogen-sensitive. This category largely overlaps with "type II" EC in older classification systems and is reviewed separately. (See 'Risk factors' above and "Endometrial carcinoma: Serous and clear cell histologies".)
●Risk factors
•The primary risk factor for grade 1 and 2 endometrioid EC is long-term exposure to increased estrogen levels from an exogenous or endogenous source (eg, chronic anovulation, obesity, estrogen-secreting tumors, early menarche, late menopause) without adequate opposition by a progestin. (See 'Risk factors' above.)
•By contrast, patients with "aggressive" tumors tend to be older at diagnosis, have a lower body mass index (BMI), and parous. Black race and a personal history of breast cancer also appear to be risk factors for such cancers. (See 'Risk factors' above and "Endometrial carcinoma: Serous and clear cell histologies", section on 'Epidemiology and risk factors'.)
●Protective factors – Estrogen-progestin or progestin-only contraceptives are protective factors against development of grade 1 and 2 endometrioid EC. (See 'Protective factors' above.)
●Prevention – Strategies of prevention of both types of EC depend, in part, on whether patients are at high or average risk for developing EC as well as their underlying risk factors. Hysterectomy is the most aggressive approach; more conservative approaches include achieving and maintaining a normal body mass index and using progestin-dominant contraceptives. (See 'Strategies for prevention' above.)
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