Endometrial Cancer: Symptoms, Types, Causes and Treatment

Endometrial cancer, the most common gynecological malignancy in high-income countries, is a disease that primarily affects women after menopause—but it can occur at any age. Early detection is often possible due to characteristic symptoms, leading to a favorable outlook in most cases. However, understanding the nuances of its symptoms, diverse types, underlying causes, and evolving treatment options is crucial for affected individuals and healthcare professionals alike. This article synthesizes the latest research on endometrial cancer to provide a comprehensive, evidence-based overview.

Symptoms of Endometrial Cancer

Recognizing the symptoms of endometrial cancer is essential for early diagnosis and timely treatment. While some symptoms are more common and specific, others may be subtle or even absent, especially in the early stages. Many women and even healthcare providers may not be fully aware of these warning signs, leading to delays in seeking or providing care.

Symptom	Description	Frequency/Significance	Source(s)
Bleeding	Vaginal bleeding after menopause	Most common, present in early stages	1, 2, 5
Discharge	Abnormal vaginal discharge	Common, may be bloody or watery	2, 5
Pain	Pelvic or lower abdominal pain	Less common, often late-stage	5
Asymptomatic	No symptoms	Diagnosed incidentally	5

Table 1: Key Symptoms

Postmenopausal Bleeding: The Primary Warning Sign

The hallmark symptom of endometrial cancer is abnormal vaginal bleeding, especially after menopause. Postmenopausal bleeding is reported in the majority of cases and is a strong indicator that requires immediate medical evaluation. Even a single episode should not be ignored, as early detection leads to high survival rates (1, 2, 5, 9).

Abnormal Vaginal Discharge

In addition to bleeding, many women experience unusual vaginal discharge, which may be watery, pink, or blood-tinged. Over half of endometrial cancer patients report this symptom. While discharge alone is less specific, its presence alongside bleeding increases suspicion for malignancy (2, 5).

Pelvic Pain and Other Symptoms

Pelvic or lower abdominal pain is less frequent and generally indicates a more advanced stage. Some women may also notice pain related to accumulation of blood or pus within the uterus (hematometra or pyometra), but these are relatively rare presentations (5).

Asymptomatic Cases

A small subset of women, particularly those undergoing ultrasound or surgery for other reasons, may be diagnosed with endometrial cancer in the absence of symptoms. In these instances, findings like polyps or thickened endometrial lining raise suspicion (5).

Barriers to Early Recognition

Despite the prominence of symptoms, delays in diagnosis can occur due to misconceptions—both among women and healthcare providers. Some women believe that regular cervical screening protects against all gynecological cancers, leading to a false sense of security (4). Education and awareness campaigns are needed to address these gaps (3, 4).

Types of Endometrial Cancer

Endometrial cancer is not a single disease but encompasses a spectrum of subtypes with distinct biological behaviors, risk factors, and outcomes. Understanding these types is essential for prognosis and treatment planning.

Type	Characteristics	Prognosis/Behavior	Source(s)
Type I	Estrogen-dependent, endometrioid	Low grade, good prognosis	5, 6, 7, 8, 9, 10
Type II	Estrogen-independent, serous/clear-cell	High grade, aggressive	5, 6, 7, 8, 9, 10
Subtypes	Endometrioid, serous, clear cell, etc.	Vary by histology	8, 18
Molecular	Genomic classifications emerging	May guide therapy	8, 17, 18

Table 2: Main Types and Subtypes

Type I (Estrogen-Dependent) Endometrial Cancer

Type I endometrial cancers are the most common, accounting for approximately 65–80% of cases (6, 7, 8, 9, 10). They typically:

• Occur in younger, perimenopausal or early postmenopausal women
• Are associated with risk factors that increase estrogen exposure (e.g., obesity, diabetes, polycystic ovary syndrome)
• Are usually endometrioid in histology (resembling normal endometrial glands)
• Present as low- or moderate-grade tumors and are slow growing
• Have a high sensitivity to hormonal therapy
• Tend to have a favorable prognosis, with 5-year survival rates exceeding 85% in early stages (6, 9)

Type II (Estrogen-Independent) Endometrial Cancer

Type II cancers are less common (about 20–35% of cases) but more clinically aggressive (5, 6, 7, 8, 9, 10):

• Typically arise in older, postmenopausal women
• Not clearly linked to estrogen exposure
• Include serous, clear cell, and other high-grade histologies
• Exhibit rapid progression and a higher likelihood of recurrence and metastasis
• Are less responsive to hormonal therapy and carry a worse prognosis (5-year survival rates around 58–60%) (6, 9)

Histological and Molecular Subtypes

Beyond the traditional two-type system, endometrial cancers can be further classified by histopathology (endometrioid, serous, clear cell, mixed cell) and, increasingly, by molecular/genomic features (8, 18). Genomic classification helps identify subgroups with unique behaviors and may pave the way for precision medicine and targeted therapies (8, 17, 18).

Overlap and Limitations

Recent research suggests that the boundaries between Type I and Type II are not absolute—many risk factors are shared, and even Type II cancers may not be entirely estrogen-independent (7, 8).

Causes of Endometrial Cancer

The development of endometrial cancer is multifactorial, with both hormonal and non-hormonal contributors. Many risk factors are modifiable, offering opportunities for prevention and risk reduction.

Cause/Risk Factor	Effect on Risk	Notes/Mechanism	Source(s)
Estrogen exposure	Increases	Unopposed estrogen, early menarche	1, 6, 7, 12, 13
Obesity	Increases	Raises estrogen, chronic inflammation	1, 6, 7, 12, 14
Diabetes/Hypertension	Increases	Metabolic, hormonal effects	1, 6, 12, 14
Nulliparity/Infertility	Increases	Fewer cycles with progesterone	1, 6, 12
Tamoxifen	Possible increase	Mixed evidence	1, 12
Genetics	Increases	Lynch syndrome, family history	1
Smoking, Pregnancy, OCP	Decreases	Lower estrogen exposure	7, 12, 13

Table 3: Main Causes and Risk Factors

Unopposed Estrogen Exposure

The single most important risk factor for endometrial cancer is prolonged exposure to estrogen without the counterbalancing effect of progesterone (1, 6, 7, 12, 13). This can result from:

• Early onset of menstruation (menarche) or late menopause
• Use of unopposed estrogen hormone replacement therapy
• Anovulatory cycles (as seen in polycystic ovary syndrome)
• Obesity, which increases peripheral estrogen production

Obesity, Metabolic Syndrome, and Chronic Inflammation

Obesity has a profound impact, both by increasing estrogen levels and promoting a chronic inflammatory state, which can contribute to cancer development (1, 6, 7, 12, 13, 14). Diabetes and hypertension are also linked, likely through overlapping hormonal and metabolic pathways.

Reproductive Factors

Women who have never given birth (nulliparous) or have a history of infertility are at increased risk, likely due to fewer cycles with protective progesterone (1, 6, 12). Conversely, pregnancy and use of combined oral contraceptives are protective.

Genetics and Family History

A minority of cases are linked to hereditary syndromes, most notably Lynch syndrome (hereditary nonpolyposis colorectal cancer), which dramatically raises endometrial cancer risk (1). Family history should prompt genetic counseling and, in some cases, preventive strategies.

Other Factors

• Medications: Tamoxifen, used in breast cancer treatment, has a possible association with increased risk (1, 12).
• Lifestyle: Smoking, physical activity, and low-fat diets are linked to reduced risk, though mechanisms may vary (7, 12, 13).
• Inflammation: Some researchers believe chronic inflammation plays a direct and indirect role in carcinogenesis (13).

Treatment of Endometrial Cancer

Treatment for endometrial cancer has evolved rapidly, embracing new surgical, radiological, chemotherapeutic, and molecular approaches. Choices are guided by cancer type, stage, patient health, and emerging biomarkers.

Treatment	Typical Use/Stage	Notes/Advances	Source(s)
Surgery	Mainstay, early-stage	Hysterectomy + salpingo-oophorectomy	1, 9, 15, 16, 18
Radiation	Intermediate/high risk, adjuvant	Reduces local recurrence	1, 15, 18
Chemotherapy	Advanced/recurrent, adjuvant	For high-risk, metastatic disease	1, 15, 16, 17, 18
Hormonal Therapy	Select cases, low-grade	For Type I, progestins	6, 9
Targeted/Immunotherapy	Advanced, selected cases	Trials ongoing, biomarkers used	16, 17, 18

Table 4: Treatment Modalities

Surgery: The Cornerstone

The primary treatment for most endometrial cancers is surgical removal of the uterus (hysterectomy) along with both ovaries and fallopian tubes (bilateral salpingo-oophorectomy) (1, 9, 15, 16, 18). Minimally invasive techniques (laparoscopic or robotic) are increasingly used, reducing recovery time and complications (18).

• Lymph node assessment may be performed based on risk factors, but its role is debated and varies by country (15, 17, 18).
• Surgery serves both for definitive treatment and accurate staging.

Radiation Therapy

Radiation is often used as an adjuvant (additional) treatment in women at intermediate or high risk of recurrence (1, 15, 18). It effectively reduces the chance of local recurrence, though its value in all subgroups is still being refined.

Chemotherapy

For advanced, high-risk, or recurrent disease, chemotherapy is an important tool (1, 15, 16, 17, 18). It may be combined with radiation (chemoradiation), especially in aggressive Type II cancers or when the disease extends beyond the uterus.

• Ongoing research is evaluating the best combinations and sequence of therapies (15, 17, 18).

Hormonal Therapy

Low-grade, hormone-sensitive (Type I) cancers often respond to progestin-based therapies, especially in women who are not surgical candidates or wish to preserve fertility (6, 9).

Targeted and Immunotherapies

Recent advances in molecular biology are enabling the development of targeted therapies and immunotherapies:

• Pembrolizumab (an anti–PD-1 immunotherapy) is FDA-approved for select cases with specific genetic features (16, 17).
• Clinical trials are ongoing to identify patients who will benefit most from these novel treatments (17, 18).

Survivorship and Prevention

Survivors, especially those with low-grade disease, face an increased risk of cardiovascular disease—the leading cause of death in this group (11). Lifestyle modifications, such as weight management and physical activity, are crucial both in prevention and after treatment (1, 11, 14).

Conclusion

Endometrial cancer is a complex and evolving disease, but early recognition and modern treatment options offer hope for most patients. Understanding the spectrum of symptoms, the diverse cancer types, underlying causes, and the latest in treatment strategies is key to improving outcomes and survivorship.

Key Points:

• Symptoms: Postmenopausal bleeding is the most common symptom; abnormal discharge and pelvic pain may also occur, but some cases remain asymptomatic (1, 2, 5).
• Types: Type I (estrogen-dependent) cancers are most common and have a good prognosis; Type II (estrogen-independent) cancers are rarer but more aggressive. Molecular subtypes are increasingly important (5, 6, 7, 8, 9, 10, 18).
• Causes: Prolonged unopposed estrogen exposure, obesity, metabolic syndrome, certain reproductive factors, and genetics all play a role. Many risk factors are modifiable (1, 6, 7, 12, 13, 14).
• Treatment: Surgery is the mainstay; radiation, chemotherapy, hormonal therapy, and novel targeted agents are tailored to individual risk. Survivorship care should address cardiovascular health (1, 9, 11, 15, 16, 17, 18).

Empowering women and healthcare professionals with knowledge about endometrial cancer is crucial for early detection, effective treatment, and improved quality of life.