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This is a clinician-written, evidence-based summary aligned to the USMLE Step 2 CK Content Outline. It is intended for medical students preparing for USMLE Step 2 CK. Management reflects current ACC/AHA, USPSTF, and APA guidelines. Always cross-reference with UpToDate, institutional protocols, and clinical judgment.
Key points
- Postmenopausal bleeding is endometrial cancer until proven otherwise
- Major risk factor: unopposed estrogen from obesity, chronic anovulation/PCOS, estrogen-only therapy, nulliparity, early menarche, late menopause, or tamoxifen
- First-line evaluation: endometrial biopsy or transvaginal ultrasound depending on scenario
- Endometrial thickness <=4 mm in postmenopausal bleeding has high negative predictive value, but persistent bleeding still needs biopsy
- Treatment is surgical staging with total hysterectomy and bilateral salpingo-oophorectomy for most patients
Overview
Endometrial cancer is the most common gynecologic malignancy in the United States. Type I endometrioid cancers are estrogen-related and often preceded by hyperplasia; type II tumors are more aggressive and less estrogen-dependent.
Epidemiology
Incidence rises after menopause. Obesity is a major driver through peripheral aromatization. Lynch syndrome markedly increases endometrial, colorectal, ovarian, and other cancer risks.
Clinical Features
Symptoms
Postmenopausal bleeding
Abnormal uterine bleeding age >=45
Heavy irregular bleeding in younger patients with obesity/chronic anovulation
Watery or blood-tinged discharge
Pelvic pain, weight loss, early satiety suggests advanced disease
Signs
Pelvic examination may be normal early
Blood from cervical os without cervical lesion suggests uterine source
Enlarged uterus may be present
Adnexal mass, ascites, nodularity suggests advanced malignancy
Anemia signs from chronic bleeding
Investigations
First-line
Endometrial biopsyOffice biopsy first-line for many patients with postmenopausal bleeding or AUB age >=45/risk factors
Transvaginal ultrasoundStripe <=4 mm in postmenopausal bleeding has low cancer risk; persistent bleeding needs sampling
CBCAssess anemia
Second-line
Hysteroscopy with D&CIf biopsy inadequate, negative despite persistent bleeding, or focal lesion suspected
Pathology and gradeDetermines histology, grade, and staging needs
Lynch syndrome assessmentBased on age, family history, and tumor testing protocols
Specialist
Gynecologic oncology referralConfirmed or strongly suspected cancer
Staging imagingSelected high-grade, advanced, or non-endometrioid disease
1
Evaluation of bleeding
- Postmenopausal bleeding requires prompt biopsy or TVUS
- Endometrial biopsy for AUB age >=45
- Biopsy younger patients with persistent AUB plus obesity, PCOS, chronic anovulation, tamoxifen, or Lynch risk
- Persistent bleeding requires histology even with thin stripe
2
Definitive treatment
- Total hysterectomy with bilateral salpingo-oophorectomy and surgical staging for most
- Sentinel lymph node mapping or lymph node assessment based on risk
- Adjuvant radiation/chemotherapy depending on stage/grade/histology
3
Fertility-sparing option
- Selected young patients with grade 1 endometrioid cancer confined to endometrium may receive high-dose progestin or LNG-IUD under specialist care
- Requires careful sampling surveillance and definitive surgery after childbearing
4
Risk reduction
- Weight management and treatment of chronic anovulation
- Progestin protection for prolonged unopposed estrogen
- Lynch syndrome genetic counseling and risk-reducing surgery after childbearing
Complications
- Myometrial invasion: Drives staging and recurrence risk
- Metastatic disease: Lymphatic, peritoneal, or distant spread
- Anemia: Chronic bleeding
- Infertility: Definitive hysterectomy or treatment
- Lynch-associated cancers: Colon, ovarian, gastric, urinary tract, and others
USMLE Step 2 CK Exam Tips
- 1Postmenopausal bleeding = endometrial cancer until proven otherwise
- 2Key risk concept = unopposed estrogen
- 3Obesity increases risk via aromatization to estrogen
- 4PCOS increases risk via chronic anovulation
- 5Endometrial stripe >4 mm with postmenopausal bleeding = biopsy
- 6Persistent postmenopausal bleeding requires biopsy even with thin stripe
- 7AUB age >=45 = endometrial biopsy
- 8Tamoxifen increases endometrial cancer risk
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