II. Associated Conditions
III. Risk Factors
IV. Pathophysiology
- Unopposed Estrogen causes accumulation of endometrial tissue
V. Associated Conditions: Endometrial Cancer
- Simple hyperplasia
- Without cellular atypia: 1% risk of progression to Endometrial Cancer if untreated
- With cellular atypia: 8% risk of of progression to Endometrial Cancer if untreated
- Complex hyperplasia
- Without cellular atypia: 3% risk of progression to Endometrial Cancer if untreated
- With cellular atypia: 29% risk of of progression to Endometrial Cancer if untreated
VI. Precaution
- Endometrial Hyperplasia with atypia is associated with co-existing Endometrial Cancer in as many as 42% of cases
VII. Signs
VIII. Differential Diagnosis
- See Dysfunctional Uterine Bleeding Causes
IX. Diagnosis
X. Evaluation: Indications for Endometrial Cancer Screening
-
Hereditary Nonpolyposis Colorectal Cancer (HNPCC or Lynch Syndrome)
- High risk of Endometrial Cancer (22-50% lifetime risk)
- Offer annual Endometrial Biopsy starting at age 35 years
- Women with Lynch Syndrome should track menstrual periods on calendar to identify irregularities
- Postmenopausal women
- Any postmenopausal woman with Vaginal Discharge
- Any postmenopausal woman with Vaginal Bleeding (outside of first 6 months on continuous Hormone Replacement)
- Menstruating women
- Any woman over age 35 years with Anovulatory Bleeding (Metrorrhagia)
- Women at any age with refractory Dysfunctional Uterine Bleeding (or prolonged unnopposed Estrogen)
- Pap Smear findings requiring further evaluation
XI. Imaging: Transvaginal Ultrasound
- Indications
- Premenopausal women to identify other causes of Dysfunctional Uterine Bleeding
- Time Ultrasound to end of Menses when endometrium is thinnest (if still menstruating)
- Postmentopausal women to risk stratify based on endometrial thickness
- Endometrial Biopsy for stripe >5 mm
- Endomtrial Cancer is very unlikely if stripe <4 mm (Negative Predictive Value 99.3%)
- Further testing not required unless otherwise indicated
- Premenopausal women to identify other causes of Dysfunctional Uterine Bleeding
- Contraindications to using pelvic Ultrasound to risk stratify to Endometrial Biopsy or additional testing
- Morbid Obesity
- Uterine Fibroid tumors
- Structural abnormalities of the Uterus
- Disadvantages
- Incomplete imaging in 10% of cases
- Occurs most commonly if prior uterine procedures, fibroids, Obesity or atypical uterine positioning
- Saline infusion improves sensitivity (but with an increased False Positive Rate)
- Incomplete imaging in 10% of cases
XII. Diagnostics
-
Endometrial Biopsy (first-line)
- Indicated as first-line evaluation for women who meet evaluation criteria above
- Pelvic Ultrasound may risk stratify postmenopausal women for Endometrial Biopsy if endometrial stripe <4mm and adequate study
-
Saline Infusion Sonography (Sonohysterography)
- Indications as second line study (rarely used)
- Focal endometrial lesions
- Non-diagnostic Ultrasound
- Endometrial Biopsy or persistent symptoms
- Contraindications
- Endometrial Biopsy or other findings suggests Endometrial Cancer (risk of peritoneal seeding)
- Technique
- Ultrasound performed after sterile saline infused into Uterus
- Allows for better visualization of uterine cavity
- Ultrasound-guided biopsy of focal lesions can also be done
- Indications as second line study (rarely used)
- Hysteroscopy
- Second-line study indicated for diagnosis of Endometrial Cancer where other testing is non-diagnostic
- Commonly used and high Test Sensitivity (99.2%) and moderate Test Specificity (86.4%) for Endometrial Cancer
- MRI Pelvis
- May offer additional structural information about uterine abnormalities
- In contrast, CT and PET are not generally useful in evaluation of possible Endometrial Cancer
XIII. Indications: Gynecology Referral
-
Endometrial Biopsy results
- Endometrial Cancer
- Endometrial Hyperplasia with atypia
- Patients who fail usual sampling
- Insufficient sampling
- Inconsistency between Endometrial Biopsy and pelvic Ultrasound
- Patients who fail conservative therapy
- Endometrial Hyperplasia
- Perimenopausal Dysfunctional Uterine Bleeding
- Anovulatory Dysfunctional Uterine Bleeding
XIV. Management: Endometrial Hyperplasia with cellular atypia
- Precautions
- Hysterectomy is the optimal definitive management in complex atypical Endometrial Hyperplasia
- Lymphadenectomy at time of Hysterectomy not recommended unless intraabdominal signs
- Supracervical procedures (Cervix sparing Hysterectomy) are not recommended by ACOG
- Risk of residual cancer
- Fertility preserving measures
- Step 1: Complete evaluation by gynecology for co-existing Endometrial Cancer (42% of cases)
- Step 2: High dose Progesterone therapy (if no Endometrial Cancer identified)
- Step 3: Re-evaluate to confirm Endometrial Hyperplasia effectively treated
- Step 4: Periodic surveillance for recurrence of Endometrial Hyperplasia per local consultant recommendations
- Step 5: Hysterectomy when child-rearing completed
- Postmenopausal or no future fertility desired
XV. Management: Endometrial Hyperplasia without cellular atypia
-
Progestin Options
- Medroxyprogesterone acetate (Provera) 10 mg orally for 10-14 days per month
- Megestrol (Megace) 40 mg orally daily (continuous)
- Levonorgestrel-releasing IUD (Mirena)
XVI. Prevention
- Manage Unopposed Estrogen states