Endometrial Hyperplasia

Simple hyperplasia
1. Without cellular atypia: 1% risk of progression to Endometrial Cancer if untreated
2. With cellular atypia: 8% risk of of progression to Endometrial Cancer if untreated
Complex hyperplasia
1. Without cellular atypia: 3% risk of progression to Endometrial Cancer if untreated
2. With cellular atypia: 29% risk of of progression to Endometrial Cancer if untreated

Endometrial Hyperplasia with atypia is associated with co-existing Endometrial Cancer in as many as 42% of cases

Hereditary Nonpolyposis Colorectal Cancer (HNPCC or Lynch Syndrome)
1. High risk of Endometrial Cancer (22-50% lifetime risk)
2. Offer annual Endometrial Biopsy starting at age 35 years
3. Women with Lynch Syndrome should track menstrual periods on calendar to identify irregularities
Postmenopausal women
1. Any postmenopausal woman with Vaginal Discharge
2. Any postmenopausal woman with Vaginal Bleeding (outside of first 6 months on continuous Hormone Replacement)
Menstruating women
1. Any woman over age 35 years with Anovulatory Bleeding (Metrorrhagia)
2. Women at any age with refractory Dysfunctional Uterine Bleeding (or prolonged unnopposed Estrogen)
Pap Smear findings requiring further evaluation
1. All women with Pap Smears showing atypical glandular cells or atypical endometrial cells
2. All postmenopausal women with Pap Smears showing benign endometrial cells

Indications
1. Premenopausal women to identify other causes of Dysfunctional Uterine Bleeding
  1. Time Ultrasound to end of Menses when endometrium is thinnest (if still menstruating)
2. Postmentopausal women to risk stratify based on endometrial thickness
  1. Endometrial Biopsy for stripe >5 mm
  2. Endomtrial Cancer is very unlikely if stripe <4 mm (Negative Predictive Value 99.3%)
    1. Further testing not required unless otherwise indicated
Contraindications to using pelvic Ultrasound to risk stratify to Endometrial Biopsy or additional testing
1. Morbid Obesity
2. Uterine Fibroid tumors
3. Structural abnormalities of the Uterus
Disadvantages
1. Incomplete imaging in 10% of cases
  1. Occurs most commonly if prior uterine procedures, fibroids, Obesity or atypical uterine positioning
  2. Saline infusion improves sensitivity (but with an increased False Positive Rate)

Endometrial Biopsy (first-line)
1. Indicated as first-line evaluation for women who meet evaluation criteria above
2. Pelvic Ultrasound may risk stratify postmenopausal women for Endometrial Biopsy if endometrial stripe <4mm and adequate study
Saline Infusion Sonography (Sonohysterography)
1. Indications as second line study (rarely used)
  1. Focal endometrial lesions
  2. Non-diagnostic Ultrasound
  3. Endometrial Biopsy or persistent symptoms
2. Contraindications
  1. Endometrial Biopsy or other findings suggests Endometrial Cancer (risk of peritoneal seeding)
3. Technique
  1. Ultrasound performed after sterile saline infused into Uterus
  2. Allows for better visualization of uterine cavity
  3. Ultrasound-guided biopsy of focal lesions can also be done
Hysteroscopy
1. Second-line study indicated for diagnosis of Endometrial Cancer where other testing is non-diagnostic
2. Commonly used and high Test Sensitivity (99.2%) and moderate Test Specificity (86.4%) for Endometrial Cancer
  1. Clark (2002) JAMA 288(13): 1610-21 [PubMed]
MRI Pelvis
1. May offer additional structural information about uterine abnormalities
2. In contrast, CT and PET are not generally useful in evaluation of possible Endometrial Cancer

Endometrial Biopsy results
1. Endometrial Cancer
2. Endometrial Hyperplasia with atypia
3. Patients who fail usual sampling
  1. Insufficient sampling
  2. Inconsistency between Endometrial Biopsy and pelvic Ultrasound
Patients who fail conservative therapy
1. Endometrial Hyperplasia
2. Perimenopausal Dysfunctional Uterine Bleeding
3. Anovulatory Dysfunctional Uterine Bleeding

Precautions
1. Hysterectomy is the optimal definitive management in complex atypical Endometrial Hyperplasia
2. Lymphadenectomy at time of Hysterectomy not recommended unless intraabdominal signs
3. Supracervical procedures (Cervix sparing Hysterectomy) are not recommended by ACOG
  1. Risk of residual cancer
Fertility preserving measures
1. Step 1: Complete evaluation by gynecology for co-existing Endometrial Cancer (42% of cases)
2. Step 2: High dose Progesterone therapy (if no Endometrial Cancer identified)
3. Step 3: Re-evaluate to confirm Endometrial Hyperplasia effectively treated
4. Step 4: Periodic surveillance for recurrence of Endometrial Hyperplasia per local consultant recommendations
5. Step 5: Hysterectomy when child-rearing completed
Postmenopausal or no future fertility desired
1. Hysterectomy

Progestin Options
1. Medroxyprogesterone acetate (Provera) 10 mg orally for 10-14 days per month
2. Megestrol (Megace) 40 mg orally daily (continuous)
3. Levonorgestrel-releasing IUD (Mirena)