Endometrial Hyperplasia

Aka: Endometrial Hyperplasia, Endometrial Cancer Screening

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II. Associated Conditions

  1. Endometrial Cancer

III. Risk Factors

  1. See Endometrial Cancer Risk Factors

IV. Pathophysiology

  1. Unopposed Estrogen causes accumulation of endometrial tissue

V. Associated Conditions: Endometrial Cancer

  1. 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
  2. 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

VI. Precaution

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

VII. Signs

  1. See Dysfunctional Uterine Bleeding

VIII. Differential Diagnosis

  1. See Dysfunctional Uterine Bleeding Causes

IX. Diagnosis

  1. See Endometrial Biopsy

X. Evaluation: Indications for Endometrial Cancer Screening

  1. 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
  2. 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)
  3. 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)
  4. 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

XI. Imaging: Transvaginal Ultrasound

  1. 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
  2. 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
  3. 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)

XII. Diagnostics

  1. 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
  2. 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
  3. 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]
  4. 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

XIII. Indications: Gynecology Referral

  1. 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
  2. Patients who fail conservative therapy
    1. Endometrial Hyperplasia
    2. Perimenopausal Dysfunctional Uterine Bleeding
    3. Anovulatory Dysfunctional Uterine Bleeding

XIV. Management: Endometrial Hyperplasia with cellular atypia

  1. 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
  2. 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
  3. Postmenopausal or no future fertility desired
    1. Hysterectomy

XV. Management: Endometrial Hyperplasia without cellular atypia

  1. 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)

XVI. Prevention

  1. Manage Unopposed Estrogen states

XVII. References

  1. Apgar (2013) Am Fam Physician 87(12): 836-43 [PubMed]
  2. Braun (2016) Am Fam Physician 93(6): 468-74 [PubMed]
  3. Buchanan (2009) Am Fam Physician 80(10): 1075-88 [PubMed]
  4. Sorosky (2008) Obstet Gynecol 111(2 pt 1): 436-47 [PubMed]

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Related Studies

Ontology: Endometrial Hyperplasia (C0014173)

Definition (NCI_NCI-GLOSS) An abnormal overgrowth of the endometrium (the layer of cells that lines the uterus). There are four types of endometrial hyperplasia: simple endometrial hyperplasia, complex endometrial hyperplasia, simple endometrial hyperplasia with atypia, and complex endometrial hyperplasia with atypia. These differ in terms of how abnormal the cells are and how likely it is that the condition will become cancer.
Definition (NCI) A proliferation of the endometrial cells resulting in glandular enlargement and budding. The proliferation may or may not be associated with atypia of the endometrial cells. When the hyperplastic changes are excessive, there is formation of complex epithelial structures (complex endometrial hyperplasia).
Definition (MSH) Benign proliferation of the ENDOMETRIUM in the UTERUS. Endometrial hyperplasia is classified by its cytology and glandular tissue. There are simple, complex (adenomatous without atypia), and atypical hyperplasia representing also the ascending risk of becoming malignant.
Concepts Disease or Syndrome (T047)
MSH D004714
ICD9 621.30, 621.3
ICD10 N85.0 , N85.00
SnomedCT 237072009, 21588004
English Endometrial Hyperplasia, Endometrial Hyperplasias, Hyperplasias, Endometrial, ENDOMETRIAL HYPERPLASIA, Hyperplasia, Endometrial, endometrial hyperplasia (diagnosis), endometrial hyperplasia, Hyperplasia endometrial, Endometrial hyperpla NOS, Hyperplasia of endometrium, Endometrial hyperplasia, unspecified, Endometrial Hyperplasia [Disease/Finding], endometrium hyperplasia, Hyperplasia;endometrium, hyperplasia endometrial, Endometrial hyperplasia, Endometrial hyperplasia (disorder), endometrium; hyperplasia, hyperplasia; endometrial, Endometrial hyperplasia, NOS, Hyperplasia of Endometrium, Hyperplasia of the Endometrium, Endometrial hyperplasia NOS
Portuguese HIPERPLASIA ENDOMETRIAL, Hiperplasia do endométrio, Hiperplasia Endometrial
Dutch hyperplasie endometrium, endometrium; hyperplasie, hyperplasie; endometrium, endometriumhyperplasie, Endometriumhyperplasie, Hyperplasie, endometrium-
German Hyperplasie des Endometriums, ENDOMETRIUM HYPERPLASIE, Endometriumhyperplasie
Italian Iperplasia endometriale, Iperplasia dell'endometrio
Swedish Endometriehyperplasi
Japanese ｼｷｭｳﾅｲﾏｸｿﾞｳｼｮｸｼｮｳ, 子宮内膜増殖症, 子宮内膜肥厚症
Czech endometrium - hyperplazie, Hyperplazie endometria, Endometriální hyperplazie
Finnish Kohdun limakalvon hyperplasia
Russian ENDOMETRIIA GIPERPLAZIIA, ЭНДОМЕТРИЯ ГИПЕРПЛАЗИЯ
Spanish ENDOMETRIO, HIPERPLASIA, hiperplasia endometrial (trastorno), hiperplasia endometrial, Hiperplasia endometrial, Hiperplasia Endometrial
French HYPERPLASIE DE L'ENDOMETRE, Hyperplasie de l'endomètre, Hyperplasie endométriale
Croatian ENDOMETRIJSKA HIPERPLAZIJA
Polish Rozrost endometrium, Rozrost endometrialny, Hiperplazja endometrium, Rozrost błony śluzowej macicy, Hiperplazja błony śluzowej macicy
Hungarian Endometrium hyperplasia, Endometrium hyperplasiája
Norwegian Endometriehyperplasi
Derived from the NIH UMLS (Unified Medical Language System)

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