Endometrial Hyperplasia - Hyperexcision

Last updated: November 11, 2024

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Endometrial hyperplasia is endometrial thickening with a proliferation of irregularly sized and shaped glands. Tends to be symptomatic in post-menopausal women. Endometrial hyperplasia in a post-menopausal woman (around 10mm) would be a normal endometrial thickness for a pre-menopausal woman in the secretory phase of her cycle. The class of hyperplasia is determined by histology. Endometrial tissue is extremely responsive to estrogen. Hyperplasia may be a precancerous lesion, although a majority do not develop into adenocarcinoma. Treatment depends on the age of the woman and whether or not there is atypia. MDPA or Megestrol is the medical treatment of choice.

1 in 38 women will develop endometrial cancer in their lifetime.

Risk factors
- Hyperestrogenism (unopposed estrogen)
  - High-dose menopausal estrogens
  - Obesity (more aromatase more estrogen)
  - Nulliparity
  - Early menarche (≤ 11 years)
  - Late menopause
  - Use of Tamoxifen (SERM given for ER+ Breast cancer. Estrogen agonist in the uterus)
  - PCOS (anovulation → unopposed estrogen)
- Type 2 diabetes, Hypertension, and Gallbladder Disease (may be independent, but occur more commonly in obese women)
- White race
- High socio-economic sttus
- Older age
- Living in North America or Northern Europe
Patient History
- Use of post-menopausal estrogen supplements
- Use of Tamoxifen
- Nulliparity
- Early onset of menarche and Late menopause
- Family History of malignancies (Lynch syndrome etc.)
- Ensure that pap smear is up to date
Signs and Symptoms
- Abnormal uterine bleeding
  - Post-menopausal women: Post-menopausal bleeding
  - Pre-menopausal women: Menorrhagia, Intermenstrual spotting
Physical Exam
- Pelvic exam (bimanual and speculum): feel for masses (fibroid, polyps, ovarian tumours), exclude lacerations, foreign bodies, cervical cancer
Investigations
- Transvaginal ultrasound: measure the endometrial stripe. Imaging modality of choice.
  - For post-menopausal women:
    - Endometrial stripe < 5mm: Likely endometrial atrophy
    - Endometrial stripe ≥ 5 mm: Likely endometrial hyperplasia
  - For pre-menopausal women
    - Normal endometrium varies from 4 – 16 mm
- Endometrial biopsy
- Labs:
  - Qualitative hCG
  - CBC (haemoglobin)
  - TFTs
Indications for endometrial biopsy
- Age > 40 years
- Risk factors for endometrial carcinoma
- Significant intermenstrual bleeding
- Failure of medical treatment for abnormal bleeding

Terms used to describe the histology of endometrial hyperplasia

Term	Description
Simple	Normal endometrial architecture but increased glands and stroma (ratio may be slighly increased > 1:1)
Complex	Changes in endometrial architecture (crowding, invaginations) and/or increased gland to stroma ratio (> 3:1)
Atypia	Changes in the nuclear structure of the cells (prominent nucleoli, salt-pepper chromatin, mitotic figaures etc…)

Risk of progression to cancer

Histology	Risk
Simple without atypia	1%
Complex without atypia	3%
Simple with atypia	8%
Complex with atypia	29%

Treatment for hyperplasia with NO atypia
- Premenopausal: MDPA 10-20 mg qd for 12-14 days q1mos for 3-6 months
- Postmenopausal: MDPA 2.5 mg qd continuously for 3-6 months
- Stop progestins then Repeat biopsy after 2-6 weeks (when tissue returns to normal)
- If no response, MDP 40-100 mg qd or Megestrol 160 mg qd
Treatment for hyperplasia with atypiaThe risk of cancer is so high
- Hysterectomy (most patients will be postmenopausal)
- High dose MDPA if preservation of fertility* (ability to bear children) is desired in premenopausal women

Nonatypical vs Atypical endometrial hyperplasia — Non-atypical vs Atypical endometrial hyperplasia

Reference Intervals ›

Biochemistry

ACTH	P: <80 ng/L
ALT	P: 5–35 U/L
Albumin	P: 35–50 g/L
Aldosterone	P: 100–500 pmol/L
Alk. phosphatase	P: 30–130 U/L
α-Amylase	P: 0–180 IU/dL
α-Fetoprotein	S: <10 kU/L
Angiotensin II	P: 5–35 pmol/L
ADH	P: 0.9–4.6 pmol/L
AST	P: 5–35 U/L
Bicarbonate	P: 24–30 mmol/L
Bilirubin	P: 3–17 μmol/L
BNP	P: <50 ng/L
CRP	P: <10 mg/L
Calcitonin	P: <0.1 mcg/L
Calcium (ionized)	P: 1.0–1.25 mmol/L
Calcium (total)	P: 2.12–2.60 mmol/L
Chloride	P: 95–105 mmol/L
Cholesterol	P: <5.0 mmol/L
VLDL	P: 0.128–0.645 mmol/L
LDL	P: <2.0 mmol/L
HDL	P: 0.9–1.93 mmol/L
Cortisol AM	P: 450–700 nmol/L
Cortisol Midnight	P: 80–280 nmol/L
CK ♂	P: 25–195 U/L
CK ♀	P: 25–170 U/L
Creatinine	P: 70–100 μmol/L
Ferritin	P: 12–200 mcg/L
Folate	S: 2.1 mcg/L
FSH	P: 2–8 U/L ♂; >25 menopause
GGT ♂	P: 11–51 U/L
GGT ♀	P: 7–33 U/L
Glucose (fasting)	P: 3.5–5.5 mmol/L
Growth hormone	P: <20 mu/L
HbA1C (DCCT)	B: 4–6%
HbA1C (IFCC)	B: 20–42 mmol/mol
Iron ♂	S: 14–31 μmol/L
Iron ♀	S: 11–30 μmol/L
Lactate (venous)	P: 0.6–2.4 mmol/L
Lactate (arterial)	P: 0.6–1.8 mmol/L
LDH	P: 70–250 U/L
LH	P: 3–16 U/L
Magnesium	P: 0.75–1.05 mmol/L
Osmolality	P: 278–305 mosmol/kg
PTH	P: 0.8–8.5 pmol/L
Potassium	P: 3.5–5.3 mmol/L
Prolactin ♂	P: <450 U/L
Prolactin ♀	P: <600 U/L
PSA	P: 0–4 mcg/mL
Protein (total)	P: 60–80 g/L
Red cell folate	B: 0.36–1.44 μmol/L
Renin (erect)	P: 2.8–4.5 pmol/mL/h
Renin (recumbent)	P: 1.1–2.7 pmol/mL/h
Sodium	P: 135–145 mmol/L
TBG	P: 7–17 mg/L
TSH	P: 0.5–4.2 mU/L
T4	P: 70–140 nmol/L
Free T4	P: 9–22 pmol/L
TIBC	S: 54–75 μmol/L
Triglycerides	P: 0.50–2.3 mmol/L
T3	P: 1.2–3.0 nmol/L
Troponin T	P: <0.1 mcg/L
Urate ♂	P: 210–480 μmol/L
Urate ♀	P: 150–390 μmol/L
Urea	P: 2.5–6.7 mmol/L
Vitamin B12	S: 0.13–0.68 nmol/L
Vitamin D	S: 50 nmol/L

Arterial Blood Gases

pH	7.35–7.45
PaCO₂	4.7–6.0 kPa
PaO₂	>10.6 kPa
Base excess	±2 mmol/L

Urine

Cortisol (free)	<280 nmol/24h
Hydroxyindole acetic acid	16–73 μmol/24h
Hydroxymethylmandelic acid	16–48 μmol/24h
Metanephrines	0.03–0.69 μmol/mmol cr.
Osmolality	350–1000 mosmol/kg
17-Oxogenic steroids ♂	28–30 μmol/24h
17-Oxogenic steroids ♀	21–66 μmol/24h
17-Oxosteroids ♂	17–76 μmol/24h
17-Oxosteroids ♀	14–59 μmol/24h
Phosphate (inorganic)	15–50 mmol/24h
Potassium	14–120 mmol/24h
Protein	<150 mg/24h
Protein/creatinine ratio	<3 mg/mmol
Sodium	100–250 mmol/24h

Haematology

WCC	4.0–11.0 ×10⁹/L
RBC ♂	4.5–6.5 ×10¹²/L
RBC ♀	3.9–5.6 ×10¹²/L
Hb ♂	130–180 g/L
Hb ♀	115–160 g/L
PCV ♂	0.4–0.54 L/L
PCV ♀	0.37–0.47 L/L
MCV	76–96 fL
MCH	27–32 pg
MCHC	300–360 g/L
RDW	11.6–14.6%
Neutrophils	2.0–7.5 ×10⁹/L (40–75%)
Lymphocytes	1.0–4.5 ×10⁹/L (20–45%)
Eosinophils	0.04–0.44 ×10⁹/L (1–6%)
Basophils	0–0.10 ×10⁹/L (0–1%)
Monocytes	0.2–0.8 ×10⁹/L (2–10%)
Platelets	150–400 ×10⁹/L
Reticulocytes	0.8–2.0% / 25–100 ×10⁹/L
Prothrombin time	10–14 s
APTT	35–45 s

Paediatric

Pulse Rate (bpm)
Neonate	140–160
Infant <1yr	120–140
1–5 years	110–130
5–12 years	80–120
>12 years	70–100
Respiratory Rate (tachypnoea)
0–2 months	≥60/min
2–12 months	≥50/min
1–5 years	≥40/min
>5 years	≥30/min
Blood Pressure (mmHg)
Term	65/45
1 year	75/50
4 years	85/60
8 years	95/65
10 years	100/70
Weight Formulas
3–12 months	(a + 9)/2 kg
1–6 years	2a + 8 kg
>6 years	(7a − 5)/2 kg
Haemoglobin (g/dL)
Term newborn	13–20
1 month	11–18
2 months	10–15
1–2 years	10–13
>2 years	11–14
MUAC (6 months–5 years)
Obese	>17.5 cm
Normal	13.5–17.4 cm
At risk	12.5–13.4 cm
Moderate malnutrition	11.5–12.4 cm
Severe malnutrition	<11.5 cm
Developmental Milestones
Social smile	1.5 months
Head control	4 months
Sits unsupported	7 months
Crawls	10 months
Stands unsupported	10–12 months
Walks	12–13 months
Talks	18 months
CSF WBC (/mm³)
Term newborn	0–25
>2 weeks	0–5

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