Clinical Aplications and Management

Endometrial Hyperplasia

Nugraha UP
 Definition of Endometrial Hyperplasia

• irregular proliferation of the endometrial glands with

an increase in the gland to stroma ratio when
compared with proliferative endometrium
 Epidemiology

Age and symptoms

• Premenopause : EH without atypia <5%
with atypia < 1 %
• Postmenopause : EH without atypia < 4%
with atypia < 2 %
Endometrial Ca 24 %
• EH : precursor of endometrial cancer (the Western world)
• EH = 3x vs endometrial cancer.

Gol K, Saracoglu F, Ekici A, Sahin I. Endometrial patterns and endocrinologic characteristics of asymptomatic menopausal women. Gynecol Endocrinol.
2001;15:63–67. Ash SJ, Farrell SA, Flowerden G. Endometrial biopsy in DUB. J Reprod Med. 1996;41:892–896.
 Symptoms

The most common presentation of endometrial

hyperplasia is abnormal uterine bleeding (AUB):
• heavy menstrual bleeding
• inter-menstrual bleeding
• irregular bleeding
• unscheduled bleeding on HRT postmenopausal
bleeding
 Risk Factors

• Increasing of body mass index (BMI) : excessive peripheral

conversion of androgens in adipose tissue to estrogen.
• anovulation associated with the perimenopause or polycystic
ovary syndrome (PCOS)
• estrogen-secreting ovarian tumors ( granulosa cell tumors )
prevalence of EH.
• drug-induced endometrial stimulation (HRT or tamoxifen)
• Diabetes
• Hereditary Nonpolyposis Colorectal Cancer

Elwood JM, Cole P, Rothman KJ, Kaplan SD. Epidemiology of endo- metrial cancer. J Natl Cancer Inst. 1977;59:1055–1060. Writing Group for the

PEPI Trial.Effects of hormone replacement therapy on endometrial histology in postmenopausal women: the Postmenopausal Estrogen/Progestin

Interventions (PEPI) Trial. JAMA. 1996; 275:370–375.

 Diagnosis

Abnormal uterine bleeding

Transvaginal ultrasound
Histological examination: endometrial sampling
Hysteroscopy during D&C
Histologic Diagnosis of EH
New WHO 2014 classification of endometrial hyperplasias :
1. non-atypical endometrial hyperplasia (benign hyperplasia),
2. atypical endometrial hyperplasia or Endometrial Intraepithelial Neoplasia
(EIN)/well differentiated carcinoma.
 Progestins

• Progestins :orally, intramuscular injection, insertion of a

progestin- containing uterine device.
• Medroxyprogesterone acetate ,megestrol acetate,nor-
ethisterone, levonorgestrel, and lynestrenol.
• This T- shaped IUD: ‘‘levonorgestrel intrauterine system (LNG-
IUS),’’ 52 mg levonorgestrel, and is replaced every 5 years.
• Recent studies have verified that that the progestin- releasing
IUD does not increase risk of DVT.

Ozdegirmenci O, Kayikcioglu F, Bozkurt U, Akgul MA, Haberal A. Comparison of the efficacy of three progestins in the treatment of sim-

ple endometrial hyperplasia without atypia [published online ahead of print January 25, 2011]. Gynecol Obstet Invest. 2011;72:10–14.
 Management

• Conservative therapy
Progestin therapy
oral, IM, intrauterine

• Surgical therapy
 Progestins

• systematic review of 24 studies with 1001 patients demon-

strated that progestin-releasing IUD therapy is more likely
than oral progestin therapy
regression of complex EH (regression rates, 92% vs 66%)
EH with atypia (90% vs 69%);
regression of simple EH (96% vs 89%).

• Decisions should be made : symptom and adverse effect

profiles, cost, and patient compliance.

Gallos ID, Shehmar M, Thangaratinam S, Papapostolou TK, Coomarasamy A, Gupta JK. Oral progestogens vs levonorgestrel-

releasing intrauterine system for endometrial hyperplasia: a system- atic review and metaanalysis. Am J Obstet Gynecol. 2010;203:

547.e1–547.e10.
 Progestins

• Treatment :continuous or cyclic oral progestins for 3 to 6

months or longer .The median time to resolution was 6
months.
• There are fewer data on fertility in women with EH with
atypia after progestin treatment.
• Rates of disease recurrence or progression while attempting
pregnancy are high.

Shirali E, Yarandi F, Eftekhar Z, Shojael H, Khazaeipour Z. Pregnancy outcome in patients with stage 1a endometrial adenocarcinoma, conser- vatively

treated with megestrol acetate. Arch Gynecol Obstet. 2012;285: 791–795

 Surgical Therapy

• Hysterectomy
EH with atypia.
Medical management failed

• Endometrial resection or ablation not recommended

Vilos GA, Harding PG, Ettler HC. Resectoscopic surgery in women with abnormal uterine bleeding and nonatypical endometrial hyperpla-

sia. J Am Assoc Gynecol Laparosc. 2002;9:131–137.

 Take Home Message

• Diagnosis and treatment of EH :a critical aspect of gynecologic

care.
• EH : precursor endometrial carcinoma.
• EH without atypia, progestin therapy is the standard
treatment
• EH with atypia, hysterectomy remains the treatment of choice
in women who have completed childbearing.
• EH with atypia who desire to maintain fertility.  treatment
must be individualized.
Terima Kasih