Endometrial Hyperplasia

Endometrial hyperplasia is a condition characterized by the thickening of the endometrium, the inner lining of the uterus. This overgrowth occurs when there's an imbalance between estrogen and progesterone hormones, leading to abnormal uterine bleeding and potentially increasing the risk of endometrial cancer if left untreated.

Medical Disclaimer: This information is for educational purposes only and should not replace professional medical advice. Always consult with a qualified healthcare provider for diagnosis and treatment.

Overview

Endometrial hyperplasia occurs when the cells lining the uterus grow excessively, resulting in a thickened endometrium. This condition typically develops due to prolonged exposure to estrogen without the counterbalancing effects of progesterone. While not cancer itself, certain types of endometrial hyperplasia can progress to endometrial cancer if left untreated, making early detection and management crucial.

The condition is classified into different types based on the appearance of cells under a microscope. Simple hyperplasia without atypia has the lowest risk of progressing to cancer (about 1%), while complex hyperplasia with atypia (also called endometrial intraepithelial neoplasia or EIN) carries a much higher risk, with up to 40% of cases potentially progressing to endometrial cancer. This classification system helps guide treatment decisions and determine the appropriate level of intervention.

Endometrial hyperplasia most commonly affects women during perimenopause, when hormonal fluctuations are common, but it can occur at any age in women who have irregular ovulation or excess estrogen exposure. The condition is particularly important to diagnose and treat because it represents a potentially reversible precancerous state. With appropriate treatment, most women with endometrial hyperplasia can avoid progression to cancer and maintain their reproductive health.

Symptoms

The symptoms of endometrial hyperplasia primarily relate to abnormal uterine bleeding patterns. Many women may not experience symptoms in the early stages, making regular gynecological care important for detection. When symptoms do occur, they can significantly impact quality of life and daily activities.

Primary Bleeding Symptoms

  • Heavy menstrual flow - Excessive bleeding during periods (menorrhagia)
  • Unpredictable menstruation - Irregular timing and flow
  • Bleeding between periods (metrorrhagia)
  • Prolonged menstrual periods lasting more than 7 days
  • Shorter menstrual cycles (less than 21 days)
  • Spotting or light bleeding when not expecting a period

Postmenopausal Symptoms

  • Vaginal bleeding after menopause - Any bleeding after 12 months without periods
  • Brown or bloody vaginal discharge
  • Spotting that may be mistaken for bladder or bowel bleeding

Associated Symptoms

  • Back weakness - May occur with heavy bleeding and anemia
  • Pelvic pain or cramping, especially during bleeding episodes
  • Bloating or feeling of pelvic fullness
  • Fatigue from chronic blood loss and anemia
  • Pale skin and weakness from iron deficiency

Urinary Symptoms

Some women may experience:

  • Involuntary urination - Due to pelvic pressure or weakness
  • Increased urinary frequency
  • Urgency to urinate
  • Difficulty emptying bladder completely

Impact on Daily Life

  • Need to change sanitary products frequently (every 1-2 hours)
  • Passing large blood clots
  • Soaking through protection at night
  • Limiting activities due to heavy bleeding
  • Anxiety about unpredictable bleeding
  • Sexual dysfunction due to bleeding or fear of bleeding

When Symptoms Warrant Immediate Attention

  • Soaking through one or more pads/tampons every hour for several hours
  • Bleeding lasting more than 14 days
  • Signs of severe anemia (chest pain, shortness of breath, rapid heartbeat)
  • Passing clots larger than a quarter
  • Any postmenopausal bleeding

Causes

Endometrial hyperplasia develops when the endometrium is exposed to estrogen without adequate opposing progesterone. This hormonal imbalance disrupts the normal menstrual cycle, preventing the regular shedding of the uterine lining and leading to its abnormal thickening.

Hormonal Imbalance

The primary mechanism involves:

  • Excess estrogen stimulation: Promotes endometrial cell growth and proliferation
  • Insufficient progesterone: Fails to counteract estrogen's growth-promoting effects
  • Absence of ovulation: No corpus luteum formation means no progesterone production
  • Continuous endometrial stimulation: Without progesterone, the lining continues to thicken

Conditions Leading to Excess Estrogen

  • Polycystic ovary syndrome (PCOS): Chronic anovulation with persistent estrogen production
  • Obesity: Fat tissue converts androgens to estrogen through aromatization
  • Ovarian tumors: Granulosa cell tumors producing estrogen
  • Early menarche/late menopause: Extended lifetime estrogen exposure
  • Perimenopause: Irregular ovulation with unopposed estrogen

Exogenous Estrogen Sources

  • Estrogen-only hormone therapy: Without progesterone in women with intact uterus
  • Tamoxifen therapy: Acts as estrogen agonist in the uterus
  • Herbal supplements: Some contain phytoestrogens
  • Environmental estrogens: Xenoestrogens from plastics and pesticides

Metabolic and Endocrine Factors

  • Insulin resistance: Increases ovarian androgen production and aromatase activity
  • Diabetes mellitus: Associated with hormonal imbalances
  • Thyroid disorders: Can affect menstrual regularity
  • Hyperprolactinemia: Suppresses ovulation
  • Cushing's syndrome: Cortisol excess affects reproductive hormones

Genetic and Molecular Factors

  • Lynch syndrome: Hereditary cancer syndrome increasing endometrial cancer risk
  • PTEN mutations: Tumor suppressor gene alterations
  • Microsatellite instability: DNA mismatch repair defects
  • K-ras mutations: Oncogene activation in some cases

Lifestyle and Environmental Factors

  • Sedentary lifestyle: Associated with obesity and metabolic dysfunction
  • High-fat diet: May increase estrogen levels
  • Alcohol consumption: Can increase estrogen levels
  • Stress: Chronic stress affects hormonal balance

Risk Factors

Understanding risk factors for endometrial hyperplasia helps identify women who may benefit from increased surveillance and preventive measures. Many risk factors relate to conditions that cause prolonged estrogen exposure without adequate progesterone.

Major Risk Factors

  • Age over 35: Particularly during perimenopause (45-55 years)
  • Obesity: BMI >30 increases risk 3-fold; severe obesity increases risk up to 10-fold
  • Polycystic ovary syndrome (PCOS): Chronic anovulation and insulin resistance
  • Never having been pregnant (nulliparity): Lack of progesterone exposure during pregnancy
  • Infertility: Often associated with anovulation
  • Late menopause: After age 55, prolonged estrogen exposure
  • Early menarche: Before age 12, extended reproductive years

Medical Conditions

  • Diabetes mellitus: Type 2 diabetes doubles the risk
  • Hypertension: Often coexists with other metabolic risk factors
  • Thyroid disease: Both hypo- and hyperthyroidism
  • Gallbladder disease: May indicate estrogen metabolism issues
  • Lynch syndrome: 40-60% lifetime risk of endometrial cancer
  • Breast or ovarian cancer: Shared hormonal risk factors

Medication-Related Risks

  • Unopposed estrogen therapy: Without progesterone in intact uterus
  • Tamoxifen use: For breast cancer treatment or prevention
  • Sequential hormone therapy: Less protective than continuous combined therapy
  • Long-term high-dose estrogen: For various medical conditions

Lifestyle Factors

  • Sedentary behavior: Contributes to obesity and insulin resistance
  • High-calorie diet: Especially high in animal fats
  • Low fiber intake: May affect estrogen metabolism
  • Excessive alcohol: More than 1 drink daily
  • Lack of physical activity: Less than 150 minutes weekly

Protective Factors

Factors that may reduce risk include:

  • Multiple pregnancies
  • Combined oral contraceptive use
  • Regular physical activity
  • Maintaining healthy weight
  • Progestin-containing IUD
  • Breastfeeding

Diagnosis

Accurate diagnosis of endometrial hyperplasia requires tissue sampling to examine the endometrial cells microscopically. Early diagnosis is crucial for preventing progression to cancer and preserving fertility options when desired.

Clinical Evaluation

  • Medical history: Menstrual patterns, bleeding episodes, risk factors
  • Symptom assessment: Duration, severity, and pattern of bleeding
  • Medication review: Hormones, tamoxifen, anticoagulants
  • Family history: Endometrial, colon, ovarian cancers (Lynch syndrome)
  • Physical examination: BMI, signs of PCOS, thyroid disease

Diagnostic Procedures

Transvaginal Ultrasound

  • Initial screening tool for abnormal bleeding
  • Measures endometrial thickness
  • Postmenopausal: >4-5mm warrants further evaluation
  • Premenopausal: Thickness varies with cycle, >16mm concerning
  • Can identify polyps or structural abnormalities

Endometrial Biopsy

  • Office procedure: Using pipelle or similar device
  • Gold standard: For histologic diagnosis
  • Adequate sampling: Important for accurate diagnosis
  • Limitations: May miss focal lesions, 10% insufficient samples
  • When indicated: Postmenopausal bleeding, persistent abnormal bleeding

Hysteroscopy with Directed Biopsy

  • Direct visualization of endometrial cavity
  • Targeted biopsy of suspicious areas
  • Can identify and remove polyps
  • Higher diagnostic accuracy than blind biopsy
  • Performed in office or operating room

Dilation and Curettage (D&C)

  • More comprehensive sampling than office biopsy
  • Therapeutic and diagnostic
  • Requires anesthesia
  • May be combined with hysteroscopy
  • Used when other methods insufficient

Histologic Classification

WHO Classification System

  • Hyperplasia without atypia: Benign endometrial hyperplasia
  • Atypical hyperplasia/EIN: Premalignant condition requiring treatment

Features Assessed

  • Gland-to-stroma ratio
  • Architectural pattern
  • Cellular atypia presence
  • Mitotic activity
  • Nuclear features

Additional Testing

  • Complete blood count: Assess for anemia
  • Thyroid function tests: If clinically indicated
  • Coagulation studies: For severe bleeding
  • Pregnancy test: In reproductive-age women
  • CA-125: May be elevated but not diagnostic

Surveillance After Diagnosis

  • Repeat biopsy after treatment (usually 3-6 months)
  • Annual surveillance for hyperplasia without atypia
  • More frequent monitoring for atypical hyperplasia
  • Long-term follow-up even after resolution

Treatment Options

Treatment of endometrial hyperplasia depends on the histologic type, patient age, desire for fertility preservation, and risk factors for progression to cancer. The goal is to eliminate abnormal endometrial tissue and prevent recurrence or progression to malignancy.

Medical Management

Progestin Therapy

First-line treatment for most cases:

  • Oral progestins:
    • Medroxyprogesterone acetate (10-20mg daily)
    • Megestrol acetate (40-160mg daily)
    • Norethindrone acetate (5-15mg daily)
    • Treatment duration: 3-6 months minimum
  • Levonorgestrel IUD (Mirena):
    • Delivers high local progestin levels
    • Lower systemic side effects
    • 95% regression rate for non-atypical hyperplasia
    • Can remain in place for 5 years
  • Injectable progestins:
    • Depo-Provera for patients with compliance issues
    • Every 3 months administration

Combined Hormonal Therapy

  • Continuous combined oral contraceptives
  • For premenopausal women desiring contraception
  • Regulates cycles and provides progesterone
  • May be used long-term for prevention

Surgical Management

Hysterectomy

Definitive treatment for:

  • Atypical hyperplasia in postmenopausal women
  • Failed medical management
  • Progression to cancer
  • Women who have completed childbearing
  • Concurrent high-risk factors
  • Approaches: Vaginal, laparoscopic, robotic, or abdominal

Endometrial Ablation

  • For women not desiring fertility
  • Alternative to hysterectomy in selected cases
  • Various techniques: thermal, radiofrequency, cryotherapy
  • Requires prior sampling to rule out atypia
  • Not appropriate for atypical hyperplasia

Treatment by Type

Hyperplasia Without Atypia

  • Observation acceptable for low-risk patients
  • Progestin therapy for 3-6 months
  • Re-biopsy at 3-6 month intervals
  • Long-term suppression if recurrent
  • 1% cancer risk, often regresses spontaneously

Atypical Hyperplasia/EIN

  • Hysterectomy preferred for postmenopausal women
  • High-dose progestin for fertility preservation
  • Close surveillance with biopsy every 3 months
  • 40% risk of concurrent or future cancer
  • Consider oncology referral

Fertility Preservation Options

  • High-dose progestin therapy: With close monitoring
  • Assisted reproduction: After initial treatment response
  • Hysterectomy timing: After childbearing complete
  • Egg/embryo freezing: Before definitive treatment
  • Success rates: 70-80% initial response with progestins

Monitoring During Treatment

  • Endometrial biopsy every 3-6 months
  • Document regression, persistence, or progression
  • Monitor for side effects of therapy
  • Annual imaging after complete response
  • Long-term surveillance even after hysterectomy

Management of Treatment Side Effects

  • Weight gain: Diet counseling, exercise program
  • Mood changes: Consider antidepressants if severe
  • Irregular bleeding: Adjust progestin dose or route
  • Bloating: Dietary modifications
  • Headaches: Usually improve with time

Prevention

While not all cases of endometrial hyperplasia can be prevented, many risk factors are modifiable. Prevention strategies focus on maintaining hormonal balance and addressing underlying conditions that promote excess estrogen exposure.

Weight Management

  • Maintain healthy BMI: Between 18.5-24.9 kg/m²
  • Weight loss if obese: Even 5-10% reduction beneficial
  • Regular physical activity: 150 minutes moderate exercise weekly
  • Dietary modifications: Low-fat, high-fiber diet
  • Avoid yo-yo dieting: Maintain stable weight

Hormonal Balance

  • Treat PCOS: Regulate cycles with hormonal contraception
  • Address anovulation: Induce regular menses
  • Progesterone supplementation: If taking estrogen therapy
  • Regular menstrual cycles: Investigate irregularities promptly
  • Avoid unopposed estrogen: Always pair with progesterone

Medical Management

  • Diabetes control: Maintain optimal blood sugar levels
  • Blood pressure management: Reduces metabolic syndrome risk
  • Thyroid optimization: Treat hypo- or hyperthyroidism
  • Regular screening: For high-risk individuals
  • Genetic counseling: For Lynch syndrome families

Lifestyle Modifications

  • Limit alcohol: Maximum one drink daily
  • Quit smoking: Improves overall health
  • Stress reduction: Yoga, meditation, counseling
  • Adequate sleep: 7-9 hours nightly
  • Environmental toxin avoidance: Limit xenoestrogen exposure

Protective Medications

  • Combined oral contraceptives: 50% risk reduction with 5 years use
  • Progestin-containing IUD: Local endometrial protection
  • Depot medroxyprogesterone: For high-risk women
  • Metformin: For women with insulin resistance

When to See a Doctor

Prompt medical evaluation of abnormal bleeding is crucial for early detection and treatment of endometrial hyperplasia. Any change in menstrual patterns or unexpected bleeding warrants investigation.

Seek Immediate Medical Care For:

  • Heavy bleeding soaking more than one pad/tampon per hour
  • Bleeding with signs of severe anemia (chest pain, shortness of breath)
  • Passing large clots with severe cramping
  • Dizziness, fainting, or rapid heartbeat with bleeding
  • Fever with abnormal bleeding

Schedule an Appointment For:

Risk-Based Screening:

  • Women with PCOS: Annual evaluation
  • Obese women with irregular periods: Regular monitoring
  • Women on tamoxifen: Before starting and annually
  • Lynch syndrome carriers: Annual screening from age 35
  • Postmenopausal women on estrogen: Regular surveillance

Related Conditions

Endometrial hyperplasia shares risk factors and may coexist with several other gynecological and metabolic conditions. Understanding these relationships helps in comprehensive management.

Gynecological Conditions

Hormonal Disorders

Metabolic Conditions

Cancer Syndromes

Frequently Asked Questions

Can endometrial hyperplasia turn into cancer?

Simple hyperplasia without atypia rarely progresses to cancer (about 1% risk). However, atypical hyperplasia (also called endometrial intraepithelial neoplasia) has a much higher risk, with up to 40% progressing to endometrial cancer if left untreated. This is why proper diagnosis and treatment are essential.

Can I get pregnant if I have endometrial hyperplasia?

Yes, pregnancy is possible, but hyperplasia often occurs with conditions that affect fertility, like PCOS or chronic anovulation. Treatment with progestins can restore normal endometrial function. Many women successfully conceive after treatment, though close monitoring is recommended during fertility treatment.

How long does treatment take to work?

Most women respond to progestin therapy within 3-6 months. Regression rates are about 80-90% for hyperplasia without atypia and 70-80% for atypical hyperplasia. Follow-up biopsies are needed to confirm resolution. Some women may need longer treatment or maintenance therapy.

Will I need a hysterectomy?

Not necessarily. Many cases respond well to medical management with progestins. Hysterectomy is typically recommended for: postmenopausal women with atypical hyperplasia, failed medical therapy, progression to cancer, or women who have completed childbearing and prefer definitive treatment.

Can endometrial hyperplasia come back after treatment?

Yes, recurrence is possible, especially if underlying risk factors persist. Recurrence rates are about 15-30% for hyperplasia without atypia and higher for atypical cases. Long-term monitoring and addressing risk factors like obesity and PCOS help prevent recurrence.

Is endometrial hyperplasia hereditary?

While most cases aren't directly inherited, some genetic conditions increase risk. Lynch syndrome significantly increases risk for endometrial hyperplasia and cancer. Family history of endometrial cancer, especially at young ages, warrants genetic counseling and enhanced screening.

References

  1. Committee on Practice Bulletins—Gynecology. ACOG Practice Bulletin No. 194: Endometrial Intraepithelial Neoplasia. Obstet Gynecol. 2018;131(5):e124-e129.
  2. Kurman RJ, et al. The 2014 WHO Classification of Tumors of the Female Genital Tract. Int J Gynecol Pathol. 2014;33(4):297-300.
  3. Gallos ID, et al. Regression, relapse, and live birth rates with fertility-sparing therapy for endometrial cancer and atypical complex endometrial hyperplasia: a systematic review and metaanalysis. Am J Obstet Gynecol. 2012;207(4):266.e1-12.
  4. Royal College of Obstetricians and Gynaecologists. Management of Endometrial Hyperplasia. Green-top Guideline No. 67. RCOG; 2016.
  5. Trimble CL, et al. Management of endometrial precancers. Obstet Gynecol. 2012;120(5):1160-1175.
  6. Lacey JV Jr, et al. Absolute risk of endometrial carcinoma during 20-year follow-up among women with endometrial hyperplasia. J Clin Oncol. 2010;28(5):788-792.