Thickened Endometrium: Causes, Risk Factors, Symptoms, Diagnosis, Types, Treatment, Prevention and Prognosis

Also called endometrial hyperplasia (HD), it is a condition in which the lining of the uterus is thicker than normal.

It can have many causes, but the most important association is with endometrial malignancy .

Endometrial hyperplasia is defined as the excessive proliferation of cells in the inner lining of the uterus, known as the endometrium.

This occurrence is generally considered to be a precursor to the development of endometrial cancer and has been shown to be the result of unopposed estrogens, as seen in exogenous estrogen therapy, anovulatory cycles, polycystic ovarian syndrome (PCOS), or obesity. .

For this reason, it is mandatory to distinguish between the different types of endometrial hyperplasia, that is, those that are benign and those that are precancerous.

The condition, although not cancerous, is sometimes associated with uterine cancer. Endometrial hyperplasia describes a condition in which the lining of the uterus, called the endometrium, becomes too thick.

The condition itself is not cancerous; however, it can sometimes lead to uterine cancer. Most cases of endometrial hyperplasia are the result of high levels of estrogen, combined with insufficient levels of progesterone.

Unopposed estrogen stimulation of the endometrium causes proliferative changes of the glandular epithelium, including glandular remodeling, which results in variably irregularly distributed glands.

Risk factors for the development of endometrial cancer include obesity, unbalanced estrogen therapy, tamoxifen treatment, polycystic ovarian syndrome, and nulliparity.

Endometrial hyperplasia is common in women ages 50 to 54 with a body mass index (BMI) greater than 30. The average age for endometrial hyperplasia is 52 years, nine years older than the average age for endometrial cancer.

The increased risk of endometrial cancer among overweight (BMI> 25) and obese people appears to be higher in postmenopausal women than in younger women.

Consequently, the growing obesity epidemic in Poland, in conjunction with an aging cohort, has the potential to result in a significant increase in endometrial cancer and its precursors.

Endometrial hyperplasia is one of the most common causes of abnormal uterine bleeding, leading to endometrial cancer if left untreated.

In 10% of premenopausal women with abnormal uterine bleeding, histological findings show endometrial hyperplasia, and in 6% of postmenopausal women with uterine bleeding, endometrial cancer is found.

The main role of endometrial sampling in patients with abnormal uterine bleeding is to determine whether carcinomatous or premalignant lesions are present by evaluating histological specimens.

A study by the Gynecological Oncology Group on the diagnosis of atypical hyperplasia based on biopsy found 42.6% concurrent endometrial carcinoma in hysterectomy specimens.

The most useful tool for evaluating the endometrium and making a preliminary diagnosis is ultrasound imaging (USG TV).

Tissue sampling should be performed in women with risk factors for endometrial cancer , who have symptoms of abnormal vaginal bleeding or pathological vaginal discharge.

The correct clinical evaluation of endometrial hyperplasia is further complicated by the different staging systems that are still in use.

The pathological diagnosis of premalignant lesions must use criteria and terminology that clearly distinguish the clinicopathological entities that must be treated differently.

Many attempts to reclassify retrospectively collected data have resulted in an extensive lexicon for endometrial cancer precursors. Traditional histopathologic staging systems for endometrial hyperplasia exhibit wide and variable degrees of diagnostic reproducibility.

As a consequence, developing standardized patient management procedures can be challenging.

The risk of coexisting cancer in women with a diagnosis of endometrial hyperplasia on evaluation of the endometrial biopsy / curettage specimen is due to limitations in endometrial sampling and differences in diagnostic classification between pathologists.

There are some technical issues that limit the diagnosis of endometrial curettage specimens.

Some of these factors include insufficient clinical data, curettage performed in the wrong cycle phase, inadequate sampling, technical problems such as inadequate fixation and insufficient staining quality, and lack of experience of the pathologist in evaluating endometrial tissue.

Some studies have reported that insufficient material is the leading cause of misdiagnosis.

For the correct diagnosis of endometrial hyperplasia, the differential diagnostic criteria must be determined.

Many of the diagnostic features for atypia (nuclear irregularity, loss of polarity, prominent nucleolus, thickening of chromatin) can also be seen in hormonal irregularities, regeneration, and metaplastic changes.

Endometrial hyperplasia is one of the most frequently misdiagnosed (overdiagnosed) lesions. Endometrial polyps are often diagnosed as hyperplasia due to fixation problems, poor conduction of sections, and excessively bleeding bleeds.

Atypical hyperplasia / endometrial intraepithelial neoplasia is a precancerous lesion and requires a different approach to treatment than other types of hyperplasia and adenocarcinomas. In contrast, the development of invasive carcinomas is very rare in cases of hyperplasia without atypia (<5%).

Hyperplasia without atypia responds well to progestins. Hyperplasia with atypia requires definitive treatment with hysterectomy due to the high rate of concurrent endometrial cancer.

What Causes Endometrial Hyperplasia (Thickened Endometrium)?

The endometrium is an inner epithelial layer of the human female uterus. During typical menstrual cycles, this layer thickens and is then shed according to fluctuations in various hormones, such as estrogen.

The reason for the thickening of the endometrium is to prepare for the potential of pregnancy as vascular space would be needed to accommodate a growing placenta and the developing fetus.

Endometrial hyperplasia is an abnormal overgrowth of endometrial tissue, and most commonly due to long-term exposure to unopposed estrogen.

This creates an imbalance of other hormones that regulate the menstrual cycle, primarily progesterone, leading to proliferation of the endometrium. Causes that can lead to unopposed estrogen stimulation include:

If your body has too much estrogen hormone without progesterone hormone, you can develop endometrial hyperplasia.

To understand how endometrial hyperplasia develops, it can be helpful to first understand how hormonal changes during a typical menstrual cycle affect your uterine lining.

Estrogen is produced by the ovaries during the first part of their cycle. That leads to the growth of the lining to prepare your body for pregnancy.

However, after an egg is released (ovulation), progesterone increases with the goal of maintaining a fertilized egg.

But if pregnancy does not occur, the levels of both hormones decrease. That decrease in progesterone is what triggers your period, the shedding of the lining.

If you don’t ovulate, progesterone isn’t made and the lining doesn’t shed. So the lining can continue to grow in response to estrogen, and over time, the cells in the lining can become abnormal.

Having irregular periods, especially associated with polycystic ovary syndrome or infertility, obesity. Long-term use of estrogen hormone replacement therapy to treat menopausal symptoms.

Complications of endometrial hyperplasia include:

  • An increased risk of developing endometrial cancer, especially in those women who have atypical changes, a third of cases are associated with endometrial polyps, the risk increases after menopause.
  • In some women, the overgrowth, called hyperplasia, can lead to cancer.

Thickened endometrial risk factors

It is generally observed that women around 35-40 years of age are the age group that can develop endometrial hyperplasia.

However, it is not until these women become postmenopausal (generally older than 48-50 years) that most cases are diagnosed.

There are several risk factors that predispose women to developing endometrial hyperplasia, however, it is important to note that having a risk factor does not mean that you will develop the condition.

Having a risk factor listed simply increases the likelihood that you may have endometrial hyperplasia compared to someone without the same risk factor.

However, some risk factors are more important than others, contributing to an increased risk, while others may have minor associations with endometrial hyperplasia. The following are the risk factors for developing endometrial hyperplasia:

Being over 35 years old, being Caucasian, periods of early onset (before the age of 12) or late menopause (Having reached menopause after the age of 55), obesity, being a cigarette smoker, having a history family member of uterine cancer, colon cancer or ovarian cancer.

Having a history of diabetes, polycystic ovary syndrome (PCOS), gallbladder disease, or thyroid disease.

Being postmenopausal, having thyroid gland disorders, gallbladder disorders, use of a drug for the treatment of breast cancer called tamoxifen, infertility, not having children or having been pregnant (nulliparous women).

If you are concerned that you may have one or more of the risk factors listed above, speak with your healthcare provider for further evaluation.

Symptoms

The most common symptom is abnormal uterine bleeding (heavier than usual bleeding between periods). People with endometrial hyperplasia may have:

Abnormal menstrual bleeding that does not coincide with menstrual cycles, prolonged or heavy menstrual bleeding, short menstrual periods less than 21 days, vaginal discharge, vaginal bleeding in postmenopausal women.

If you have a menstrual cycle less than 21 days, check with your doctor. Count from the first day of your period to the first day of your next one.

If you are postmenopausal, report any uterine bleeding to your healthcare provider.

How to diagnose thickened endometrium

Most cases of endometrial hyperplasia will initially be brought to the patient’s attention through the presentation of abnormal vaginal bleeding, prompting them to seek the advice of a medical professional.

The doctor will then take a thorough medical history to help rule out any possible causes. A physical exam may also be done to help identify any other signs of underlying disease. This often includes a Pap test that can help identify any cell abnormalities.

The most accurate diagnostic tests will assess the thickness of the endometrial tissue. This can be done with a pelvic ultrasound, and if it is found to be more than 4mm thick, suspicions of endometrial hyperplasia or malignancy are likely.

The most accurate test to determine a diagnosis of endometrial hyperplasia will involve taking a biopsy with hysteroscopy for examination under a microscope.

This is usually done in the office during a pelvic exam and has the added benefit of being relatively quick to perform. This will allow the identification of benign or cancerous forms of endometrial hyperplasia.

If you have abnormal uterine bleeding, your doctor may order certain exams and tests, including:

  • Transvaginal ultrasound.
  • Biopsy.
  • Dilation and curettage (D and C).
  • Hysteroscopy

Types of endometrial hyperplasia (thickened endometrium)

Your doctor and other healthcare providers will check for certain cell changes before diagnosing the exact type of endometrial hyperplasia.

The currently most widely used classification system is based on the Kurman et al scheme, which uses architectural features and cytological atypia (glandular complexity and nuclear atypia) to identify precursor lesions, called atypical endometrial hyperplasia (HAE). .

The parallel use of the previous 1994 World Health Organization (WHO) classification system caused confusion among physicians. Classification of the world health organization 1994 (WHO94):

  • Simple hyperplasia.
  • Complex hyperplasia.
  • Simple hyperplasia with atypia.
  • Complex hyperplasia with atypia.

The categories of the World Health Organization (WHO) division are descriptive and their interpretation does not suggest any specific management algorithm. Several studies indicate poor reproducibility of the classification of individual cases.

The diagnoses often overlap due to the different classification systems in use today. As a consequence, hysterectomies for hyperplasia without atypia or gestagen treatment given for atypical hyperplasia can also be performed.

Pathologists also experience difficulties understanding predetermined classifications. A great deal of terminology is not standardized and undefined, and diagnostic criteria are not reproducible.

It is hardly possible to retrospectively compare and interpret published studies on precancerous endometrial conditions.

The scheme of the world health organization (WHO) is the most used by pathologists, but the transition to the endometrial nomenclature of intraepithelial neoplasia (EIN) would be of greater benefit for clinical management.

Endometrial hyperplasia can often be treated with progestin. This synthetic hormone is administered orally, topically as a vaginal cream, by injection, or with an intrauterine device.

If you have simple or “mild” hyperplasia, which is the most common type, the risk of it becoming cancerous is very small. If you have atypical hyperplasia, your chances of developing cancer are higher.

For simple atypical, the chances of it turning into cancer is about 8 percent if left untreated. The atypical complex turns into cancer in 29 percent of untreated cases.

If the diagnosis is atypical and you have finished having children, your doctor may recommend removal of the uterus (hysterectomy), as the risk of uterine cancer increases with atypical hyperplasia.

Treatment

Treatment of endometrial hyperplasia depends on the etiology and direction of the lesion, so factors that determine the choice of treatment include:

  • Histopathological diagnosis.
  • If the woman wants to conceive again.
  • If she is currently exposed to estrogens.
  • Severity of symptoms.
  • General health.

Treatment of endometrial hyperplasia without atypia

In most cases, benign endometrial hyperplasia is treated conservatively. Attention is paid to the identification and elimination of sources of estrogens, whether exogenous or endogenous.

Having a case of non-cancerous endometrial hyperplasia will often involve hormonal manipulation treatment, which will help to reestablish any hormonal imbalance that may have occurred.

This may include the removal of any unopposed estrogen source, such as an estrogen hormone-producing tumor. Modifiable risk factors for this condition include:

Sedentary lifestyle with lack of exercise, diabetes mellitus, unhealthy diet that promotes weight gain.

Obesity in which peripheral fatty tissue containing the enzyme aromatase converts androgens to estrogens, promoting endometrial thickening

The use of estrogen-only hormone replacement therapy in postmenopausal women, or other estrogen delivery systems, which must be replaced with combined continuous or cyclical hormone replacement therapy.

About 1% of patients receiving combination hormone replacement therapy develop benign endometrial hyperplasia.

Treatment of precancerous endometrial hyperplasia

Having a diagnosis of precancerous forms of endometrial hyperplasia will require treatment that depends on the underlying cause of the disease. Doctors will often approach each case on a case-by-case basis, as treatment may not be the same for all patients. Treatment measures may include:

Hormone manipulation, endometrial ablation: destroy endometrial abnormalities, proper treatment for obesity and diabetes

Surgical removal (hysterectomy): Usually performed if the production of a baby has been completed. Avoid or quit smoking, treating any underlying disorder causing the condition.

Natural treatment for endometrial hyperplasia

The following are some natural treatments that may be helpful in thinning the endometrium, not curing it. Therefore, it is important to obtain approval and recommendation for any cause of abnormal vaginal bleeding before trying any of the following methods.

Ice pack – Placing an ice pack near the pelvic region for about 15 minutes can help relieve pain associated with endometrial hyperplasia.

Castor oil : When applied to the abdominal and pelvic area, castor oil can help relieve pain associated with endometrial hyperplasia.

Clay Packs – Made from clay and water, the clay packs can be applied to the abdomen in at least a half-inch thickness. Once this is done, cover it with a cotton cloth and let it dry for at least an hour. This can help your body reduce endometrial thickness.

Fish oil : Containing omega-3 fatty acids, fish oil can prevent overgrowth of endometrial cells.

Goldenseal – Known for having anti-inflammatory, antibiotic, and astringent properties. This makes it ideal for those with excessive menstruation, helping to relieve stomach pain and cramps.

Prevention and prognosis of thickened endometrium

Unfortunately, there is no known safe method to prevent the development of endometrial hyperplasia. However, there are several things a woman can do to reduce her risk.

This includes quitting smoking, avoiding obesity, taking a combination of oral contraceptives, seeking early treatment for underlying conditions, and undergoing a regular medical examination.

The risk of developing endometrial cancer with precancerous forms of endometrial hyperplasia is approximately 25 to 33 percent. This is quite high and affected women are advised to get proper treatment and adhere to frequent follow-up visits.