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Atypical Endometrial Hyperplasia

Last updated May 2, 2018

Approved by: Krish Tangella MD, MBA, FCAP

Atypical Endometrial Hyperplasia is a condition that occurs in the endometrium due to an abnormally increased growth of the endometrial glands.


What are the other Names for this Condition? (Also known as/Synonyms)

  • Complex Atypical Endometrial Hyperplasia
  • Endometrial Hyperplasia with Atypia
  • Simple Atypical Endometrial Hyperplasia

What is Atypical Endometrial Hyperplasia? (Definition/Background Information)

  • Atypical Endometrial Hyperplasia is a condition that occurs in the endometrium due to an abnormally increased growth of the endometrial glands. On examination of a biopsy specimen under a microscope, the pathologist may observe cell abnormalities (cytological atypia)
  • The condition is also known as Atypical Hyperplasia/Endometrioid Intraepithelial Neoplasia (AH/EIN). AH/EIN is a premalignant condition i.e., a precursor to endometrioid carcinoma of endometrium
  • Atypical Endometrial Hyperplasia develops from benign endometrial hyperplasia that generally occurs due to long-term exposure to estrogen hormone that is not counterbalanced by progesterone hormone - a condition described as unopposed estrogen stimulation
  • A majority of Atypical Endometrial Hyperplasia cases are seen in women following menopause. The risk factors for the condition include a positive family history of the condition, obesity, polycystic ovarian syndrome, and treatment for breast cancer using the drug tamoxifen
  • Atypical Endometrial Hyperplasia results in an uncharacteristic thickening of the endometrium, which is the lining of the uterus. It can lead to signs and symptoms, such as abnormal vaginal bleeding/discharge, and the presence of a polypoid mass in the endometrium
  • The most important and significant complication of Atypical Endometrial Hyperplasia is that it portends a high risk for endometrial carcinoma (sometimes, as high as 45 times). Some studies inform that between 25-40% of the women with AH/EIN are observed to develop endometrial cancer
  • Atypical Endometrial Hyperplasia is treated on a case-by-case basis depending on the underlying cause. The treatment options may include hormonal manipulation, endometrial ablation, and in some cases, a hysterectomy, when necessary. The prognosis is related to the underlying cause and the response to treatment

Who gets Atypical Endometrial Hyperplasia? (Age and Sex Distribution)

  • Atypical Endometrial Hyperplasia is a condition observed in adult women around and after the age of 35-40 years
  • A majority of cases are generally noted in postmenopausal women; women above 48-50 years, average age 53 years
  • No racial or ethnic group predilection is observed, although Caucasians are at a higher risk for some unknown reason

What are the Risk Factors for Atypical Endometrial Hyperplasia? (Predisposing Factors)

The risk factors for Atypical Endometrial Hyperplasia may include the following conditions:

  • Women on unopposed estrogen therapy
  • Postmenopausal status in women
  • Excess estrins in the body (known as hyperestrinism) that may be internally-induced or externally administered (through medication therapy)
  • Menstrual cycle: Women who got their period before the age of 12 years, and those who reached menopause after age 55 years have an elevated risk. The longer the duration between menarche and menopause, the greater is the risk. This is due to hormonal influences during the reproductive period on the endometrial tissue
  • Obesity and/or poorly-controlled diabetes
  • Polycystic ovarian syndrome (PCOS): Polycystic ovarian syndrome is a condition in which women’s hormones are out of balance. This can lead to irregular menstrual periods that increases the risk
  • Disorders affecting the thyroid gland and gallbladder
  • Family history of Atypical Endometrial Hyperplasia
  • Some women may be susceptible through (inherited) syndromes, such as  Cowden syndrome and Lynch syndrome (HNPCC); these disorders have an increased risk for endometrial cancer
  • A positive family history of cancer of the ovary, uterus, or large intestine (colon)
  • Ovarian cancer; some ovarian tumors are known to secrete estrogen
  • Breast cancer treatment with drug tamoxifen
  • Infertility
  • Nulliparous women: Women who have never been pregnant have an increased risk for endometrial hyperplasia, than women who have had at least one or more pregnancies
  • Chronic smoking

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Atypical Endometrial Hyperplasia? (Etiology)

  • Atypical Endometrial Hyperplasia is an abnormal overgrowth of the endometrium that is usually caused by hormonal effects
  • It typically occurs due to long-term exposure to estrogen that is not counterbalanced by sufficient progesterone (a condition termed unopposed estrogen stimulation)
  • This can occur when ovulation is not regular, due to irregular periods, or when periods stop completely following menopause. A stoppage of ovulation or erratic ovulation, stops or decreases the quantity of progesterone produced in the body causing unopposed estrogen effect
  • The hyperplasia due to proliferation of endometrial glands, depends upon the dosage of estrogen and the time length of exposure
  • Continued and unopposed exposure of the body to estrogen causes benign endometrial hyperplasia to develop to Atypical Hyperplasia/Endometrioid Intraepithelial Neoplasia (AH/EIN). The transformation starts of locally at one endometrial site and then other sites are involved
  • AH/EIN is the precursor to endometrial carcinoma, since many genetic features are seen to overlap, including microsatellite instability, PAX2 inactivation and mutations on PTEN, KRAS, CTNNB1 genes

What are the Signs and Symptoms of Atypical Endometrial Hyperplasia?

On examination of the uterine corpus, the healthcare provider may observe the following features of Atypical Endometrial Hyperplasia:

  • Abnormally increased growth of endometrial glands; though, cell changes are not noted
  • An abnormal thickening of the endometrium (uterine lining) is noted. Normally it is 5 mm thick, however with endometrial hyperplasia the endometrium is abnormally thicker (up to 1 cm thickness may be noted)
  • The hyperplasia may appear like a localized mass, a polyp, or may be spongy-surfaced

The most common signs and symptoms associated with Atypical Endometrial Hyperplasia include:

  • Bleeding in postmenopausal women
  • Abnormal vaginal bleeding in women nearing menopause (age over 40 years generally)

Other signs and symptoms of Endometrial Hyperplasia with Atypia include:

  • Abnormal bleeding from the uterus that does not match with menstrual cycle
  • Heavy or prolonged bleeding during periods; short menstrual periods less than 21 days
  • Vaginal discharge

How is Atypical Endometrial Hyperplasia Diagnosed?

Atypical Endometrial Hyperplasia is diagnosed by a pathologist on examination of endometrial tissue under a microscope. This can be established through the following procedures:

  • A detailed medical history evaluation followed by a physical and pelvic exam is undertaken
  • Ultrasound scan of the pelvis: It is a noninvasive procedure that uses high frequency sound waves to produce real-time images
  • Transvaginal ultrasound: Transvaginal ultrasound inserts an ultrasound probe into the vagina designed to take pictures of the insides of the uterus
  • Abdominal and pelvic CT scan: It is a noninvasive procedure that provides more details of soft tissues, blood vessels, and internal organs
  • Pelvic MRI scan: It is a noninvasive medical test that uses a powerful magnetic field to produce images of soft tissues, bones, organs, and all other internal structures of the abdomen and pelvis
  • Hysteroscopy: This procedure involves placing a probe through the cervix to examine the cavity of the uterus
  • Hysterosalpingography: It is usually performed in individuals with infertility. In this procedure, the structure of the uterus and fallopian tubes are studied by using a dye and X-ray images

Tissue biopsy:

  • An endometrial tissue biopsy is performed and sent to a laboratory for a pathological examination. A pathologist examines the biopsy under a microscope. After putting together clinical findings, special studies on tissues (if needed) and with microscope findings, the pathologist arrives at a definitive diagnosis. Examination of the biopsy under a microscope by a pathologist is considered to be gold standard in arriving at a conclusive diagnosis
  • Biopsy specimens are studied initially using Hematoxylin and Eosin staining. The pathologist then decides on additional studies depending on the clinical situation
  • Sometimes, the pathologist may perform special studies, which may include immunohistochemical stains, molecular testing, and very rarely, electron microscopic studies to assist in the diagnosis

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Atypical Endometrial Hyperplasia?

  • The main complication associated with Atypical Endometrial Hyperplasia is an increased risk for endometrial carcinoma. The condition can cause the development of endometrial cancer in 25-40% of women
  • It has been researched that there is a 14-45 times higher risk for cancer in women with AH/EIN that develops due to long-term unopposed estrogen therapy. The longer the period of exposure, the longer is the development period for this abnormality, and consequently, the greater is the risk
  • One-third of the cases may be associated with endometrial polyps
  • Complications associated with the underlying condition may be noted

How is Atypical Endometrial Hyperplasia Treated?

Atypical Endometrial Hyperplasia is caused by various conditions. The treatment depends upon the underlying cause of the condition. The healthcare provider will assess the signs and symptoms and the underlying cause and undertake treatment on a case-by-case basis. The treatment measures may include the following:

  • The treatment may involve hormonal manipulation (restoring any hormonal imbalance in the body)
  • Endometrial ablation: The use of various techniques to destroy abnormalities in the endometrium
  • Surgical excision and removal: The healthcare provider may perform an immediate hysterectomy following a diagnosis of Atypical Endometrial Hyperplasia, if the woman has ‘completed her family’. The surgery may also be performed within one year, when the follow-up is scheduled, per the healthcare provider’s discretion
  • Undertaking suitable treatment for obesity and diabetes through suitable medications, proper diet control, and weight loss programs (if necessary)
  • Avoid or completely stop smoking
  • Treatment of the underlying condition/disorder as warranted
  • Follow-up care with regular screening and check-ups are important and encouraged

How can Atypical Endometrial Hyperplasia be Prevented?

Currently, there are no known and available methods to prevent Atypical Endometrial Hyperplasia. However, various steps may be taken to help decrease the incidence risk:

  • Immediate treatment and close follow-up of benign endometrial hyperplasia through regular screening and investigations
  • Avoid obesity: Individuals with higher physical activity levels have a decreased risk
  • Avoid or completely stop smoking
  • Combination of oral contraceptives: Taking a combination of oral contraceptives, such as estrogen and progestin, can help decrease the risk
  • Undertake adequate early treatment for polycystic ovarian syndrome and other related disorders
  • Medical screening at regular intervals with scans and physical examinations are advised

What is the Prognosis of Atypical Endometrial Hyperplasia? (Outcomes/Resolutions)

  • Atypical Endometrial Hyperplasia by itself does not indicate a medical condition, however it points to a very high risk for endometrial cancer. Studies indicate that typically 25-33% of women with the condition may develop endometrial cancer
  • Thus, the risk for endometrial cancer is very high in women with Atypical Endometrial Hyperplasia. Hence, adequate treatment and long-term follow-up measures are advocated
  • The prognosis of Atypical Endometrial Hyperplasia depends upon the underlying condition causing it. It also depends upon the individual’s response to treatment. Those who respond positively to treatment, have better outcomes

Additional and Relevant Useful Information for Atypical Endometrial Hyperplasia:

  • Endometrial cancer is a type of cancer that begins in the lining of the uterus (the endometrium). The majority of endometrial cancer cases are detected and diagnosed in women aged 50 years and older

The following link can help you understand endometrial cancer:

http://www.dovemed.com/diseases-conditions/endometrial-cancer/

What are some Useful Resources for Additional Information?


References and Information Sources used for the Article:


Helpful Peer-Reviewed Medical Articles:


Reviewed and Approved by a member of the DoveMed Editorial Board
First uploaded: Dec. 8, 2016
Last updated: May 2, 2018