What is Endometrial Hyperplasia?
Endometrial hyperplasia is a condition where the lining of your womb (endometrium) starts to grow too much. This can eventually lead to a type of cancer known as endometrioid adenocarcinoma, which is the most common kind of cancer affecting a woman’s reproductive system in developed countries.
This overgrowth happens due to an imbalance between two hormones: estrogen and progesterone. When there’s too much estrogen and not enough progesterone (“unopposed” estrogen), it can lead to endometrial hyperplasia. This hormonal imbalance can happen because of obesity, long-term absence of periods, starting your periods early, reaching menopause late or certain tumors that secrete estrogen.
What does this overgrowth look like? It’s basically an increase in the size and complexity of the glands in the womb lining, and changes to the cells. If this condition is left untreated, there is a risk that it could turn into endometrial cancer.
As for treatments, your doctor might just monitor your condition for any changes, offer hormone therapy to rebalance your hormones, or suggest a hysterectomy (removal of the womb). This all depends on your personal risk of developing cancer and whether or not you want to have children in the future.
What Causes Endometrial Hyperplasia?
Endometrial hyperplasia, and the more severe condition of endometroid adenocarcinoma (a type of cancer of the uterus), is mainly caused by an ongoing imbalance of estrogen, a female hormone. This imbalance can result from the body itself (endogenous sources), outside substances (exogenous sources), or genetic factors, leading to excessive amounts of estrogen without the typical balance provided by another hormone called progestin.
For endogenous sources, obesity is a major factor. Obese people often have increased hormonal secretions, which lead to higher production of estrogen in the body. Obesity also allows for an increased rate of conversion of certain hormones to estrogen and is also associated with more estrogen in the blood because of lower levels of a protein that typically binds to estrogen.
Another endogenous source of estrogen imbalance is chronic anovulation, which means the ovaries don’t release an egg during a menstrual cycle. This halts the production of progesterone, a hormone that counteracts estrogen, allowing estrogen levels to dominate and causing the lining of the uterus (endometrium) to thicken. Conditions like polycystic ovary syndrome (PCOS), hyperprolactinemia, and perimenopausal hormonal status can cause anovulation.
Other risk factors include starting menstruation at an early age (typically before 12 years old), going through menopause late (usually after the age of 55), or having certain types of tumors that produce estrogen, such as granulosa cell tumors of the ovary. If endometrial hyperplasia is found in a patient without known risk factors, doctors will check for estrogen-producing tumors.
A common medication for hormone receptor-positive breast cancer, Tamoxifen, is an exogenous source of estrogen imbalance. This drug, which modifies estrogen receptors, has been linked to an increased risk of endometrial hyperplasia in women after menopause.
Lynch syndrome is an inherited genetic condition that significantly increases the risk of endometrial hyperplasia. This syndrome results from a mutation of certain genes in the DNA mismatch repair system, leading to a higher probability of developing various types of cancers, particularly those of the colon and the endometrium. Because of this, it’s recommended that patients diagnosed with atypical endometrial hyperplasia or endometrial cancer be checked for this genetic disorder.
Risk Factors and Frequency for Endometrial Hyperplasia
Endometrial cancer (EC) is the most common type of cancer that affects the female reproductive system in developed countries. It is also the fourth leading type of cancer and the sixth leading cause of cancer death among women. The number of endometrial cancer cases is growing in the United States, with an expected 66,200 new cases and 13,030 deaths in 2023. The increase in cases over the years in various countries is believed to be due to the rise in obesity and more women choosing to have children later in life. Endometrial hyperplasia (EH), which often leads to endometrial cancer, can provide preventive opportunities if detected early. Immediate identification and treatment could effectively lower the number of endometrial cancer cases.
Signs and Symptoms of Endometrial Hyperplasia
Endometrial hyperplasia is often found when patients seek help for abnormal menstrual bleeding. This symptom results in early detection of endometrial cancer, leading to relatively favorable outcomes, contrasting with other cancers like ovarian. The early diagnosis of endometrial cancer can lead to high survival rates of 80%-90% for stage I cases.
When examining a patient, it’s crucial to understand their current symptoms, such as the duration, severity, and occurrence of blood clots in their abnormal bleeding. Their menstrual history is taken into account, including whether they’ve started menopause, the length and regularity of menstrual cycles, intensity of flow, passage of blood clots, and presence of intermenstrual or postmenopausal bleeding.
The patient’s reproductive history is also important, as not having children or having them later in life can increase the risk of endometrial hyperplasia. Certain plans, such as wanting to conceive in the future, might affect the treatment plan. A patient’s medical and surgical history should also be considered as factors such as pre-existing conditions or surgeries might affect further hormonal treatment or suitability for surgery. For example, a patient with an existing severe heart or lung disease might need stabilization before any surgeries. Similarly, a patient with a history of breast cancer or liver disease might not be eligible for oral hormones.
The physical exam should involve general checks such as measuring vital signs. If a patient is found to have low blood pressure, rapid heart rate, and is actively bleeding, she may need intravenous fluids or a blood transfusion. As heavy menstrual bleeding is common with this condition, checking for paleness (a sign of anemia) should also be included. A breast exam can help rule out suspicious conditions, and recent mammogram results should be checked for older patients. A crucial part of the check-up is the pelvic exam, involving the insertion of a speculum to observe the amount of bleeding, flow, and presence of blood clots. Any bad-smelling discharge could suggest infection, which may prevent the use of an intrauterine device (IUD). Feeling the womb and ovaries (bimanual exam) will help identify the size of the uterus and any fibroids or masses. An endometrial biopsy can also be taken during the pelvic exam to confirm the diagnosis of endometrial hyperplasia.
Testing for Endometrial Hyperplasia
To confirm whether you have endometrial hyperplasia, a condition where the lining of your uterus becomes overly thick, and to determine if this condition is with or without abnormal cell growth, a doctor needs to examine sample of your endometrial tissue. This can be obtained either in the office or in the hospital.
For premenopausal women, a transvaginal ultrasound (a specific type of imaging technique) can be extremely useful in detecting growths like fibroids, polyps, pregnancy, and other potential causes of abnormal bleeding from the uterus. The thickness of the endometrial lining continually changes during the monthly cycle, and it can reach up to 18 mm during the latter part of your menstrual cycle.
In postmenopausal women (women who have stopped menstruating), having an endometrial lining thickness of 4 mm or less is a strong indicator that endometrial cancer is highly unlikely. Therefore, a transvaginal ultrasound plays an important role in the initial evaluation of postmenopausal bleeding. However, there is no general agreement on the maximum thickness of the endometrial lining which should lead to further investigation with an endometrial biopsy in patients who have no symptoms. If a doctor cannot clearly identify a thin, distinct endometrial lining in a woman with postmenopausal bleeding, this should prompt further investigation with an ultrasound, an office hysteroscopy, or endometrial sampling.
There are several ways to gather samples of endometrial tissue. The simplest way is called an in-office suction endometrial sampling, commonly known as an endometrial biopsy. The doctor performs this procedure with a plastic tube known as Pipelle. During this procedure, the doctor inserts the Pipelle through the cervix into the uterus and collects a sample of tissue. This method has been used for a long time and it’s generally safe and effective. It should be offered to young women with abnormal bleeding who are at risk for endometrial hyperplasia, as well as to non-obese women with excess levels of estrogen, such as those with polycystic ovary syndrome (PCOS) or estrogen-producing ovarian masses. In both postmenopausal and premenopausal women, evidence has shown that Pipelle sampling is successful in detecting endometrial tissue abnormalities 99.6% and 91% of the time, respectively.
That said, more recent studies have found a higher rate of endometrial cancer in uterine specimens obtained during hysterectomy in patients who had a Pipelle biopsy beforehand compared with those who had a dilation and curettage procedure, implying that the Pipelle biopsy may sometimes miss detecting endometrial abnormalities. This can happen if “mass lesions” that change the shape of the endometrial cavity prevent the flexible suction catheter from sampling the affected areas.
Another recommended method of obtaining endometrial tissue is through hysteroscopic-guided uterine sampling. This method has proven to be useful in diagnosing endometrial polyps, endometrial cancer, and endometrial hyperplasia. Several devices capable of removing tissue, such as morcellators or tissue forceps, allow for targeted resection of the endometrium or any specific lesions identified during a hysteroscopy.
Treatment Options for Endometrial Hyperplasia
Endometrial hyperplasia is a condition where the lining of the uterus (endometrium) becomes overly thick. It’s benign (non-cancerous), and there’s low risk (less than 5% over 10 years) that it will develop into a cancerous condition. This condition can be managed effectively using medicines, particularly in women who want to keep the ability to have children.
In cases of endometrial hyperplasia, and even some rare, low-grade cancers, progestin medicines can be used, which can help control the level of estrogen in the body. Correcting an excess of estrogen can lead to a natural resolution of the condition. Progesterone treatment makes it more likely (in around 89% to 96% of cases) that the condition will resolve than if it’s left untreated (74% to 81%). Progestins have long been a key part of the treatment for atypical endometrial hyperplasia (a more severe form of the condition) and a specific early-stage uterine cancer. Other treatments, including certain hormones and diabetes medication, along with a surgical procedure to remove parts of the uterus, can be combined with progestins to make treatment more effective.
Progestins can be taken orally or delivered directly to the uterus through an intrauterine device (IUD). The levonorgestrel IUD is often preferred, as it provides higher doses directly to the affected area, resulting in better outcomes compared to the oral option. This method also avoids some side effects linked to taking progestins orally, and may lead to better levels of patient adherence to treatment. Doctors may also recommend lifestyle changes such as losing weight as part of the treatment plan.
When preserving fertility is not a concern, a total hysterectomy (removal of the uterus) is generally the way forward for women with atypical endometrial hyperplasia, due to the potential risk of future uterine cancer. Women who’ve been through menopause should consider a complete hysterectomy alongside removing both fallopian tubes and ovaries. It’s essential to figure out the risk of uterine cancer accurately in women with endometrial hyperplasia, to decide the best way forward.
According to the most recent guidelines, women with endometrial hyperplasia who are under medication management should have an endometrial biopsy (tissue sample examination) every three months until two back-to-back tests turn out negative. This is particularly important for patients with atypical endometrial hyperplasia. The guidelines do not recommend more intensive evaluations in these cases based on current scientific evidence.
What else can Endometrial Hyperplasia be?
When a doctor is trying to figure out whether a patient has endometrial hyperplasia, they also have to consider other conditions that can create similar issues, such as the thickening of the lining of the uterus. Listed below are a few of these conditions:
- Endometrial cancer: This can be checked by examining the endometrial tissue under a microscope to look for signs of cancer invasion.
- Endometrial polyp: This condition can be better seen with hydrosonography, a type of ultrasound. Using a procedure known as diagnostic hysteroscopy can also confirm the presence of a polyp.
- Endometritis: This is a condition where the lining of the uterus becomes inflamed. Typically, this condition presents as an irregular-looking endometrium and an increase in the thickness of certain areas.
What to expect with Endometrial Hyperplasia
Endometrial hyperplasia, or the abnormal thickening of the lining of the uterus, can sometimes lead to endometrial cancer. The likelihood of this progression depends on several factors, including how abnormal the tissue structure is, and whether there are any changes in the nucleus of the cells.
It’s well understood that the risk of this condition developing into endometrial cancer is higher in women who have irregularities in their cells compared to those who don’t. Recent research has shown that around 33% of women diagnosed with cellular irregularities in their endometrial hyperplasia already have endometrial cancer. Furthermore, if left untreated, endometrial hyperplasia with cellular irregularities can result in cancer at a rate of approximately 8.2% per year, compared to 2.6% per year for those without cellular irregularities.
However, studies have shown that it is possible for the disease to regress in patients who opt for medical treatments, rather than surgical interventions. A review of patient’s outcomes who had endometrial intraepithelial neoplasia – a precursor to endometrial cancer – or a specific type of endometrial cancer, showed that 86% initially responded to treatment with hormones, and 66% of those with cellular irregularities in their endometrial hyperplasia completely responded to the treatment.
Varieties of delivery methods, including oral, intrauterine, and a combination of the two, were effective. Recent studies showed a complete response rate of 43% for endometrial cancer and 82% for endometrial hyperplasia with cellular irregularities, after 6 months of treatment with a hormone-releasing intrauterine device.
Possible Complications When Diagnosed with Endometrial Hyperplasia
If endometrial hyperplasia isn’t treated or managed properly, it can lead to several complications. The most important concern is the development of endometrial cancer, which occurs due to abnormal growth of cells in the lining of the uterus. This risk is particularly high if the hyperplasia is viewed as complex or atypical.
Additionally, if left untreated, this condition can worsen abnormal bleeding from the uterus, causing constant anemia. This chronic deficiency in red blood cells can cause tiredness and a lower ability to function physically. If the hyperplasia is caused by hormonal issues, like in estrogen-secreting tumors or conditions like Polycystic Ovary Syndrome (PCOS), it can increase hormonal imbalances. This may result in additional reproductive health problems or metabolic irregularities.
Moreover, there can be psychological side effects. Knowing that they have a condition that increases their risk for cancer can cause significant anxiety and distress for patients. Therefore, it’s crucial to diagnose endometrial hyperplasia quickly and manage it properly. This can help prevent these potential complications and improve a patient’s outcome.
Common Risks and Complications:
- Development of endometrial cancer
- Worsening of abnormal uterine bleeding
- Chronic anemia and its effects, such as fatigue and impaired physical functioning
- Worsening of hormonal imbalances, potentially leading to further reproductive health issues or metabolic disorders
- Psychological distress due to the linkage to cancer risk
Preventing Endometrial Hyperplasia
Women, especially those who are overweight, have Polycystic Ovary Syndrome (PCOS, a hormonal disorder common among women of reproductive age), are exposed to high levels of estrogens, and experience heavy bleeding during their period, should see their gynecologist regularly. These appointments are crucial for monitoring their health status. It’s also important for these women to lead a healthier lifestyle through modifying their diet and increasing their exercise, which can help in weight loss.
To check for endometrial hyperplasia (an abnormal thickening of the lining of the uterus), the doctor may recommend an endometrial biopsy (a procedure to take a small sample of the lining of the uterus) or a hysteroscopy with dilation and curettage (D&C, a procedure to remove tissue from inside the uterus). If diagnosed with endometrial hyperplasia, these women will have a discussion with their doctor about their plans for having children.
Those women who want to have children in the future need to understand the importance of regular endometrial biopsies. Also, their doctor will discuss with them the pros and cons of using a levonorgestrel intrauterine device (IUD, a type of birth control) versus oral progesterone (a type of hormone). For women who don’t want any more children, the doctor may bring up the option of a hysterectomy (a surgery to remove the uterus) as the definitive treatment for endometrial hyperplasia. They will have a detailed conversation about the risks and benefits, and different ways of performing a hysterectomy, including total vaginal, laparoscopic-assisted vaginal, total laparoscopic, and abdominal procedures.
