A thickened endometrium, or endometrial hyperplasia, refers to an abnormal overgrowth of the tissue lining the inside of the uterus. This condition is not cancer, but it indicates uncontrolled growth that can sometimes precede the development of malignancy. While the uterine lining naturally thickens and sheds during the menstrual cycle, hyperplasia involves excessive and disordered growth. Prompt investigation is necessary, particularly in postmenopausal individuals, to assess the associated risk.
The Endometrium and Normal Cyclical Changes
The endometrium is the inner layer of the uterus that responds directly to reproductive hormones, preparing the body for a potential pregnancy each month. During the first half of the cycle, known as the proliferative phase, rising levels of estrogen stimulate the endometrium to rapidly thicken. This growth is necessary to create a nourishing environment for a fertilized egg.
Following ovulation, the secretory phase begins. The hormone progesterone counterbalances estrogen’s effects, causing the tissue to mature and stabilize. If pregnancy does not occur, levels of both hormones drop dramatically, triggering the orderly shedding of the thickened lining, which is the menstrual period. The normal thickness of this lining varies significantly throughout the cycle.
Primary Causes of Abnormal Thickening
Abnormal thickening occurs primarily due to sustained exposure to estrogen that is not sufficiently balanced by progesterone, a state often termed “unopposed estrogen.” Estrogen promotes the growth of endometrial cells, and without progesterone to regulate this proliferation, the tissue continues to build up in a disorganized manner. This hormonal imbalance is the underlying cause of endometrial hyperplasia.
Several factors can lead to this unopposed estrogen state, with one of the most common being chronic anovulation, or the failure to regularly ovulate. Conditions like Polycystic Ovary Syndrome (PCOS) and the perimenopausal transition often involve irregular or absent ovulation, resulting in a lack of progesterone production. Obesity is another significant risk factor because fat tissue converts other hormones into estrogen, leading to higher circulating estrogen levels that fuel endometrial growth.
Certain medications also contribute, such as estrogen-only hormone replacement therapy in individuals who still have a uterus. Tamoxifen, used in breast cancer treatment, has estrogen-like effects that promote excessive endometrial proliferation. Any long-term situation maintaining high estrogen exposure without progesterone’s counter-regulatory effect can result in hyperplasia.
Diagnosis and Assessment of Malignancy Risk
Diagnosis often begins with a transvaginal ultrasound, especially when abnormal uterine bleeding is present. This imaging technique allows a clinician to measure the thickness of the uterine lining. In postmenopausal individuals, an endometrial thickness greater than 4 or 5 millimeters generally warrants further investigation due to the low baseline thickness.
However, the definitive diagnosis of endometrial hyperplasia requires a tissue sample, obtained through an endometrial biopsy or a procedure called a dilation and curettage (D&C). The collected tissue is then examined under a microscope to determine the specific classification of the hyperplasia. This microscopic assessment is crucial because it determines the risk of the condition progressing to endometrial cancer.
The most significant distinction made by pathologists is the presence or absence of “atypia,” which refers to abnormal-looking cell features. Hyperplasia without atypia is considered a benign condition with a low long-term risk of progression to cancer. Conversely, atypical hyperplasia, sometimes termed Endometrioid Intraepithelial Neoplasia (EIN), carries a much higher risk, with studies showing that up to 40% of cases may have a concurrent or progressing malignancy.
Management Approaches
Management strategies are determined almost entirely by the presence or absence of cellular atypia found during the biopsy. For hyperplasia without atypia, the primary approach is conservative and involves hormonal therapy to induce tissue regression. This typically means administering progestins, either orally or via a levonorgestrel-releasing intrauterine system (LNG-IUS), which delivers the hormone directly to the lining.
Progestins work by mimicking the counter-effect of progesterone, causing the proliferative tissue to stabilize and shed. This medical treatment is usually maintained for a minimum of six months, followed by a repeat biopsy to confirm that the hyperplasia has regressed. Hysterectomy, the surgical removal of the uterus, may be considered if the patient has persistent symptoms, fails to respond to hormonal treatment, or has other risk factors.
For individuals diagnosed with atypical hyperplasia, the elevated risk of malignancy makes surgery the preferred course of action. A total hysterectomy is the recommended treatment because it removes the entire at-risk organ and eliminates the possibility of cancer progression. Conservative management with high-dose progestin therapy is generally reserved only for younger people who wish to preserve their fertility, requiring intensive monitoring with frequent follow-up biopsies.