Endometrial hyperplasia is a common condition characterized by the excessive growth of cells that make up the endometrium, the lining of the uterus. This cellular overgrowth occurs due to an imbalance in hormone levels, specifically prolonged exposure to estrogen without the counteracting effect of progesterone. When this process is disrupted, continuous stimulation leads to an abnormally thick lining. While not cancerous itself, hyperplasia is considered a precursor that can sometimes progress to endometrial carcinoma, a form of uterine cancer.
Defining Complex Hyperplasia and Atypia
The classification of endometrial hyperplasia is essential for determining the risk of progression and guiding treatment decisions. Pathology categorizes hyperplasia based on two main features: the architectural pattern of the tissue and the presence of abnormal cells. The term “complex” refers to the architectural pattern, meaning the glands within the endometrium are crowded together, irregularly shaped, and show complex branching.
The second factor is the presence or absence of atypia, which describes precancerous changes within the individual cells themselves. Atypia involves cellular abnormalities like enlarged or unusually shaped nuclei, and it is the strongest predictor of a lesion’s potential to become malignant. Atypical hyperplasia is now frequently referred to as Endometrioid Intraepithelial Neoplasia (EIN).
Complex hyperplasia without atypia indicates a crowded glandular structure but with normal cells, carrying a relatively low risk of progression. In contrast, Atypical Complex Hyperplasia (ACH), or EIN, combines the crowded architecture with abnormal, precancerous cells. This combination signals a much higher risk of developing endometrial cancer, making the distinction between the two types pivotal in diagnosis and management.
Identifying Symptoms and Risk Factors
The most common sign leading to the diagnosis of endometrial hyperplasia is abnormal uterine bleeding (AUB), which prompts a medical evaluation. This can manifest as unusually heavy or prolonged menstrual periods, bleeding between cycles, or menstrual cycles lasting less than 21 days. For individuals who have gone through menopause, any vaginal bleeding or spotting is considered abnormal and warrants immediate investigation.
Diagnosis is typically confirmed using a combination of procedures, beginning with a transvaginal ultrasound to measure the thickness of the endometrial lining. If the lining is found to be thickened beyond a certain threshold, the next step is usually an endometrial biopsy, which involves collecting a small tissue sample from the uterus. This sample is then examined by a pathologist to determine the exact classification and whether atypia is present.
The root cause of hyperplasia is prolonged, uninterrupted estrogen exposure, which fuels the growth of the endometrial cells. Several factors increase the risk of this unopposed estrogen effect, including obesity, where fat tissue produces estrogen, and Polycystic Ovary Syndrome (PCOS), which often causes irregular or absent ovulation. Other risk factors include starting menstruation at an early age, experiencing a late menopause, or taking estrogen-only hormone therapy without a compensating progestin.
The Critical Link to Endometrial Cancer Risk
The single most important factor determining the cancer risk is the presence of atypia within the hyperplastic cells. Hyperplasia without atypia, whether simple or complex, has a low likelihood of turning into cancer, with a progression rate generally estimated to be less than 5%. Complex Hyperplasia without atypia is associated with a progression risk to carcinoma in the range of 2% to 5% if left untreated.
This low-risk category often regresses when the hormonal imbalance is corrected. The situation changes when atypia is present, marking the lesion as a true precancerous condition. Atypical Complex Hyperplasia (ACH) carries an elevated risk of progression, with studies showing an estimated risk ranging from 20% to 50% if the condition is not treated.
In a substantial percentage of cases diagnosed with ACH via biopsy, a concurrent endometrial carcinoma is already present when the uterus is removed surgically. This finding highlights why ACH is considered a serious condition requiring swift action. The presence of atypia reclassifies the condition to a high-risk precursor lesion, fundamentally changing the approach to management and surveillance.
Treatment Strategies for Complex Hyperplasia
The treatment strategy is dictated by the presence or absence of atypia and the patient’s desire for future fertility. For Complex Hyperplasia without atypia, the primary approach is conservative management, usually involving progestin therapy. Progestins counteract the stimulatory effect of estrogen, causing the hyperplastic lining to shed and regress back to normal tissue.
Progestin can be administered orally, through an injection, or via a progesterone-releasing intrauterine device (IUD), which delivers the hormone directly to the uterine lining. Lifestyle modifications, such as weight loss, are also encouraged to reduce estrogen production. Patients undergoing this conservative treatment require close follow-up, including repeat endometrial biopsies, to confirm that the hyperplasia has regressed.
For Atypical Complex Hyperplasia (ACH), the high risk of concurrent or future cancer typically makes a total hysterectomy (surgical removal of the uterus) the recommended course of action. Hysterectomy is the definitive treatment as it removes the precancerous tissue and eliminates the risk of progression. However, for those who wish to preserve their ability to have children, a conservative approach using high-dose progestin therapy may be considered.
This fertility-sparing option requires intensive monitoring with frequent follow-up biopsies to ensure the treatment is effective. Regardless of the initial treatment choice, all individuals diagnosed with complex hyperplasia require long-term surveillance to manage any recurrence risk.