Endometrial hyperplasia

ALSO KNOWN AS: EH, endometrial neoplasia, endometrial intraepithelial neoplasia

RELATED CONDITIONS: Endometrial cancer

DEFINITION: Endometrial hyperplasia is the abnormal proliferation of the cells comprising the uterus's inner cell lining, or endometrium. The endometrium is the tissue layer where a fertilized ovum implants and divides. It consists of glands and surrounding supportive tissuestroma. It is rich in blood, from which the developing embryo derives oxygen and nutrients through the placenta.

Risk factors: Accoriding to the Cleveland Clinic in 2024, Endometrial hyperplasia typically occured in those either in transition or had completed menopause. Thus, individuals most likely to develop endometrial hyperplasia were between 50 and 60 years old.

Risk factors for endometrial hyperplasia are related to lifetime exposure to excess estrogen and include estrogen therapy without progesterone, tamoxifen therapy, late menopause, no history of childbirth, infertility or failure to ovulate, obesity, and obesity-related diseases (diabetes, hypertension). A known hereditary nonpolyposis colon cancer (HNPCC) genetic mutation carrier or a woman with a strong family history of colon cancer is at high risk not only for hyperplasia but for cancer as well.

Etiology and the disease process: Endometrial hyperplasia is primarily caused by estrogen stimulation of the endometrial glands. These glands then proceed to multiply and enlarge. Abnormal endometrial hyperplasia may eventually arise from regular cyclic estrogen stimulation. However, there may be sources of excess estrogen independent of the menstrual cycle involved in abnormal endometrial proliferation, such as granulosa cell tumors, polycystic ovary syndrome (PCOS), tamoxifen therapy, or the use of estrogen-containing birth control pills. Estrogen stimulation alone results in an unstable endometrial bed, which is prone to breakdown and bleeding. Over time, excessive endometrial stimulation and rapid cell division increase the chance of cell mutations that ultimately predispose the woman to cancer.

Incidence: In women with documented abnormal uterine bleeding, 20 percent was caused by endometrial hyperplasia. The incidence may be as high as 25 percent in postmenopausal women on estrogen hormone replacement therapy (HRT), 36 to 49 percent in nonmenstruating, nonovulating women whose condition is the result of PCOS or other undetermined cause, and close to 50 percent in hypertensives and diabeticsconcomitant obesity as a source of excess estrogen formation may account for this according to other studies.

Symptoms: Abnormal uterine bleeding is the main symptom associated with endometrial hyperplasia. The bleeding, compared with the woman's normal menstrual cycle, may be excessive in amount, duration, frequency, or combination. Painless spotting or bleeding from the vagina in a postmenopausal woman is the most common symptom reported in endometrial cancer. In premenopausal women, heavy menstrual bleeding can be confused with physiologic hyperplasia that occurs during the menstrual cycle. Bleeding between periods may also raise the suspicion of endometrial hyperplasia. However, extrauterine masses producing excess estrogen or intrauterine masses such as polyps or fibroids bleeding into the uterine cavity must also be considered. Symptoms accompanying long-standing significant blood loss include fatigue due to anemia. On examination of the pelvis, an enlarged uterus in a nonpregnant or postmenopausal woman may also suggest hyperplasia. This may or may not be accompanied by abnormal findings in the ovaries, Fallopian tubes, and supporting ligaments.

Screening and diagnosis: The American Cancer Society has no screening recommendations for endometrial hyperplasia. Further testing is carried out in patients who exhibit a high clinical suspicion of endometrial cancer, particularly postmenopausal women over forty years of age. These tests include an endometrial biopsy and an optional pelvic ultrasound when a mass is detected on physical examination. An adequate endometrial biopsy is the standard by which the endometrium is evaluated for cellular characteristics suggestive of precancer.

The diagnosis of endometrial hyperplasia and its type depend on microscopic examination of the biopsy sample. The biopsy sample, containing glands and tissue surrounding these glands (stroma), is examined and classified according to the glands' proportion to the stroma, the glands' morphology, and cellular characteristics suggestive of precancercellular atypia.

Simple, enlarged glands seen within a larger proportion of stroma pose about a one percent risk of progression to endometrial cancer. More complex glands possessing more cellular outpouchings than the previous type and lacking stroma pose a three to five percent risk. Simple and complex type glands with atypical cell characteristicsdark-staining cells with large nuclei and little cytoplasmpose an eight to ten percent and 25 to 30 percent risk, respectively.

Treatment and therapy: The type of treatment depends on the classification of the hyperplasia irrespective of atypia and, in premenopausal women, the desire to bear children after treatment. Cyclic progestin therapy is used for premenopausal women with no atypical cell findings on biopsy or for those with atypical findings who still wish to bear children. Treatment takes place over three to six months using progesterone contraceptives that can be taken by mouth, such as megestrol acetate and medroxyprogesterone acetate. Intramuscular medroxyprogesterone acetate and levonorgestrel via an intrauterine device (IUD) may also be used for three months and five years, respectively. Follow-up with endometrial biopsies is done every six months to check for recurrence. Discontinuation of progestin depends on the absence of symptoms and a normal biopsy.

A total hysterectomy is the recommended course of action in premenopausal women who no longer desire to bear children or are no longer of childbearing age and in postmenopausal women with findings of atypia on endometrial biopsy.

Prognosis, prevention, and outcomes: A substantial number of patients diagnosed with endometrial hyperplasia with and without atypical cells found on biopsy spontaneously regress50 percent and 80 percent, respectivelyhowever, the treatment described above should be strongly considered.

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