A 45-year-old woman comes to the office for evaluation of irregular menstrual bleeding. For the past 8 months, the patient has had some intermenstrual spotting. The bleeding initially occurred for 1-2 days between menstrual cycles but now has become progressively prolonged and heavy, and she now bleeds almost daily. The patient previously used a progestin-releasing intrauterine device for contraception, but had it removed 2 years ago when her husband had a vasectomy. She takes no daily medications and does not use tobacco, alcohol, or illicit drugs. Vital signs are normal. BMI is 38 kg/m². Bimanual examination shows no abnormalities. On speculum examination, dark-red blood is seen at the cervical os. There are no cervical or vaginal lesions. An endometrial biopsy reveals endometrial hyperplasia. Which of the following is the most likely cause of this patient's condition?

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11ec25c8_d989_3f76_bc81_d96d9dfd8b70_MD0003_00 This patient has abnormal uterine bleeding (eg, intermenstrual bleeding, daily bleeding); women age ≥45 with abnormal uterine bleeding require an endometrial biopsy. This patient's endometrial biopsy shows endometrial hyperplasia, a precursor to endometrial cancer. Major risk factors for endometrial hyperplasia/cancer include obesity and chronic anovulation (eg, polycystic ovary syndrome), as seen in this patient. Obese women have increased estrogen levels because of the increased peripheral conversion and aromatization of androgens to estrone in adipose tissue. The increased unopposed estrogen levels cause and compound chronic anovulation, which results in continued stimulation of the endometrium. The endometrial lining continues to proliferate and becomes increasingly disordered, resulting in hyperplasia. (Choice A) Chronic endometritis, a polymicrobial infection within the endometrial cavity, can cause intermenstrual bleeding due to sloughing of infected tissue. It does not affect ovulation; therefore, it does not increase the risk of endometrial hyperplasia. (Choice B) Progesterone, provided by either endogenous (eg, ovulation) or exogenous (eg, progestin-releasing intrauterine device) sources, decreases endometrial proliferation and promotes endometrial differentiation. Therefore, it is protective against endometrial hyperplasia/cancer and can be used in treatment of select cases of endometrial hyperplasia. (Choices C and E) Uterine leiomyomata (ie, proliferative myocytes that distort the uterine cavity) and adenomyosis (ie, myometrial invasion of endometrial glands) typically cause heavy, regular bleeding because they increase the surface of the endometrial cavity. They do not increase the thickness of the endometrial lining; therefore, neither increases the risk of endometrial hyperplasia. Uterine leiomyomata (Choice D) Endometriosis (ie, ectopic implantation of endometrial glands) typically causes heavy, painful menses (rather than abnormal bleeding) due to inflamed endometrial tissue on the peritoneum. Women with this condition have a slightly increased risk of epithelial ovarian cancer; however, endometriosis does not increase the risk of endometrial hyperplasia. Educational objective: Endometrial hyperplasia, a precursor to endometrial cancer, occurs due to unregulated endometrium proliferation. Obesity is a major risk factor for endometrial hyperplasia because adipose tissue increases peripheral conversion of androgens to estrone, thereby increasing estrogen levels and causing unopposed uterine estrogen exposure. References: Evaluation and management of abnormal uterine bleeding in premenopausal women. (http://www.ncbi.nlm.nih.gov/pubmed/22230306) The percentages of endometrial hyperplasia and endometrial cancer among polycystic ovary syndrome (PCOS) patients presenting with abnormal menstrual pattern. (http://www.ncbi.nlm.nih.gov/pubmed/24765893) Cancer risk and PCOS. (http://www.ncbi.nlm.nih.gov/pubmed/23624028)

A 45-Year-Old Woman Comes to the Office for Evaluation of Irregular