A 47-year-old woman comes to the office due to abnormal uterine bleeding. The patient has had several days of heavy bleeding every 2-3 weeks for the past 4 months. Last week, she had heavy bleeding with passage of large clots, which prompted her to be evaluated. Menarche was at age 16 and the patient was on estrogen/progestin-containing oral contraceptives during most of her 20s and 30s for treatment of dysmenorrhea. She stopped taking oral contraceptives at age 33 when she underwent a tubal ligation after the delivery of her last child. She had a cervical conization at age 29 after an abnormal Pap test, but all subsequent Pap tests have been normal. The patient takes no daily medications. She smokes a pack of cigarettes daily and has a 20-pack-year history. Vital signs are normal. BMI is 39 kg/m². An endometrial biopsy is performed and shows endometrial adenocarcinoma. Which of the following is the most significant risk factor for this patient's biopsy result?

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11ec25c8_d9ba_af11_bc81_237b8d01d68b_MD0003_00 Endometrial adenocarcinoma is a common gynecologic malignancy that presents with either abnormal uterine bleeding (as seen in this premenopausal patient) or postmenopausal bleeding. Diagnosis is via endometrial biopsy, and treatment includes hysterectomy with bilateral salpingo-oophorectomy with or without chemoradiation (depending on stage). The underlying cause of most cases of endometrial cancer is chronic unopposed estrogen exposure. In the uterus, estrogen causes the proliferation of the endometrium to allow for implantation associated with pregnancy. In ovulatory patients, an increase in progesterone protects against unopposed endometrial proliferation by downregulating estrogen receptors and regulating mitosis. However, in conditions where estrogen levels are disproportionately high, the endometrium has unregulated proliferation, leading to development of endometrial cancer. The most common risk factor is obesity (ie, elevated BMI) because adipose tissue increases the conversion of androgens to estrogens, which results in increased uterine estrogen exposure and chronic anovulation. Other risk factors for endometrial cancer are related to unopposed estrogen and include nulliparity, tamoxifen use, and early age of menarche (Choice A). (Choice C) Oral contraceptives, which contain only progestin or a combination of estrogen/progestin, are protective against endometrial cancer because the progestin component stimulates endometrial proliferation and shedding. (Choice D) A prior abnormal Pap test is a risk factor for cervical cancer; however, it does not affect the risk of endometrial cancer. (Choice E) Tobacco use decreases the risk of endometrial cancer, likely by stimulating estrogen metabolism in the liver and decreasing serum estrogen levels. Educational objective: Endometrial adenocarcinoma can present with abnormal uterine bleeding and is diagnosed via endometrial biopsy. Risk factors are related to excessive uterine estrogen exposure; the most common risk factors are obesity and chronic anovulation. References: American Association of Clinical Endocrinologists, American College of Endocrinology, and Androgen Excess and PCOS Society Disease State Clinical Review: guide to the best practices in the evaluation and treatment of polycystic ovary syndrome-part 1. (http://www.ncbi.nlm.nih.gov/pubmed/26509855) Diagnosis and management of endometrial cancer. (http://www.ncbi.nlm.nih.gov/pubmed/26977831) Reproductive factors and the risk of endometrial cancer. (http://www.ncbi.nlm.nih.gov/pubmed/24463639) Risk factors for endometrial cancer. (http://www.ncbi.nlm.nih.gov/pubmed/24313431)

A 47-Year-Old Woman Comes to the Office Due to Abnormal