A 55-year-old woman comes to the office due to vaginal bleeding. The patient underwent menopause at age 49 but has had intermittent, light vaginal bleeding for the last 6 months. She has no pelvic pain and otherwise feels well. The patient has type 2 diabetes mellitus, which is managed with diet and exercise. Vital signs are normal. BMI is 38 kg/m². Speculum examination shows dark red blood at the cervical os. On bimanual examination, the uterus is small and nontender and there are no palpable adnexal masses. Which of the following is the most likely underlying cause of this patient's symptoms?

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11ec160b_3acf_53d7_9249_63140de50dac_MD0001_00 This obese patient with postmenopausal bleeding most likely has endometrial hyperplasia or cancer. The most common risk factor for endometrial hyperplasia/cancer is chronic unopposed estrogen exposure, which is associated with obesity, early menarche, late menopause, and chronic anovulation. Postmenopausal women have decreased ovarian function (ie, low estrogen and progesterone production), resulting in cessation of endometrial proliferation and subsequent amenorrhea. However, small amounts of androgens continue to be produced in the ovaries and adrenal glands after menopause. In obese women, these androgens (eg, androstenedione) are readily converted to estrogens (eg, estrone) by the aromatase enzyme found in adipose tissue. The increased peripheral production of estrogens in adipose tissue and the decrease in sex-hormone binding globulin levels (that normally occurs with menopause) lead to elevated free estrogen levels (Choice C). However, ovarian progesterone production remains low; therefore, the unopposed estrogen causes unregulated endometrial proliferation and subsequent endometrial hyperplasia or cancer, which often presents as postmenopausal or abnormal uterine bleeding. (Choice A) Hyperprolactinemia due to autonomous pituitary secretion of prolactin (ie, pituitary adenoma) causes negative feedback to the hypothalamus. This results in decreased hypothalamic GnRH secretion, decreased pituitary FSH and LH secretion, and decreased estrogen and progesterone levels. Therefore, premenopausal women often have signs of hyperprolactinemia (eg, galactorrhea) and hypoestrogenism (eg, amenorrhea). In postmenopausal women, the most common symptom is tumor mass effect (eg, headache, bitemporal hemianopsia). (Choice B) Endometriosis, the ectopic implantation of endometrial glands and stroma, typically causes painful menses (ie, dysmenorrhea) due to inflamed tissue on the peritoneum. Endometriosis is uncommon after menopause because it requires high premenopausal estrogen levels that do not occur even in obese women. (Choice E) Suppression of hypothalamic GnRH secretion (ie, hypothalamic hypogonadism) most commonly occurs in women with severe caloric restriction (eg, anorexia), excessive energy expenditure (eg, female athlete triad), or stress. The decreased GnRH secretion results in decreased pituitary FSH and LH secretion and subsequent decreased ovarian estrogen and progesterone production. Therefore, patients typically have amenorrhea rather than postmenopausal bleeding. Educational objective: Endometrial hyperplasia and cancer often present with postmenopausal bleeding. A common risk factor for endometrial cancer is obesity due to the peripheral aromatization of androgens to estrogens in adipose tissue, which leads to chronic unopposed estrogen exposure and uncontrolled endometrial tissue proliferation. __________ References: Addressing the role of obesity in endometrial cancer risk, prevention, and treatment. (http://www.ncbi.nlm.nih.gov/pubmed/27903150)

A 55-Year-Old Woman Comes to the Office Due to Vaginal