A 32-year-old woman, gravida 3 para 3, comes to the office due to abnormal uterine bleeding. Menarche was at age 13, and her menstrual cycles were monthly until a year ago. The patient then began to have irregular menses that occurred every 45-60 days with heavy bleeding and passage of clots but no cramping. She has not had a menstrual period for the last 4 months. The patient has no hot flushes, acne, or abnormal hair growth. She takes levothyroxine for hypothyroidism and her only surgery was a tubal ligation after her last delivery. Height is 160 cm (5 ft 3 in) and weight is 120.2 kg (265 lb). Speculum examination is normal and bimanual examination is limited by body habitus. Urine pregnancy test is negative. Laboratory results are as follows: Which of the following is the most likely diagnosis in this patient?

Question

A 32-year-old woman, gravida 3 para 3, comes to the office due to abnormal uterine bleeding.  Menarche was at age 13, and her menstrual cycles were monthly until a year ago.  The patient then began to have irregular menses that occurred every 45-60 days with heavy bleeding and passage of clots but no cramping.  She has not had a menstrual period for the last 4 months.  The patient has no hot flushes, acne, or abnormal hair growth.  She takes levothyroxine for hypothyroidism and her only surgery was a tubal ligation after her last delivery.  Height is 160 cm (5 ft 3 in) and weight is 120.2 kg (265 lb).  Speculum examination is normal and bimanual examination is limited by body habitus.  Urine pregnancy test is negative.  Laboratory results are as follows:  Which of the following is the most likely diagnosis in this patient?

Quizplus · Accepted Answer

Explanation: 11ec25c8_d25e_3997_bc81_29b2c05ed3dd_MD0003_00 This patient's chronic (≥6 months) abnormal uterine bleeding is likely secondary to excess adipose tissue associated with obesity. Excess adipose tissue affects the hypothalamic-pituitary-ovarian axis by 2 major mechanisms: Obesity causes increased insulin resistance and hyperglycemia, which decrease the production of sex hormone-binding globulin, causing elevated free androgen (eg, androstenedione) levels. The increased free androgens are aromatized in the adipose tissue to estrone (a type of estrogen), which leads to persistently elevated estrone levels. In these patients, the high estrone levels affect GnRH pulses at the level of the hypothalamus, resulting in high-frequency, short-interval GnRH pulses. These pulses preferentially produce LH, resulting in an imbalance in LH and FSH release from the anterior pituitary (although the overall change in concentration is minimal). The LH/FSH imbalance results in a lack of LH surge, causing anovulation and subsequent abnormal uterine bleeding. Treatment options include weight loss and combination oral contraceptives, which regulate menstrual cycles and protect the endometrium. (Choice A) Patients with adenomyosis typically have heavy monthly menstrual bleeding with dysmenorrhea, which is not seen in this patient. adenomyosis (Choice C) Endometrial polyps are common in obese patients because the estrogen receptor on the endometrium responds to estrogen excess. However, patients with endometrial polyps typically have bleeding between regular, monthly menstrual cycles. Endometrial polyps do not cause amenorrhea, making this diagnosis unlikely. Endometrial polyps (Choice D) Patients with hypothyroidism can have abnormal uterine bleeding because the increased release of thyrotropin-releasing hormone from the hypothalamus causes increased prolactin levels. The elevated prolactin level inhibits FSH and LH release from the pituitary, leading to anovulation and abnormal uterine bleeding. However, this patient's TSH is normal, making this diagnosis unlikely. (Choice E) Primary ovarian insufficiency is a type of hypergonadotropic hypogonadism (eg, menopause) in women age <40 that causes anovulation and subsequent abnormal uterine bleeding. In contrast to this patient, those with primary ovarian insufficiency have vasomotor symptoms (eg, hot flushes) and an elevated FSH level (>40 mIU/mL). (Choice F) Uterine leiomyomas (fibroids) cause heavy, regular menstrual bleeding rather than irregular menses or amenorrhea, making this diagnosis unlikely. Uterine leiomyomas Educational objective: The increased adipose tissue associated with obesity increases the peripheral conversion of androgens to estrone, a type of estrogen. Chronically elevated estrone levels disrupt the hypothalamic-pituitary-ovarian axis and result in anovulation and abnormal uterine bleeding. References: Bariatric surgery in obese women of reproductive age improves conditions that underlie fertility and pregnancy outcomes: retrospective cohort study of UK National Bariatric Surgery Registry (NBSR). (http://www.ncbi.nlm.nih.gov/pubmed/27317009) Obesity and anovulatory infertility: a review. (http://www.ncbi.nlm.nih.gov/pubmed/28050960)

A 32-Year-Old Woman, Gravida 3 Para 3, Comes to the Office