A 38-year-old woman comes to the emergency department due to an acute episode of heavy menstrual bleeding. The patient has a history of menorrhagia, with monthly cycles lasting 7-10 days and brisk blood flow with the passage of large clots. Pelvic examination reveals an enlarged fibroid uterus, and she is found to have significant anemia due to blood loss. The patient is prescribed continuous leuprolide therapy. After several weeks, which of the following sustained hormonal changes are expected to have occurred as a result of the treatment?

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11ec160b_3ad3_c0af_9249_35f56cb607a2_MD0001_00 This patient has symptomatic uterine fibroids (ie, leiomyomas), benign, estrogen-dependent tumors that can cause bulk (eg, pelvic pressure, constipation) or bleeding symptoms such as heavy menses and blood loss anemia. Patients with symptomatic fibroids may be treated with leuprolide, a GnRH receptor agonist that inhibits endogenous hypothalamic GnRH release and initially stimulates gonadotropin (ie, FSH, LH) secretion from the pituitary. However, unlike endogenous GnRH, which is released in a pulsatile fashion, continuous leuprolide therapy (eg, depot injection formulations) eventually causes desensitization and downregulation of pituitary GnRH receptors, leading to decreased FSH (hypogonadotropic) and decreased estrogen (hypogonadal) levels. This hypogonadotropic, hypogonadal state can shrink estrogen-dependent fibroids and induce amenorrhea, thereby improving bleeding symptoms. However, patients typically also experience intolerable menopausal symptoms (eg, vasomotor symptoms, decreased bone density); therefore, leuprolide is typically used short term (eg, 3-6 months) to decrease fibroid size and to improve anemia prior to surgical management. (Choice A) Clomiphene, used for ovulation induction to treat infertility, acts on the hypothalamus by interfering with hypothalamic estrogen receptors, thereby inhibiting normal negative feedback from estrogen; this promotes GnRH and FSH secretion and stimulates ovulation. (Choice B) Letrozole, an aromatase inhibitor, decreases peripheral (ie, adipose) and ovarian conversion of androgens to estrogens; the decreased estrogen level releases estrogenic negative feedback on the hypothalamus to increase GnRH and FSH secretion. Letrozole is used as adjuvant therapy for estrogen receptor-positive breast cancer in postmenopausal women (by decreasing estrogen levels) and for ovulation induction (by stimulating GnRH and FSH release). (Choice C) Depot medroxyprogesterone acetate (DMPA), a progesterone contraceptive, inhibits pituitary secretion of gonadotropins (ie, FSH, LH) to prevent ovulation. The decrease in FSH causes increased hypothalamic GnRH secretion and suppressed ovarian estrogen production. (Choice D) Exogenous estrogen-containing medications (eg, combined estrogen-progestin oral contraceptives, menopausal hormone therapy) increase estrogen levels, producing negative feedback at the hypothalamus and decreased GnRH and FSH levels. Educational objective: Leuprolide is a GnRH agonist used to treat symptomatic uterine fibroids (eg, heavy menses, anemia). When administered in a continuous fashion, leuprolide inhibits the release of endogenous hypothalamic GnRH and downregulates pituitary GnRH receptors, thereby decreasing GnRH, FSH, and estrogen levels (ie, hypogonadotropic hypogonadism). __________ References: Preoperative medical therapy before surgery for uterine fibroids. (http://www.ncbi.nlm.nih.gov/pubmed/29139105) Hypothalamic-pituitary-ovarian axis disorders impacting female fertility. (http://www.ncbi.nlm.nih.gov/pubmed/30621143)

A 38-Year-Old Woman Comes to the Emergency Department Due to an Acute