A 24-year-old woman comes to the office for an infertility evaluation. The patient has had irregular menstrual cycles for the past 5 years, with menstrual periods every 2-3 months. Medical history is notable for an appendectomy 8 years ago but is otherwise not significant. The patient takes no medications. Blood pressure is 125/86 mm Hg and pulse is 72/min. BMI is 33 kg/m². Physical examination shows facial acne and excessive hair growth on the upper lip and chin. Which of the following pathologic findings is most likely to be seen in this patient?

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11ec160b_3ad2_882d_9249_6105a76a6004_MD0001_00 This patient with menstrual irregularities, infertility, obesity, and hirsutism likely has polycystic ovary syndrome (PCOS). The etiology is heterogeneous and multifactorial (eg, hormonal, genetic, environmental), but patients characteristically have elevated levels of both androgen and estrogen. Hyperandrogenism, which can be diagnosed clinically (eg, hirsutism, acne) or biochemically (ie, elevated testosterone), occurs due to increased ovarian androgen production. Androgens are then converted to estrogens in the peripheral adipose tissue and ovaries by the enzyme aromatase; patients with PCOS are commonly obese and have increased peripheral and ovarian estrogen production (ie, estrone and estradiol). The consistent elevation in estrogen acts on the hypothalamic-pituitary-ovarian axis and causes menstrual irregularities and anovulatory infertility. During a normal menstrual cycle, the growth of a dominant follicle causes a gradual increase in estrogen, which triggers hypothalamic GnRH release in a high-frequency pulse pattern that preferentially stimulates greater LH than FSH production in the anterior pituitary (ie, the LH surge to trigger oocyte release). Following ovulation, GnRH release returns to a low-frequency pattern that allows FSH to stimulate the next follicular phase. In contrast, patients with PCOS have consistently elevated estrogen levels, leading to a persistent imbalance in the LH/FSH ratio. Because FSH remains low relative to LH, there is no maturation and release of a single, dominant ovarian follicle (ie, anovulation). Instead, multiple, smaller follicles accumulate fluid to cause the classic appearance of bilateral, enlarged, polycystic ovaries. (Choice A) Endometrial proliferation is estrogen dependent. An atrophic endometrium is associated with low estrogen (eg, menopause); in contrast, patients with PCOS have chronically elevated estrogen levels and are at increased risk for endometrial hyperplasia or cancer. (Choices B and D) Cushing syndrome is caused by cortisol excess, usually due to a hyperfunctioning adrenal adenoma (which causes compensatory contralateral, not bilateral, adrenal atrophy) or an ACTH-producing pituitary adenoma. Although Cushing syndrome and PCOS share several clinical features (eg, obesity, hirsutism, menstrual irregularities), patients with Cushing syndrome typically also have moon facies, enlarged fat pads, hypertension, and proximal muscle weakness. (Choice E) Polycystic kidney disease is an inherited condition with juvenile and adult forms. Patients typically have hypertension, flank pain, hematuria, and renal insufficiency. It does not cause menstrual irregularities or hirsutism. Educational objective: Polycystic ovary syndrome (PCOS) may present with menstrual irregularities, signs of hyperandrogenism (eg, acne, hirsutism), and obesity. Patients with PCOS typically have bilateral, enlarged, cystic ovaries. __________ References: Genetic, hormonal and metabolic aspects of PCOS: an update. (http://www.ncbi.nlm.nih.gov/pubmed/27423183) GnRH pulsatility, the pituitary response and reproductive dysfunction. (http://www.ncbi.nlm.nih.gov/pubmed/19609045)

A 24-Year-Old Woman Comes to the Office for an Infertility