Polycystic Ovary Syndrome Flashcards Preview

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Flashcards in Polycystic Ovary Syndrome Deck (19)
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1
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characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovaries. Its etiology remains unknown, and treatment is largely symptom based and empirical. PCOS has the potential to cause substantial metabolic sequelae, including an increased risk of diabetes and cardiovascular disease, and these factors should be considered when determining long-term treatment.

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2
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Women with PCOS commonly present with menstrual disorders (from amenorrhea to menorrhagia) and infertility.

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3
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In addition, women with PCOS appear to be at increased risk for complications of pregnancy, including gestational diabetes, and hypertensive disorders (8). The risk of complications is further exacerbated by iatrogenic multiple pregnancy from infertility treatment.

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4
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Skin disorders, especially those due to peripheral androgen excess such as hirsutism and acne, and to a lesser degree androgenic alopecia, are common in women with PCOS (9). Women with PCOS are at increased risk of insulin resistance and its associated conditions, such as the metabolic syndrome (see Box 2) (10), nonalcoholic fatty liver disease (11), and obesity-related disorders such as sleep apnea (12). In turn, all of these conditions are risk factors for long-term metabolic sequelae, such as type 2 diabetes and cardiovascular disease. Women with PCOS also have multiple risk factors for endometrial cancer, including chronic anovulation, centripetal obesity, and diabetes, although the strength of the association with PCOS per se is debated (13). In recent years, there has been increased recognition of mood disturbances and depression among women with PCOS (14).

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5
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The history should focus on the onset and duration of the various signs of androgen excess, the menstrual history, and concomitant medications, including the use of exogenous androgens. A family history of diabetes and cardiovascular disease (especially first-degree relatives with premature onset of cardiovascular disease [male younger than 55 years and female younger than 65 years]) is important.

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6
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The physical examination should include evaluation of balding, acne, clitoromegaly, and body hair distribution, as well as pelvic examination to look for ovarian enlargement. The presence and severity of acne should be noted. Signs of insulin resistance such as hypertension, obesity, centripetal fat distribution, and the presence of acanthosis nigricans should be recorded. Acanthosis nigricans is a dermatologic condition marked by velvety, mossy, verrucous, hyperpigmented skin. It has been noted on the back of the neck, in the axillae, underneath the breasts, and even on the vulva. The presence of acanthosis nigricans appears to be more a sign of insulin resistance or medication reaction than a distinct disease unto itself. Other pathologic conditions rarely associated with acanthosis nigricans should be considered, such as insulinoma and malignant disease, especially adenocarcinoma of the stomach. Clitoromegaly is rarely associated with PCOS, and its presence should elicit a search for other causes.

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7
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Androgen-secreting tumors of the ovary or adrenal gland are invariably accompanied by elevated circulating androgen levels. However, there is no absolute level that is pathognomonic for a tumor, just as there is no minimum androgen level that excludes a tumor. In the past, testosterone levels above 2 ng/mL and dehydroepiandrosterone sulfate (DHEAS) levels greater than 700 micrograms/dL were regarded as suspicious for a tumor of ovarian and adrenal etiology, respectively, but these cutoff levels have poor sensitivity and specificity (16).

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8
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Mild elevations in prolactin are common in women with PCOS (18). A prolactin level can identify prolactinomas that secrete large amounts of prolactin and that may stimulate ovarian androgen production, but this is an extremely rare cause of hyperandrogenic chronic anovulation. Evaluating serum levels of thyroid-stimulating hormone also is useful given the protean manifestations and frequency of thyroid disease in women with menstrual disorders.

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9
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Multiple studies have shown that weight loss can improve the fundamental aspects of the endocrine syndrome of PCOS by lowering circulating androgen levels and causing spontaneous resumption of menses. Reduction in body weight has been associated with improved pregnancy rates and decreased hirsutism, as well as improvements in glucose and lipid levels (2

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10
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Although there are few well designed trials in women with PCOS, in general, combined hormonal contraceptives offer benefits through a variety of mechanisms, including suppression of pituitary luteinizing hormone secretion, suppression of ovarian androgen secretion, and increased circulating SHBG. Individual preparations may have different doses and drug combinations and thus have varying risk–benefit ratios. For instance, various progestins have been shown to have different effects on circulating SHBG levels (46), but whether that results in a clinical benefit is uncertain. There is insufficient evidence to determine the most effective combination hormonal contraceptive for women with PCOS to treat menstrual disorders.

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11
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The regimen of cyclic oral progestin therapy or progestin-containing intrauterine devices that most effectively prevent endometrial cancer in women with PCOS is unknown. Progestin-only contraceptives or progestin-containing intrauterine devices are an alternative for endometrial protection, but they are associated with abnormal bleeding patterns in 50–89% of users (47).

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12
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Nonetheless, improving insulin sensitivity with these agents is associated with a decrease in circulating androgen levels, improved ovulation rate, and improved glucose tolerance

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13
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Gastrointestinal symptoms (diarrhea, nausea, vomiting, abdominal bloating, flatulence, and anorexia) are the most common adverse reactions and may be ameliorated by starting at a small dose and gradually increasing the dose or by using the sustained-release version now available in the United States. The dose most commonly used to treat women with PCOS is 1,500–2,000 mg per day given in divided doses.

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14
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One half of all women who are going to conceive using clomiphene will do so at the 50-mg starting dose, and another 20% will do so at the 100-mg per day dose (67). Most pregnancies will occur within the first six ovulatory cycles, although a constant monthly pregnancy rate was noted suggesting there may continued benefit to longer use (65).

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15
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Gonadotropins are frequently used to induce ovulation in women with PCOS for whom clomiphene treatment has failed. Low-dose therapy with gonadotropins offers a higher rate of ovulation and monofollicular development, with a significantly lower risk of ovarian hyperstimulation syndrome (71). This low-dose regimen is recommended when using gonadotropins in women with PCOS (63).

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16
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Aromatase inhibitors such as letrozole and anastrazole have been proposed as both primary and secondary treatment for ovulation induction and results appear comparable to clomiphene from small trials (75). Proposed benefits include oral administration, a shorter half-life than clomiphene, potentially higher implantation rates, and lower multiple pregnancy rates due to monofollicular ovulation. Further study of these agents is needed to verify these claims, and fetal effects need to be more completely monitored. These agents are not approved by the FDA for ovulation induction.

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17
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. Metformin has no known human teratogenic risk or embryonic lethality in humans and appears safe in pregnancy (it is also classified as Pregnancy Category B).

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18
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Approximately 20% of women using spironolactone will experience increased menstrual frequency (80). Because it can cause and exacerbate hyperkalemia, spironolactone should be used cautiously in women with renal impairment. Rarely, exposure has resulted in ambiguous genitalia in male infants.

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19
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As a class, antiandrogens are teratogenic and pose a risk of feminization of the external genitalia in a male fetus (ambiguous genitalia) should the patient conceive. Therefore, they are frequently used in combination with oral contraceptives.

Spironolactone

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