Aromatase Inhibitors in Gynecology Flashcards
Aromatase inhibitors have been used for the treatment of breast cancer, ovulation induction, endometriosis, and other estrogen-modulated conditions. For women with breast cancer, bone mineral density screening is recommended with long-term aromatase inhibitor use because of risk of osteoporosis due to estrogen deficiency.
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Based on long-term adverse effects and complication safety data, when compared with tamoxifen, aromatase inhibitors are associated with a reduced incidence of thrombosis, endometrial cancer, and vaginal bleeding. For women with polycystic ovary syndrome and a body mass index greater than 30, letrozole should be considered as first-line therapy for ovulation induction because of the increased live birth rate compared with clomiphene citrate.
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For women with breast cancer, bone mineral density screening is recommended with long-term aromatase inhibitor use because of risk of osteoporosis due to estrogen deficiency.
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Based on long-term adverse effects and safety data, when compared with tamoxifen, aromatase inhibitors are associated with a reduced incidence of thrombosis, endometrial cancer, and vaginal bleeding.
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For women with polycystic ovary syndrome and a body mass index (BMI) greater than 30, letrozole should be considered as first-line therapy for ovulation induction because of the increased live birth rate compared with clomiphene citrate. Lifestyle changes that result in weight loss should be strongly encouraged.
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Aromatase inhibitors are a promising therapeutic option that may help manage endometriosis-associated pain in combination therapy with progestins.
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Aroma-tase is a microsomal cytochrome P450 hemoprotein-containing enzyme (P450arom, the product of the CYP19 gene), and it is widely expressed in tissues, such as brain, breast, placenta, ovary, testes, endometrium, skin, bone, and fat. Within these tissues, aromatase mediates the conversion of androstenedione to estrone and the conversion of testosterone to estradiol in situ. Thus, for tissues that express this enzyme, conversion of circulating androgens from an adrenal or ovarian source will significantly increase the in situ estrogen concentrations and provide these tissues with a proliferative advantage.
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The 10-year follow-up study results demonstrated that anastrozole is better than tamoxifen in the prevention of recurrence of breast cancer in postmenopausal women with early-stage hormone receptor-positive tumors
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There is a growing body of evidence that supports effective use of aromatase inhibitors with ovarian suppression in select populations, such as women who remained premenopausal after completing chemotherapy and who were at sufficient risk of recurrence to warrant adjuvant chemotherapy (9). Aromatase inhibitors should be avoided in premenopausal women who have chemotherapy-induced amenorrhea with breast cancer because ovarian function can resume after the initiation of an aromatase inhibitor regimen, which renders the treatment ineffective (
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or women with breast cancer, bone mineral density screening is recommended with long-term aromatase inhibitor use because of the risk of osteoporosis due to estrogen deficiency. T
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. To reduce the risk of osteoporosis in high-risk patients, bisphosphonates are typically co-administered to patients during long-term treatment with aromatase inhibitors (16). Potential risks of bisphosphonates reported after marketing include osteonecrosis of the jaw, seizures, atypical fractures of the femoral shaft, and esophageal cancer. A precise understanding of the true risk of these events has been difficult to determine because of the lack of data on the incidence of these problems in the general population. Although rare cases of osteonecrosis of the jaw have been reported in patients using bisphosphonates for osteoporosis, it has been seen most commonly after dental extractions in those being treated with large intravenous doses of bisphosphonates in association with supportive cancer therapy
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Based on long-term adverse effects and safety data, when compared with tamoxifen, aromatase inhibitors are associated with a reduced incidence of thrombosis, endometrial cancer, and vaginal bleeding (20, 21). Aromatase inhibitors have been shown to have adverse effects on the cardiovascular system and lipid profiles compared with tamoxifen (20, 21). Most of those who discontinue the use of aromatase inhibitors do so because of musculoskeletal symptoms, fatigue, forgetfulness, or sleep disturbances (20–22).
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If prescribing letrozole, the starting dose is 2.5 mg/day for 5 days typically starting on day 3, 4, or 5 after a spontaneous menses or progestin-induced bleed. If ovulation does not occur, the dose can be increased to 5 mg/day for 5 days with a maximum dose of 7.5 mg/day. Doses higher than 7.5 mg/day have been associated with thinning of the endometrium as seen with clomiphene citrate (26).
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However, in a more recent randomized controlled trial, letrozole was more effective than clomiphene citrate with a higher live birth rate (27.5% versus 10.1%. P=.007), and cumulative ovulation rate (61.7% versus 48.3%, P
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In women with a BMI greater than or equal to 30.3, ovulation induction with letrozole resulted in a higher live birth rate when compared with clomiphene citrate (29, 30). Therefore, for women with PCOS and a BMI greater than 30, letrozole should be considered first-line therapy for ovulation induction because of the increased live birth rate compared with clomiphene citrate.
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