Fabian Carol J, Kimler Bruce F
Division of Clinical Oncology, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas 66160-7820, USA.
Drugs Aging. 2002;19(1):43-78. doi: 10.2165/00002512-200219010-00004.
Estrogen administration is associated with reduction in perimenopausal symptoms and the risk for several conditions affecting postmenopausal women. As estrogen administration also increases the risk for breast cancer, a common dilemma facing many women and their physicians is whether to use estrogen replacement therapy (ERT), a selective estrogen receptor modulator (SERM) that antagonises estrogenic effects in breast tissue but retains some estrogen agonist properties in other organs, or neither. For women with average to moderate risk of breast cancer and with perimenopausal symptoms, ERT may be the best short-term choice. For very high-risk women (>1% per year) with menopausal symptoms, alternatives to ERT might be offered and tried first. A diagnosis of ductal carcinoma in situ or invasive breast cancer within the last 2 to 5 years should be considered a relative contraindication for ERT unless the tumour was estrogen receptor negative. High-risk women without menopausal symptoms are the best candidates for the only currently approved drug for breast cancer risk reduction, tamoxifen. Although the drug is approved for women with a 5-year risk of breast cancer > or = 1.7% (0.34% per year), postmenopausal women most likely to experience a favourable benefit/risk ratio are those with a Gail estimated risk of >0.5% per year without a uterus or >1% per year if they retain their uterus. Tamoxifen should not be used in women with prior history of thromboembolic or precancerous uterine conditions. Tamoxifen is often used in Europe in conjunction with transdermal ERT in hysterectomised women without obvious loss of efficacy or increased risk of thromboembolism. Raloxifene is a second generation SERM with estrogen-like agonist effects on bone but with less uterine estrogen agonist activity than tamoxifen. Raloxifene may have less potent breast antiestrogenic effects than tamoxifen, particularly in a moderate- to high-estrogen environment. Raloxifene is approved for use in reducing risk of osteoporosis, but not breast cancer. Whether it is as effective as tamoxifen in reducing breast cancer risk in postmenopausal women is the subject of a current trial. All women regardless of breast cancer risk are advised to employ nonpharmacological risk reduction measures, including normalisation of bodyweight, exercise, adequate calcium and vitamin D intake, and avoidance of smoking and alcohol. The preventive options are best weighed during an individualised consultation where a woman's menopausal symptoms and risk for breast cancer and other diseases can be examined, and the options for improving postmenopausal health can be discussed.
雌激素给药与围绝经期症状减轻以及影响绝经后女性的多种疾病风险降低相关。由于雌激素给药也会增加乳腺癌风险，许多女性及其医生面临的一个常见困境是是否使用雌激素替代疗法（ERT），一种选择性雌激素受体调节剂（SERM），它可拮抗乳腺组织中的雌激素作用，但在其他器官中保留一些雌激素激动剂特性，或者两者都不使用。对于乳腺癌平均风险至中度风险且有围绝经期症状的女性，ERT可能是最佳的短期选择。对于绝经症状明显且乳腺癌风险非常高（每年>1%）的女性，可首先提供并尝试ERT的替代方案。过去2至5年内诊断为原位导管癌或浸润性乳腺癌应被视为ERT的相对禁忌证，除非肿瘤为雌激素受体阴性。没有绝经症状的高风险女性是目前唯一被批准用于降低乳腺癌风险的药物他莫昔芬的最佳适用人群。尽管该药物被批准用于乳腺癌5年风险≥1.7%（每年0.34%）的女性，但绝经后女性中最可能获得有利效益/风险比的是那些根据盖尔模型估计每年风险>0.5%且无子宫的女性，或保留子宫且每年风险>1%的女性。有血栓栓塞或癌前子宫疾病病史的女性不应使用他莫昔芬。在欧洲，他莫昔芬通常与经皮ERT联合用于子宫切除的女性，疗效无明显损失，血栓栓塞风险也未增加。雷洛昔芬是第二代SERM，对骨骼具有雌激素样激动作用，但子宫雌激素激动活性比他莫昔芬低。雷洛昔芬的乳腺抗雌激素作用可能比他莫昔芬弱，尤其是在中高雌激素环境中。雷洛昔芬被批准用于降低骨质疏松症风险，但不能降低乳腺癌风险。它在降低绝经后女性乳腺癌风险方面是否与他莫昔芬一样有效是当前一项试验的主题。建议所有女性，无论乳腺癌风险如何，都采取非药物性风险降低措施，包括体重正常化、运动、充足的钙和维生素D摄入，以及避免吸烟和饮酒。最好在个体化咨询过程中权衡预防方案，在此过程中可以检查女性的绝经症状、乳腺癌及其他疾病风险，并讨论改善绝经后健康的方案。
