LHRH agonists and the prevention of breast and ovarian cancer.
LHRH agonists and the prevention of breast and ovarian cancer.
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DOI：
10.1038/bjc.1989.237
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发表时间：
1989-07
影响因子：
8.8
通讯作者：
Henderson, B E
中科院分区：
文献类型：
--
作者：
Pike, M C;Ross, R K;Lobo, R A;Key, T J;Potts, M;Henderson, B E
过早自然绝经或双侧卵巢切除术大大降低了女性一生中患乳腺癌的风险。可逆的“双侧卵巢切除术”现在可以通过“大剂量”促黄体生成激素释放激素（LHRH）激动剂（LHRHAs）来实现。这种医学可逆性双侧卵巢切除术的有害影响，特别是冠心病和骨质疏松症的风险增加，很可能可以通过“低剂量”雌激素替代疗法（ERT），特别是在每个28天的治疗周期中持续21天0.625 mg缀合的马雌激素（CEE），并且这种ERT的使用将仅在相对小的程度上抵消这种双侧卵巢切除术对乳腺癌风险的有益作用。我们计算出，这种LHRHA加低剂量ERT方案给予绝经前妇女10年，除了是一种最有效的避孕药外，还可使其一生中患乳腺癌的风险降低50%以上。我们计算出，这样一个10年的方案也将使她患卵巢癌的风险降低三分之二。这种方案应该不会改变子宫内膜癌的风险和骨代谢，并可能降低心脏病的风险。在每个28天的治疗周期中，在该方案中添加“低剂量”孕激素12天将对子宫内膜有益，但它会对心脏病的风险因素产生不利影响，并且可能会显着降低该方案对乳腺癌的益处。一个令人满意的折衷方案可能是以较低的频率间隔加用低剂量孕激素12天。另一种可能性是使用宫内节育器将孕激素单独输送到子宫内膜;这种方案的益处是显著降低乳腺癌、卵巢癌和子宫内膜癌的发病率。
Early age at natural menopause or bilateral ovariectomy substantially reduce a woman's lifetime risk of breast cancer. Reversible 'bilateral ovariectomy' can now in effect be achieved by 'high-dose' luteinising hormone releasing hormone (LHRH) agonists (LHRHAs). The harmful effects of such medical reversible bilateral ovariectomy, in particular the increased risks of coronary heart disease and osteoporosis, can in all likelihood be obviated by 'low-dose' oestrogen replacement therapy (ERT), specifically 0.625 mg of conjugated equine oestrogens (CEE) for 21 days in each 28-day treatment cycle, and such ERT use will only negate to a relatively small extent the beneficial effect of such bilateral ovariectomy on breast cancer risk. We calculate that such an LHRHA plus low-dose ERT regimen given to a premenopausal woman for 10 years will, in addition to being a most effective contraceptive, decrease her lifetime risk of breast cancer by more than 50%. We calculate that such a 10-year regimen will also decrease her risk of ovarian cancer by two-thirds. This regimen should leave endometrial cancer risk and bone metabolism unaltered, and may reduce the risk of heart disease. The addition of a 'low-dose' progestogen to the regimen for 12 days in each 28-day treatment cycle would be beneficial to the endometrium, but it will adversely affect risk factors for heart disease and it may significantly reduce the benefit of the regimen as regards breast cancer. A satisfactory compromise may be to add a low-dose progestogen for 12 days at less frequent intervals. Another possibility may be to deliver a progestogen solely to the endometrium with an intra-uterine device; the benefits of such a regimen would be a significant reduction in the incidence of breast, ovarian and endometrial cancer.