Zoma Willie D, Baker R Scott, Kopernik Gideon, Mershon John L, Clark Kenneth E
Division of Reproductive Endocrinology, College of Medicine, University of Cincinnati, Ohio 45267, USA.
Am J Obstet Gynecol. 2002 Dec;187(6):1555-60. doi: 10.1067/mob.2002.127600.
Hormone replacement therapy has been implicated in the increased incidence of breast cancer, although selective estrogen receptor modulators have been shown to be effective in the prevention of breast cancer. Breast cancers are associated with increased mammary blood flow compared to benign breast lesions. However, few studies have examined the hemodynamic effects of hormonal agents on the mammary circulation that promote or reduce the risk of breast cancers. Although estradiol-17beta has been shown to increase mammary blood flow, the effect of selective estrogen receptor modulators remains undetermined. We therefore compared the vascular effects of selective estrogen receptor modulators and estrogens on mammary blood flow.
Fourteen nonpregnant ovariectomized ewes were instrumented to measure mean arterial pressure, heart rate, and uterine and mammary blood flows. Compounds were administered intravenously on separate days, and responses were monitored up to 4 hours. Compounds that were studied included estradiol-17beta (1 microg/kg), conjugated equine estrogens (0.625 and 1.25 mg), tibolone (2.5 and 5 mg), raloxifene (10 microg/kg), and tamoxifen (300 microg/kg).
None of these compounds significantly affected mean arterial pressure or heart rate, but all of the compounds significantly increased uterine blood flow. Estradiol-17beta increased mammary blood flow by 98% +/- 25%; conjugated equine estrogen increased mammary blood flow by 46% +/- 6% and 68% +/- 13% at the 0.625 and 1.25 mg doses, respectively. Tibolone increased mammary blood flow by 37% +/- 13% at the 2.5-mg dose and by only 14% +/- 4% at the 5-mg dose. Neither raloxifene nor tamoxifen significantly altered mammary blood flow.
Although estrogens and selective estrogen receptor modulators induced similar increases in uterine blood flow, they had differential effects on mammary blood flow.
激素替代疗法被认为与乳腺癌发病率增加有关，尽管选择性雌激素受体调节剂已被证明对预防乳腺癌有效。与良性乳腺病变相比，乳腺癌患者的乳腺血流增加。然而，很少有研究探讨激素制剂对乳腺循环的血流动力学影响，而这种影响可能会增加或降低患乳腺癌的风险。虽然已证明雌二醇-17β可增加乳腺血流，但选择性雌激素受体调节剂的作用仍未确定。因此，我们比较了选择性雌激素受体调节剂和雌激素对乳腺血流的血管效应。
对14只未怀孕的去卵巢母羊进行仪器安装，以测量平均动脉压、心率以及子宫和乳腺血流。在不同日期静脉注射化合物，并监测长达4小时的反应。所研究的化合物包括雌二醇-17β（1微克/千克）、结合马雌激素（0.625毫克和1.25毫克）、替勃龙（2.5毫克和5毫克）、雷洛昔芬（10微克/千克）和他莫昔芬（300微克/千克）。
这些化合物均未显著影响平均动脉压或心率，但所有化合物均显著增加子宫血流。雌二醇-17β使乳腺血流增加98%±25%；结合马雌激素在0.625毫克和1.25毫克剂量时，分别使乳腺血流增加46%±6%和68%±13%。替勃龙在2.5毫克剂量时使乳腺血流增加37%±13%，在5毫克剂量时仅增加14%±4%。雷洛昔芬和他莫昔芬均未显著改变乳腺血流。
虽然雌激素和选择性雌激素受体调节剂均可使子宫血流出现类似增加，但它们对乳腺血流的影响存在差异。
