Marttunen M B, Pyrhönen S, Tiitinen A E, Viinikka L U, Ylikorkala O
Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Finland.
Prostaglandins. 1996 Oct;52(4):317-26. doi: 10.1016/s0090-6980(96)00092-5.
To explore the mechanism(s) by which antiestrogens may protect against the development of cardiovascular disorders, we measured the production of vasodilatory, antiaggregatory prostacyclin (PGI2) and that of vasoconstrictive, proaggregatory thromboxane A2 (TxA2) before and after 6 months' use of antiestrogens in postmenopausal patients after operation for stage II breast cancer (n = 38). Urine samples were assayed by high performance liquid chromatography and radio-immunoassays for 2,3-dinor-6-ketoprostaglandin F1 alpha (= metabolite of PGI2, dinor-6-keto) and for 2,3-dinor-thromboxane B2 (= metabolite of TxA2, dinor-TxB2). In addition, in 35 of these 38 patients we assayed the capacity of platelets to produce thromboxane A2 during standardized blood clotting. The 4 patients using low-dose aspirin had low thromboxane production, and were excluded from further analysis of the data. An antiestrogen regimen consisting either of tamoxifen (n = 15) or of toremifene (n = 19) caused no changes in production of PGI2 or TxA2, or in their ratio, and in this regard, these antiestrogens behaved similarly. Hypertensive patients (n = 7) using different anti-hypertensive agents were characterized by reduced urinary out-put of dinor-6-keto (18.5 +/- 6.1 vs 35.5 +/- 18.5 ng/mmol, mean +/- SD, p < 0.05) and reduced platelet capacity to produce TxA2 (62.6 +/- 67.8 vs 134.6 +/- 75.6 ng/mL, p < 0.05). The patients (n = 15) who had used estrogen replacement therapy (ERT) up until diagnosis of breast cancer showed reduced dinor-TxB2 excretion (15.5 +/- 12.7 vs 29.9 +/- 20.9 ng/mmol, p < 0.05) before initiation of antiestrogens, and elevated dinor-6-keto output during the antiestrogen regimen (32.4 +/- 21.2 vs 22.7 +/- 8.7 ng/mmol, p = 0.07). Smokers (n = 6) had elevated dinor-TxB2 output before and during antiestrogen use. Thus we conclude that the cardiovascular protection provided by an antiestrogen regimen is unlikely to be mediated through vaso- and platelet active PGI2 and TxA2.
为探究抗雌激素药物预防心血管疾病发生的机制，我们对38例II期乳腺癌术后绝经后患者在使用抗雌激素药物6个月前后，测量了血管舒张性、抗聚集性的前列环素（PGI2）以及血管收缩性、促聚集性的血栓素A2（TxA2）的生成量。通过高效液相色谱法和放射免疫分析法检测尿样中的2,3 - 二去甲 - 6 - 酮前列腺素F1α（= PGI2的代谢产物，二去甲 - 6 - 酮）和2,3 - 二去甲 - 血栓素B2（= TxA2的代谢产物，二去甲 - TxB2）。此外，在这38例患者中的35例，我们检测了标准化血液凝固过程中血小板生成血栓素A2的能力。4例使用低剂量阿司匹林的患者血栓素生成量较低，被排除在进一步的数据分析之外。由他莫昔芬（n = 15）或托瑞米芬（n = 19）组成的抗雌激素治疗方案，在PGI2或TxA2的生成量及其比值方面均未引起变化，在这方面，这些抗雌激素药物表现相似。使用不同抗高血压药物的高血压患者（n = 7）的特征是二去甲 - 6 - 酮的尿排出量降低（18.5±6.1 vs 35.5±18.5 ng/mmol，平均值±标准差，p < 0.05）以及血小板生成TxA2的能力降低（62.6±67.8 vs 134.6±75.6 ng/mL，p < 0.05）。在诊断乳腺癌之前一直使用雌激素替代疗法（ERT）的患者（n = 15）在开始使用抗雌激素药物之前二去甲 - TxB2排泄量降低（15.5±12.7 vs 29.9±20.9 ng/mmol，p < 0.05），在抗雌激素治疗期间二去甲 - 6 - 酮排出量升高（32.4±21.2 vs 22.7±8.7 ng/mmol，p = 0.07）。吸烟者（n = 6）在使用抗雌激素药物之前和期间二去甲 - TxB2排出量升高。因此我们得出结论，抗雌激素治疗方案提供的心血管保护不太可能通过血管和血小板活性的PGI2和TxA2介导。
