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屈洛昔芬与雌激素对绝经后女性甲状腺功能的影响。

The effect of droloxifene and estrogen on thyroid function in postmenopausal women.

作者信息

Marqusee E, Braverman L E, Lawrence J E, Carroll J S, Seely E W

机构信息

Thyroid Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.

出版信息

J Clin Endocrinol Metab. 2000 Nov;85(11):4407-10. doi: 10.1210/jcem.85.11.6975.

Abstract

Estrogen is known to increase serum T4-binding globulin (TBG) concentrations, thereby increasing serum total T4 concentrations. Serum free T4 concentrations, however, remain normal. Tamoxifen, a selective estrogen receptor modifier (SERM), also raises serum TBG concentrations, but whether newer SERMs with less stimulatory action on the endometrium do so is not known. We, therefore, compared the effect of droloxifene, a SERM, and conjugated equine estrogen on pituitary-thyroid function in normal postmenopausal women. Ten women were treated for 6 weeks with conjugated estrogen (Premarin), 0.625 mg/day, and droloxifene, 60 mg/day, in a double-blind crossover study with an intervening 4-week no-treatment period. We measured serum T4, T3, TBG, free T4 index, and TSH at baseline and at the end of each 6-week period. The baseline values were compared with the 6-week values using paired t tests. The mean (+/- SD) serum TBG concentrations increased significantly during both treatment periods (baseline, 1.5+/-0.4 mg/dL; conjugated estrogens, 2.7+/-0.6 mg/dL; droloxifene, 2.1+/-0.6 mg/dL; P < 0.001 and P = 0.001, respectively). There were no significant changes in the serum free T4 index. Serum T4 and T3 concentrations increased during both treatment periods, however, the increase was significant only for T4 during the conjugated estrogen treatment period. The serum TSH concentrations increased significantly during both treatment periods (18% during conjugated estrogen and 11% during droloxifene), and the values remained within the normal range in all women. Administration of both conjugated estrogen and droloxifene for 6 weeks increases serum TSH and TBG concentrations, but does not alter free T4 index values in postmenopausal women.

摘要

已知雌激素可增加血清甲状腺素结合球蛋白(TBG)浓度,从而提高血清总T4浓度。然而,血清游离T4浓度仍保持正常。他莫昔芬是一种选择性雌激素受体调节剂(SERM),也会提高血清TBG浓度,但对子宫内膜刺激作用较小的新型SERM是否如此尚不清楚。因此,我们比较了一种SERM——屈洛昔芬与结合马雌激素对正常绝经后女性垂体-甲状腺功能的影响。在一项双盲交叉研究中,10名女性接受为期6周的治疗,分别为每日服用0.625 mg结合雌激素(普瑞马林)和每日服用60 mg屈洛昔芬,中间有4周的未治疗期。我们在基线以及每个6周治疗期结束时测量血清T4、T3、TBG、游离T4指数和促甲状腺激素(TSH)。使用配对t检验将基线值与6周时的值进行比较。在两个治疗期内,血清TBG平均浓度(±标准差)均显著升高(基线时为1.5±0.4 mg/dL;结合雌激素治疗后为2.7±0.6 mg/dL;屈洛昔芬治疗后为2.1±0.6 mg/dL;P分别<0.001和P = 0.001)。血清游离T4指数无显著变化。在两个治疗期内,血清T4和T3浓度均升高,然而,仅在结合雌激素治疗期T4的升高具有显著性。在两个治疗期内,血清TSH浓度均显著升高(结合雌激素治疗期升高18%,屈洛昔芬治疗期升高11%),且所有女性的值均保持在正常范围内。给予结合雌激素和屈洛昔芬6周均会增加绝经后女性的血清TSH和TBG浓度,但不会改变游离T4指数值。

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