Taxel Pamela, Fall Pamela M, Albertsen Peter C, Dowsett Robert D, Trahiotis Margaret, Zimmerman Jill, Ohannessian Christine, Raisz Lawrence G
Division of Endocrinology and Metabolism, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030-1317, USA.
J Clin Endocrinol Metab. 2002 Nov;87(11):4907-13. doi: 10.1210/jc.2002-020539.
To examine the effect of estradiol (E(2)) without the confounding effect of hypothalamic-pituitary feedback, we studied men with prostate cancer in whom gonadotropin secretion was suppressed by LH-releasing hormone agonists (LHRH-A). Fourteen men over 65 yr of age and receiving established LHRH-A treatment (EST group) without bony metastases and 12 men who received LHRH-A as neoadjuvant therapy for locally advanced prostate cancer (NEO group) were randomized (double blind) to receive either 1 mg/d micronized E(2) (n = 12) or placebo (PL; n = 13) for 9 wk. E(2), estrone, testosterone, SHBG, PTH, and 25-hydroxy- and 1,25-dihydroxyvitamin D levels as well as markers of bone resorption [N- and C-telopeptide cross-links (NTX and CTX) and deoxypyridinoline] and bone formation (bone-specific alkaline phosphatase, osteocalcin, and N-terminal type I collagen) were measured before LHRH-A in the NEO group, before [baseline (BL)] and after 9 wk of E(2) or PL in all patients, and 6 wk after E(2) treatment in the EST group. In the NEO group, hormone levels fell 3 wk after the initial LHRH-A injection, and deoxypyridinoline increased significantly (P = 0.006). At BL, the EST group had higher bone turnover due to the longer duration of LHRH-A treatment. With E(2) treatment, E(2) levels rose into the normal male range, and two resorption markers decreased significantly from BL by 33% for NTX (P < 0.001) and 28% for CTX (P = 0.009). Bone formation markers did not change. PTH increased by 43% from BL (P < 0.01) in the E(2) group and decreased 16% from BL in the PL group (P < 0.01). Ionized calcium did not change in the E(2) group, but increased in the PL group by 2.3% (P < 0.01). NTX and CTX increased 6 wk after E(2) withdrawal in the EST group. We conclude that E(2) inhibits bone resorption in hypogonadal men through a direct skeletal effect that is independent of PTH. Low dose estrogen may be an option for the prevention and/or treatment of bone loss in this population.
为了研究雌二醇（E₂）的作用而不受下丘脑 - 垂体反馈的混杂影响，我们对患有前列腺癌且促性腺激素分泌被促黄体生成素释放激素激动剂（LHRH - A）抑制的男性进行了研究。14名年龄超过65岁且正在接受既定LHRH - A治疗（EST组）且无骨转移的男性以及12名接受LHRH - A作为局部晚期前列腺癌新辅助治疗的男性（NEO组）被随机（双盲）分为接受1mg/d微粒化E₂（n = 12）或安慰剂（PL；n = 13），为期9周。在NEO组中，在使用LHRH - A之前，在所有患者中在使用E₂或PL之前[基线（BL）]和9周后，以及在EST组中在E₂治疗6周后，测量了E₂、雌酮、睾酮、性激素结合球蛋白、甲状旁腺激素、25 - 羟基维生素D和1,25 - 二羟基维生素D水平以及骨吸收标志物[N - 末端和C - 末端交联肽（NTX和CTX）和脱氧吡啶啉]和骨形成标志物（骨特异性碱性磷酸酶、骨钙素和I型胶原N末端）。在NEO组中，首次注射LHRH - A后3周激素水平下降，脱氧吡啶啉显著增加（P = 0.006）。在BL时，由于LHRH - A治疗时间较长，EST组的骨转换较高。使用E₂治疗后，E₂水平升至正常男性范围，两个骨吸收标志物从BL显著下降，NTX下降33%（P < 0.001），CTX下降28%（P = 0.009）。骨形成标志物没有变化。E₂组中甲状旁腺激素从BL增加了43%（P < 0.01），PL组中从BL下降了16%（P < 0.01）。E₂组中离子钙没有变化，但PL组中增加了2.3%（P < 0.01）。EST组在停用E₂ 6周后NTX和CTX增加。我们得出结论，E₂通过独立于甲状旁腺激素的直接骨骼效应抑制性腺功能减退男性的骨吸收。低剂量雌激素可能是该人群预防和/或治疗骨质流失的一种选择。
