Cline J Mark, Register Thomas C, Clarkson Thomas B
Comparative Medicine Clinical Research Center, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Menopause. 2002 Nov-Dec;9(6):422-9. doi: 10.1097/00042192-200211000-00007.
To measure the effects of 2 years of treatment with tibolone on the breasts of cynomolgus macaques (Macaca fascicularis) in comparison with conventional hormone replacement therapy.
Ovariectomized cynomolgus macaques were randomized into five groups and treated for 2 years. Groups included controls (n = 31) and four drug treatments, including tibolone at 0.05 mg/kg (LoTIB, n = 30) or 0.2 mg/kg (HiTIB, n = 31), conjugated equine estrogens at 0.042 mg/kg (CEE, n = 28), or CEE + medroxyprogesterone acetate (MPA) at 0.167 mg/kg (CEE + MPA, n = 29). Endpoints included histologic, histomorphometric, and immunohistochemical assessment of the mammary gland.
Tibolone did not cause stimulation of the breast in contrast to distinct proliferative responses of the breast to CEE and CEE + MPA, as measured by increases in breast epithelial tissue area and expression of the proliferation marker Ki67 in breast epithelial cells. Tibolone at the higher dose increased progesterone receptor expression in the breast relative to controls, indicating partial estrogen-agonist activity, but without induction of proliferation. Progesterone receptor expression was also induced by CEE.
Tibolone may have an advantage over conventional hormone replacement therapy because it does not stimulate proliferation in the breast. This lack of mammotrophic effect may reflect a lower risk for promotion of breast cancer.
与传统激素替代疗法相比，测量替勃龙治疗2年对食蟹猴（猕猴）乳房的影响。
将去卵巢的食蟹猴随机分为五组并治疗2年。分组包括对照组（n = 31）和四种药物治疗组，包括0.05 mg/kg的替勃龙（低剂量替勃龙组，n = 30）或0.2 mg/kg的替勃龙（高剂量替勃龙组，n = 31）、0.042 mg/kg的结合马雌激素（CEE组，n = 28）或0.167 mg/kg的CEE + 醋酸甲羟孕酮（MPA）（CEE + MPA组，n = 29）。观察终点包括乳腺的组织学、组织形态计量学和免疫组化评估。
与CEE和CEE + MPA引起的乳房明显增殖反应不同，替勃龙未引起乳房刺激，这通过乳腺上皮组织面积增加和乳腺上皮细胞增殖标志物Ki67的表达来衡量。较高剂量的替勃龙相对于对照组增加了乳腺中孕激素受体的表达，表明具有部分雌激素激动剂活性，但未诱导增殖。CEE也诱导了孕激素受体表达。
替勃龙可能优于传统激素替代疗法，因为它不会刺激乳腺增殖。这种缺乏促乳腺生长作用可能反映出乳腺癌发生风险较低。
