Heald Adrian, Kaushal Kalpana, Anderson Simon, Redpath Mark, Durrington Paul N, Selby Peter L, Gibson Martin J
Department of Diabetes and Endocrinology, University of Manchester, Salford Royal Hospitals University Trust, Salford, UK.
Gynecol Endocrinol. 2005 Mar;20(3):176-82. doi: 10.1080/09513590400027406.
Hormone replacement therapy (HRT) in postmenopausal women is controversial, with an elevated cardiovascular event rate for combined estrogen-progestogen but no adverse cardiovascular effect and possible cumulative benefit for estrogen alone. Here we measured the effects of differing estrogen/progestogen combinations on the insulin-like growth factor (IGF)/IGF binding protein (IGFBP) system which has been implicated in the pathophysiological mechanisms underlying cardiovascular disease, higher IGFBP-1 levels having been linked with a reduced cardiovascular risk.
Oral conjugated equine estrogens (CEE) alone, or in combination with the increasingly androgenic progestogens medroxyprogesterone acetate, desogestrel or norethisterone, were given in a randomized triple crossover fashion to 35 healthy postmenopausal women. Serum concentrations of IGFs and the principal circulating IGFBPs were measured.
Circulating IGF-I, IGFBP-3 and IGF-I/IGFBP-3 molar ratio were significantly reduced by CEE. These effects were reversed by progestogens according to their androgenicity. Plasma IGFBP-1 concentration increased from baseline to CEE alone. This rise was opposed by progestogens of increasing androgenicity. IGFBP-2 levels fell and IGFBP-4 increased with CEE, with no further change with addition of progestogens. CEE increased the proportional contribution of IGFBP-1 and IGFBP-4 to total IGFBP binding and decreased the IGFBP-3 contribution. This was reversed by progestogens.
There are marked changes in molar ratios of the IGFBPs in relation to estrogen/progestogens in HRT. The effect of progestogens on IGF bioavailability could be an important determinant of the longer-term risks of specific HRT preparations by opposing the potentially beneficial effects of CEE alone on cardiovascular risk.
绝经后女性的激素替代疗法（HRT）存在争议，联合使用雌激素 - 孕激素会使心血管事件发生率升高，但单独使用雌激素无不良心血管影响且可能有累积益处。在此，我们测量了不同雌激素/孕激素组合对胰岛素样生长因子（IGF）/IGF结合蛋白（IGFBP）系统的影响，该系统与心血管疾病的病理生理机制有关，较高的IGFBP - 1水平与降低心血管风险相关。
将单独的口服共轭马雌激素（CEE），或与雄激素活性逐渐增强的孕激素醋酸甲羟孕酮、去氧孕烯或炔诺酮联合使用，以随机三重交叉方式给予35名健康绝经后女性。测量血清中IGF和主要循环IGFBP的浓度。
CEE显著降低循环中的IGF - I、IGFBP - 3和IGF - I/IGFBP - 3摩尔比。这些影响根据孕激素的雄激素活性而被逆转。单独使用CEE时，血浆IGFBP - 1浓度从基线升高。这种升高被雄激素活性增加的孕激素所抵消。CEE使IGFBP - 2水平下降，IGFBP - 4升高，添加孕激素后无进一步变化。CEE增加了IGFBP - 1和IGFBP - 4对总IGFBP结合的比例贡献，并降低了IGFBP - 3的贡献。这被孕激素逆转。
在HRT中，IGFBP的摩尔比与雌激素/孕激素有关，存在显著变化。孕激素对IGF生物利用度的影响可能是特定HRT制剂长期风险的重要决定因素，因为它会抵消CEE单独对心血管风险的潜在有益作用。
