Helle S I, Omsjø I H, Hughes S C, Botta L, Hüls G, Holly J M, Lønning P E
Department of Oncology, Haukeland University Hospital, Bergen, Norway.
Clin Endocrinol (Oxf). 1996 Dec;45(6):727-32. doi: 10.1046/j.1365-2265.1996.8610870.x.
Conflicting results have been reported on the effects of oral and transdermal oestrogen replacement therapy on IGF-I, while little information exists regarding the effects on IGFBP -1 and -3. In this study we evaluated the effects of oral and transdermal oestrogens on these parameters in post-menopausal women in a randomized cross-over study.
A group of 14 post-menopausal women were randomized to receive progestin-opposed oestrogen replacement therapy administered orally (Trisekvens Novo: 17 beta-oestradiol 2 mg daily on days 1-22 and 1 mg daily on days 23-28, norethisterone 1 mg days 13-22) or transdermally (Estracomb CIBA: oestradiol 50 micrograms/24 h on days 1-28, norethisterone 250 micrograms/24 h on days 15-28) for 6 months after which they were crossed over to the alternative treatment option. Fasting blood samples were obtained before treatment, and after 3, 6, 9 and 12 months on treatment.
IGF-I, IGF-II, IGFBP-1, IGFBP-3, oestradiol and norethisterone were analysed by radioimmuno-assays. In addition, IGFBPs were evaluated with Western ligand blots (WLB) in a subgroup of 12 patients.
Plasma levels of oestradiol were not significantly different during oral and transdermal treatment. Norethisterone levels were below the detection limit in all situations in 8 patients, while 6 patients had detectable levels in one or several samples during treatment. Oral treatment caused a significant decrease (16%, P < 0.005) in IGF-I and a non-significant decrease in IGFBP-3. A similar effect was observed when samples containing detectable levels of norethisterone were excluded from the analysis. No significant effect on IGFBP-1 was observed when all samples were included in the analysis. However, when samples with detectable norethisterone were excluded IGFBP-1 increased by 46% (P < 0.01) during oral therapy. Contrary, transdermal treatment with oestrogens did not influence any of the parameters measured. None of the treatments had any effect on plasma IGF-II levels or IGFBP profile evaluated by WLB.
Treatment with oral hormone replacement therapy significantly suppresses plasma IGF-1 levels and increases plasma IGFBP-1 while transdermal treatment had no influence. This may be due to the route of administration, as plasma oestradiol levels showed little difference between the groups. The effect of oral oestrogens on IGFBP-1 seems to be attenuated by progestins.
关于口服和经皮雌激素替代疗法对胰岛素样生长因子-I（IGF-I）的影响，已有相互矛盾的报道，而关于其对胰岛素样生长因子结合蛋白-1（IGFBP -1）和-3的影响则知之甚少。在本项随机交叉研究中，我们评估了口服和经皮雌激素对绝经后女性这些参数的影响。
一组14名绝经后女性被随机分为接受口服孕激素对抗的雌激素替代疗法（Trisekvens Novo：第1 - 22天每日服用17β-雌二醇2mg，第23 - 28天每日服用1mg，第13 - 22天服用炔诺酮1mg）或经皮雌激素替代疗法（Estracomb CIBA：第1 - 28天每日释放雌二醇50微克/24小时，第15 - 28天每日释放炔诺酮250微克/24小时），为期6个月，之后交叉接受另一种治疗方案。在治疗前、治疗3、6、9和12个月时采集空腹血样。
采用放射免疫分析法分析IGF-I、IGF-II、IGFBP-1、IGFBP-3、雌二醇和炔诺酮。此外，对12名患者的亚组采用Western配体印迹法（WLB）评估IGFBP。
口服和经皮治疗期间，血浆雌二醇水平无显著差异。8名患者在所有情况下炔诺酮水平均低于检测限，而6名患者在治疗期间的一个或多个样本中可检测到炔诺酮水平。口服治疗导致IGF-I显著降低（16%，P < 0.005），IGFBP-3有非显著降低。当排除含有可检测到炔诺酮水平的样本进行分析时，观察到类似效果。当所有样本纳入分析时，未观察到对IGFBP-1有显著影响。然而，当排除含有可检测到炔诺酮的样本时，口服治疗期间IGFBP-1增加了46%（P < 0.01）。相反，经皮雌激素治疗对所测任何参数均无影响。任何一种治疗对血浆IGF-II水平或通过WLB评估的IGFBP谱均无影响。
口服激素替代疗法显著抑制血浆IGF-1水平并增加血浆IGFBP-1，而经皮治疗无影响。这可能归因于给药途径，因为各组间血浆雌二醇水平差异不大。口服雌激素对IGFBP-1的作用似乎被孕激素减弱。
