Sharp C A, Evans S F, Risteli L, Risteli J, Worsfold M, Davie M W
Charles Salt Centre, Robert Jones & Agnes Hunt Orthopaedic and District Hospital NHS Trust, Oswestry, Shropshire, UK.
Eur J Clin Invest. 1996 Sep;26(9):763-71. doi: 10.1046/j.1365-2362.1996.2000550.x.
The minimum dosage of transcutaneous hormone replacement therapy (HRT) able to exert protective effects on postmenopausal bone mass, especially in older women, is uncertain. This study investigates the effects of transcutaneous HRT at two different doses of oestradiol [Estraderm 25 and 50 (E25, E50)] over 2 years in 44 postmenopausal women younger than 67 years and 27 of 67 years and older. Circulating biochemical markers of bone and connective tissue turnover, collagen type I (intact PINP, PICP) and type III (PIIINP) propeptides and type I telopeptide (ICTP), osteocalcin (OC) and alkaline phosphatase (AP) were measured. The responses of the biochemical markers in all the groups were very similar, and most of the observed changes occurred within the first year of treatment. E25 had an effect on the bone markers similar to that of E50, and there was little difference in response according to the patient's age. PINP fell markedly after 1 year in all groups to about half the pretreatment level, with a smaller drop in the second year. PICP responded more variably, and mean values were little changed. There was a slight fall at the higher dose in the younger women, and also in the older women (whose baseline level was higher) on the lower dose. The correlation between PINP and PICP was 0.52 at pretreatment and 0.84 after 2 years of treatment. PIIINP showed no changes. OC and AP both fell in all groups by the first year, but less markedly than PINP. Their response was slightly less pronounced in the older women. ICTP fell marginally in the younger women, and only after 2 years, regardless of dose. Postmenopausal serum oestradiol levels increased after HRT and were associated with decreased binding globulin (SHBG) levels in all groups. After E25 patch application individual serum oestradiol levels were variable and peaked between 13 and 36 h with a median value of 83.8 pmol L-1. Our data suggest that low-dose transcutaneous HRT restores circulating oestradiol levels in postmenopausal osteopenic women of all ages as effectively as conventional-dose HRT and is associated with decreased circulating markers of bone and connective tissue turnover.
经皮激素替代疗法（HRT）对绝经后骨量，尤其是老年女性骨量产生保护作用的最低剂量尚不确定。本研究调查了两种不同剂量雌二醇（雌二醇透皮贴25和50，即E25、E50）的经皮HRT在44名67岁以下绝经后女性和27名67岁及以上绝经后女性中持续2年的效果。检测了骨和结缔组织转换的循环生化标志物，即I型胶原（完整PINP、PICP）和III型胶原（PIIINP）前肽以及I型端肽（ICTP）、骨钙素（OC）和碱性磷酸酶（AP）。所有组中生化标志物的反应非常相似，且大多数观察到的变化发生在治疗的第一年。E25对骨标志物的作用与E50相似，且根据患者年龄的反应差异不大。所有组中，PINP在1年后显著下降至治疗前水平的约一半，第二年下降幅度较小。PICP的反应变化更大，平均值变化不大。年轻女性中较高剂量组以及老年女性（其基线水平较高）中较低剂量组均有轻微下降。治疗前PINP与PICP的相关性为0.52，治疗2年后为0.84。PIIINP无变化。OC和AP在所有组中到第一年时均下降，但不如PINP明显。老年女性中的反应略不明显。ICTP在年轻女性中仅在2年后略有下降，且与剂量无关。HRT后绝经后血清雌二醇水平升高，且所有组中均与结合球蛋白（SHBG）水平降低相关。应用E25贴剂后，个体血清雌二醇水平各不相同，在13至36小时达到峰值，中位数为83.8 pmol/L。我们的数据表明，低剂量经皮HRT与传统剂量HRT一样有效地恢复了所有年龄段绝经后骨质减少女性的循环雌二醇水平，且与骨和结缔组织转换的循环标志物降低相关。
