Kuchel G A, Tannenbaum C, Greenspan S L, Resnick N M
UConn Center on Aging, University of Connecticut Health Center, Farmington, Connecticut 06030-5215, USA.
J Womens Health Gend Based Med. 2001 Mar;10(2):109-16. doi: 10.1089/152460901300039449.
Hormone replacement therapy (HRT) has been proposed for the prevention and treatment of many chronic conditions, ranging from osteoporosis, heart disease, urinary incontinence, and Alzheimer's disease. With the exception of osteoporosis, however, many of the suggested benefits remain controversial. Part of the controversy stems from the relative absence of randomized controlled trials, particularly those enrolling sufficient numbers of elderly women. We propose that another factor may also contribute, one that has been overlooked - failure to consider the variable endogenous estrogen status of elderly women. Highly variable levels of estrogens are present in nearly all postmenopausal women, even at advanced ages. Similar to other endocrine systems, estrogen deficiency and the need for its replacement are, therefore, likely to be relative rather than absolute. Recent studies indicate that elderly women who are less able to compensate for declining ovarian 17beta-estradiol production by adipose synthesis of estrone (E1) may be at greater risk for certain chronic conditions associated with relative estrogen deficiency. Because many markers of estrogen deficiency exhibit overlap between risk groups, their clinical usefulness as predictors of frailty, disability, and response to HRT has been limited. Future studies will need to focus not only on the use of highly variable circulating serum estrogen levels but also on markers of overall estrogenic effects at the level of individual target tissues (i.e., markers of bone turnover, karyopyknotic index on a vaginal wall smear). We propose that a clinical approach that takes into consideration the remarkable heterogeneity (physiological as well as psychological) of elderly women will enable us to approach the decision about HRT in a more individualized and possibly better targeted fashion.
激素替代疗法（HRT）已被提出用于预防和治疗多种慢性病，包括骨质疏松症、心脏病、尿失禁和阿尔茨海默病。然而，除了骨质疏松症外，许多所谓的益处仍存在争议。部分争议源于相对缺乏随机对照试验，尤其是那些纳入足够数量老年女性的试验。我们认为，另一个因素可能也起了作用，而这个因素一直被忽视——未能考虑老年女性内源性雌激素状态的差异。几乎所有绝经后女性，即使到了高龄，雌激素水平也存在很大差异。因此，与其他内分泌系统类似，雌激素缺乏及其替代需求可能是相对的而非绝对的。最近的研究表明，那些通过脂肪合成雌酮（E1）来补偿卵巢17β - 雌二醇分泌下降能力较弱的老年女性，可能面临与相对雌激素缺乏相关的某些慢性病的更高风险。由于许多雌激素缺乏的标志物在风险组之间存在重叠，它们作为虚弱、残疾和对HRT反应的预测指标的临床实用性有限。未来的研究不仅需要关注高度可变的循环血清雌激素水平，还需要关注个体靶组织水平上整体雌激素效应的标志物（即骨转换标志物、阴道壁涂片上的核固缩指数）。我们认为，一种考虑到老年女性显著异质性（生理和心理方面）的临床方法，将使我们能够以更个体化且可能更有针对性的方式来做出关于HRT的决策。
