Can variability in the hormonal status of elderly women assist in the decision to administer estrogens?

Hormone replacement therapy (HRT) has been proposed for the prevention and treatment of many chronic conditions, ranging from osteoporosis, heart dise ase, urinary incontinence, and Alzheimer's disease. With the exception of o steoporosis, however, many of the suggested benefits remain controversial. Part of the controversy stems from the relative absence of randomized contr olled trials, particularly those enrolling sufficient numbers of elderly wo men. We propose that another factor may also contribute, one that has been overlooked-failure to consider the variable endogenous estrogen status of e lderly women. Highly variable levels of estrogens are present in nearly all postmenopausal women, even at advanced ages. Similar to other endocrine sy stems, estrogen deficiency and the need for its replacement are, therefore, likely to be relative rather than absolute. Recent studies indicate that e lderly women who are less able to compensate for declining ovarian 17 beta -estradiol production by adipose synthesis of estrone (El) may be at greate r risk for certain chronic conditions associated with relative estrogen def iciency. Because many markers of estrogen deficiency exhibit overlap betwee n risk groups, their clinical usefulness as predictors of frailty, disabili ty, 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 b ut also on markers of overall estrogenic effects at the level of individual target tissues (i.e., markers of bone turnover, karyopyknotic index on a v aginal wall smear). We propose that a clinical approach that takes into con sideration the remarkable heterogeneity (physiological as well as psycholog ical) of elderly women will enable us to approach the decision about HRT in a more individualized and possibly better targeted fashion.