HORMONE REPLACEMENT THERAPY AND MAJOR RISK FACT ORS FOR REPRODUCTIVE CANCERS, OSTEOPOROSIS, AND CARDIOVASCULAR-DISEASES - EVIDENCE OF CONFOUNDING BY EXPOSURE CHARACTERISTICS

Observational studies have yielded reports on long-term effects of hor mone replacement therapy (HRT) for cardiovascular, osteoporosis relate d, and cancer diseases. There is concern that risk estimates may be co nfounded by complex mechanisms of selection with regard to important r isk determinants. In this study, we tested the hypothesis that baselin e characteristics of women vary with exposure characteristics, i.e., t he choices of complying with prescriptions, using different compounds and regimens, and continuing intake long term. We analyzed the prevale nce of relevant risk factors and their relationships to characteristic s of exposure among 11,231 Swedish women who had received prescription s for HRT. Associations were studied through logistic regression, with comparisons of women with ever-use versus non-compliance, long-term ( 73+ months) versus short-term use (1-72 months), intake of conjugated estrogens versus estradiol compounds, and intake of estrogens only ver sus estrogens combined with progestins, respectively. We found that wo men denying intake or using HRT short-term had higher parity, earlier age at first birth and a lower prevalence of hysterectomy or oophorect omy than those complying or exposed long term. A high level of educati on was associated with compliance and long term exposure, and heavy ph ysical exercise and high intake of food fibers were associated with co mpliance. Climacteric symptoms were associated with compliance, long-t erm intake and use of conjugated estrogens, whereas a history of oral contraceptive intake was associated with use of estrogens alone withou t progestins. We conclude that selection biases in studies of HRT effe cts are important and complex in that they may vary with the reported exposure. Our findings are important, as they point to the need for im proved methods for measuring, in particular, factors linked to lifesty le and health behavior, in order to account more fully for confounding in the analyses of risk relationships. (C) 1997 Elsevier Science Inc.