EFFECTS OF TAMOXIFEN AND TRANSDERMAL HORMONE REPLACEMENT THERAPY ON CARDIOVASCULAR RISK-FACTORS IN A PREVENTION TRIAL

The combination of tamoxifen and transdermal hormone replacement thera py (HRT) may potentially reduce risks and side-effects of either agent , but an adverse interaction could attenuate their beneficial effects. We assessed the effects of their combination on cardiovascular risk f actors within a prevention trial of tamoxifen. Baseline and 12-month m easurements of total, low-density lipoprotein (LDL)- and high-density lipoprotein (HDL)-cholesterol, platelets and white blood cells were ob tained in the following four groups: tamoxifen (n = 1117), placebo (n = 1112), tamoxifen and HRT (n = 68), placebo and HRT (n = 87). The ana lysis was further extended to women who were on HRT at randomization b ut discontinued it during the 12-month intervention period (n = 33 on tamoxifen and n = 35 on placebo) and to women who were not on HRT but started it during intervention (n = 36 in both arms of the study). Com pared with small changes in the placebo group, tamoxifen was associate d with changes in total, LDL- and HDL-cholesterol of approximately -9% , -19% and +0.2% in continuous HRT users compared with -9%, -14% and - 0.8% in never HRT users. Similarly, there was no interaction on platel et count. In contrast, the decrease in total and LDL-cholesterol level s induced by tamoxifen was blunted by two-thirds in women who started HRT while on tamoxifen (P = 0.051 for the interaction term), We conclu de that the beneficial effects of tamoxifen on cardiovascular risk fac tors are unchanged in current HRT users, whereas they may be attenuate d in women who start transdermal HRT while on tamoxifen. Whereas a tri al of tamoxifen in women already on transdermal HRT is warranted, pres cription of HRT during tamoxifen may attenuate its activity.