Differential effects of selective estrogen receptor modulators and estrogens on mammary blood flow in the ovine.

Abstract

Hormone replacement therapy has been implicated in the increased incidence of breast cancer, although selective estrogen receptor modulators have been shown to be effective in the prevention of breast cancer. Breast cancers are associated with increased mammary blood flow compared to benign breast lesions. However, few studies have examined the hemodynamic effects of hormonal agents on the mammary circulation that promote or reduce the risk of breast cancers. Although estradiol-17beta has been shown to increase mammary blood flow, the effect of selective estrogen receptor modulators remains undetermined. We therefore compared the vascular effects of selective estrogen receptor modulators and estrogens on mammary blood flow. Fourteen nonpregnant ovariectomized ewes were instrumented to measure mean arterial pressure, heart rate, and uterine and mammary blood flows. Compounds were administered intravenously on separate days, and responses were monitored up to 4 hours. Compounds that were studied included estradiol-17beta (1 microg/kg), conjugated equine estrogens (0.625 and 1.25 mg), tibolone (2.5 and 5 mg), raloxifene (10 microg/kg), and tamoxifen (300 microg/kg). None of these compounds significantly affected mean arterial pressure or heart rate, but all of the compounds significantly increased uterine blood flow. Estradiol-17beta increased mammary blood flow by 98% +/- 25%; conjugated equine estrogen increased mammary blood flow by 46% +/- 6% and 68% +/- 13% at the 0.625 and 1.25 mg doses, respectively. Tibolone increased mammary blood flow by 37% +/- 13% at the 2.5-mg dose and by only 14% +/- 4% at the 5-mg dose. Neither raloxifene nor tamoxifen significantly altered mammary blood flow. Although estrogens and selective estrogen receptor modulators induced similar increases in uterine blood flow, they had differential effects on mammary blood flow.