Estrogens and women's health: interrelation of coronary heart disease, breast cancer and osteoporosis

The determinants of blood levels of estrogen, estrogen metabolites, and rel ation to receptors and post-transitional effects are the likely primary cau se of breast cancer. Very high risk women for breast cancer can now be iden tified by measuring bone mineral density and hormone levels. These high ris k women have rates of breast cancer similar to risk of myocardial infarctio n. They are candidates for SERM therapies to reduce risk of breast cancer. The completion of the Women's Health Initiative and other such trials will likely provide a definite association of risk and benefit of both estrogen alone and estrogen-progesterone therapy, coronary heart disease, osteoporot ic fracture, and breast cancer. The potential intervention of hormone repla cement therapy, obesity, or weight gain and increased atherogenic lipoprote inemia may be of concern and confound the results of clinical trials. Estro gens, clearly, are important in the risk of bone loss and osteoporotic frac ture, Obesity is the primary determinant of postmenopausal estrogen levels and reduced risk of fracture. Weight reduction may increase rates of bone l oss and fracture. Clinical trials that evaluate weight loss should monitor effects on bone. The beneficial addition of increased physical activity, hi gher dose of calcium or vitamin D, or use of bone reabsorption drugs in coo rdination with weight loss should be evaluated. Any therapy that raises blo od estrogen or metabolite activity and decreases bone loss may increase ris k of breast cancer. Future clinical trials must evaluate multiple endpoints such as CHD, osteoporosis, and breast cancer within the study. The use of surrogate markers such as bone mineral density, coronary calcium, carotid i ntimal medial thickness and plaque, endothelial function, breast density, h ormone levels and metabolites could enhance the evaluation of risk factors, genetic-environmental intervention, and new therapies. (C) 2000 Elsevier S cience Ltd. All rights reserved.