Reducing cancer risk in women through lifestyle-mediated changes in hormone levels

The major hormone-associated cancers of women, viz. breast, endometrium, and ovary, account for some 40% of all female cancers in the U. S. Variable expression of estrogens and progestins account for major differences in the incidence of breast and endometrial cancer. Identified differences in premenopausal ovarian hormone expression and the known effects of post-menopausal weight on estrogen metabolism now permit an essentially complete hormonal explanation of the epidemiology of endometrial cancer. Recent confirmation of decreased ovarian steroid levels in certain Oriental women now permits a hormonal explanation of the four- to sixfold differences in breast cancer rates between Japanese and U.S. women, and a complete hormonal explanation of the epidemiology of breast cancer is almost at hand. A delay of 2 years in the age at menarche plus a low postmenopausal weight are predicted to lead to a more than 50% lifelong reduction in both breast cancer and endometrial cancer. A 2-year delay in menarche is predicted to lead to an 18% reduction in ovarian cancer. The lifestyle basis of variable premenopausal ovarian hormone expression is poorly understood and should be the focus of a major research effort. Profound effects on estrogen and progestin expression and on cancer rates are obtained from use of hormonal contraceptives and menopausal hormone replacement therapy; it appears possible to use this knowledge to construct a LHRHA-plus-estrogen contraceptive regimen that should produce a major lifelong reduction in current U.S. breast cancer rates (32% reduction from 5 years use; 55% from 10 years use). The proposed regimen should also cause a major lifelong reduction in ovarian cancer rates (40% reduction from 5 years use; 66% from 10 years use). Addition of a progestin-containing IUCD to such a regimen should also cause a major lifelong reduction in endometrial cancer rates (55% reduction from 5 years use; 82% reduction from 10 years use).