Early age at natural menopause or
bilateral ovariectomy substantially reduce a woman's lifetime risk of
breast cancer. Reversible '
bilateral ovariectomy' can now in effect be achieved by 'high-dose' luteinising
hormone releasing
hormone (
LHRH) agonists (LHRHAs). The harmful effects of such medical reversible
bilateral ovariectomy, in particular the increased risks of
coronary heart disease and
osteoporosis, can in all likelihood be obviated by 'low-dose' oestrogen replacement
therapy (ERT), specifically 0.625 mg of conjugated equine oestrogens (CEE) for 21 days in each 28-day treatment cycle, and such ERT use will only negate to a relatively small extent the beneficial effect of such
bilateral ovariectomy on
breast cancer risk. We calculate that such an LHRHA plus low-dose ERT regimen given to a premenopausal woman for 10 years will, in addition to being a most effective
contraceptive, decrease her lifetime risk of
breast cancer by more than 50%. We calculate that such a 10-year regimen will also decrease her risk of
ovarian cancer by two-thirds. This regimen should leave
endometrial cancer risk and bone metabolism unaltered, and may reduce the risk of
heart disease. The addition of a 'low-dose'
progestogen to the regimen for 12 days in each 28-day treatment cycle would be beneficial to the endometrium, but it will adversely affect risk factors for heart disease and it may significantly reduce the benefit of the regimen as regards
breast cancer. A satisfactory compromise may be to add a low-dose
progestogen for 12 days at less frequent intervals. Another possibility may be to deliver a
progestogen solely to the endometrium with an intra-uterine device; the benefits of such a regimen would be a significant reduction in the incidence of breast, ovarian and
endometrial cancer.