Issues to debate on the Women's Health Initiative: failure of estrogen plus progestin therapy for prevention of breast cancer risk.
Several studies on hormone replacement therapy (HRT) in the USA have been published. They revealed that the risk of breast cancer is increased with HRT more than with estrogen alone (ERT). A progestin has been given with each dose of ERT, as was the case in the Women's Health Initiative (WHI) study. The results of studies in Europe show similar trends. The increased risk of breast cancer in the WHI study was significantly higher only in women who had used HRT for several years before entering the study. The study was non-blind in 3444 cases, i.e. 40.5% of women in the estrogen plus progestin group and 6.8% in controls. If the women in the HRT group had more mammographic examinations it could change the validity of the results of the study. Estradiol-containing drugs have now been added to the list of carcinogens and the packages of these drugs have warning labels. The results of the WHI study do not support this labelling. The results of the WHI study show that the administration of HRT increases the risks of stroke and pulmonary embolism. It is reasonable to think that in the case of bleeding, at least at weekends in nursing homes (when staff levels may be low) patients were immobilized in their beds. Immobilization among women on HRT could have been more dangerous than the HRT itself. Progestins need to be delivered to the endometrium in a manner that will have the least effect on the breast. Systemic administration can be replaced by releasing progestin locally in the uterine cavity. Endometrial protection with a levonorgestrel-releasing intra-uterine system (IUS) is well tolerated. The high hepatic concentrations of estrogens given orally could be avoided by transdermal administration. New studies should be planned to reflect the situation in clinical practice. The time to start HRT in healthy menopausal women is between the ages of 45 to 55 years.
Luukkainen
T
T
Institute of Biomedicine, Biochemistry, Biomedicum Helsinki, P.O. Box 63, FIN-00014 University of Helsinki, Finland. Tapani.Luukkainen@helsinki.fi
D001943:Breast Neoplasms / Q000209:etiology / Q000517:prevention & control*; D002318:Cardiovascular Diseases / Q000209:etiology / Q000517:prevention & control; D003327:Coronary Disease / Q000209:etiology / Q000517:prevention & control; D015914:Estrogen Replacement Therapy / Q000009:adverse effects*; D005060:Europe; D005260:Female; D006801:Humans; D012307:Risk Factors; D014481:United States; D016387:Women's Health