Cancer risk in women receiving estrogen-progestin replacement therapy

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Objectives and methods: The epidemiological literature was reviewed in order to evaluate the relationship between hormone replacement therapy and risk of cancer in the breast and reproductive organs. Results: For breast cancer, there is no evidence of an overall increase in the risk. According to several studies, but not all, the duration of intake seems to affect the risk. Many years of intake of both estradiol compounds and conjugated estrogens can be assumed to increase the risk of breast cancer 1.5-2-fold. The addition of progestins does not seem to alter (reduce) the duration-risk relationship. The magnitude of risk increase is likely to be small and may be explained partly by methodological problems, or by differences in study populations. The prognosis in patients with HRT-related breast cancer seems to be more favourable than for non-exposed breast cancer patients. Because of the importance of the issue, and inconsistencies in results, further research is urgent. Especially, there is an urgent need to define sub-groups of women who would be susceptible to an adverse influence of HRT. Regarding endometrial cancer, a duration-dependent strong risk relationship with long-term intake of estrogens only is established. The level of risk increase is about 10-fold after 10 or more years of intake, a risk relationship that seems to decrease after discontinuation of treatment. Added progestins for at least 10 days per cycle can reduce or eliminate the risk increase. Tumors occurring after estrogen replacement have favourable biological characteristics. Future research will be needed to define the long-term safety of various progestin regimens. Ovarian cancer risk does not seem to be affected by HRT. Available data are inconsistent and contradictory. Due to the pronounced protective effect of oral contraceptives, further research is needed to measure effects of estrogen-progestin combined regimens. Cervical cancer risk has not been shown to be affected by HRT. Conclusions: It is concluded that hormone replacement therapy, with estrogens alone or estrogens combined with progestins, may have important effects on the risk of cancer, particularly in the breast and endometrium. Therefore, when making a risk-benefit assessment of long-term HRT, possible risk relationships should be considered.