The adverse effects of hormone replacement therapy.

This article reviews epidemiological data on potential adverse effects of hormone replacement therapy (HRT) on the risk of breast, endometrial and ovarian cancer, on the risk of stroke, and on the risk of venous and pulmonary thromboembolism. As for the potential adverse effects on cancer risk, most information on HRT and breast cancer is included in a re-analysis of individual data from 51 epidemiological studies (including over 90% of the world's data), showing a 2.3% increase of the relative risk of breast cancer for each year of use which, however, levels off after stopping use. This corresponds to a cumulative excess of approximately 2 in 1,000 women who started taking HRT at age 50 and used it for 5 years, 6 in 1,000 women who used it for 10 years and 12 in 1,000 women who used it for 15 years. Unopposed estrogen use is strongly related to endometrial cancer risk mainly in lean women, but the cyclic combined oestrogen-progestin treatment appears to largely or totally reduce this effect if progestin is taken for more than 10 days per cycle. The data on epithelial ovarian cancer allows exclusion of any strong association with HRT, although a moderate positive relationship remains open to debate. As for other adverse effects of HRT, the relationship between HRT and stroke is still debated, although any strong and consistent association can be excluded. Current HRT use, but not past use, is associated with venous and pulmonary thromboembolism. Thus, most adverse effects of HRT are restricted to current or recent use, and long term HRT use should be carefully considered on an individual basis, taking into account any other personal risk factors for breast and endometrial cancer and for venous/pulmonary thromboembolism, and the potential benefits of HRT on cardiovascular disease and osteoporosis.