Hormone replacement therapy and the risk of reproductive cancers

The current literature evaluating the associations between hormone replacement therapy (HRT) and breast, endometrial and ovarian cancers is reviewed. These associations are examined in the context of risks conveyed by exposure to endogenous hormones, as well as other exogenous exposures, particularly oral contraceptive use. The extensive and controversial literature on HRT and breast cancer risk is reviewed in detail. On balance, these data suggest a small increased risk (RR = 1.2-1.3) for long-term, current users of HRT. The most recent and largest cohort study found a greater risk, even for lower estrogen formulations (≤ 0.625 mg/day), particularly among older women who have used HRT for at least 5 years (RR = 1.7). There is little evidence that the addition of progestin protects against this risk. The extent to which associations vary by: subject characteristics (such as type of menopause, or family history), exposure characteristics (dose, duration and type of hormone) and study design issues (study quality, case-control vs. cohort) is discussed. The well-documented duration-dependent increase in endometrial cancer with unopposed estrogen (RR = 9.5 for 10+ years) is reviewed briefly, as well as the somewhat weaker data suggesting little or no increased risk with the addition of progestin for at least 10 days per cycle. The limited data available on HRT and ovarian cancer risk, suggesting little or no association, are also presented.