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Fertil Steril. 1994 Dec;62(6 Suppl 2):168S-175S.

Links between hormone replacement therapy and neoplasia.

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  • 1Department of Epidemiology, School of Public Health, University of North Carolina, Chapel Hill 27599-7400.



To evaluate the literature on exogenous estrogens and progestins on risk of breast and endometrial cancers.


Review of epidemiologic literature.


Population- and hospital-based studies.


Postmenopausal women.


Sex steroid hormone in hormone replacement regimens.


Breast carcinoma and endometrial carcinoma.


Estrogens cause cell proliferation in in vitro systems and enhance tumor formation in carcinogen-exposed animal models. Estrogen effects in humans vary by tissue type, exposure patterns, and subject groups. Doses commonly used for estrogen replacement therapy (ERT) are sufficient to cause proliferation, hyperplasia, and carcinoma of the endometrium. After 10 to 15 years of estrogen use, endometrial cancer risk increases nearly 10-fold, but the cancers produced are generally of low grade and stage with an excellent prognosis. Adding a progestin for > or = 10 d/mo reduces or eliminates the estrogen-induced risk. Breast tissue responds differently to sex steroid hormones. Long-term estrogen use increases breast cancer risk modestly (relative risk approximately 1.3 to 1.5). Particular subgroups, such as those with family history, benign proliferative disease, or late natural menopause, may experience greater risk. None of these characteristics are sufficiently well defined to be clear-cut contraindications to ERT. Adding a progestin does not improve the situation; relative risks may be higher for estrogen plus progestin than for estrogen alone. The effect of low dose progestin, e.g., 2.5 mg Provera, administered continuously with the estrogen, is not known. A small increase in relative risk has a large impact on number of women developing breast cancer because of the high baseline rates. For U.S. women age 65, the baseline rate is 210 new cases per 100,000 women per year. A relative risk as small as 1.2 increases a women's chances of developing breast cancer each year from 1 in 250 to 1 in 200.

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