FERTILITY AND STERILITY Copyright (t'J 1992 The American Fertility Society

Vol. 57, No.3, March 1992

Printed on acid-free paper in U.S.A.

Progestins, breast cancer, and the limitations of epidemiology

David A. Grimes, M.D. Professor Department of Obstetrics and Gynecology, University of Southern California School of Medicine, Los Angeles, California

Received December 23, 1991. Reprint requests: David A. Grimes, M.D., Department of Obstetrics and Gynecology, Women's Hospital, 1240 North Mission Road, Los Angeles, California 90033.

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Editor's corner

Because the risk of breast cancer is clearly related to endogenous hormones (1), the hypothesis that exogenous hormones may playa role as well has been intensively studied. The review in this issue by Staffa and associates (2) synthesizes recent information concerning the potential impact of progestins on this cancer. The authors approach this question by examining three very different exposures to progestins: oral contraceptives (OCs), hormone replacement therapy, and injectable contraceptives. What lessons can be learned? Studying the effect of progestins on breast cancer risk by examining use of combination OCs containing progestins is analogous to studying the impact of calcium on osteoporosis by examining use of prenatal vitamin supplements containing calcium. How does one isolate the effect of the single exposure (hormone or element) of interest? In the case of OCs in the United States, six different progestins have been used in various doses and combinations with two different estrogens. If an effect were found, how could one then tease out the contribution of the progestin as opposed to that of the estrogen? The dose, duration, and timing of progestin exposure in relation to age and reproductive events such as births may all playa role. In addition, findings related to OCs used before the mid-1980s may be irrelevant (3). Only since then have the majority of pills used in the United States been low-dose formulations with

Progestins, breast cancer, and the limitations of epidemiology.

Critical comment on the potential impact of progestins on breast cancer is presented. The limitations of epidemiology for identifying small risks are ...
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