This monograph evaluates evidence for an increased risk of cancer in women using combined oral contraceptives, progestogen-only hormonal contraceptives, post-menopausal oestrogen therapy, and post-menopausal oestrogen-progestogen therapy. Although the carcinogenicity of these preparations has been extensively investigated, the book stresses the many complex methodological issues that must be considered when interpreting findings and weighing results. Evidence of an association between use of these preparations and positive effects on health, including a reduced risk of some cancers, is also critically assessed.

The first and most extensive monograph evaluates evidence of an association between the use of combined oral contraceptives and cancer at nine sites. Concerning breast cancer, the evaluation concludes that, even if the association is causal, the excess risk for breast cancer associated with patterns of use that are typical today is very small. Studies of predominantly high-dose preparations found an increased risk of hepatocellular carcinoma in the absence of hepatitis viruses. Citing these findings, the evaluation concludes that there is sufficient evidence in humans for the carcinogenicity of combined oral contraceptives. The evaluation also found sufficient evidence for the carcinogenicity of some, but not all, combined preparations in animals. Combined oral contraceptives were classified as carcinogenic to humans. The evaluation also cites conclusive evidence that these agents have a protective effect against cancers of the ovary and endometrium. Progestogen-only contraceptives are evaluated in the second monograph, which considers the association with cancer at six sites. The evaluation found no evidence of an increased risk for breast cancer. Although the evaluation found sufficient evidence in animals for the carcinogenicity of medroxyprogesterone acetate, evidence for the carcinogenicity of progestogen-only contraceptives in humans was judged inadequate. Progestogen-only contraceptives were classified as possibly carcinogenic to humans.

The third monograph, on post-menopausal oestrogen therapy, considers evidence of an association with cancer at eight sites. Findings from a large number of epidemiological studies indicate a small increase in the risk of breast cancer in women who have used these preparations for five years or more. Studies consistently show an association between use of post-menopausal oestrogen therapy and an increased risk for endometrial cancer. Data on the association with other cancers were either inconclusive or suggested no effect on risk. The evaluation concludes that post-menopausal oestrogen therapy is carcinogenic to humans.

The final monograph evaluates the association between the use of post-menopausal oestrogen-progestogen therapy and cancer at four sites. The evaluation of limited data on breast cancer found an increased relative risk observed with long-term use. Data were judged insufficient to assess the effects of past use and of different progestogen compounds, doses, and treatment schedules. For endometrial cancer, the evaluation found an increase in risk relative to non-users when the progestogen was added to the cycle for 10 days or fewer. Post-menopausal oestrogen-progestogen therapy was classified as possibly carcinogenic to humans. Concerning post-menopausal therapy in general, the book notes that evidence of carcinogenic risks must be placed in perspective of potential benefits. The prevention of osteoporotic fractures is cited as the best-established benefit. Evidence also suggests that oestrogen prevents heart disease and may prevent memory loss and dementia.

Contents

• NOTE TO THE READER
• LIST OF PARTICIPANTS
• PREAMBLE
• GENERAL REMARKS
• THE MONOGRAPHS
  • Oral contraceptives, combined
    • 1. Exposure
    • 2. Studies of Cancer in Humans
    • 3. Studies of Cancer in Experimental Animals
    • 4. Other Data Relevant to an Evaluation of Carcinogenicity and its Mechanisms
    • 5. Summary of Data Reported and Evaluation
    • 6. References
  • Hormonal contraceptives, progestogens only
    • 1. Exposure
    • 2. Studies of Cancer in Humans
    • 3. Studies of Cancer in Experimental Animals
    • 4. Other Data Relevant to an Evaluation of Carcinogenicity and its Mechanisms
    • 5. Summary of Data Reported and Evaluation
    • 6. References
  • Post-menopausal oestrogen therapy
    • 1. Exposure
    • 2. Studies of Cancer in Humans
    • 3. Studies of Cancer in Experimental Animals
    • 4. Other Data Relevant to an Evaluation of Carcinogenicity and its Mechanisms
    • 5. Summary of Data Reported and Evaluation
    • 6. References
  • Post-menopausal oestrogen–progestogen therapy
    • 1. Exposure
    • 2. Studies of Cancer in Humans
    • 3. Studies of Cancer in Experimental Animals
    • 4. Other Data Relevant to an Evaluation of Carcinogenicity and its Mechanisms
    • 5. Summary of Data Reported and Evaluation
    • 6. References
• SUMMARY OF FINAL EVALUATIONS
• ANNEX 1. Chemical and physical data and information on production and use for oestrogens and progestogens used in oral contraceptives, progestogen-only contraceptives and post-menopausal hormonal therapy
• ANNEX 2. Preparations of oestrogens, progestogens and combinations of oestrogens and progestogens that are or have been used as hormonal contraceptives and for post-menopausal hormonal therapy, with known trade names

Corrigenda to the IARC Monographs are published online at: http://monographs.iarc.fr/ENG/Publications/corrigenda.php

LIBRARY CATALOGUING DATA

This publication represents the views and expert opinions of an IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, which met in Lyon, 2–9 June 1998

Lyon, France - 1999