Summary
An overview of the available epidemiological evidence on the connection between oral contraceptives and cancer or vascular disease is presented, including the observation that epidemiological studies have produced important indications for changing both the composition and prescription patterns of oral contraceptives to avoid a large proportion of vascular side effects. Further, the evidence is remarkably clear and consistent in relation to the elevated risks of cervical neoplasms and, although based on a limited number of small studies, of primary liver cancer; protection against endometrial and ovarian cancers up to middle age; and the absence of association with malignant melanoma. There are still uncertainties regarding breast cancer, mainly related to the role of time factors, and the potential persisting risk related to long term use at younger age: published studies, in fact, show elevated risks for long term use in women below age 35 or perhaps up to age 45, but no evidence of association in middle age. Since breast cancer and ovarian cancer account for most of the mortality burden in women up to age 50 or 55 in developed countries, a clarification of the risk relationship for these 2 neoplasms will determine most of the quantitative evaluation on positive or adverse effects of oral contraceptives. The impact of other neoplasms and of cardiovascular disease, on the basis of current oral contraceptive composition, is comparatively limited, if not negligible.
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References
Adam SA, Sheaves JK, Wright NH, Mosser G, Harris RW, et al. A case-control study of the possible association between oral contraceptives and malignant melanoma. British Journal of Cancer 44: 45–50, 1981
Andolsek L, Kovacic U, Kozuh M, Litt B. Oral contraceptives and cervical cancer. Lancet 2: 1310, 1983
Bain C, Hennekens CH, Speizer FE, Rosner B, Willett W, et al. Oral contraceptive use and malignant melanoma. Journal of the National Cancer Institute 68: 537–539, 1982
Beral V, Evans S, Shaw H. Oral contraceptive use and malignant melanoma in Australia. British Journal of Cancer 50: 681–685, 1984
Beral V, Ramcharan S, Faris R. Malignant melanoma and oral contraceptive use among women in California. British Journal of Cancer 36: 804–809, 1977
Booth M, Beral V, Smith P. Risk factors for ovarian cancer: a case-control study. British Journal of Cancer 60: 592–598, 1989
Brinton LA, Huggins GR, Lehman HF, Mallin K, Savitz DA, et al. Long-term use of oral contraceptives and risk of invasive cervical cancer. International Journal of Cancer 38: 339–344, 1986
Bruzzi P, Negri E, La Vecchia C, Decarli A, Palli D, et al. Short term increase in risk of breast cancer after full term pregnancy. British Medical Journal 297: 1096–1098, 1988
CASH (Cancer and Steroid Hormone Study of the Centers for Disease Control and the National Institute of Child Health and Human Development). Combination oral contraceptive use and the risk of endometrial cancer. Journal of the American Medical Association 257: 796–800, 1987a
CASH (Cancer and Steroid Hormone Study of the Centers for Disease Control and the National Institute of Child Health and Human Development). The reduction in risk of ovarian cancer associated with oral contraceptive use. New England Journal of Medicine 316: 650–655, 1987b
Casagrande JT, Louie EW, Pike MC, Roy S, Ross RK, et al. ‘Incessant ovulation’ and ovarian cancer. Lancet 2: 170–172, 1979
Celentano DD, Klassen AC, Weisman CS, Rosenshein NB. The role of contraceptive use in cervical cancer: the Maryland cervical cancer case-control study. American Journal of Epidemiology 126: 592–604, 1987
Cramer DW, Hutchison GB, Welch WR, Scully RE, Knapp RC. Factors affecting the association of oral contraceptives and ovarian cancer. New England Journal of Medicine 307: 1047, 1982
Fasal E, Simmons ME, Kampert JB. Factors associated with high and low risk of cervical neoplasia. Journal of the National Cancer Institute 66: 631–636, 1981
Forman D, Vincent TJ, Doll R. Cancer of the liver and the use of oral contraceptives. British Medical Journal 292: 1355, 1986
Gallagher RP, Elwood JM, Hill GB, Coldman AJ, Threlfall WJ, et al. Reproductive factors, oral contraceptives and risk of melanoma. Western Canada Melanoma Study. British Journal of Cancer 52: 901–907, 1985
Green A, Bain C. Hormonal factors and melanoma in women. Medical Journal of Australia 142: 446–448, 1985
Harlow BL, Weiss NS, Roth GJ, Chu J, Daling JR. Case-control study of borderline ovarian tumors: reproductive history and exposure to exogenous female hormones. Cancer Research 48: 5849–5852, 1988
Helmrich SP, Rosenberg L, Kaufmann DW, Miller DR, Schottenfeld D, et al. Lack of elevated risk of malignant melanoma in relation to oral contraceptive use. Journal of the National Cancer Institute 72: 617–620, 1984
Henderson BE, Preston-Martin S, Edmondson HA, Peters RL, Pike MC. Hepatocellular carcinoma and oral contraceptives. British Journal of Cancer 48: 437, 1983
Hildreth NG, Kelsey JL, LiVolsi VA, Fischer DB, Holford TR, et al. An epidemiologic study of epithelial carcinoma of the ovary. American Journal of Epidemiology 114: 398–405, 1981
Holly EA, Weiss NS, Liff JM. Cutaneous melanoma in relation to exogenous hormones and reproductive factors. Journal of the National Cancer Institute 70: 827–831, 1983
Holman CDJ, Armstrong BK, Heenan PJ. Cutaneous malignant melanoma in women: exogenous sex hormones and reproductive factors. British Journal of Cancer 50: 637–680, 1984
Hulka BS, Chambless LE, Kaufmann DG, Fowler Jr WC, Green-berg BG. Protection against endometrial carcinoma by combination-product oral contraceptives. Journal of the American Medical Association 247: 475–477, 1982
Irwin KL, Rosero-Bixby L, Oberle MW, Lee NC, Whatley AS, et al. Oral contraceptives and cervical cancer risk in Costa Rica: detection bias or causal association? Journal of the American Medical Association 259: 59–64, 1988
Jick H, Dinan B, Rothman KJ. Oral contraceptives and nonfatal myocardial infarction. Journal of the American Medical Association 239: 1403–1406, 1978
Jick SS, Walker AM, Stergachis A, Jick H. Oral contraceptives and breast cancer. British Journal of Cancer 59: 618–621, 1989
Kaufman DW, Shapiro S, Slone D, Rosenberg L, Miettinen OS, et al. Decreased risk of endometrial cancer among oral-contraceptive users. New England Journal of Medicine 303: 1045–1047, 1980
Kay CR, Hannaford PC. Breast cancer and the pill: a further report from the Royal College of General Practitioners’ oral contraception study. British Journal of Cancer 58: 675–680, 1988
Kay CR. Malignant melanoma and oral contraceptives. British Journal of Cancer 44: 479, 1981
Kay TJA, Pike MC. The dose-effect relationship between ‘unopposed’ oestrogens and endometrial mitotic rate: its central role in explaining and predicting endometrial cancer risk. British Journal of Cancer 57: 205–212, 1988
La Vecchia C, Bruzzi P, Boyle P. Some further consideration on the role of oral contraceptives in breast carcinogenesis. Tumori 76: 220–224, 1990
La Vecchia C, Decarli A, Fasoli M, Franceschi S, Gentile A, et al. Oral contraceptives and cancers of the breast and of the female genital tract: interim results from a case-control study. British Journal of Cancer 54: 311–317, 1986
La Vecchia C, Negri E, Parazzini F. Oral contraceptives and primary liver cancer. British Journal of Cancer 59: 460–461, 1989
Lubin JH, Burns PE, Blot WJ, Lees AW, May C, et al. Risk factors for breast cancer in women in Northern Alberta, Canada, as related to age at diagnosis. Journal of the National Cancer Institute 68: 211–217, 1982
Mann JI, Inman WHW, Thorogood M. Oral contraceptive use in older women and fatal myocardial infarction. British Medical Journal 2: 445–447, 1976
McPherson K, Vessey MP, Neil A, Doll R, Jones L, et al. Early oral contraceptive use and breast cancer results of another case-control study. British Journal of Cancer 56: 653–660, 1987
Meirik O, Lund E, Adami HO, Bergström R, Christoffersen T, et al. Oral contraceptive use and breast cancer in young women: a joint national case-control study in Sweden and Norway. Lancet 2: 650–654, 1986
Miller DR, Rosenberg L, Kaufman DW, Stolley P, Warshauer ME, et al. Breast cancer before age 45 and oral contraceptive use: new findings. American Journal of Epidemiology 129: 269–280, 1989
Molina R, Thomas DB, Dabancens A, Lopez J, Ray RM, et al. Oral contraceptives and cervical carcinoma in situ in Chile. Cancer Research 48: 1011–1015, 1988
Neuberger J, Forman D, Doll R, Williams R. Oral contraceptives and hepatocellular carcinoma. British Medical Journal 292: 1355, 1986
Newhouse ML, Pearson RM, Fullerton JM, Boesen EAM, Shannon HS. A case-control study of carcinoma of the ovary. British Journal of Preventative and Social Medicine 31: 148, 1977
Olsson H, Möller TR, Ranstam J. Early oral contraceptive use and breast cancer among premenopausal women: final report from a study in Southern Sweden. Journal of the National Cancer Institute 81: 1000–1004, 1989
Ory HW, Conger SB, Naib Z, Tyler Jr CW, Hatcher RA. Preliminary analysis of oral contraceptive use and risk of developing premalignant lesion of the uterine cervix. In Garattini & Ber-endes (Eds) Pharmacology of steroid contraceptive drugs, pp. 211–224, Raven Press, New York, 1977
Osterlind A, Tucker MA, Stone BJ, Jensen OM. The Danish case-control study of cutaneous malignant melanoma: III. Hormonal and reproductive factors in women. International Journal of Cancer 42: 821–824, 1988
Palmer JR, Rosenberg L, Kaufman DW, Warshauer ME, Stolley P, et al. Oral contraceptive use and liver cancer. American Journal of Epidemiology 130: 878–882, 1989
Paul Ch, Skegg DCG, Spears GFS, Kaldor JM. Oral contraceptives and breast cancer a national study. British Medical Journal 293: 723–726, 1986
Pike MC, Henderson BE, Krailo MD, Duke A, Roy S. Breast cancer in young women and use of oral contraceptives: possible modifying effect of formulation and age at use. Lancet 2: 926–930,1983
Piper JM, Kennedy DL. Oral contraceptives in the United States: trends in content and potency. International Journal of Epidemiology 16: 215–221, 1987
Prentice RL. Thomas DB. On the epidemiology of oral contraceptives and disease. Advances in Cancer Research 49: 285–401, 1987
Ramcharan S, Pellegrin FA, Ray R, Hsu JP. A prospective study of the side effects of oral contraceptives. The Walnut Creek Contraceptive Study, Vol. 3, NIH Publication No. 81–564, Be-thesda, 1981
Ravnihar B, Zakelj MP, Kosmelj K, Stare J. A case-control study of breast cancer in relation to oral contraceptive use in Slovenia. Neoplasma 35: 109–121, 1988
RCGP (Royal College of General Practitioners). Oral contraceptives and health: an interim report from the Oral Contraception Study of the Royal College of General Practitioners, Pitman Medical, London, 1974
Romieu I, Willett WC, Colditz GA, Stampfer MJ, Rosner B, et al. Prospective study of oral contraceptive use and risk of breast cancer in women. Journal of the National Cancer Institute 81: 1313–1321, 1989
Rosenberg L, Miller DR, Kaufman DW, Helmrich SP, Stolley PD, et al. Breast cancer and oral contraceptive use. American Journal of Epidemiology 119: 167–176, 1984
Rosenberg L, Shapiro S, Slone D, Kaufman DW, Helmrich SP, et.al. Epithelial ovarian cancer and combination oral contraceptives. Journal of the American Medical Association 247: 3210–3212, 1982
Shapiro S, Slone D, Rosenberg L, Kaufman DW, Stolley PD, et al. Oral-contraceptive use in relation to myocardial infarction. Lancet 1: 743–747, 1979
Shu XO, Brinton LA, Gao YT, Yuan JM. Population-based case-control study of ovarian cancer in Shanghai. Cancer Research 49: 3670–3674, 1989
Slone D, Shapiro S, Kaufman DW, Rosenberg L, Miettinen OS, et al. Risk of myocardial infarction in relation to current and discontinued use of oral contraceptives. New England Journal of Medicine 305: 420–424, 1981
Stadel BV. Oral contraceptives and cardiovascular disease. New England Journal of Medicine 305: 612–618, 672–677, 1981
Stadel BV, Rubin GL, Webster LA, Schlesselman JJ, Wingo PA. Oral contraceptives and breast cancer in young women. Lancet 2: 970–973, 1985
Stampfer MJ, Willett WC, Colditz GA, Speizer FE, Hennekens CH. A prospective study of past use of oral contraceptive agents and risk of cardiovascular diseases. New England Journal of Medicine 319: 1313–1317, 1988
Stanford JL, Brinton LA, Hoover RN. Oral contraceptives and breast cancer: results from an expanded case-control study. British Journal of Cancer 60: 375–381, 1989
Thomas DB. Relationship of oral contraceptives to cervical car-cinogenesis. Obstetrics and Gynecology 40: 508–518, 1972
Tzonou A, Day NE, Trichopoulos D, Walker A, Saliaraki M, et al. The epidemiology of ovarian cancer in Greece: a case-control study. European Journal of Cancer and Clinical Oncology 20: 1045–1052, 1984
UK National Case-Control Study Group. Oral contraceptive use and breast cancer risk in young women. Lancet 1: 974–982, 1989
Vessey MP, Villard-Mackintosh L, McPherson K, Yeates D. Mortality among oral contraceptive users: 20 year follow up of women in a cohort study. British Medical Journal 299: 1487–1491, 1989
Vessey MP, Doll R. Investigation of relation between use of oral contraceptives and thromboembolic disease. British Medical Journal 2: 199–205, 1968
Vessey M, Doll R, Peto R, Johnson B, Wiggins P. A long-term follow-up study of women using different methods of contraception: an interim report. Journal of Biosocial Science 8: 373–427, 1976
Weiss NS, Lyon JL, Liff JM, Vollmer WM, Daling JR. Incidence of ovarian cancer in relation to the use of oral contraceptives. International Journal of Cancer 28: 669–671, 1981
Weiss NS, Sayvetz TA. Incidence of endometrial cancer in relation to the use of oral contraceptives. New England Journal of Medicine 302: 551–554, 1980
WHO Collaborative Study of Neoplasia and Steroid Contraceptives. Combined oral contraceptives and liver cancer. International Journal of Cancer 43: 254–259, 1989b
WHO Collaborative Study of Neoplasia and Steroid Contraceptives. Endometrial cancer and combined oral contraceptives. International Journal of Epidemiology 17: 263–269, 1988
WHO Collaborative Study of Neoplasia and Steroid Contraceptives. Invasive cervical cancer and combined oral contraceptives. British Medical Journal 290: 961–965, 1985
WHO Collaborative Study of Neoplasia and Steroid Contraceptives. Epithelial ovarian cancer and combined oral contraceptives. International Journal of Epidemiology 18: 538–545, 1989a
Willett WC, Bain C, Hennekens CH, Rosner B, Speizer FE. Oral contraceptives and risk of ovarian cancer. Cancer 48: 1684–1687, 1981
Zanetti R, Rosso S, Faggiano F, Roffino R, Colonna S, et al. Etude cas-témoins sur le mélanome de la peau dans la province de Torino, Italie. Revue d’Epidemiologie et de Santé Publique 36: 309–317, 1988
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La Vecchia, C., Franceschi, S., Bruzzi, P. et al. The Relationship Between Oral Contraceptive Use, Cancer and Vascular Disease. Drug-Safety 5, 436–446 (1990). https://doi.org/10.2165/00002018-199005060-00004
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DOI: https://doi.org/10.2165/00002018-199005060-00004