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PROGRESS. 1988; (8):7-8.The World Health Organization's Special Program of Research, Development, and Research Training convened a Meeting on Breast Cancer and Oral Contraceptives in June, 1988, to review the available epidemiological data on the relationships between oral contraceptives and breast cancer. The studies remained inconsistent and inconclusive, possibly because the effects of oral contraceptives vary depending on the length of time they are used or because they contain different kinds and amounts of hormones or possibly because of recall or selection bias in the populations studied. The committee recommended further research on the biological effects of the pill, further epidemiologic studies to look for patterns of contraceptive use and trends in breast cancer incidence and mortality, and further case-control studies. It was also suggested that a ranking system for oral contraceptives be developed so that a standardized basis for comparisons of the different preparations would be available.
People. 1984; 11(1):33.Recent suggestions that there might be a causal link between oral contraceptives (OCs) and breast and cervical cancer are not based on evidence strong enough to warrant any change in prescribing practice, according to the medical advisers of the International Planned Parenthood Federation (IPPF). A US study suggests that for women who use OCs for several years before the age of 25 there may be a slightly increased risk of developing breast cancer later in their lives. The risk of breast cancer was influenced by the type of OCs the women took. They suggest that those brands with a high level of progestogen potency are the culprits. The other study from the UK suggests that women who use OCs for several years are more likely to develop cancer of the uterine cervix than women who use IUDs for similar lengths of time. Both studies left the Medical Advisory Panel of IPPF convinced that there is insufficient evidence to make it advisable for family planning programs to change their prescribing policies. The breast cancer study has several methodological weaknesses which could have influenced its results and these differed from results published by other, large scale studies. There is strong disagreement in the medical profession about the validity of the way the US team assessed progestogen potency. The Panel agreed that the number of women in the study who used each brand of OC was too small to justify drawing any definite conclusions about which OCs to prescribe for women aged under 25. The Panel noted that the cervical cancer study failed to take into account the sexual history of the subjects even though the age at 1st intercourse and the number of sexual partners a woman has are known to affect the likelihood of her developing cervical cancer. This, combined with the fact that other studies have not shown a relationship between OC use and cervical cancer, led the Panel to recommend to change in current practice. Data from the 2 studies are currently being analyzed again, to look specifically at the association between breast cancer and OC use. This reanalysis will be closely monitored by the Panel which will review its own recommendations as further evidence becomes available.
LAKARTIDNINGEN. 1979 Apr 25; 76(17):1625-7.An overview of the risk of developing cancer related to oral contraceptive (o.c.) use is presented. A committee of experts affiliated with WHO studied the problem of developing cancer related to o.c. use. O.c. use for more than 2 years prevents the formation of benign breast tumors, even after discontinuing o.c. use. The effect is due to the progestin component. There is no clear indication that o.c. use increases the risk of breast cancer. A higher risk of endometrial cancer is associated with sequential preparation use, but not with the use of combination preparations. Cervical neoplasms and pituitary adenoma may be more frequent among predisposed women who use o.c.s. Studies show a reduced risk of ovarian cancer with o.c. use, but more studies are necessary. There is a marked increase in the relative risk of developing hepatocellular adenoma among women who use o.c.s for longer than 3 years. The risk increases with the hormone dosage, the duration of treatment, and the age of the patient. There is no reliable data to indicate that the risk of malignant melanoma increases with o.c. use. More study is needed to determine the possible cancer risks of injection preparations. Combination preparations can cause an increased risk of vaginal epithelial metaplasia. Diethylstilbestrol taken during early pregnancy can cause vaginal neoplasms in the offspring. More epidemiological studies and clinical and laboratory studies on the carcinogenic effects of o.c.s and the endocrinological effects of o.c.s on younger women should be undertaken. It is recommended that o.c.s with the lowest possible hormone dosages be used. O.c.s should not be prescribed to women with vaginal adenosis. (Summary in ENG)
MEDICAL JOURNAL OF AUSTRALIA. 1979 Oct 20; 2(8):406-7.Drug toxicity testing is required by the U.S. Food and Drug Administration in bitches of beagle dogs for 7 years and in female rhesus monkeys for 10 years at 25-50 times the human dosage. Progesterone, medroxyprogesterone acetate, megesterol acetate, chlormadinone acetate, chloroethynl norethisterone and chloroethynyl norgestrel are some compounds which have induced tumors in beagle dogs. However, the endocrinology of the beagles is unlike that of a woman and binding affinity of synthetic progestogens to breast cytoplasmic progesterone receptors of the beagle and women have striking differences. Some progestogen compounds which do not produce neoplasia in dogs because of too low a dose are most potent in women. Both the WHO and the Committee on Safety of Medicines concluded that progestogen-induced breast tumors in beagles are unhelpful in predicting possible breast cancer in women who use oral contraceptives.
Contraception. 1970 Jun; 1(6):409-445.This article reviews the validity of previously published material linking oral contraceptive usage to health hazards. The statistical methods involved in such studies are thoroughly examined, particularly those studies relating oral contraceptive usage to thromboembolic disease incidence. Problems inherent to the basic designs of such studies are discussed. Some relationship between thromembolic disease and oral contraceptive usage has been established. Studies on animals relating oral contraceptive usage with carcinogenesis are inconclusive due to the different metabolic rates obtained for different animals and different strains and the high dosage used to produce tumors. Review of the data relating oral contraceptives with alterations in carbohydrate metabolism, serum lipids, etc., show pure speculation of conclusion. Endrocrine effects persisting after discontinuation of oral contraceptives were rare; apparently both types of steroids play some part. It was suggested that most data on this subject is faulty and filled with fixed opinions which should be avoided.
Ippf Medical Bulletin. 1983 Dec; 17(6):1-2.The response of the International Medical Advisory Panel (IMAP) of the International Planned Parenthood Federation to 2 recent papers suggesting a link between cancer and oral contraceptive (OC) use is reported. The 1st paper by Pike et al. suggested an increased risk of breast cancer in women who use OCs containing high potency progestogens before age 25 for at least 4 years. It is noted that several methodological problems with the study design could have introduced a degree of selection of ascertainment bias. These issues include the procedures used for age matching between cases and controls, the 1/3 loss to follow-up among cancer cases, and the use of telephone interviews to ascertain OC use history. Moreover, data from other studies suggest that ever-users of OCs who develop breast cancer may be more likely to survive than women with breast cancer who have never used OCs, leading to the overrepresentation of women in the former group among surviving cases. The ranking of OCs by progestogen potency does not take the estrogen content into consideration. In addition, assessment of progestogen potency by use of a delay of menses test may not correlate with the degree of effect on the breast and has produced conflicting results when used by different researchers. Finally, the numbers of women using some OC brands were too small and the possibility that women may have changed OC brand over the study period was not considered. Largescale studies such as the UK Oxford-Family Planning Association contraceptive study and the Centers for Disease Control Cancer and Steroidal Hormone Study are curently being reanalyzed, controlling for type and amount of progestogen in the OCs. Until new data become available, IMAP believes there is insufficient evidence to recommend modification of existing practice. The 2nd study by Vessey et al. suggested a higher incidence of cervical cancer in OC users as compared to IUD users. However, several key modifying factors on the risk of cervical cancer, including age at 1st sexual intercourse and number of partners, could not be controlled for. Moreover, a high proportion of OC use involved preparations containing 50 mcg or more of estrogen. Although regular cervical smears are recommended for OC users, the IMAP again does not recommend any change in current practice. The IMAP noted that the possible cancer-related risks of OCs must be weighed against the protective effects of OCs against cancers of the endometrium and ovary, pelvic inflammatory disease, and unwanted pregnancies.