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Geneva, Switzerland, WHO, 1978. (World Health Organization Technical Report Series No. 619) 54 pStudies on steroid contraception (SC) and risk of neoplasia are reviewed. Methodological issues in neoplasia etiology studies include: 1) possibility of a latent period between exposure to cause and disease development; 2) cumulative effects of prolonged or repeated SC exposure; 3) discontinued drugs or dosage schedules; 4) time of exposure (adolescence or prenatal, e.g.); 5) isolation of specific causes among multiple risks; and 6) variations in neoplasma diagnoses. The 4 epidemiological approaches to SC-associated neoplasia studies have inherent shortcomings, but cohorts yield significant associations. Relative risk (ratio of disease incidence among exposed vs. nonexposed persons) is an index of association only, not evidence of cause and effect. Benign breast neoplasia risk was reduced by current SC use of >2 years, and weak evidence points to a residual protective effect, apparently associated with progestogen dose. Aggregated breast cancer data show no clear adverse or beneficial effect of SC use; however, evidence suggests SCs may increase breast cancer risk in population subgroups (e.g., young women). Only short-term evidence is available; hence, no inference of long-term SC breast cancer effects is possible. No beneficial effect of SCs on uterine fibroids is evident, but sequential SCs, no longer marketed, may have increased risk to endometrial carcinoma. Inconclusive data suggest SCs may decrease ovarian cancer risk. Increased risk of cervical dysplasia and carcinoma in situ is associated with SC use, especially long-term use by women with predisposing factors. Risk of hepatocellular adenoma of the liver increases with prolonged SC exposure, especially high dose. Relevance of existing data from more developed countries to disease risk in less developed ones is discussed, and recommendations made.
In: Diczfalusy, E., ed. Regulation of human fertility. (Proceedings of the WHO Symposium on Advances in Fertility Regulation, Moscow, USSR, November 16-19, 1976) Copenhagen, Denmark, Scriptor, 1977. p. 283-321This review of low-dose gestagen contraception emphasizes the variety of findings from different studies. For example, studies of chlormadinone acetate have found pregnancy rates of 1.1-12/100 woman-years. Results of trials of megestrol acetate suggested that a 500-mcg dose level yielded unacceptable pregnancy rates. No significant difference between various doses of norgestrel which have been studied were found (e.g., 50 and 75 mcg daily of dl-norgestrel or 30 mcg daily of the d-isomer). Pregnancy rate reported for most trials with this gestagen and also norethisterone and quingestanol were within an acceptable range. With 1 exception, pregnancy rates reported in trials of lynestrenol were remarkable low. Cumulative results of trials with various gestagens show Pearl Index rates between 2 and 3, except for lynestrenol. Dose level was the critical variable; i.e., it must be sufficiently high to exert antifertility action and low enough to avoid a high incidence of irregular bleeding. Apart from menstrual irregularities, other side effects from the minipill seem minor and in general less severe than those encountered with combined 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.