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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. 253-282This review of combined oral contraceptive (OC) preparations presents formulations, pregnancy rates, biochemical parameter changes, morbidity, and OC indications in 15 tables. The OC preparations are based on 2 different estrogens and 14 progestagens. Though steroid content differs among products, all act primarily to inhibit ovulation by suppression of midcycle release of pituitary gonadotropins. Variable-dose products are associated with higher pregnancy rates than fixed-dose preparations. Side effects of OCs, while difficult to identify, fall into 2 categories: 1) common adverse associations similar to responses to inert placeboes; and 2) serious biochemical and physiological alterations. There is no evidence of any increase in morbidity due to OC use, whereas avoidance of risks associated with pregnancy is beneficial. No convincing evidence of carcinogenic hazard is presented. Some evidence of reduced systemic side effects by lower-dose products is presented, though gynecological side effects, such as irregular bleeding, may increase. Drug interaction with OCs is described; rifampicin causes the most serious of these. OCs induce wide-ranging metabolic changes in many organ systems. These may relate to undesirable side effects (psychological or neurological signs, skin disorders, and blood pressure changes).
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.
IPPF Medical Bulletin. 1969; 3(1):4.At the end of its 2-day meeting in London in December 1968, the IPPF Central Medical Committee issued the following press statement, which gives its views about 2 suggested adverse effects of oral contraceptives: Cervical carcinoma in situ: "The International Planned Parenthood Federation Central Medical Committee has reviewed unpublished studies reporting a statistical association between carcinoma in situ of the cervix and the use of oral contraceptives, and has come to the conclusion that the available evidence is insufficient to confirm or exclude a causal relationship. Other studies are in progress in several countries. Where cytological service is available, an annual cervical s mear makes possible the detection of carcinoma in situ at a stage when a complete cure can be effected. Therefore, existing facilities for annual cytological examinations should be used, and where such facilities do not exist they should be established if possible. The Committee, fully cognizant of its responsibilities, recommends that no programme of hormonal contraception should be deferred or interrupted since, at the present time, the Committee is of the opinion that the benefits to health of widespread use of oral contraceptives out-weigh the probable risks." Thromboembolism: "Recently published studies in th e United Kingdom reveal a significant statistical association between the use of oral contraceptives, venous thrombosis, pulmonary embolism, and possibly cerebral arterial thrombosis. There is no evidence that the risk varies with the duration of use or the type of compound. The excess risk of mortality due to thrombo-embolic disease among women using oral contraceptives in the United Kingdom appears to be of the order of 3 per 100,000 per year. Further studies should be undertaken in other parts of the world before accepting the above rate generally. The risk to life due to thrombo-embolic disease must be weighed against the mortality of pregnancy and childbirth, which ranges from about 20 deaths per 100,000 pregnancies in developed countries to 300 or more in developing countries." (FULL TEXT)
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.