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Cardiovascular disease and use of oral and injectable progestogen-only contraceptives and combined injectable contraceptives. Results of an international, multicenter, case-control study. World Health Organization Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception.
CONTRACEPTION. 1998 May; 57(5):315-24.As part of a World Health Organization Collaborative Study conducted at 21 centers in Africa, Asia, Europe, and Latin America in 1989-93, the risks of cardiovascular disease associated with use of oral and injectable progestogen-only and combined injectable contraceptives were investigated. 3697 cases of cardiovascular disease (59% stroke, 31% venous thromboembolism, and 10% acute myocardial infarction) were available for analysis and age-matched with up to three controls. 53 cases were current users of oral progestogen-only contraception, 37 were using an injectable progestogen-only method, and 13 were using combined injectable contraception. The adjusted odds ratios for all cardiovascular diseases compared with nonusers of any type of steroid hormone contraceptive were 1.4 (95% confidence interval (CI), 0.79-1.63) for current users of oral progestogen-only methods, 1.02 (95% CI, 0.68-1.54) for users of injectable progestogen-only contraceptives, and 0.95 (95% CI, 0.49-1.86) for use of combined injectable contraceptives. No significant changes in risk for stroke, venous thromboembolism, or acute myocardial infarction or these three conditions combined was apparent in association with any of the contraceptive methods. However, a nonsignificant increase in risk of venous thromboembolism was apparent for both types of progestogen-only contraceptives. Among women with a history of hypertension, the odds ratio for stroke rose from 7.2 (95% CI, 6.1-8.5) among nonusers of any type of steroid hormonal contraceptive method to 12.4 (95% CI, 4.1-37.6) among current users of all oral progestogens.
In: Diczfalusy, E., ed. Regulation of human fertility. (Proceedings of the WHO Symposium on Advances in Fertility Regulation, Moscow, USSR, November 16-19, 1976) Copenhagan, Denmark, Scriptor, 1977. p. 323-360Long-acting systemic contraceptives inhibit fertility either at a central or peripheral level. In some instances, a mixed reaction is likely to be working: during the 1st portion of the drug's life-span the contraceptive effect is exerted at a hypothalamic central level, whereas later on--when ovulation is restored--the action is on the cervix or uterus. The most important factor holding back utilization of long-acting agents is serious interference with regularity of the menstrual cycle, and delivery systems must be devised with zero-order release rates to improve cycle control and acceptability. Monthly injectables consisting of synthetic progestins alone proved unsuitable for contraception because of frequent and prolonged amenorrhea. Addition of an estrogenic substance helped cycle control, and a dihydroxyprogesterone acetophenide plus estradiol enanthate combination seems most worthy of clinical investigation; so far, 15,000 woman-months of experience have yielded no unwanted pregnancies. Few bleeding pattern irregularities were reported, but premenstrual tension, dysmenorrhea, and libido changes occurred. Reversibility of drug-induced anovulation has been shown by spontaneous ovulation resumption 12-42 weeks after cessation. Tri-monthly injections of Depo Provera resulted in pregnancy rates averaging .5/100 woman-years of use. Biannual injectable and sustained release systems are discussed and data are presented.