Relative Risk Of Venous Thromboembolism Research Articles

Oral Contraceptive Estrogen Dose and the Risk of Deep Venous Thromboembolic Disease

Despite the well-recognized association between oral contraceptives and deep venous thromboembolism, little is known about the risks associated with currently marketed formulations containing less than 50 micrograms of estrogen. To assess the venous thrombogenicity of low-estrogen oral contraceptives (those containing less than 50 micrograms of estrogen) relative to intermediate-dose (50 micrograms of estrogen) and high-dose (greater than 50 micrograms of estrogen) formulations, we conducted a cohort study of oral contraceptive users between the ages of 15 and 44 years in the Michigan Medicaid population. The period of the study was from 1980 through the third quarter of 1986. A total of 2,739,400 oral contraceptive prescriptions received by 234,218 women were analyzed. Using the low-estrogen cohort as the referent group, the age and calendar period adjusted relative risk of venous thromboembolism in users of intermediate-dose formulations was 1.5 (95% confidence interval (CI) 1.0-2.1, p = 0.04), and the relative risk in users of high-dose formulations was 1.7 (95% CI 0.9-3.0, p = 0.06). These data provide evidence that the dose-response relation between oral contraceptive estrogen and venous thromboembolism extends from 50 to 30 micrograms of estrogen, the dose range of currently marketed formulations.

Problems in contraception.

Earlier projections of birth rate were erroneous because of inadequate appreciation of the many and changing variables: rates of industrialization, educational levels, changes in economic activity, rates of family formation, marriage, timing of births, and so forth. Although a decline in fertility may be projected over the next few years, the rising proportion of women of child-bearing age will result in higher birth rates. Many women still have more children than they say they want, and family planning has been accepted by most American women. Although only a few women receiving oral contraceptives become hypertensive, almost all women show an increase in plasma renin activity, plasma renin substrate, and angiotensin II. Hemodynamic studies show small but consistent. increases in cardiac output and mean arterial blood pressure. The oral contraceptives have been associated with an increased risk of thromboembolic disorders and death from pulmonary embolism. The relative risk of venous thromboembolism increases with increasing dose of estrogen, leading to the recommendation that the oral contraceptives contain no more than 50 µg of mestranol or ethinyl estradiol. Survey of the processes in sperm and ovum maturation and fertilization shows many areas where other approaches to contraception may be fruitful. These include several areas of basic scientific interest: the meiotic stage of spermatogenesis, the control of follicle-stimulating hormone secretion, regulation of corpus-luteum life span and steroid synthesis, and the role of progesterone in maintaining a secretory endometrium.