The pharmacologic and metabolic effects of oral contraceptives

The oral contraceptive formulations in use today consist of three types. One type has a fixed dose of a combination of a synthetic estrogen and a synthetic progestin, the second has varying doses of each of these steroids, and the third consists of a fixed dose of a progestin without an estrogen. The estrogen in the older formulations contained mestranol, while all those developed since 1974 contain ethinyl estradiol. The estrogen is combined with varying dosages of nine different progestins to produce a wide variety of formulations. The major metabolic effects of the estrogen are an increase in hepatic production of globulins, some of which cause hypercoagulability, and an increase in blood pressure in certain users. By varying HDL-cholesterol, the estrogen has a beneficial effect upon lipids. Other estrogenic effects include fluid retention, depression, and breast tenderness. Most of the progestins have androgenic effects, being derived from 19-nortestosterone. These include peripheral insulin resistance, a lowering of HDL-cholesterol, nitrogen retention, and nervousness. Both the estrogen and progestins metabolic effects are dose-related and with the newer, low-dose formulations, the adverse metabolic and clinical effects are minimal. Thus the results of the epidemiologic studies performed 10 to 15 years ago, when women were using high-dose formulations, are not relevant to the oral contraceptive formulations in use today. Recent epidemiologic studies show that healthy, nonsmoking women using oral contraceptives do not have an increased risk of developing cardiovascular disease.