The metabolic impact of oral contraceptives

Abstract

The hormonal components of oral contraceptives exert major effects on plasma lipoprotein metabolism. Estrogens may increase production of plasma triglycerides, leading to increased levels of very low-density lipoproteins, but they may also reduce levels of cholesterol-enriched and potentially atherogenic intermediate- and low-density lipoproteins. Furthermore, estrogens increase levels of high-density lipoproteins (HDLs), particularly the HDL2 subspecies, an effect linked to reduced mortality rates from cardiovascular disease in postmenopausal women receiving hormone replacement therapy. All combination oral contraceptives in use in the United States tend to raise levels of plasma triglycerides, low-density lipoprotein, and HDL3 to varying degrees. In contrast, changes in HDL and HDL2 reflect the combined effects of estrogen dose and relative androgenicity of the progestin component. Although in general, the lipoprotein changes are greater in magnitude with higher dose oral contraceptive preparations, they can be significant in lower dose preparations as well. Oral contraceptives also affect carbohydrate metabolism, primarily through the activity of progestin. Studies have demonstrated insulin resistance, rises in plasma insulin, and relative glucose intolerance by means of curve analysis of glucose tolerance tests. These effects are far less pronounced with lower dose preparations and with formulations using the newer progestins.

PIP: Many preclinical and clinical studies reveal that changes in lipoprotein metabolism are a major contributing factor to atherosclerosis. Hormones in oral contraceptive (OC) formulations strongly influence lipoprotein metabolism. Specifically, estrogens bring about increases in plasma triglycerides which then cause a rise in the very low density lipoprotein. They also decrease levels of the intermediate and low density lipoprotein which cause build up of plaque on arterial walls. Estrogens also lead to rising high density lipoprotein (HDL) levels, especially the HDL2 subspecies. Increased HDL levels are associated with lower mortality rates from cardiovascular conditions in women who have already experienced menopause and are on hormone replacement therapy. Combination OCs used in the US increase plasma triglycerides, low density lipoprotein, and HDL3. The estrogen dose and the relative androgenicity of the progestin together influence the changes in HDL and HDL2. Even though low dose combined OCs bring about lipoprotein changes which are lower than those of higher dose OCs, the changes often remain significant. The progestin component of OCs is responsible for most changes in carbohydrate metabolism. Specifically OC use can lead to increased levels of plasma insulin, insulin resistance, and relative glucose intolerance. A curve analysis of glucose tolerance tests reveals this intolerance effect of OCs. The changes in carbohydrate metabolism are not as great in women using the lower dose OCs or formulations using the new progestins, however.