A prospective, one-year study on the effects of two long acting injectable contraceptives (depot-medroxyprogesterone acetate and norethisterone oenanthate) on serum and lipoprotein lipids

Abstract

Two parenterally administered progestins (depot medroxyprogesterone acetate, DMPA, 150 mg/12 weeks and norethisterone oenanthate, NET, 200 mg/8 weeks respectively) were given to women seeking contraceptive advice. Before treatment and after 1, 6, 7, 12 and 13 months blood samples were taken. In serum and in the ultracentrifugally separated lipoprotein fractions the levels of total and free cholesterol, triglycerides and phospholipids were assayed, as were the apolipoprotein A1 and B levels in serum. At the end of the study NET had induced a decrease in all lipid components of the HDL (high density lipoprotein) fraction of approximately 30% and tended to increase LDL (low density lipoprotein) lipids. DMPA also decreased HDL-lipids, approximately 15%. There was also a transient decrease in apolipoprotein A1 after one month in both patient groups. From epidemiological studies it is inferred that low HDL-levels and high LDL-levels are independent risk factors for the development of atherosclerosis and cardiovascular disease. Thus our findings might indicate an adverse effect in this respect of long term treatment with these progestins, particularly with NET.

PIP: Lipids known to be independent risk factors for cardiovascular disease were determined in 24 users of the injectable contraceptive depot medroxyprogesterone acetate (DMPA) and in 18 taking norethisterone enanthate (NET), in a prospective 12-month study. The progestins were administered in, DMPA 150 mg every 12 weeks, and NET 200 mg every 8 weeks. Blood was sampled after 1, 6, 7, 12, and 13 months, and analyzed for total and free cholesterol, triglycerides, phospholipids, and apolipoprotein A1 and B. Total cholesterol, free cholesterol, triglycerides and phospholipids were determined with kits from Boehringer Mannheim in serum and in lipoprotein fractions. Apolipoproteins A1 and B were determined by electroimmunoassay. 16 women completed the DMPA study, and 8 women completed the NET study. Reasons for dropping out were irregular bleeding, mood changes, and weight gain. Both depots decreased phospholipid levels throughout the study. NET decreased very low density lipoproteins only. NET increased LDL total cholesterol at 1 and 13 months. DMPA decreased high density lipoprotein (HDL) total and free cholesterol at almost all time points from 10% to 20%. NET lowered all HDL lipids at all time points: there was a 30% decrease at 13 months. Both drugs decreased apo-A1 at 1 month. NET increased apo B at 7, 12, and 13 months. Epidemiological studies indicate that the degree of decrease in HDL is related to risk of cardiovascular disease.