Various synthetic progestogens that are used as contraceptives have been reported to influence lipid and lipoprotein fractions differently. Depo-medroxyprogesterone acetate (DMPA), a synthetic progestogen, is used by Nepalese women as a contraceptive agent. Our study aims to determine the effects of long-term use of DMPA on lipid metabolism. We performed this study on 60 healthy Nepalese women who had been using DMPA for more than 2 yr and age- and weight-matched control subjects who were not using hormonal contraceptives. Fasting blood samples were collected from the subjects for the estimation of total cholesterol (TC) and triglyceride (TG) levels, and the levels of high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were estimated using the Friedewald's equation. TC and LDL-C levels in DMPA users were significantly higher than those in non-users. Our study concluded that DMPA use induces lipid metabolism changes that can increase the risk of cardiovascular diseases.