Increase in Lipid Levels With Oral Contraceptive Use

Source: Staudt A, Kiechl SJ, Gande N, et al. Influence of oral contraceptives on lipid profile and trajectories in healthy adolescents-data from the EVA-Tyrol study. J Adolesc Health. 2024;75(3):479-486; doi: 10.1016/j.jadohealth.2024.04.017.Investigators from the Medical University of Innsbruck, Innsbruck, Austria, and Hochzirl Hospital, Zirl, Austria, conducted a study to evaluate the association between oral contraceptive use and lipid profiles in adolescent females. Participants were females 14 to 19 years old who either used or did not use oral hormonal contraceptives and were enrolled in a large cohort study assessing cardiovascular risk factors and behaviors in adolescents in Austria and Italy. Adolescent females using non-oral hormonal contraceptives were excluded from the current study. Demographic information, use and type of oral contraceptive, use of alcohol, cigarette smoking, anthropometric data, and blood pressure were collected on participants. Fasting total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglyceride levels were obtained. Follow-up lipid levels were measured on some participants. The primary outcomes were lipid levels, which were compared in participants who were using oral contraceptives and those who were not using linear regression, after adjusting for multiple possible confounders. For study participants with multiple lipid levels, change from baseline to follow-up was assessed. Multivariate regression was used to compare changes among those who initiated oral contraceptives after baseline and those who never used contraceptives, as well as between continuous and never users.Data were analyzed on 828 adolescent females, with 317 using hormonal oral contraceptives and 511 not using contraceptives. Those using contraceptives were slightly older (median ages, 17.3, 17.0; P <0.001) and were more likely to be cigarette smokers and use alcohol than non-users. Most users were on combined oral contraceptives; 13 were using progestin-only products. After adjustment for confounders, females using oral contraceptives had significantly higher levels of total cholesterol (mean values, 179.6 ±32.1 vs 162.4 ±27.7 mg/dL; P <0.001), LDL-C (106.4 ±28.6 vs 94.6 ±25.5, P <0.001) and triglycerides (median values, 104 vs 67; P <0.001) than non-users. There was no difference between groups in HDL-C levels. Follow-up levels were obtained on 558 participants at a mean duration of 22 months after baseline. Compared to never users, the change in triglycerides from baseline to follow-up was 15.4 mg/dL higher among those who initiated oral contraceptives after baseline (P <0.001) and 19.6 mg/dL higher among those used oral contraceptives throughout the study period (P = 0.02).The authors conclude that use of hormonal oral contraceptives in adolescent females was associated with increased triglycerides and LDL-C levels.Dr Raphael has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.More than 50% of sexually active adolescents in the United States (US) have tried oral contraceptives (OCs).1 Additionally, an estimated 1 in 5 US adolescents have at least 1 abnormality in lipid levels, and youths with abnormal lipid levels are at risk of premature atherosclerosis. (See AAP Grand Rounds. 2024;52[2]:15.)2 Hence, the role of OCs on lipid levels is a critical area of study.The results of the current study add to existing evidence by providing information on the effect of recent formulations of OCs with less estrogen on lipid levels. Of note, 24.8% of the study participants were current smokers. Smoking rates among adolescents (12.6%) and young adults (5.3%) in the US are much lower.3,4 Similarly, the rate of regular alcohol consumption was very high in the study population (87.7%). As lifestyle and genetic factors mediate cardiovascular risk, the generalizability of this study’s findings beyond the local Italian/Austrian population needs to be considered. Additionally, in the 68.8% of study participants for whom follow-up data were available, despite increased LDL-C and triglyceride levels among OC users, the levels remained largely within normal limits. The results of previous studies have indicated that increases in lipid levels may not persist with continued OC use and are reversed with discontinuation.5A balanced approach to contraceptive counseling that considers patient-specific risks, patient preference, non-contraceptive benefits (See AAP Grand Rounds. 2024;51[3]:30),6 and the risks associated with not using a reliable contraceptive method and experiencing an unplanned pregnancy, is vital. In the 2024 update of the US medical eligibility criteria for contraceptive use, the Centers for Disease Control and Prevention does not include hyperlipidemia alone as a consideration when selecting a contraceptive method and advises against routine measurement of lipid levels. However, among individuals with multiple significant atherosclerotic risk factors (eg, older age, smoking, diabetes, hypertension, low HDL, high LDL, or high triglyceride levels), the risks of combined hormonal contraceptive use may outweigh benefits.7Adolescent oral contraceptive users appear to have higher baseline and follow-up LDL-C and triglyceride levels than non-users, a consideration when advising regarding contraceptive choices.