Oral contraceptives: balancing intended use with metabolic syndrome risk
Article information
Oral contraceptives (OCs) have been increasingly used worldwide due to their numerous benefits, including reliable contraception, menstrual regulation, and a reduced risk of certain cancers. However, as the global incidence of cardiovascular disease, type 2 diabetes, and stroke continues to rise, caution is warranted in OC use, as these agents can contribute to metabolic syndrome (MetS), thereby increasing the risk of these diseases.
A recent study published in the Kosin Medical Journal adds to a growing body of evidence indicating a concerning association between OC use and the risk of MetS in women. Utilizing data from the Korea National Health and Nutrition Examination Survey collected between 2012 and 2020, the study by Park and Kim [1] included a total of 11,084 Korean women. The prevalence of MetS was higher among OC users (11.5%) compared to nonusers (8.1%) (p<0.001). OC users also demonstrated increased risks of abdominal obesity (odds ratio [OR], 1.319; 95% confidence interval [CI], 1.119–1.555), hypertension (OR, 1.557; 95% CI, 1.302–1.863), and hypertriglyceridemia (OR, 1.521; 95% CI, 1.287–1.797) [1]. These findings suggest that the risk of metabolic disease should be carefully considered and monitored when prescribing these widely used medications.
Several previous studies support this association. For example, Chasan-Taber et al [2]. observed an elevated risk of hypertension with OC use in a prospective cohort of U.S. women. The ENIGMA study [3] also reported increased arterial stiffness—a surrogate marker for cardiovascular risk—among young female OC users. Further research has suggested that OCs may influence renal function, including effects on urinary albumin excretion and glomerular filtration rate, potentially exacerbating vascular risk [4]. A meta-analysis focusing on Asian populations similarly identified a significant relationship between OC use and MetS, reinforcing the relevance of this concern in regional healthcare contexts [5].
Although the precise mechanisms by which OCs may induce MetS have not been fully elucidated, several plausible pathways have been proposed.
First, the hormonal components of OCs, primarily estrogens and progestins, can affect insulin sensitivity. Progestins, especially those with androgenic properties, may impair insulin signaling in muscle and adipose tissue, thereby promoting insulin resistance. Estrogens can have dual effects, either enhancing or reducing insulin sensitivity, depending on their formulation and dosage [6].
Second, OCs impact lipid metabolism. Estrogens generally elevate triglycerides and high-density lipoprotein (HDL) cholesterol, but may also increase very-low-density lipoproteins (LDL). In contrast, androgenic progestins tend to lower HDL and raise LDL cholesterol, contributing to an atherogenic lipid profile [7]. These alterations may shift the metabolic balance toward dyslipidemia, a core feature of MetS.
Third, OCs may influence blood pressure regulation. Estrogens upregulate hepatic angiotensinogen production, promoting vasoconstriction through the renin-angiotensin-aldosterone system. They may also impair endothelial function and increase sodium retention. Some progestins can exacerbate these effects, although generally to a lesser extent [8].
Finally, changes in body composition—particularly increased abdominal fat—have been reported among some OC users. These shifts may result from hormonal effects on appetite, fluid retention, or fat distribution, all of which can contribute to central obesity and MetS development [9].
It is important to note that metabolic responses to OCs are highly individualized. Genetic predisposition, pre-existing metabolic health, dietary habits, physical activity levels, and even gut microbiome composition can all influence an individual’s reaction to OCs [10,11]. Furthermore, the specific formulation and dosage of the contraceptive play a critical role. Contemporary low-dose OCs may offer a more favorable metabolic profile than earlier high-dose formulations. Nonetheless, individualized risk assessment remains essential.
Given the widespread use of OCs and the increasing burden of cardiometabolic diseases, clinicians must carefully weigh the benefits and risks. For patients with pre-existing metabolic risk factors—such as obesity, hypertension, or a family history of diabetes—alternative contraceptive options or more vigilant monitoring may be appropriate. Regular assessments of weight, blood pressure, lipid profiles, and glucose metabolism should be considered when initiating or continuing OCs in higher-risk individuals.
In summary, while OCs remain a safe and effective option for most women, emerging evidence suggests that their use may not be metabolically neutral. The association between OC use and MetS warrants careful consideration, particularly in patients with underlying vulnerabilities. As the research landscape continues to evolve, clinicians are encouraged to embrace a personalized approach to contraceptive counseling, grounded in both scientific evidence and patient-specific factors.
The relationship between OC use and MetS is complex and multifactorial. Recent evidence, including findings from the Korean population, highlights the need to move beyond a one-size-fits-all approach to OC prescription. Given the variability in metabolic responses, there is a clear need for individualized prescribing strategies that account for each patient’s specific risk profile. Future research should focus on identifying biomarkers or clinical predictors of adverse metabolic responses to OCs, stratifying risk by hormonal composition and dosage, and assessing long-term outcomes in diverse populations. In the interim, clinicians are advised to remain vigilant, balancing reproductive benefits with the potential long-term effects on metabolic health.
Notes
Conflicts of interest
No potential conflict of interest relevant to this article was reported.
Funding
None.
Author contributions
All the work was done by Bukyung Kim.