Effect of oral contraceptive use on cardiorespiratory and immune function in premenopausal women involved in exercise: a systematic review and meta-analysis.

BACKGROUND: The beneficial effect of regular physical activity across all bodily functions is well known. The use of oral contraceptives (OCs) is highly prevalent among premenopausal women due to their contraceptive efficacy and favorable safety profile. However, the impact of combined oral contraceptives (COCs) in exercise conditions remains controversial and inconclusive. We aim to explore the effects of COCs on cardiorespiratory and immune function in premenopausal women engaged in exercise when compared with non-COC users. METHODS: Extensive searches of relevant databases, including MEDLINE, CINAHL, Cochrane CENTRAL, and other health sources, were conducted on the EBSCOhost interface from January 2024 to May 2026. All studies that included healthy, physically active premenopausal women and female athletes (15-40 years old) on COC and non-COC users were appraised using the relevant JBI appraisal tools. Data analysis was performed using Review Manager (RevMan) version 5.3. The certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) tool. RESULT: The review and meta-analysis included 29 studies comprising 726 participants (recreationally active and trained female athletes) involved in exercise, of whom 390 (53.7%) used COC, and 336 (46.3%) were non-COC users. Overall, 19 studies with a comparator group were included in our meta-analysis. The overall pooled estimates suggest that the use of COC had little to no difference on certain makers of cardiorespiratory and immune function such as heart rate [MD = 0.02, 95% CI (-1.85, 1.9), p = 0.98], respiratory parameters [SMD = -0.07, 95% CI (-0.18, 0.04), p = 0.28], and IL-6 levels [MD = -0.88, 95% CI (2.75, 0.98), p = 0.35)] when compared with the non-COC group. Similarly, there is little to no difference in the body composition (BMI) [MD = -0.21, 95% CI (-0.59, 0.18), p = 0.3)] and metabolic changes [SMD = -0.15, 95% CI (-0.43, 0.12), p = 0.36)] among COC users compared with the non-COC group. Nonetheless, the certainty of evidence across all measured outcomes in the included studies is low. CONCLUSION: The current evidence does not demonstrate a consistent detrimental effect of COC use on cardiorespiratory or immune outcomes among physically active premenopausal women; however, confidence in these findings remains limited due to the low certainty of the available evidence. The low certainty of the evidence across the included studies is attributable to small sample sizes, high risk of bias, varied methodological approaches, and a lack of data from specific geographical locations, among other factors. Thus, caution should be exercised when extrapolating these findings for consultation or decision-making regarding COC use in and out of clinical settings. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/CRD42021265257, identifier CRD42021265257.