Beyond birth control: how oral contraceptives impact skeletal muscle health: a systematic review and meta-analysis

Oral contraceptive pills (OCPs) are one of the most prescribed medications, yet we lack an understanding of whether and how OCPs affect nonreproductive tissues. Given the well-documented effects of sex hormones on skeletal muscle, including on muscle mass, regeneration, and recovery, our review was aimed at assessing the impact of OCPs on skeletal muscle physiology in female humans and animals. We performed a literature search, title through full text screening, and citation search in accordance with PROSPERO guidelines. Rigor and reproducibility were assessed using the Modified Downs and Black Checklist. Meta-analyses were performed to assess the impact of OCPs on skeletal muscle outcomes. Although our search included both clinical and preclinical studies, the 40 included studies were all clinical, with no identified preclinical studies. Studies focused on young (20-30 yr) sedentary to active females with a healthy BMI (18-27 kg/m²) and included primarily strength and serum-based outcomes. All studies were retrospective and level III evidence. Notably, despite this literature spanning from the 1990s to 2025, rigor was in the 69th ± 6.5 percentile, and there was no correlation with rigor and year of publication. Meta-analyses did not detect an effect of OCPs on examined outcome measures; however, heterogeneity was high, suggesting the lack of rejection of the null hypothesis may be driven by variations in studies, making it challenging to draw conclusions. Taken together, we recommend prospective preclinical and well-controlled clinical studies to examine the impact of OCPs on skeletal muscle in the setting of injury, disease, and varying demographics. Our ultimate goal is to understand sex-based differences in skeletal muscle health and empower females with reliable information to inform decisions about their health. This systematic review and meta-analysis was a step toward the goal of understanding the role of OCPs on skeletal muscle health.