Abstract
BACKGROUND: Polypharmacy is common among the elderly and may negatively impact quality of life (QoL). This study aims to investigate the association between polypharmacy and physical and mental components of QoL among older adults, with separate analyses by gender, in a Southern Iranian population. METHODS: In this cross-sectional study, individuals aged over 60 years from the Bushehr Elderly Health Program were categorized by medication use: polypharmacy (≥ 5 medications) versus no polypharmacy (< 5 medications). QoL was measured using the 12-Item Short Form Survey (SF-12). Multivariable linear regression evaluated the association between polypharmacy and physical and mental QoL components, adjusting for age, body mass index, physical activity, and mental and physical comorbidities. RESULTS: Among 2,399 participants (52% women), polypharmacy prevalence was 33.3% in women and 20.8% in men. Those with polypharmacy had significantly lower QoL scores. The largest mean differences were in mental health (MD: 3.22; 95% CI: 1.56–4.87; p = 0.001) and bodily pain (MD: 3.16; 1.70–4.62; p < 0.001) for women, and general health (MD: 3.78; 2.32–5.23; p < 0.001) and vitality (MD: 2.30; 0.84–3.76; p = 0.002) for men. Polypharmacy was significantly associated with lower Physical Component Summary (PCS) scores (men: β= -1.76, 95% CI: -2.79 to -0.73, p = 0.001; women: β= -1.98, -3.02 to -0.95, p < 0.001) and Mental Component Summary (MCS) scores (men: β= -1.74, -2.86 to -0.63, p = 0.002; women: β= -2.28, -3.56 to -1.01, p < 0.001). After adjustment, the association with MCS scores remained significant (men: β= -1.64, -2.72 to -0.55, p < 0.001; women: β= -1.80, -3.00 to -0.61, p = 0.009), whereas PCS associations attenuated and became nonsignificant (men: β = -0.68, -1.67 to 0.30, p = 0.17; women: β = -0.83, -1.77 to 0.11, p = 0.08). CONCLUSION: Polypharmacy is prevalent among Southern elderly Iranians and is linked to reduced QoL, especially mental health, in both sexes. These findings highlight the need for careful medication management and prescription review in older adults. Limitations include the cross-sectional design that restricts causal interpretations and potential residual confounding. Future longitudinal studies should investigate causality and interventions to minimize polypharmacy and improve QoL in this population. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12889-025-25474-2.