The Relationship Between Sexual Activity, CRP, IL-6, and Musculoskeletal Pain in Premenopausal Women: A systematic review and Meta-Analysis

Abstract

Hormonal fluctuations in premenopausal women may increase systemic inflammation and musculoskeletal pain. Recent evidence indicates that sexual activity may modulate inflammation by reducing C-reactive protein (CRP) and interleukin-6 (IL-6), key biomarkers of inflammatory processes. Understanding the relationship between sexual activity, inflammatory markers, and musculoskeletal pain in premenopausal women is essential for identifying non-pharmacological strategies to improve health. Previous studies have largely overlooked the interconnected role of sexual activity, inflammation, and pain in reproductive-aged women, leaving a gap in understanding these relationships. To address this, the present review provides novel insights by specifically analyzing CRP and IL-6 levels in this population. A systematic review and meta-analysis were conducted by searching PubMed, Scopus, ScienceDirect, and Google Scholar until April 2025. Inclusion criteria were studies in premenopausal women that examined sexual activity, CRP, IL-6, and/or musculoskeletal pain. The selection process followed the PRISMA diagram. The result off the 530 articles identified, 14 studies met the inclusion criteria, and 6 were included in the meta-analysis. Most studies showed that higher sexual activity was associated with lower CRP and IL-6 levels and less musculoskeletal pain. Meta-analysis showed that higher sexual activity was significantly associated with lower CRP (SMD= -0.39, 95% CI: -0.58 to -0.20, p<0.001) and IL-6 (SMD= -0.41, 95% CI: -0.67 to -0.15, p=0.002). Regular sexual activity has the potential to reduce CRP and IL-6 levels and musculoskeletal pain in premenopausal women. Further longitudinal studies are needed to strengthen the evidence of causality.

Keywords: CRP, IL-6, musculoskeletal pain, premenopause, sexual activity