The effects of menstrual cycle phases on immune function and inflammation at rest and after acute exercise: A systematic review and meta-analysis

Abstract

The immune system plays an important role in mediating exercise responses and adaptations. However, whether fluctuating hormone concentrations across the menstrual cycle may impact these processes remains unknown. The aim of this systematic review with meta-analysis was to compare baseline concentrations as well as exercise-induced changes in immune and inflammatory parameters between menstrual cycle phases. A systematic literature search was conducted according to the PRISMA guidelines using Pubmed/MEDLINE, ISI Web of Science, and SPORTDiscus. Of the 159 studies included in the qualitative synthesis, 110 studies were used for meta-analysis. Due to the designs of the included studies, only the follicular and luteal phase could be compared. The estimated standardized mean differences based on the random-effects model revealed higher numbers of leukocytes (-0.48 [-0.73; -0.23], p < 0.001), monocytes (-0.73 [-1.37; -0.10], p = 0.023), granulocytes (-0.85 [-0.1.48; -0.21], p = 0.009), neutrophils (-0.32 [-0.52; -0.12], p = 0.001), and leptin concentrations (-0.37 [-0.5; -0.23], p = 0.003) in the luteal compared to the follicular phase at rest. Other parameters (adaptive immune cells, cytokines, chemokines, and cell adhesion molecules) showed no systematic baseline differences. Seventeen studies investigated the exercise-induced response of these parameters, providing some indications for a higher pro-inflammatory response in the luteal phase. In conclusion, parameters of innate immunity showed cycle-dependent regulation at rest, while little is known on the exercise responses. Due to a large heterogeneity and a lack of cycle phase standardization among the included studies, future research should focus on comparing at least three distinct hormonal profiles to derive more specific recommendations for exercise prescription.

Keywords: adipokines; chemokines; cytokines; follicular phase; leukocytes; luteal phase; lymphocytes.