Fat-Free Mass Is Associated with Migraine Disability in Perimenopausal Women: A Pre-Specified Exploratory Analysis of the MEDEA Study

Background/Objectives: Migraine is three times more common in women and worsens during perimenopause, a phase in which estrogen fluctuations are accompanied by deterioration in body composition — increased fat mass (FM) and reduced fat-free mass (FFM) — amplifying systemic inflammation. Despite this biological link, body composition is not systematically assessed in perimenopausal migraine management. This pre-specified exploratory analysis of the MEDEA study evaluates whether body composition, measured by bioelectrical impedance analysis (BIA), is associated with migraine disability in perimenopausal women, and secondarily describes changes in body composition during an anti-inflammatory nutritional intervention with prebiotics and probiotics. Methods: Single-arm, single-center, prospective interventional study (MEDEA study, Neurological Clinic ASUFC, Udine); the present work is a pre-specified exploratory secondary analysis. Seventeen women (mean age 52 ± 2.6 years) with episodic or chronic migraine, intestinal dysbiosis, and perimenopausal status (STRAW classification) were assessed with Akern BIA at baseline (T0), 3 months (T3), and 6 months (T6). Changes over time were analyzed with the Wilcoxon signed-rank test; correlations with migraine disability with Spearman's rho. Results: Over the intervention period, FM decreased selectively (median −1.60 kg at T3, p = 0.001; median −3.00 kg at T6, p < 0.001), with FFM remaining broadly stable. At baseline, higher FFM correlated with lower migraine disability (MIDAS: rho = −0.667, p = 0.009, n = 14). Longitudinal Δ-Δ associations (ECW, phase angle) are reported as exploratory. Conclusions: These exploratory findings suggest that fat-free mass is associated with migraine disability in perimenopause and warrant confirmation, with multivariable adjustment, in the complete sample (n = 54).