Lactate metabolic plasticity across the menopausal transition: a hypothesis-generating framework linking ovarian hormone variability, exercise, and skeletal muscle remodeling

Abstract

The menopausal transition combines marked ovarian-hormone variability with changes in body composition, insulin sensitivity, vascular function, skeletal muscle, and exercise substrate use. Established lactate-shuttle, maximal-lactate-steady-state, metabolic-flexibility, and Lactate-Carbohydrate models already explain that lactate is an oxidative fuel, a gluconeogenic precursor, and an informative but protocol-dependent marker of substrate use rather than a waste product. The unresolved menopause-specific question is whether changing ovarian status alters the coordination of systemic lactate appearance and disappearance during exercise and recovery. This Mini Review therefore distinguishes evidence from natural perimenopause from evidence in established postmenopause and other populations, defines testable stage-specific hypotheses, and proposes a component measurement profile for future studies. The profile combines standardized absolute and relative exercise workloads, serial blood lactate concentrations, stable-isotope estimates of lactate rate of appearance, rate of disappearance, oxidation and recycling, repeated estradiol and follicle-stimulating hormone measurements, and muscle or vascular phenotyping. A structured narrative search identified no study that directly measured lactate flux or whole-body metabolic clearance during natural perimenopause. The novelty of the proposed framework therefore lies in its menopause-specific evidence hierarchy and study design, not in reclassifying lactate biology. Longitudinal studies are needed before any component can be treated as a menopausal biomarker or used to individualize exercise prescription.

The authors' abstract, as published at the source. Frontiers in Physiology, 2026 · DOI ↗