Plasma proteomic signature of the human menstrual cycle.

Abstract

The menstrual cycle is one of the most fundamental biological rhythms in human physiology, yet its systemic molecular changes remain poorly understood. Here we show that the menstrual cycle is accompanied by widespread changes in the circulating proteome. By profiling nearly 3,000 plasma proteins in 2,760 women from the UK Biobank, we identified 198 proteins that vary across the cycle, forming distinct temporal patterns aligned with menstrual phases. These proteins include reproductive hormones, cytokines and growth factors, many of which are enriched in endometrial tissue and expressed in epithelial and stromal cell types, highlighting their biological specificity. Several proteins were linked to common reproductive disorders, including endometriosis, leiomyoma and abnormal bleeding. Finally, we developed a proteomic score on the basis of 75 proteins that accurately predicts menstrual cycle phase. Together, these findings provide a systems-level atlas of menstrual cycle biology and inform biomarker discovery in women's health.