Associations Between Female Reproductive Milestones and Later-life Diabetes and High Cholesterol Risk

Metabolic health generally concerns with optimal levels of blood glucose, triglycerides, high-density lipoprotein (HDL) cholesterol, blood pressure, and waist circumference without medication therapy. Poor metabolic health is responsible for a substantial population burden of disability, disease, and death. 

A new review published in the Cell Metabolism reports available evidence led by researchers at the Harvard Pilgrim Health Care Institute suggesting that female reproductive characteristics may be overlooked as risk factors that contribute to later metabolic dysfunction.

Recent evidence suggests that female reproductive characteristics may be overlooked as risk factors that contribute to later metabolic dysfunction. These reproductive traits include the age at menarche, menstrual irregularity, the development of polycystic ovary syndrome, gestational weight change, gestational dysglycemia and dyslipidemia, and the severity and timing of menopausal symptoms. 

Alterations in the metabolic characteristics may lead to the development of type 2 diabetes or cardiovascular disease and many other diseases.

"Our review provides insights into potential underlying causes and risk factors for poorer metabolic function," said lead author Amy R. Nichols PhD, MS, RD, a research fellow at the Harvard Pilgrim Health Care Institute and the Harvard T.H. Chan School of Public Health.

"Current evidence linking certain female reproductive traits to chronic metabolic health and disease suggests that screening for reproductive risk factors across the lifecourse may be an initial step to aid prevention or treatment of chronic metabolic diseases."

These reproductive risk factors include early age of first menstruation, menstrual irregularity, the development of polycystic ovary syndrome (PCOS), high weight change in pregnancy, abnormal blood sugar and lipid levels during pregnancy, and the severity and timing of menopausal symptoms.

The authors note these traits may share underlying mechanisms leading to poorer metabolic health, including genetic influences, hormonal fluctuations, or body fat.

Though acknowledging these reproductive milestones as risk factors is one step toward better understanding the development of metabolic dysfunction, the study teams says future research is needed to understand these complex relationships.

"Disentangling the relationship between risk factors and metabolic dysfunction is challenging," said senior author Emily Oken MD, MPH, Harvard Medical School Professor and Chair of the Department of Population Medicine at the Harvard Pilgrim Health Care Institute. "Clinical evidence gathered in the health care setting across the female reproductive lifespan may be critical for patient education, implementing prevention strategies, and staving off disease onset."

Reference:

Amy R. Nichols, Jorge E. Chavarro, Emily Oken. Reproductive risk factors across the female lifecourse and later metabolic health. Cell Metabolism, 2024; DOI: 10.1016/j.cmet.2024.01.002.