Perinatal Endocrine-Cardiac Axis: A Narrative Review of Long-Term Cardiovascular Risks in Women with Gestational Diabetes, Hypertensive Disorders, and Thyroid Dysfunction.

Purpose: To review the long-term cardiovascular risks associated with three common perinatal endocrine disorders-gestational diabetes mellitus (GDM), hypertensive disorders of pregnancy (HDP), and thyroid dysfunction (including postpartum thyroiditis)-and to identify opportunities for early risk stratification and prevention. Materials and

Methods

We conducted a structured literature search of PubMed and Web of Science for peer-reviewed articles published between January 2000 and December 2025. Search terms included combinations related to GDM, HDP, thyroid dysfunction, and cardiovascular disease (CVD). We prioritized prospective cohort studies, meta-analyses, systematic reviews, and major clinical guidelines. Key findings were synthesized thematically.

Results

GDM is associated with a 1.6- to 2-fold increased risk of future CVD, HDP with a 1.8-fold increase, and subclinical hypothyroidism with a two-fold increase. These risks persist for decades, are independent of traditional risk factors, and are amplified by obesity, recurrence, and social determinants of health. Converging pathophysiological mechanisms include persistent insulin resistance, chronic low-grade inflammation, endothelial dysfunction, autonomic dysregulation, epigenetic modifications, and subclinical myocardial remodeling. The placenta serves as a central endocrine-cardiovascular interface, releasing anti-angiogenic factors, pro-inflammatory cytokines, and exosomal microRNAs. Despite this evidence, postpartum screening uptake remains below 50%, care is fragmented, and pregnancy history is not incorporated into CVD risk calculators.

Conclusion

A life-course approach integrating structured postpartum screening (6-12 weeks and annually), lifestyle interventions, targeted pharmacotherapy, and multidisciplinary cardio-obstetrics programs is urgently needed to reduce the global burden of premature heart disease, stroke, and heart failure in women.