Adriana Raquel Dias Fernandes

Gynecologic health represents a dynamic interaction between endocrine regulation, metabolic homeostasis, inflammatory signaling, and cardiovascular adaptation across the female lifespan. Increasing evidence demonstrates that reproductive conditions such as polycystic ovary syndrome, endometriosis, uterine fibroids, hypertensive disorders of pregnancy, and menopause are not isolated clinical entities but manifestations of broader systemic processes. This review integrates high-impact clinical guidelines, consensus statements, and epidemiologic syntheses to construct a lifespan-based conceptual framework linking gynecologic milestones with long-term cardiometabolic risk. Polycystic ovary syndrome exemplifies the convergence of hyperandrogenism and insulin resistance with persistent vascular vulnerability. Endometriosis illustrates immune–endocrine interactions and chronic inflammatory pathways with potential systemic implications. Pregnancy-related hypertensive disorders function as prognostic markers of future cardiovascular disease, while the menopausal transition represents an endocrine inflection point that amplifies preexisting metabolic trajectories. The synthesis highlights inflammation as a unifying biological mediator and underscores the influence of global obesity and metabolic syndrome on reproductive outcomes. By reframing gynecology within systems medicine, this work emphasizes preventive reasoning, longitudinal risk stratification, and interdisciplinary care. A lifespan-integrated approach may strengthen medical education, improve early detection of cardiometabolic vulnerability, and redefine gynecologic practice as a cornerstone of long-term systemic health.

Hormonal regulation in women plays a fundamental role not only in reproductive physiology, but also in metabolic and cardiovascular homeostasis throughout life. Recent scientific evidence demonstrates that endocrine transitions and hormonal disorders influence endothelial function, lipid metabolism, insulin sensitivity, inflammatory pathways, adipose tissue distribution, and long-term cardiovascular risk. This review aimed to analyze the systemic effects of female hormonal regulation beyond reproduction, emphasizing its relationship with metabolic and cardiovascular health through an interdisciplinary perspective integrating gynecology, endocrinology, cardiology, and public health. A narrative and integrative literature review methodology was employed using peer-reviewed scientific publications indexed in internationally recognized databases, including PubMed, Scopus, ScienceDirect, and Google Scholar. Contemporary evidence related to menopause, polycystic ovary syndrome, hypertensive disorders of pregnancy, hormonal therapies, endothelial dysfunction, insulin resistance, and cardiometabolic disease was analyzed and synthesized. The reviewed evidence demonstrated that menopause is strongly associated with endothelial dysfunction, visceral adiposity, dyslipidemia, insulin resistance, and increased cardiovascular risk. Polycystic ovary syndrome was identified as a multisystemic endocrine-metabolic disorder closely linked to obesity, chronic inflammation, hyperandrogenism, and future risk of type 2 diabetes mellitus. Additionally, pregnancy-related hypertensive disorders such as preeclampsia and gestational hypertension were associated with elevated long-term risk of chronic hypertension, ischemic heart disease, and cerebrovascular disease. Hormonal therapies and contraceptive methods demonstrated both beneficial vascular effects and potential thrombotic risks depending on patient characteristics and individualized cardiovascular profiles.

The enteric nervous system (ENS), commonly referred to as the “second brain,” has emerged as a key integrative network in clinical medicine. This review analyzes its role beyond gastrointestinal physiology, emphasizing its involvement in neurological, nephrological, and urological conditions through interconnected mechanisms such as the gut–brain, gut–kidney, and gut–bladder axes. A structured analysis of current scientific literature was conducted to identify the main pathways linking ENS dysfunction with multisystem disease, including microbiota dysbiosis, neuroimmune activation, autonomic imbalance, epithelial barrier disruption, and visceral hypersensitivity. The findings demonstrate that while gastrointestinal manifestations remain predominant, ENS-related alterations are strongly associated with systemic inflammation, neurological symptoms, and urinary dysfunction. Additionally, emerging therapeutic strategies highlight the importance of integrative approaches, including dietary interventions, microbiota modulation, neuromodulation, and anti-inflammatory treatments. These results support the concept of the ENS as a central regulator in multisystem physiology and reinforce the need for interdisciplinary clinical reasoning. Understanding the ENS from a systems-based perspective provides valuable insights for improving diagnosis, treatment, and medical education in the context of complex and chronic diseases.

Cardiovascular disease remains the leading cause of mortality worldwide, and traditional risk stratification models based on static variables are often insufficient to explain the complexity of cardiometabolic disorders. In this context, metabolic flexibility—defined as the ability of the organism to adapt substrate utilization according to physiological demands—has emerged as a relevant integrative concept linking endocrinology and cardiovascular disease. This review analyzes metabolic flexibility as a central mechanism in cardiovascular risk, exploring its physiological basis, its relationship with insulin resistance and metabolic disorders, and its implications in cardiovascular pathology. Evidence shows that impaired metabolic flexibility is associated with altered substrate utilization, mitochondrial dysfunction, systemic inflammation, and increased cardiovascular risk. These alterations contribute to inefficient myocardial energy metabolism, vascular dysfunction, and disease progression. Additionally, current therapeutic strategies that improve metabolic regulation have demonstrated significant cardiovascular benefits, supporting the relevance of metabolic pathways in disease prevention and management. The analysis also highlights the importance of considering metabolic flexibility in populations with a high burden of cardiometabolic disease, particularly in Latin American countries such as Mexico, Colombia, and Ecuador.

Aging is associated with a progressive increase in chronic low-grade inflammation, known as inflammaging, which has been identified as a key mechanism underlying the development of multimorbidity. This review aims to analyze the role of inflammaging in aging and its impact across internal medicine, immunology, and gynecology. A structured narrative review was conducted using high-impact scientific literature, focusing on biological mechanisms, clinical implications, and interdisciplinary perspectives. The findings indicate that inflammaging is driven by interconnected processes such as immune dysregulation, cellular senescence, mitochondrial dysfunction, metabolic imbalance, and hormonal changes. These mechanisms contribute to the development of chronic diseases including cardiovascular disorders, type 2 diabetes, frailty, neurodegeneration, and postmenopausal alterations. Additionally, inflammatory biomarkers such as IL-6, TNF-α, and CRP were consistently associated with disease progression. The results also highlight the importance of lifestyle interventions, metabolic control, and emerging geroscience-based therapies in modulating chronic inflammation. Overall, inflammaging represents a central biological axis that links aging with multimorbidity, supporting the need for integrated and preventive approaches in clinical practice.