Reproductive aging is a dynamic, systemic process that encompasses more than the decline in ovarian function. It involves coordinated changes across neuroendocrine, immune, metabolic, and mitochondrial systems. Central to this transition is the depletion of ovarian follicles, leading to reduced estradiol and progesterone production and subsequent disruption of the hypothalamic-pituitary-gonadal (HPG) axis. This hormonal shift remodels hypothalamic signaling networks - particularly those involving kisspeptin, neurokinin B (NKB), and GABA - driving alterations in gonadotropin-releasing hormone (GnRH) pulsatility, vasomotor symptoms (VMS), and loss of reproductive cycling. Simultaneously, chronic inflammation, oxidative stress, and mitochondrial dysfunction further accelerate both ovarian and neural aging. Estrogen receptor subtypes (ERα and ERβ) play critical and region-specific roles in mediating tissue responses to hormonal withdrawal, contributing to variability in symptom expression and therapeutic outcomes. Genetic, cultural, and environmental factors - such as diet, endocrine disruptors, and APOE genotype - further influence the trajectory and severity of menopause-related changes. Emerging treatments, including neurokinin receptor antagonists and ERβ-selective modulators, offer targeted alternatives to conventional hormone therapy. This review frames menopause not as a singular endocrine endpoint but as a neuroimmune transition, highlighting the need for mechanistic insight and personalized therapeutic approaches to improve health outcomes during reproductive aging.

Alzheimer’s disease (AD) affects women more than men, with risk increasing during and after the menopausal transition. Estrogen deficiency has long been a leading explanation for this sex difference, but emerging evidence suggests that follicle-stimulating hormone (FSH) may represent an additional, contributory endocrine factor. This narrative and mechanistic review integrates evidence on reproductive aging, AD pathobiology, and sex differences in AD, with particular emphasis on endocrine, metabolic, protein-clearance, inflammatory, and vascular mechanisms. PubMed and Google Scholar were searched for peer-reviewed human studies, animal models, and mechanistic investigations published through September 2026, prioritizing primary research and systematic reviews concerning FSH signaling, ApoE biology, and AD pathophysiology. Circulating FSH rises markedly across the menopausal transition and has been associated with cerebral amyloid burden in women, although the magnitude of this association is modest relative to established genetic risk factors such as APOE ε4 and causal directionality has not been established in humans. Preclinical studies further suggest that elevated FSH may influence pathways relevant to AD, including C/EBPβ–δ-secretase signaling, neuronal glucose metabolism, mitochondrial function, autophagic-lysosomal clearance, and apolipoprotein biology. Several steps within these proposed mechanisms, including the predominance of Gαi coupling by neuronal FSH receptors and any direct FSH action on microglia, remain incompletely established. Dysregulation across these interrelated systems may contribute to Aβ accumulation, tau pathology, impaired protein clearance, and chronic neuroinflammation, while reproductive aging is also associated with vascular and blood-brain barrier changes that may precede classical AD pathology. Taken together, current evidence supports a model in which sustained FSH elevation may act as one component of the broader biological changes accompanying reproductive aging that influence AD vulnerability. Further human and mechanistic studies are needed to determine the magnitude, cellular pathways, and therapeutic relevance of this contribution.

At the time of this writing, SARS-CoV-2 has reportedly claimed the lives of approximately 1.94 million people worldwide. However, there is still disagreement concerning the origin of SARS-CoV-2, its true nature, and the extent of its pathogenicity. Thus, the purpose of this manuscript is to highlight and critically analyze these differences so that research efforts can be geared towards addressing these concerns. For this purpose, the author studied the perspectives (about SARS-CoV-2) of both conventional and non-conventional scientists, physicians, and researchers in an attempt to understand the points of contention and the reasons for the vast gulf in perspective. And after so doing, it has become clear that if the scientific community is to quiet or satisfy the minds of those who dissent against the dominant consensus, the predominant scientific community (particularly the microbiologist/immunologist) must carry out the requisite scientific procedures and encourage governmental/academic transparency.

At the time of this writing, SARS-CoV-2 has reportedly claimed the lives of millions of people worldwide. However, there is still disagreement concerning the origin of SARS-CoV-2, its true nature, and the extent of its pathogenicity. Thus, the purpose of this manuscript is to highlight and critically analyze these differences so that research efforts can be geared toward addressing these concerns. For this purpose, the author studied the perspectives of both conventional and non-conventional scientists, physicians, and researchers in an attempt to understand the points of contention and the reasons for the vast gulf in perspective. After reviewing the varying but divergent perspective pertaining to the origin of SARS-CoV-2 and the premises used to justify them, it has become clear that if the scientific community is to put a halt to the spread of misinformation pertaining to the origin of SARS-CoV-2 and COVID-19, the predominant scientific community (particularly the microbiologist/immunologist) must carry out the requisite scientific procedures and encourage governmental/academic transparency.

Respiratory viral infections are a major cause of global morbidity and mortality, partly because they increase susceptibility to secondary bacterial pneumonia and sepsis. Coronaviruses, influenza viruses, parainfluenza viruses, rhinoviruses, and respiratory syncytial virus have each been associated with impaired macrophage antibacterial function, although the underlying evidence differs among virus families. Direct lysosomal-pH measurements and mechanistically resolved links between infection and lysosomal de-acidification are strongest for coronaviruses. Using β-coronaviruses as the primary model for the effect of direct lysosomal disruption on macrophage antimicrobial capacity, this review examines lysosomal exploitation during viral egress, impaired phagosome-lysosome fusion, E-protein-mediated proton conductance, and ORF3a-associated lysosomal injury. It further proposes that the magnitude of these effects is shaped by host-dependent immunometabolic processes. Mitochondrial dysfunction, NAD⁺ depletion, and disrupted mitochondria-lysosome coupling may reduce the ability of macrophages to preserve lysosomal acidity, autophagic competence, and bacterial killing during viral challenge. Together, these mechanisms describe how coronavirus infection compromises macrophage antibacterial defense, and how the resulting susceptibility to secondary bacterial infection is further modulated by the metabolic and inflammatory state of the host cell.