Sex-specific physiological and pharmacokinetic differences significantly alter the efficacy and safety of antihypertensive drugs between men and women, necessitating sex-conscious treatment guidelines.
This review highlights significant sex-based disparities in hypertension pathophysiology and pharmacotherapy, advocating for sex-stratified precision medicine approaches to improve outcomes.
Hypertension manifests with striking sex-based disparities in prevalence, pathophysiology, and therapeutic outcomes, necessitating the reappraisal of current management paradigms. For example, men exhibit higher blood pressure (BP) in early adulthood, while post-menopausal women suffer from accelerated cardiovascular risk owing to estrogen depletion, endothelial dysfunction, and distinct aging trajectories. Moreover, the renin–angiotensin–aldosterone system (RAAS) operates rather divergently: testosterone upregulates vasoconstrictive angiotensin II type 1 receptors in men, whereas estrogen enhances nitric oxide bioavailability and modulates angiotensin II type 2 receptor in premenopausal women. These hormonal influences extend to cardiovascular aging, as women develop greater arterial stiffness post-menopause, predisposing them to heart failure with preserved ejection fraction. Conversely, men demonstrate higher endothelial dysfunction and cardiomyocyte apoptosis. Furthermore, sex-specific pharmacokinetic profiles (e.g., renal clearance, hepatic metabolism) and pharmacodynamic responses to antihypertensives underscore the inadequacy of uniform treatment strategies. This is demonstrated in women by the observed reduced efficacy of angiotensin-converting enzymes inhibitors, but superior blood pressure control using diuretics. Men, however, respond more robustly to beta blockers. Emerging evidence highlights epigenetic modifiers, including X-chromosome-linked microRNAs (miRNAs) and sex-hormone-driven transcriptional regulators, as pivotal mediators of vascular tone and drug metabolism disparities. Despite these insights, clinical guidelines remain relatively inadequately stratified by sex, perpetuating suboptimal outcomes. This review synthesizes molecular, physiologic, and pharmacotherapeutic axes of sexual dimorphism in hypertension. It also advocates for precision medicine approaches that integrate hormonal status, aging-related vascular remodeling, and genetic polymorphisms. Addressing these physiological paradigms promises to bridge the translational gap between bench and bedside, ultimately mitigating the global burden of hypertensive disease, while mitigating shortcomings in sex-based antihypertensive management.
Yaacoub et al. (Fri,) conducted a review in Hypertension. Antihypertensive therapy was evaluated. Sex-specific physiological and pharmacokinetic differences significantly alter the efficacy and safety of antihypertensive drugs between men and women, necessitating sex-conscious treatment guidelines.