Gender Variations in Anesthesia

Gender variations in anesthesia reflect a complex interplay between physiology, hormonal profiles, anatomy, and pharmacodynamics. These differences significantly influence how patients respond to anesthetic agents, how pain is perceived, and how cardiovascular and respiratory systems behave during surgery. A growing body of evidence highlights the importance of sex-specific considerations in anesthetic practice, supporting the movement toward personalized anesthetic care.

Sex-Based Cardiovascular Differences

Baseline Physiology

Men generally have larger cardiac dimensions and higher stroke volumes, contributing to greater cardiac output. In contrast, women typically have smaller hearts but compensate with higher resting heart rates, resulting in a distinct hemodynamic response to anesthesia. These structural and functional variations can influence intraoperative stability (Modern Heart and Vascular Institute, 2022).

Vascular compliance also differs. Women exhibit greater arterial compliance and lower systemic vascular resistance, predisposing them to more pronounced hypotension during anesthesia, particularly with neuraxial techniques (PMC, 2020).

Autonomic nervous system tone further contributes to variation. Women display dominant parasympathetic tone and higher baseline vagal activity, increasing their susceptibility to anesthetic-induced bradycardia and hypotension (Am J Physiol. 1998;275:H1569–H1577).

Anesthetic Implications

During induction and maintenance, women often require higher doses of propofol per kilogram due to lower lean body mass and altered pharmacokinetics (PubMed, 2006). However, they are also more prone to hypotension with either general or neuraxial anesthesia. Preventive strategies such as fluid coloading and early vasopressor use are therefore recommended (PMC, 2017).

Hormonal transitions also matter. Estrogen is vasoprotective and anti-inflammatory, and its decline after menopause increases cardiovascular risks (PMC, 2021; Arch Med Sci. 2022;18:12–20). Phenylephrine is commonly favored as the vasopressor of choice for neuraxial anesthesia-induced hypotension in women, due to its predictable α-adrenergic profile (Int J Clin Anesth. 2024;36:45–52).

Hormonal Shifts and Anesthesia in Women

Estrogen and Progesterone

Estrogen upregulates hepatic cytochrome P450 enzymes, accelerating metabolism of several anesthetic drugs including midazolam and fentanyl (Waxman & Holloway, Mol Pharmacol. 2009;76:215–228). Progesterone exerts sedative and anxiolytic effects, increasing central nervous system sensitivity to opioids and benzodiazepines (Cicero TJ et al. J Pharmacol Exp Ther. 2002;299:97–105).

Menstrual Cycle

During the luteal phase, elevated progesterone enhances anesthetic sensitivity and increases the risk of postoperative nausea and vomiting (PONV) (Gan TJ et al. Anesth Analg. 2014;118:85–113).

Pregnancy

Pregnancy induces physiological changes including increased cardiac output, greater sensitivity to local anesthetics, and airway challenges due to mucosal edema (Mhyre JM, D'Oria R. Obstet Anesth Dig. 2011;31:191–198).

Menopause

Estrogen withdrawal after menopause contributes to higher cardiovascular risk, osteoporosis, and altered drug responses, requiring individualized perioperative management (North American Menopause Society. 2010;17:242–255).

Gender-Based Anesthetic Considerations

Drug Metabolism

Women’s higher fat content increases the volume of distribution for lipophilic drugs such as propofol, while men’s greater muscle mass alters the pharmacokinetics of hydrophilic drugs (Knibbe CA et al. Clin Pharmacokinet. 2002;41:249–259).

Pain Perception

Women frequently report greater postoperative pain, a finding attributed to estrogenic modulation of opioid receptor pathways and nociceptive processing (Fillingim RB et al. J Pain. 2009;10:447–485).

Cardiovascular Responses

Estrogen enhances endothelial function and autonomic regulation, though this protective effect diminishes after menopause (Mendelsohn ME, Karas RH. Science. 2005;308:1583–1587). Older men also face increased cardiovascular lability due to declining testosterone levels (Maggio M et al. Eur J Endocrinol. 2011;165:11–20).

Hormonal Changes in Men

Testosterone Decline

Aging men experience reduced testosterone, leading to increased fat mass, reduced muscle mass, and altered distribution of anesthetic drugs (Grossmann M, Matsumoto AM. Lancet Diabetes Endocrinol. 2017;5:390–402). Declining testosterone also compromises cardiovascular stability during anesthesia (Maggio M et al. Eur J Endocrinol. 2011;165:11–20).

Cortisol and Growth Hormone

Aged men often have altered cortisol responses that blunt their perioperative stress adaptation (Inder WJ, Josephs MD. Best Pract Res Clin Endocrinol Metab. 2010;25:777–789). Declines in growth hormone further reduce cardiac output and oxygen delivery during stress (Ciresi A, Amato MC. Endocrine. 2016;54:394–403).

Pharmacokinetics

Elderly males exhibit slower hepatic and renal clearance of anesthetic agents, prolonging drug effects (Mclean AJ, Le Couteur DG. Pharmacol Rev. 2004;56:163–184; Klotz U. Drug Metab Rev. 2009;41:67–76).

Male-Specific Airway Challenges

Men present unique airway challenges due to anatomical and fat distribution differences. Larger neck circumference is strongly associated with obstructive sleep apnea (OSA), complicating airway maintenance and increasing intubation difficulty (J Anesth Pract. 2024;18:112–118). Prominent thyroid cartilage and elongated mandible in men can obstruct glottic visualization during laryngoscopy (Br J Anaesth. 2023;130:912–920). Variations in glottic angles and tracheal length may necessitate adjuncts such as bougies or video laryngoscopes (J Clin Anesth. 2023;85:111123). Additionally, increased pharyngeal and subcutaneous fat in men impairs mask seal and increases airway resistance, challenging effective ventilation (Anesth Analg. 2024;138:55–63).

Clinical Implications and Recommendations

Gender differences have practical consequences for anesthetic practice. Individualized drug dosing, guided by sex-specific pharmacokinetics, should be applied for agents such as propofol, midazolam, and opioids. Preemptive hemodynamic monitoring is recommended, particularly for bradycardia and hypotension in women and for cardiovascular instability in older men. Airway preparedness is crucial in male patients with large neck circumference or challenging anatomical features, with advanced tools kept readily available. Pain management should be tailored, recognizing that women often report heightened postoperative pain. Finally, consideration of hormonal milestones—including pregnancy, menstrual cycle phases, menopause, and andropause—should inform perioperative planning to optimize outcomes.