Sex plays an important role in patients’ experience with the medical system and in their treatment by health professionals.1 Patients are treated differently based on their socially constructed genders and providers may or may not have medical justification for differential treatment.1 However, in the case of drug administration, differential treatment based on biological sex is crucial to satisfactory care.2 Sex can affect the pharmacodynamics and pharmacokinetics of drugs, thus changing patient outcomes related to medications.2 Anesthesia providers in particular should account for sex throughout the perioperative period, as differences between male and female patients can arise before, during and after surgery.3 Therefore, anesthesiology practitioners should understand the pharmacology behind sex differences, implications of sex for anesthesia and possible gender stereotypes or prejudices that could affect care.
Sex differences exist in pharmacokinetics (i.e., the way the body uses drugs) and pharmacodynamics (i.e., the way drugs affect the body). The four main factors that contribute to individual differences in pharmacokinetics are bioavailability, distribution, metabolism and elimination, all of which are related to a patient’s sex.4 Research suggests that these sex differences arise from variations in bodily factors such as body weight, plasma volume, gastric emptying time, plasma protein levels, activity of the cytochrome P450 enzyme group, drug transporter function and excretion activity.4 The pharmacodynamics of drugs, such as their effects on a patient’s symptomology or reaction, are closely tied to pharmacokinetic differences. For example, female patients on average may be more sensitive to a drug due to a lower metabolism than male patients.5 Evidence shows clear sex differences in various drugs’ movement throughout the body and the effects of drugs on behavior.
Differences in pharmacology between male and female patients are important to the anesthesiology practitioner. For example, female patients have a 20 to 30 percent greater sensitivity to the muscle relaxant effects of vecuronium, pancuronium and rocuroium.2 Meanwhile, male patients are more sensitive than female patients to propofol’s effects, which may necessitate reducing the dose by 30 to 40 percent in males as compared to females in order to achieve similar recovery times.2 Though it remains unclear exactly why this phenomenon occurs with propofol, several studies have approached the biological processes involved. For example, Hoymork and Raeder found that female patients had a more rapid decline in plasma propofol at the end of anesthesia infusion.6 Another study by Gan et al. showed that female patients showed much faster recovery than male patients from general anesthesia with combined propofol, alfentanil and nitrous oxide.7 Furthermore, Buchanan et al. found that female patients recovered faster than male patients from general anesthesia combined with neuromuscular blockade.3 However, for haloperidol, an antiemetic drug, male patients responded better and had less postoperative nausea and vomiting than did female patients.8 These findings show that sex differences in drug effects may depend on the medication and can be counter to expected results. Thus, anesthesia providers must be knowledgeable about the unique sex differences for every drug they use during a procedure.
Despite clear differences between males and females in pharmacology and anesthesia, data are lacking on the anesthetic implications of sex. Having few studies on the subject may contribute to stereotypes and prejudice in treatment, which can affect a patient biologically and psychologically. For example, one study found that females reported significantly higher pain than did males for the first one to two days after surgery, but did not use more anesthetics.9 The fact that female patients have lower sensitivity to some anesthetic drugs, as shown above, may have affected these results. A study by Mavridou et al. found that female patients expressed more fear about anesthesia than did male patients, leading to greater preoperative anxiety and possibly affecting recovery outcomes.10 Awareness of this disparity could lead an anesthesia provider to provide more preoperative counseling to female patients in order to reduce complications.10 It also appears that many randomized controlled trials of interventions—even those published in high-ranking anesthesiology journals—do not stratify patients based on sex or gender, leading to a lack of clarity on the best practices for each sex.11 Low reporting of sex and gender can contribute to stereotypes and prejudices in patient care, such as considering female patients more “demanding” than male patients.1
Overall, a patient’s sex is crucial to quality of care. Differences in pharmacokinetics and pharmacodynamics of drugs may necessitate dosing changes or other special considerations, especially in the field of anesthesiology. A lack of research and poor stratification by gender may contribute to stereotypes that lead to worse patient care. Future studies should aim to optimize anesthesia provision for both female and male patients based on evidence of sex differences.
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11. Begic D, Janda-Martinac C, Vrdoljak M, Puljak L. Reporting and analyses of sex/gender and race/ethnicity in randomized controlled trials of interventions published in the highest-ranking anesthesiology journals. Journal of Comparative Effectiveness Research. 2019;8(16):1417–1423.
