Pervasive Neglect of Sex Differences in Biomedical Research

• Published in: Cold Spring Harbor perspectives in biology Vol. 14; no. 4; p. a039156
• Main Authors: Zucker, Irving, Prendergast, Brian J., Beery, Annaliese K.
• Format: Journal Article
• Language: English
• Published: United States Cold Spring Harbor Laboratory Press 17.05.2022
• Subjects: Animals; Biomedical Research - methods; Clinical trials; Dosage; Female; Females; Gender aspects; Gender differences; Humans; Male; Medical research; Mice; National Institutes of Health (U.S.); Pharmacokinetics; Rats; Sex Characteristics; Sex differences; Side effects; United States; Women; United States
• ISSN: 1943-0264; 1943-0264
• DOI: 10.1101/cshperspect.a039156

Females have long been underrepresented in preclinical research and clinical drug trials. Directives by the U.S. National Institutes of Health have increased female participation in research protocols, although analysis of outcomes by sex remains infrequent. The long-held view that traits of female rats and mice are more variable than those of males is discredited, supporting equal representation of both sexes in most studies. Drug pharmacokinetic analysis reveals that, among subjects administered a standard drug dose, women are exposed to higher blood drug concentrations and longer drug elimination times. This contributes to increased adverse drug reactions in women and suggests that women are routinely overmedicated and should be administered lower drug doses than men. The past decade has seen progress in female inclusion, but key subsequent steps such as sex-based analysis and sex-specific drug dosing remain to be implemented.