Sex and gender are important but widely neglected factors in antibiotic therapy — it’s time to change direction. That is the conclusion of a group of researchers led by Alberto Enrico Maraolo, MD, a physician and researcher in the Infectious Diseases Section at the University of Naples Federico II, Naples, Italy, who published a narrative review on the topic on January 31, 2026, in Expert Opinion on Drug Metabolism & Toxicology.

The conclusions are clear: women receive 25%-40% more antibiotic prescriptions than men, have higher drug concentrations at the same dose, and experience up to twice as many adverse reactions. Yet they remain underrepresented in clinical studies, with concrete consequences for the safety and effectiveness of treatments and for the development of resistance.

Maraolo, the lead author of the review, explained to Univadis Italy, part of Medscape Professional Network, “Awareness of gender disparity is still far too low. We know men and women metabolize antibiotics differently. And yet almost no clinical guidelines take this into account: it is estimated that only 7% do, despite evidence that women receive 25%-40% more antibiotic prescriptions than men in community settings and are twice as likely to experience adverse reactions.”

Infections and Antibiotics

Gender differences in response to infections and to antibiotics have deep biological roots. On the one hand, women have stronger immune responses mediated by estrogens, which enhance the activity of B lymphocytes and macrophages, while testosterone tends to suppress immune function. This may relate to the greater severity of some infectious diseases often observed in men, as documented for viral infections such as SARS-CoV-2 and influenza. For bacterial bloodstream infections, men have a higher incidence and longer intensive care stays. However, the picture is not always straightforward. A meta-analysis of over 132,000 patients with Staphylococcus aureus bloodstream infection found an 18% higher 90-day mortality in women than in men, even after adjustment for clinical features and treatment. It is also well known that women are much more prone to certain types of infections, such as urinary tract infections.

Pharmacokinetics and pharmacodynamics are affected as well. Oral drug absorption is influenced by slower gastric emptying in women and lower acid secretion, which affects the bioavailability of some antibiotics. Distribution is affected by factors including different expression of transporters such as P-glycoprotein and body composition: women have a higher percentage of body fat and lower total body water, which increases the volume of distribution for lipophilic drugs. Cytochrome P450 activity differs between the sexes, and women generally exhibit greater CYP3A4 activity. Finally, renal clearance is lower in women, slowing elimination of antibiotics such as aminoglycosides, cephalosporins, fluoroquinolones, and vancomycin. All these factors contribute to women having twice the incidence of adverse drug reactions compared with men — a reality rarely considered when prescribing antibiotics.

The problem is further compounded by the historical underrepresentation of women in antibiotic research. Maraolo said, “Pregnant women and transgender people are practically excluded from research, leaving us without data to treat them optimally. The development and validation of sex-specific dosing nomograms that can be integrated into electronic prescribing systems would be helpful.” He also called for antimicrobial resistance surveillance systems capable of producing sex-disaggregated data and, where possible, data by gender identity. “We need many more studies, including observational pharmacokinetic studies with results stratified by sex and factors such as ongoing hormone therapies,” the author continued.

Transgender people have different characteristics from cisgender people, both biologically and in terms of infection exposure. There are very few studies on pharmacodynamics and pharmacokinetics in transgender people, although data on antiretroviral drugs suggest differences between transgender people on hormone therapy and cisgender people of both sexes. Gender-affirming surgeries carry a significant risk for surgical and urinary tract infections and therefore the use of antibiotics. Prophylactic regimens, however, often mirror those used for cisgender patients and may ignore the microbiological characteristics of postoperative tissues, eg, artificial vaginal tissue.

Socioeconomic Factors

Several studies report that antibiotics are prescribed more often to women, especially during reproductive years and particularly for cephalosporins and macrolides; overall, the lifetime likelihood of receiving antibiotics is on average 27% higher in women. In England, for example, women receive 67% more antibiotic prescriptions than men; excluding urinary tract infections, the difference remains 43%.

According to the review’s authors, women tend to consult physicians more frequently, including in their roles as family caregivers, which may increase opportunities for prescribing. Gender bias is also at play: Women with symptoms of severe infection are often prescribed antibiotics more readily because they are perceived as more fragile; conversely, mild symptoms in women may be labeled “psychosomatic” and ignored. There are also socioeconomic and cultural barriers that are especially relevant in low- and middle-income countries: limited financial autonomy, restrictions on mobility, and dependence on male relatives for health decisions can lead to incomplete antibiotic courses or the use of unregulated sources.

Gender and Resistance

Gender also influences the dynamics of antibiotic resistance. This is recognized by the World Health Organization, which in 2024 published guidelines to address gender inequalities in the fight against resistance. Women, more exposed to antibiotics for recurrent urinary infections and reproductive issues, accumulate a higher intestinal burden of resistance genes.

Men, on the other hand, can be exposed to resistant pathogens through male-dominated occupations such as the meat industry. Surveillance data are rarely disaggregated by sex, but German data, for example, show methicillin-resistant S aureus rates 2.3 times higher in men and carbapenem-resistant Enterobacterales rates 1.7 times higher. The lack of sex-disaggregated data in surveillance systems limits the ability to design targeted interventions.

Clinical practice should nevertheless take sex into account while further data are collected, Maraolo concluded: “Physicians should adopt sex-aware prescribing, considering the patient’s sex alongside other clinical parameters. Doses should be adjusted, including by using artificial intelligence tools in the context of precision medicine, properly accounting for biological sex and factors such as hormone therapies in people undergoing gender transition or who are transgender. It is also important to consider the current hormonal state, such as menstrual cycle, menopause, and use of contraceptive pill which can modify drug effectiveness.”

This story was translated from Univadis Italy.