For a long time, medicine treated the male body as the universal standard. Only in recent years have cancer specialists begun to systematically examine gender-specific differences—and in doing so, are discovering new ways to improve cancer treatment.
Until about twenty years ago, the prevailing assumption was that there was essentially one model of the human body. “It used to be assumed that men and women were the same, period,” says Anna Dorothea Wagner, head of the gastrointestinal cancer clinic at Lausanne University Hospital. “But that was never true.”
As one oft-quoted phrase aptly puts it: “Every cell is sexed, every person is gendered.” German captures both meanings with a single word—Geschlecht —but in reality, both biological sex and social gender shape how cancer develops, is diagnosed and responds to treatment.
Melanoma provides a clear example. In a 2018 report from the European Society for Medical Oncology, Wagner and colleagues highlighted how men tend to pay less attention to skin changes, underestimate their risk, and attend checkups less often than women. These behavior patterns contribute to later diagnoses.
An analysis of nearly 12,000 patients in the Munich Cancer Registry showed that men more frequently presented with larger tumors, especially on the torso—likely due to more frequent exposure of the upper body to sunlight. Men also had significantly poorer outcomes overall.
Surprisingly, this disparity persisted even after researchers controlled for tumor size and stage. “A biological sex characteristic appears to have a significant influence on melanoma progression and survival,” the study reported. Mouse experiments reinforced this finding: male animals developed more liver metastases than females. The exact reasons remain unclear, though estrogen and other female sex hormones may have protective effects.
This protective effect might help explain why almost all non–sex-specific cancers occur more frequently in men than in women. Differences in behavior, hormones, immune function, and even the composition of gut microbiota are among the factors researchers are investigating.
Women’s immune systems tend to respond more strongly than men’s—something reflected not only in cancer susceptibility but also in the higher prevalence of autoimmune diseases such as multiple sclerosis and chronic inflammatory bowel disease.
Genetics also plays a role. Several tumor suppressor genes lie on the X chromosome. While one X chromosome is largely inactivated in each female cell during development, many tumor suppressor genes “escape” this process. This means that, in many cases, female cells retain a backup copy—an advantage male cells lack.
Wagner notes that although genetics clearly delineate biological sex, the traits of men and women overlap in many areas. Still, some differences in distribution patterns are striking—for example, women’s bodies contain proportionally more fat, while men typically carry more muscle. Fat-free mass accounts for about 80 percent of body weight in men but only about 65 percent in women.
Despite this, such physiological differences are still rarely considered in clinical practice—particularly in chemotherapy dosing. Drug dosages are often calculated based on body surface area. While this seems logical, it overlooks how rapidly a drug is metabolized.
Because muscle tissue is more metabolically active than fat tissue, many chemotherapy drugs break down more slowly in women. “This is an important reason why we see more - and often stronger - side effects in women,” says Berna Özdemir, senior oncologist at Inselspital Bern. And when dealing with potent cancer drugs, “side effects” can be life-threatening.
“It has been known for decades that significantly more women than men suffer from the side effects of chemotherapy,” Özdemir emphasizes. She believes that dosing should be based on lean body mass rather than body surface area or total weight.
In a recent collaborative study, Özdemir, Wagner, and international colleagues reviewed the metabolism of 99 cancer drugs. For 22 of them, they found clear sex-specific differences—and in every case, women’s blood levels declined significantly more slowly than men’s.
Because cancer drugs have narrow therapeutic windows—even small dosing differences can shift the balance between effectiveness and toxicity. Yet most chemotherapy dosages are based on clinical studies that included mostly male participants. “These studies are not designed to determine potentially different optimal dosages for men and women,” Özdemir notes. As a result, crucial data for gender-sensitive dosing is still missing.
Side effects in drug approval studies are also rarely reported separately by gender. Researchers who want to analyze data retroactively often face significant hurdles. Even so, public and scientific awareness of gender-specific medicine is growing. “When I was studying medicine, there was still talk of ‘atypical symptoms’ in women,” Özdemir says. “Today, students learn early on that gender matters.”
Özdemir emphasizes that the approach of paying closer attention to gender in cancer treatments benefits everyone—women, men, and those who identify as neither. She cites bone loss, or osteoporosis in medical terms, as an example. “We know that breast cancer patients have an increased risk of osteoporosis due to anti-hormonal therapy —and therefore benefit from preventive measures,” says Özdemir. This also applies to prostate cancer patients who also receive anti-hormonal therapy. “But with prostate cancer, the risk of osteoporosis is often forgotten; neither patients nor doctors think about it.”
In the report on the 2018 working meeting on gender differences, the authors led by Wagner and Özdemir cite another example that shows that men can also benefit from sex- and gender-sensitive medicine: a study on the treatment of lymphomas showed that a then-new drug called rituximab significantly improved the survival rate of female patients more than that of male patients. The researchers attributed the difference to the lower degradation and consequently longer duration of action of rituximab. They then demonstrated that the survival rate also increased in male lymphoma patients when they were given a higher dose.
“Today, everyone is talking about precision oncology. We often chase rare gene mutations whose significance is unclear,” says Wagner. “But we should not allow this to prevent us from also considering the influence of such fundamental biological variables as gender or age.” This is because these fundamental variables often lead to noticeable differences in treatment outcomes.
Unlike genetic mutations or specialized biomarkers, which can only be detected with expensive tests, gender is an important factor influencing treatment response and toxicity—and one that can be determined immediately and at no cost. “This influencing factor should no longer be overlooked, but rather better understood and exploited,” write Özdemir and Wagner. “We should ask ourselves what we can learn from gender differences in order to individualize treatment decisions and improve the ratio of efficacy to side effects for as many patients as possible,” says Wagner.
