Methotrexate in Rheumatoid Arthritis and in Cancers: Gender is a Serious Variable for Effectiveness and for Prevention of Side Effects

Gender differences in physiology and clinics were historically more related to sex hormones. But over time, gender differences went beyond sex hormones and were related to all body physiological systems. Rheumatoid arthritis (RA)[1] or cancers[2] are gender-related, and methotrexate (MTX), which inhibits the synthesis of DNA and RNA, is used for treatment. Recently, the need for gender differences in clinical studies for cancer and RA was highlighted.[3,4] Now, is the effectiveness of MTX in these diseases gender-dependent or not? Special attention is needed for the dosage use of MTX between genders.[5] In RA patients and within MTX usage, more adverse outcomes were detected which was significantly different between genders,[4] while in osteosarcoma patients, the metabolite of MTX (7-OH-MTX) related to hepatic toxicity was more in young female patients.[6] The side effects of MTX are not only dependent on gender, but can also be related to race, and different responses to MTX exist between males and females. As gender is the most important determinant of health, an approach to RA and cancer treatments with MTX must be considered by including clear guidance on what to do when differences exist. The side effects of some other sensitive drugs such as cisplatin, which is used in the treatment of cancers, are also gender dependent.[7] Finally, it is necessary to design researches in the clinic to determine the effects caused by the drug in both the genders, and the issue of gender in the clinic should be under the microscope of doctors. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.