Biomarkers are proteins or small molecules which can be measured in order to diagnose conditions, identify disease, track disease progression, or monitor therapeutic interventions.  Some examples of biomarkers include the hormone human chorionic gonadotropin, a biomarker for pregnancy, and the protein prostate specific antigen, a biomarker for prostate cancer. The identification of new biomarkers has beneficial clinical implications, yet it can often be challenging to discover reliable and reproducible biomarkers from the research perspective.

 Sex may play an important factor in the variability of biomarkers within a clinical setting as sex hormones, such as estrogen, progesterone, and testosterone, may alter the amount of biomarkers present in the blood. A study published in the journal Scientific Reports, analyzed the levels of over 170 protein and small molecule biomarkers in men and women with varying hormonal status [1]. This includes women in the follicular phase or luteal phase of the menstrual cycle, women who were post-menopausal, utilizing hormone replacement therapy, or taking oral contraceptives. The study authors found that concentration of 56% of biomarkers varied between men and women. Furthermore, the concentration of 38% of biomarkers varied between female hormonal status.  Together, these results call into question the validity and reproducibility of these biomarkers in a clinical context.

 Some of the biomarkers analyzed in this study are proposed to diagnose cancer, schizophrenia, and major depressive disorder. Therefore, the observed sex and hormonal status differences found in this study highlight the necessity to incorporate sex-specific controls when developing clinical markers in order to prevent false positive or negative results.  Taking sex-based differences and hormonal status into account in any research endeavor will lead to better clinical translation and efficacy for all. 


  1. Ramsey et al., Scientific Reports. 2016; 6:26947.