Sex Bias in Clinical Trials: How the Historical Underrepresentation of Women Shapes Drug Safety and Treatment Outcomes

Clinical trials are foundational for drug approval, dosing standards, and treatment guidelines. Yet, women were systematically excluded from these studies for much of the 20th century. To address this gap, this literature review examines how the historical exclusion of women from clinical trials has transformed drug safety and treatment outcomes for female patients. By synthesizing sources across regulatory history, trial design, clinical consequences, and reform strategies, the review shows how exclusion at one stage of research compounds into the next. Specifically, missing data from early trials produces dosing guidelines that are calibrated to male physiology, which then become the standard used in drug approval and prescription for female patients. Across the existing literature, researchers consistently find that male-centered data continues to shape clinical guidelines in ways that do not reflect female physiology. As a result of this male-centered evidence base, consequences include higher rates of adverse drug reactions, inaccurate dosing, and delayed diagnoses.