FDA revises guidance on studying sex differences, removing gender references
The US Food and Drug Administration (FDA) has reissued guidance aimed to enhance the enrollment and retention of females in clinical trials and non-interventional studies, removing references to gender, diversity, and intersex traits that were included in an earlier version released during the Biden administration.The updated guidance includes several modifications from the previous version issued in January 2025 by emphasizing the biological differences between sexes and removing language related to gender. (RELATED: FDA proposes to modernize guidance on sex, gender in clinical trials, Regulatory Focus 14 January 2025)
The update was published without a formal announcement and reflects the Trump administration's executive order issued last January, which directed the removal of any Diversity, Equity, and Inclusion (DEI) initiatives, programs, or even references to gender, race, or diversity from federal documents or programs. (RELATED: Experts: Trump executive orders create foundation for what’s to come, Regulatory Focus 24 January 2025)
The DEI purge continued in March 2025, when the FDA reissued guidelines regarding the use of sex-specific data in medical device clinical studies after removing anything related to DEI. (RELATED: FDA reissues sex-specific data guidance after sanitizing anything considered DEO-related, Regulatory Focus 2 April 2025)
The revised draft guidance addresses the importance of considering sex differences in medical product development, ways to improve the recruitment, enrollment, and retention of females in clinical trials, the design of clinical trials to inform reliable benefit-risk assessment in males and females, statistical controls to estimate treatment effects in males and females, and considerations for non-clinical testing.
The reissued version deletes multiple text references to gender. Last year’s guidance defined gender as a “multidimensional construct that encompasses how an individual self-identifies” and “gender may or may not correspond to a person’s sex assigned at birth.” The revised guidance does not include this language.
The reissued guidance also revises the term “sex.” The revision states that “the term sex refers to a biological classification based on anatomical, physiological, hormonal, and genetic (chromosomal) traits categorized as female or male. This guidance focuses on biological differences that can impact outcomes in clinical trials and non-interventional studies.”
In the previous guidance “sex” was defined as “a biological construct based on anatomical, physiological, hormonal, and genetic (chromosomal) traits. Sex is generally assigned based on anatomy at birth and is usually categorized as female or male, but variations occur. Variations of sex refers to differences in sex development or intersex traits.”
The reissued version also deletes text related to data standards. This includes references related to standards established by the Clinical Data Interchange Standards (CDISC) for organizing and reporting trial data, including templates for datasets.
The guidance indicates that historically, fewer females than males have been included in clinical trials of medical products. This lack of information has resulted in limited information for females and their health care providers about a product’s benefits and risks.
It further noted that in recent decades, there has been an improvement in the inclusion of females in clinical trials for drugs and devices, leading to greater availability of sex-specific data. However, females continue to be underrepresented in certain therapeutic areas, making it difficult to assess the benefits and risks of medical products for females in these areas.
When finalized, this guidance will replace the final guidance entitled “Guideline for the Study and Evaluation of Gender Differences in the Clinical Evaluation of Drugs” issued in July 1993.
In December, the FDA intensified its efforts to eliminate references to transgender ideology by issuing warning letters to 12 manufacturers and retailers for illegally marketing breast binders to children destined for gender-affirming surgery. (RELATED: FDA posts warning letters to manufacturers of breast binders, Regulatory Focus 19 December 2025)
These letters were issued on the same day as a Department of Health and Human Services press conference announcing a series of proposed regulatory actions aimed at limiting access to gender-affirming care for minors, including a proposed rule from the Center for Medicare & Medicaid Services (CMS) that would ban hospitals from performing sex change operations for children under 18.
Draft guidance
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