The Importance of Gender-Neutral Terminology in Risk Evaluation and Mitigation Strategy Programs: A Call to Action

Introduction

Risk evaluation and mitigation strategy (REMS) programs in dermatology should clarify how they define gender and biological sex to appropriately focus on patients’ reproductive potential and risk for birth defects (Table 1). Specifically, REMS programs should adopt proper gender-neutral terminology. While several teratogenic prescriptions are monitored by REMS programs, isotretinoin, an oral retinoid used for acne treatment is likely the most well-known. Regulated by iPLEDGE, isotretinoin prescription originally required patients to register under one of 3 categories: male, female, or female of reproductive potential [1]. This classification system posed problems as providers were required to categorize patients of gender-diverse backgrounds into limited categories. For example, transgender males with intact uteruses and ovaries might have been categorized as females of reproductive potential. In some cases, patients have forgone treatment because improper categorization conflicted with their gender identity [2].

Medical care providers may conflate gender and biological sex. Growing awareness and inadequate terminology for transgender patients have led to changes. In December 2021, the Food and Drug Administration streamlined the iPLEDGE process and introduced gender-neutral terminology, allowing for the separation of a patient’s biological sex from their gender identity (Figure 1). Dermatologists now register patients under one of 2 categories: patients who can become pregnant and those who cannot become pregnant [3,4]. This change may improve access to isotretinoin for transgender candidates such as transmasculine patients with an increased predisposition for acne secondary to exogenous testosterone therapy [5]. A registration process based on reproductive potential ultimately enhances iPLEDGE’s goal to prevent potential birth defects.

‎

Conclusions

Though recent changes to iPLEDGE do not resolve population-specific concerns faced by gender-diverse individuals, it is nonetheless a pivotal step in transgender patient care—an additional step that other REMS programs have yet to adopt. Prescription medications including thalidomide, acitretin, and mycophenolate mofetil still use a similar taxonomy to the old iPLEDGE system, with patient groupings of male, female, or female of reproductive potential [6,7]. Nevertheless, overall prescription prevalence and increasing associations of skin disease with exogenous hormone therapy indicate a potential area for the use of updated REMS terminology [8]. Future standardization of gender-neutral terminology can maximize patient enrollment, minimize distress, and prevent teratogen exposure. The revision of iPLEDGE categories with gender-neutral terminology reveals continued inadequacies; ongoing effort is needed to build REMS protocols solely around the prevention of birth defects, without regard to sex or gender.