Transgender Patients, Isotretinoin, and US Food and Drug Administration-Mandated Risk Evaluation and Mitigation Strategies: A Prescription for Inclusion.

Abstract

Caitlyn Jenner has vaulted to celebrity status, Facebook has expanded its gender nomenclature, and the Pentagon has announced plans to permit transgender servicemembers toserveopenly.Although recentnews about transgender persons is not uniformly rosy— transgender persons in the United States and elsewhere are still targets of violent, sometimes lethal attacks, and voters in Houston, Texas, recently repealed that city’s Equal Rights Ordinance—transgender visibility andequalityhavemade remarkableadvances. Those advances have paralleled strides made in scientific understandingofgender, includingreplacementof theterm gender identitydisorderwithgenderdysphoria in theDiagnosticandStatisticalManualofMentalDisorders, Fifth Edition in 2013. Interest in improving health care for transgender personshasalso increased. In2011, an InstituteofMedicine study1 highlightedgaps inunderstanding transgender (as well as lesbian, gay, and bisexual) health concerns and proposedways to bridge those gaps. The US government’s Healthy People 2020 initiative specifically seeks to improve the “health, safety, and wellbeing of lesbian, gay, bisexual, and transgender (LBGT) individuals.”2 In2014,Medicarebegancoveringgenderaffirming surgical procedures, in addition to hormonal therapies, for transgenderpersons.3 InOctober2015, the US Department of Health and Human Services mandated that systems certified under the meaningful use of electronic health records program must allow users to record, change, andaccessdataaboutaperson’sgender identity and sexual orientation.4 However, transgender persons still face important health disparities, including high prevalences of human immunodeficiency virus and other sexually transmitted diseases, mental health issues, and suicide.2 Compared with heterosexual or lesbian, gay, and bisexual persons, transgender persons are less likely to have health insurance.2 According to Healthy People 2020, many factors contribute to these disparities, including a lack of physicians who are knowledgeable and culturally competent in lesbian, gay, bisexual, and transgender health.2 Yet, even knowledgeable and culturally competent physicians must occasionally use materials that disrespectandmarginalize transgenderpatients.Examplesof suchmaterials,whicharerelatedto isotretinoinandother prescriptionmedicinesandareapprovedbytheUSFood andDrugAdministration(FDA),highlight theneedfor immediate attention to this issue. Consider the case of a transgender man in his 20s who was my patient. He was receiving depo-testosteroneandhadcystic acne thatwasunresponsive to topical therapiesandoral antibiotics.Duringhis visit,wediscussed risks andbenefitsof treatmentwith isotretinoin, which has been used to treat severe acne in transgender men receiving testosterone.5 The patient was informed that all patients using isotretinoinmust register with iPLEDGE,6 an FDA-mandated Risk Evaluation and MitigationStrategy (REMS)program. Isotretinoin is teratogenic, and the FDA aims tominimize risks of fetal exposureby requiring that all physicians,pharmacists, and patients who prescribe, dispense, or take isotretinoin must register and complywith iPLEDGE.7 The iPLEDGE program requires that patients of childbearing potential must have a negative pregnancy test result each month. Whether receiving testosterone or not, transgender men who retain natal reproductive organs can potentially become pregnant.8 The catch for my patient was that iPLEDGE recognizes only 3 categories of people, namely, men, femaleswhocanbecomepregnant, and femaleswhocannot become pregnant.6 Although iPLEDGE program materials do not specifically discuss transgender persons, theprogrammandates thatpatients likemine register as females who can become pregnant. “Whatever they’rebornwith,” an iPLEDGE representative saidduringanAugust24,2015, telephoneconversation, “they’d have to register as.” The patient refused to register as female. He did not consider himself female in any way, and he was not going to register so in iPLEDGE. There were other relative contraindications against isotretinoin use, including a history of depression and a planned revision of a recent surgical procedure that removed his breasts. Isotretinoin has been associated with depression and with abnormal wound healing. Even if we surmounted those hurdles, iPLEDGE’s requirement that he must register as female was, for him, an absolute obstacle. Theoretically, physicians could registerpatients like my patient as male. However, if discovered, the physician doing so could be deemed noncompliant with iPLEDGE, leading to warnings or termination from the program, another representative said in September 2015.Practically andprofessionally,deliberatelymisrepresenting transgender persons in iPLEDGE is a nonstarter fordermatologistsandotherphysicianswhoroutinely prescribe isotretinoin. VIEWPOINT