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Transgender Patients, Isotretinoin, and USFood

andDrugAdministrationMandated Risk

Evaluation andMitigation Strategies

A Prescription for Inclusion

Caitlyn Jennerhas vaulted to celebrity status, Face-

book has expanded its gender nomenclature, and the

Pentagon has announced plans to permit transgender

servicemembers toserveopenly. Although recent news

about transgender persons is not uniformly rosy

transgender persons in the United States and else-

where are still targets of violent, sometimes lethal at-

tacks, and voters in Houston, Texas, recently repealed

thatcitys Equal Rights Ordinancetransgender visibil-

ityand equalityhavemaderemarkableadvances.Those

advances have paralleled strides made in scientificun-

derstandingofgender,includingreplacementoftheterm

genderidentitydisorderwithgenderdysphoria intheDi-

agnosticandStatisticalManualofMentalDisorders,Fifth

Edition in 2013.

Interest in improving health care for transgender

personshas alsoincreased. In2011,an Instituteof Medi-

cinestudy1highlighted gaps in understanding transgen-

der (as well as lesbian, gay, and bisexual) health con-

cerns and proposed ways to bridgethose gaps. The US

governments Healthy People 2020 initiative specifi-

cally seeks to improve the health, safety, and well-

being of lesbian, gay, bisexual,and transgender (LBGT)

individuals.2 In2014,Medicare began covering gender-

affirming surgical procedures, in addition to hormonal

therapies,fortransgenderpersons.3

InOctober2015,theUS Department of Health and Human Services man-

dated that systems certified under the meaningful use

of electronic health records program must allow users

torecord, change, andaccess dataabout a persons gen-

der 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 bisexualpersons,

transgender persons are less likely to have health

insurance.2 According to Healthy People 2020, many

factors contribute to these disparities, including a lackof physicians who are knowledgeable and culturally

competent in lesbian, gay, bisexual, and transgender

health.2

Yet, evenknowledgeable andculturally competent

physicians must occasionally use materials that disre-

spectand marginalizetransgenderpatients.Examples of

suchmaterials,whicharerelatedtoisotretinoinandother

prescriptionmedicinesandareapprovedbytheUSFood

andDrugAdministration(FDA),highlighttheneedforim-

mediate attention to this issue.

Consider the case of a transgender man in his 20s

who was my patient. He was receiving depo-testoste-

roneand hadcysticacne that wasunresponsive totopi-

caltherapiesandoralantibiotics.Duringhisvisit,wedis-

cussed risks andbenefits oftreatmentwith isotretinoin,

which has been used to treat severe acne in transgen-

der men receiving testosterone.5 The patient was in-

formed thatall patientsusing isotretinoinmust register

with iPLEDGE,6 an FDA-mandated Risk Evaluation and

MitigationStrategy(REMS) program. Isotretinoin is tera-

togenic, and theFDA aims to minimize risks of fetal ex-

posure byrequiring that allphysicians, pharmacists,and

patients who prescribe, dispense, or take isotretinoin

mustregister andcomply withiPLEDGE.7TheiPLEDGE

program requires that patients of childbearing poten-

tial must have a negative pregnancy test result each

month. Whether receiving testosterone or not, trans-

gender men who retain natal reproductive organs can

potentially become pregnant.8

The catch for my patient wasthat iPLEDGE recog-

nizes only 3 categories of people, namely, men, fe-

maleswhocanbecomepregnant,andfemaleswhocan-

not become pregnant.6 Although iPLEDGE program

materials do not specifically discuss transgender per-

sons, theprogram mandatesthatpatientslike minereg-

ister as females who can become pregnant. Whatevertheyreborn with, aniPLEDGErepresentative saiddur-

ing an August24, 2015,telephoneconversation,theyd

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 revi-

sion of a recent surgical procedure that removed his

breasts. Isotretinoin has been associated with depres-

sion and with abnormal wound healing. Even if we

surmounted those hurdles, iPLEDGEs requirement

that he must register as female was, for him, an abso-lute obstacle.

Theoretically, physicians couldregisterpatients like

my patient as male. However, if discovered, the physi-

cian doing so could be deemed noncompliant with

iPLEDGE, leading to warnings or termination from the

program, another representative said in September

2015.Practically andprofessionally, deliberately misrep-

resenting transgender persons in iPLEDGE is a non-

starterfordermatologistsandotherphysicianswhorou-

tinely prescribe isotretinoin.

VIEWPOINT

Kenneth A. Katz,MD,

MSc,MSCE

Departmentof

Dermatology, Kaiser

Permanente,

Pleasanton, California.

Corresponding

Author: Kenneth A.

Katz, MD, MSc, MSCE,

Departmentof

Dermatology, Kaiser

Permanente, 7601

StoneridgeDr, S Bldg,

Second Floor,

Pleasanton,CA 94588

(kenneth.katz

@gmail.com).

Opinion

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mailto:kenneth.katz@gmail.commailto:kenneth.katz@gmail.commailto:kenneth.katz@gmail.commailto:kenneth.katz@gmail.comhttp://www.jamadermatology.com/?utm_campaign=articlePDF%26utm_medium=articlePDFlink%26utm_source=articlePDF%26utm_content=jamadermatol.2015.5547http://www.jamadermatology.com/?utm_campaign=articlePDF%26utm_medium=articlePDFlink%26utm_source=articlePDF%26utm_content=jamadermatol.2015.5547mailto:kenneth.katz@gmail.commailto:kenneth.katz@gmail.com

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iPLEDGEisnottheonlyFDA-mandatedREMSprogramwiththis

problem.Thalidomide,lenalidomide, pomalidomide,and mycophe-

nolatemofetilare alsocontraindicatedin pregnancy, andtheirREMS

programs use similar taxonomy in categorizing persons as men,

women who can become pregnant, and women who cannot be-

come pregnant.

Yet,it wouldbe simpleto adapttheseREMSprograms todem-

onstrate sensitivity to transgender persons. The programs shouldsimply stop categorizing patients by gender, which is neither rel-

evant in thesecases nor easily dichotomized.Rather, theprograms

should focus on whether a person could become pregnant or not.

Forsome medicines,whethera person couldimpregnatesomeone

elsemight also be a relevant considerationand,in some cases,might

makesense as a separate(and gender-free) categorization. Appro-

priate riskmanagement categories andrequirementscouldthen be

assigned. Such gender-neutral practices would signal respect and

acceptance of transgender persons andhelp ensure their access to

important medications.

A gender-neutral approach also would dovetail with efforts to

create inclusive health care environments for all people, including

transgender persons.2 For transgender individuals, such ap-

proaches include using intake forms that ask about gender iden-

tity, sexassignedat birth, andpreferredpronouns, as wellas taking

openand nonjudgmentalsexual historiesand displayingwrittenpoli-ciesagainst gender identitydiscrimination. REMSprograms should

meetthe samestandard of inclusiveness. Exclusionaryapproaches

candiscourage transgender persons fromseekingcare, resultingin

health disparities.

Physicians are trained to use all pharmacological tools at their

disposal toimprovetheirpatientshealth.We shouldbe ableto prac-

tice that way regardless of a patients assigned sexat birth or gen-

der identity. REMS programs shouldnot stand in our way.

ARTICLE INFORMATION

Published Online: January 13, 2016.

doi:10.1001/jamadermatol.2015.5547.

Conflict of Interest Disclosures: Dr Katzreported

beinga shareholder in Synta Pharmaceuticals Corp

and Arrowhead Research Corporation.No other

disclosures werereported.

AdditionalContributions: AmyKaron, DVM,MPH

(Karon Medical Writing),StephenI. Katz, MD,PhD

(NationalInstitute for Arthritis andMusculoskeletal

and SkinDiseases), and Joshua Sharfstein, MD

(Johns Hopkins BloombergSchool of Public Health),

provided helpful commentson drafts of the

manuscript. KathleenHutchins, RN (Kaiser

Permanente),assisted in theclinicalcare of the

patient.None receivedcompensationoutsideof

their usualsalary. Wethank thepatientfor granting

permissionto publish thisinformation.

REFERENCES

1. Instituteof Medicine (US)Committeeon Lesbian,

Gay, Bisexual, and Transgender Health Issuesand

Research Gapsand Opportunities. TheHealth of

Lesbian, Gay, Bisexual, andTransgender People:Building a Foundationfor BetterUnderstanding.

Washington, DC: National Academies Press; 2011.

2. HealthyPeople 2020. Lesbian, gay, bisexual, and

transgender health: overview. http://www

.healthypeople.gov/2020/topics-objectives/topic

/lesbian-gay-bisexual-and-transgender-health.

Accessed August25, 2015.

3. Departmentof Healthand Human Services.

DepartmentalAppeals Board, Appellate Division,

NCD140.3, Transsexual Surgery, DocketNo. A-13-87,

Decision No.2576. http://www.hhs.gov/dab/decisions

/dabdecisions/dab2576.pdf. Published May 30,2014.

Accessed August25, 2015.

4. Centers forMedicare& Medicaid Services

(CMS), HHS.HHS. Medicare and Medicaid

programs: Electronic Health Record Incentive

Program: stage3 and modificationsto meaningful

usein 2015 through 2017:finalruleswith comment

period. FedRegist. 2015;80(200):62761-62955.

5. Turrion-MerinoL, Urech-Garca-de-la-Vega M,

Miguel-Gomez L, Harto-Castao A, Jaen-OlasoloP.Severe acnein female-to-maletransgender

patients.JAMADermatol. 2015;151(11):1260-1261.

6. iPLEDGE program: patient introductory

brochure. https://www.iPLEDGEprogram.com

/Documents/Patient%20Intro%20Broch.pdf.

Modified April 2012. Accessed August25, 2015.

7. US National Library of Medicine.DailyMed. Label:

Sotret: isotretinoincapsule,gelatin coated; Sotret:

isotretinoincapsule,liquidfilled. http://dailymed.nlm

.nih.gov/dailymed/drugInfo.cfm?setid=d5a26c5e

-9c3e-4781-8c08-62b91d21a68d. Accessed August

25, 2015.

8. LightAD, Obedin-Maliver J, Sevelius JM, Kerns

JL. Transgendermen who experienced pregnancy

after female-to-male gender transitioning.Obstet

Gynecol. 2014;124(6):1120-1127.

Opinion Viewpoint

E 2 JA MA D erma to lo gy Publishedonline January 13, 2016 (Reprinted) jamadermatology.com

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http://jama.jamanetwork.com/article.aspx?doi=10.1001/jamadermatol.2015.5547&utm_campaign=articlePDF%26utm_medium=articlePDFlink%26utm_source=articlePDF%26utm_content=jamadermatol.2015.5547http://jama.jamanetwork.com/article.aspx?doi=10.1001/jamadermatol.2015.5547&utm_campaign=articlePDF%26utm_medium=articlePDFlink%26utm_source=articlePDF%26utm_content=jamadermatol.2015.5547http://jama.jamanetwork.com/article.aspx?doi=10.1001/jamadermatol.2015.5547&utm_campaign=articlePDF%26utm_medium=articlePDFlink%26utm_source=articlePDF%26utm_content=jamadermatol.2015.5547http://www.ncbi.nlm.nih.gov/pubmed/22013611http://www.ncbi.nlm.nih.gov/pubmed/22013611http://www.ncbi.nlm.nih.gov/pubmed/22013611http://www.ncbi.nlm.nih.gov/pubmed/22013611http://www.ncbi.nlm.nih.gov/pubmed/22013611http://www.ncbi.nlm.nih.gov/pubmed/22013611http://www.healthypeople.gov/2020/topics-objectives/topic/lesbian-gay-bisexual-and-transgender-healthhttp://www.healthypeople.gov/2020/topics-objectives/topic/lesbian-gay-bisexual-and-transgender-healthhttp://www.healthypeople.gov/2020/topics-objectives/topic/lesbian-gay-bisexual-and-transgender-healthhttp://www.hhs.gov/dab/decisions/dabdecisions/dab2576.pdfhttp://www.hhs.gov/dab/decisions/dabdecisions/dab2576.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/26477064http://www.ncbi.nlm.nih.gov/pubmed/26477064http://www.ncbi.nlm.nih.gov/pubmed/26477064http://www.ncbi.nlm.nih.gov/pubmed/25992965http://www.ncbi.nlm.nih.gov/pubmed/25992965http://www.ncbi.nlm.nih.gov/pubmed/25992965https://www.ipledgeprogram.com/Documents/Patient%20Intro%20Broch.pdfhttps://www.ipledgeprogram.com/Documents/Patient%20Intro%20Broch.pdfhttp://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d5a26c5e-9c3e-4781-8c08-62b91d21a68dhttp://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d5a26c5e-9c3e-4781-8c08-62b91d21a68dhttp://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d5a26c5e-9c3e-4781-8c08-62b91d21a68dhttp://www.ncbi.nlm.nih.gov/pubmed/25415163http://www.ncbi.nlm.nih.gov/pubmed/25415163http://www.ncbi.nlm.nih.gov/pubmed/25415163http://www.ncbi.nlm.nih.gov/pubmed/25415163http://www.jamadermatology.com/?utm_campaign=articlePDF%26utm_medium=articlePDFlink%26utm_source=articlePDF%26utm_content=jamadermatol.2015.5547http://www.jamadermatology.com/?utm_campaign=articlePDF%26utm_medium=articlePDFlink%26utm_source=articlePDF%26utm_content=jamadermatol.2015.5547http://www.ncbi.nlm.nih.gov/pubmed/25415163http://www.ncbi.nlm.nih.gov/pubmed/25415163http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d5a26c5e-9c3e-4781-8c08-62b91d21a68dhttp://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d5a26c5e-9c3e-4781-8c08-62b91d21a68dhttp://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d5a26c5e-9c3e-4781-8c08-62b91d21a68dhttps://www.ipledgeprogram.com/Documents/Patient%20Intro%20Broch.pdfhttps://www.ipledgeprogram.com/Documents/Patient%20Intro%20Broch.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/25992965http://www.ncbi.nlm.nih.gov/pubmed/26477064http://www.hhs.gov/dab/decisions/dabdecisions/dab2576.pdfhttp://www.hhs.gov/dab/decisions/dabdecisions/dab2576.pdfhttp://www.healthypeople.gov/2020/topics-objectives/topic/lesbian-gay-bisexual-and-transgender-healthhttp://www.healthypeople.gov/2020/topics-objectives/topic/lesbian-gay-bisexual-and-transgender-healthhttp://www.healthypeople.gov/2020/topics-objectives/topic/lesbian-gay-bisexual-and-transgender-healthhttp://www.ncbi.nlm.nih.gov/pubmed/22013611http://www.ncbi.nlm.nih.gov/pubmed/22013611http://www.ncbi.nlm.nih.gov/pubmed/22013611http://www.ncbi.nlm.nih.gov/pubmed/22013611http://www.ncbi.nlm.nih.gov/pubmed/22013611http://jama.jamanetwork.com/article.aspx?doi=10.1001/jamadermatol.2015.5547&utm_campaign=articlePDF%26utm_medium=articlePDFlink%26utm_source=articlePDF%26utm_content=jamadermatol.2015.5547