Prevalence: Adults (Boston) Survey: N = 28,176 Results - - PDF document

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GENDER NON-CONFORMING / TRANSGENDER YOUTH: CURRENT CONCEPTS, MANAGEMENT, & BARRIERS TO CARE

Stephen M. Rosenthal, M.D. Professor of Pediatrics

• Em. Program Director, Pediatric Endocrinology

Medical Director, Child & Adolescent Gender Center University of California, San Francisco Stephen.Rosenthal@ucsf.edu

• No relevant financial relationships with

a commercial interest to disclose

• All Rx to be discussed: “Off-label” for

Gender Dysphoric Youth

DISCLOSURE

Stephen M. Rosenthal, M.D. Professor of Pediatrics

• Em. Program Director, Pediatric Endocrinology

Medical Director, Child & Adolescent Gender Center University of California, San Francisco

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Thank You!

OBJECTIVES:

• Review epidemiology; mental health

concerns

• Review evidence for biologic

underpinnings of gender identity

• Review outcomes of current

treatment model

• Understand gaps in knowledge,

barriers to care, priorities for research

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How Common is Transgender?

• Prevalence: Adults (Boston)

–

Survey: N = 28,176

–

Results

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Self-identified as Transgender

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N = 131

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0.5%

Conron KJ et al. Am J Public Health, 2012

How Common is Transgender?

• Prevalence in Youth

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Not yet known

• Our clinical program:

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> 350 patients (1st pt 2009)

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8-10 new referrals / month

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Transgender Adolescents/ Young Adults: Mental Health Concerns

• N = 360 (Boston) 180 transgender, 180 cisgender
• Age: 12-29 yr (Avg. 19.6 yr)
• Results: 2-3 x é

é Risk (all p < 0.05)

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Depression

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Anxiety Disorder

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Suicidal Ideation

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Suicide attempt

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Self-harm without lethal intent

Reisner SL et al., J Adolesc Health 56:274-279, 2015

participant’s “not supportive” “strongly supportive” “out” “very supportive” “somewhat supportive” “not very” “not all”, “not supportive”

• ne’s

youth’s

• ne’s

youth’s “how general?” people’s “high esteem”

• ne’s

Figure 2. Proportion of trans youth age 16-24 years in

Ontario experiencing negative health and life conditions, by level of parental support

23 34 4 75 70 57

10 20 30 40 50 60 70 80 90 100

Depressive symptoms* Considered suicide, past yr Suicide attempt, past yr*

Parent(s) very supportive Parent(s) somewhat to not at all supportive * = statistically significant difference (p < 0.05)

IMPACT OF PARENTAL SUPPORT FOR TRANSGENDER YOUTH

Travers R et al. Children’s Aid Society of Toronto & Delisle Youth Services, 2012 N = 84 Youth

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A ¡report ¡prepared ¡for ¡Children’s ¡Aid ¡

• ne’s

“trans” Figure 1. Proportion of trans youth age 16-24 years in Ontario experiencing positive health and life conditions, by level of parental support

72 66 70 64 58 100 92 33 31 15 13 42 45 82

10 20 30 40 50 60 70 80 90 100

Satisfied with life* VG/excellent physical health VG/excellent mental health* High self esteem* Intent to parent Adequate housing* Adequate food

Parent(s) very supportive Parent(s) somewhat to not at all supportive

* = statistically significant difference (p < 0.05)

youth’s

IMPACT OF PARENTAL SUPPORT FOR TRANSGENDER YOUTH

Travers R et al. Children’s Aid Society of Toronto & Delisle Youth Services, 2012 N = 84 Youth

GENDER IDENTITY

• Complex interplay
• Biologic
• Environmental
• Cultural factors

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EVIDENCE FOR BIOLOGIC UNDERPINNINGS OF GENDER IDENTITY

• Insights from:
• Genetics
• Hormones
• Brain
• Not a “litmus test” of Transgender

TRANSGENDER: ROLE OF GENETICS?

• Twin Studies (Heylens G et al. J Sex Med 9:751-757, 2012)
• Concordance for Gender Dysphoria
• Comprehensive literature review
• N = 23 monozygotic (8 F, 15 M) twin pairs
• N = 21 same-sex dizygotic (5 F, 16 M) twin pairs
• N = 7 opposite sex twin pairs
• Results: Concordance for Gender Dysphoria
• Monozygotic Twin pairs: 39.1%
• Same-sex dizygotic twin pairs: 0%

(p = 0.005 vs. MZ twins)

• Opposite sex twin pairs: 0%
• Studies of individual candidate genes: inconsistent

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HORMONES & GENDER IDENTITY

• Most transgender individuals do not

have a “Disorder of Sex Development” (DSD)

• Studies in patients with DSD

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Informed our understanding of gender identity development

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Role of prenatal/ (postnatal) androgens

HORMONES & GENDER IDENTITY

• Insights from:
• Congenital Adrenal

Hyperplasia (CAH)

• 46 XY cloacal exstrophy

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SEXUAL DIFFERENTIATION Role of DHT & Androgen Receptor DSD: 2 Extremes

• -CAH (46XX)
• -Cloacal Exstrophy

(46XY)

CAH 46XX Female

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Congenital Adrenal Hyperplasia (CAH) (CYP21A2 Deficiency)

• 46 XX raised Female (F)

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N = 250

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94.8 %: F gender identity

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5.2%: M gender or gender confusion

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10-20 x é é risk vs. control

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No correlation with degree of genital virilization

• Supports “some” role of prenatal androgens

in gender development

Dessens AB et al. Arch Sex Behav 2005

Cloacal Exstrophy

• N = 16 46XY Males

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14 underwent neonatal sex reassignment to female

• Follow-up: age 5-16 yr
• Study

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Parent questionnaires

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Subjects’ stated Gender Identity

• Outcome

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8/14 declared Male Gender

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4/8 before knowing birth status

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2/16 raised as male stayed male

• Supports “some” role of prenatal

androgens in gender development

Reiner WG et al. N Engl J Med 350:333-341, 2004

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Neurobiologic Basis for Transgender?

• Dimorphic brain structures (human)
• Sexually dimorphic

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Cell groups preoptic & anterior hypothalamic areas

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INAH-1,-2,-3

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Suprachiasmatic nucleus

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Bed nucleus of the stria terminalis (BSTc)

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Anterior commissure

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Right putamen

• Sexual orientation dimorphic

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INAH-3

• Gender dimorphic?

Neurobiologic Basis for Transgender?

• Numerous Gray, White matter studies

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Sexually dimorphic structures more closely aligned with gender identity than with physical sex

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Seen even before cross-sex hormones are given

Luders E et al. NeuroImage 46:904-907, 2009 Rametti G et al. J Psychiatric Research 45:199-204, 2011 Hoekzema E. et al. Psychoneuroendocrinology, 2015

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Sex beyond the genitalia: The human brain mosaic

• MRI
• Multiple data sets (4): 1400 human brains
• Assess degree of internal consistency
• Voxel-based morphometry (VBM)
• Focused on areas which show largest sex

differences (least overlap between M, F)

• Principal finding:
• Variability more prevalent than internal

consistency

Joel D et al. PNAS, November 30, 2015

Anterior Hypothalamus: Evidence for “Functional” Gender Dimorphism

• Positron Emission Tomography (PET)

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Changes in regional blood flow

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Smelling of 2 “odorous” compounds

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Putative pheromones

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Progesterone derivative of 4,16 androstadien-3-one (AND)

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Human male sweat, saliva, semen

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Estrogen-like compound (EST)

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Urine of pregnant females

Berglund H et al. Cerebral Cortex, 2008

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Anterior Hypothalamus: Evidence for “Functional” Gender Dimorphism

• Anterior Hypothalamus activated by AND,

EST in “sexually” dimorphic manner

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Females: activated by AND

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Males: activated by EST

• Study:

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N = 12 MTF adults

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Never-received hormonal Rx !

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N = 24 controls (12 M, 12 F)

• Results:

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MTFs: Ant hypothal activated by AND (F pattern)

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Differed from Male controls (p < 0.05), not from Female controls

Berglund H et al. Cerebral Cortex, 2008

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What is the Natural History

• f Transgender/ Gender Dysphoria

in Children & Adolescents?

Children & Adolescents with GD: Natural History

• Symptoms of Gender Dysphoria in

pre-pubertal children ↓ or disappear in 70-95% of cases

• Gender Dysphoria persisting into

early puberty:

• Likely transgender as adult!

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Management of Adolescents with GD Current Practice:

• Amsterdam VU University Med Ctr
• Pubertal suppression with GnRH

agonists (GnRHa)

• Tanner 2
• Gender dysphoria from early childhood
• ↑ Gender dysphoria with pubertal onset
• Absence of psychiatric co-morbidity

that might interfere with treatment

• Adequate psychosocial support
• Demonstrated understanding of process
• “Buys time”
• Prevents experiencing puberty
• f undesired sex
• Fully reversible!
• Once puberty completed, can only be

incompletely reversed-- Difficult to “blend”

• MTF: Low voice, masculine facial & neck

features in MTF

• FTM: Breast development

GnRH Agonists in Gender Dysphoric Youth: Expected Benefits

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“Endocrine Treatment of Transsexual Persons: An Endocrine Society Clinical Practice Guideline” Pediatric/ Adolescent Recommendations:

• Dx GD made by mental health professional
• Medical providers ensure patients understand

consequences of hormone suppression & cross- sex hormone Rx prior to Rx

• Suppression of pubertal hormones with GnRH

agonist only after early puberty has been reached

• Initiate cross-sex hormone Rx at “about” age of 16

yr

• Defer surgery until at least 18 yr of age

Hembree WC et al. J Clin Endocrinol Metab 94:3132-3154, 2009

“Dutch protocol”: 6 yr Follow-Up

• N= 55 (22 MTF, 33 FTM)
• Protocol
• Puberty blockers (Avg. 14.8 yr at start of Rx)
• Cross Sex Hormones (CSH) (Avg. 16.7 yr at start of Rx)
• “Gender Reassignment Surgery” (Avg. age 20.7 yr)
• Mental Health Outcomes
• 1 yr pre-blockers, T 0 for CSH, 1 yr post-surgery
• Results

– Gender Dysphoria: Resolved – Psychological functioning: Generally improved – “Well being” > vs. same age young adults from general

population

– No patients reported regret at any phase of protocol

De Vries ALC et al. Pediatrics, 2014

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GnRH Agonists in Gender Dysphoric Youth: Potential Adverse Effects

• Bone mass, growth
• ? Ameliorated with

subsequent initiation of “cross-sex” hormone Rx

• Brain
• Fertility

Areas of Uncertainty, Controversies, Barriers to Care

• Limited safety/ efficacy data

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No data with blockers in pt < 12 yr

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No data with cross-sex hormones in pt < 16 yr

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No RCTs (likely not feasible or ethical)

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Need for prospective, long-term outcomes studies

• Limited access to Rx

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Off-label

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Expensive

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Often denied by insurance companies

• Limited access to care

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Relatively few clinical programs

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Lack of training

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Prejudice/ misunderstanding

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Management of Adolescents with GD GnRHa: Further Thoughts

• Non-intervention is not a “neutral”
• ption
• “In dubio abstine” may be harmful!
• Importance of “Team Approach”
• Need for adequate support for

patients/ families

Child and Adolescent Gender Center: UCSF / Community Collaborative

• Integrated care provided by multi-disciplinary team
• Mental Health Professionals
• Diagnostic assessment
• Psychotherapy/ counseling
• Support groups
• Pediatric Endocrinologists/ Adolescent Med/ Primary Care
• Pubertal suppression
• Cross-sex hormone Rx
• Surveillance for co-morbidities
• Advocacy Professionals
• School training: gender inclusive campuses & cultures
• Trainings with other organizations working with children

& youth

• Legal & other forms of advocacy
• Platform for Research

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R01HD082554 (08/01/2015 - 06/30/2020): National Institutes of Health (NIH)

The Impact of Early Medical Treatment

• f Transgender Youth
• Multi-Center Network
• Benioff Children’s Hospital/ UCSF
• Children’s Hospital LA/ USC
• Lurie Children’s Hospital Chicago/

Northwestern

• Boston Children’s Hospital/ Harvard

Acknowledgements

• Children’s & Adolescent Gender Center (CAGC) Colleagues

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Diane Ehrensaft, PhD

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Psychologist/ Gender Specialist

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Mental Health Director, CAGC

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Joel Baum, MS

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Director, Education & Training, Gender Spectrum

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Director of Education & Advocacy, CAGC

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Asaf Orr, JD

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Legal Director, CAGC

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Ilana Sherer, MD

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Assistant Medical Director, CAGC

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Stanley R. Vance, Jr, MD

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Fellow, Adolescent and Young Adult Medicine

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Meredith Russell, NP

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Molly Koren, LCSW