Guidelines for the Clinical Care of Persons with Gender Dysphoria
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1 Guidelines for the Clinical Care of Persons with Gender Dysphoria Friday, May 27, :15 5:00 PM 25 th Annual Scientific and Clinical Congress American Association of Clinical Endocrinologist Orlando, Fla. WYLIE HEMBREE MD COLUMBIA UNIVERSITY MEDICAL CENTER MOUNT SINAI BETH ISRAEL MEDICAL CENTER ACKERMAN INSTITUTE FOR THE FAMILY NEW YORK, NEW YORK DISCLOSURES No Grant or Financial Support No Board memberships No Company Ownership All Medications Discussed Do Not Have FDA Approval for the Indications Discussed 1
2 BEGINNING IMPORTANT ISSUES 1.Develop Effective Conversations with Transgender Persons 2.Address Important Issues for Transgender Care 3.Initiate Core Discussions 4.Prevent Misunderstandings 5.Address Social and Health Issues of Transgender Persons 1.Mental Health Professionals 2.Parents/Spouses/Children GENDER DYSPHORIA: 3.Friends COMPLEXITY 4.Work and Professional Associates 5.Health Insurance 6.Name Change 7.ID Change 8.Letter for Medical Recommendations 9.Voice Therapy 10.Facial and Body Surgery 11.Hormone Treatment 12.Genital Surgery 13.Mastectomy 14.Gonadectomy 2
3 WHAT IS GENDER DYSPHORIA? NOT GENDER IDENTITY DISORDER NOT TRANSSEXUALISM NOT GENDER NONCONFORMING PEOPLE WHY DOES GENDER DYSPHORIA OCCUR? GENDER DYSPHORIA: 1.SEX: Biological LESS and COMPLEX Physiological Characteristics that Define Persons as men and women without regard to one s specific identity; 2.NATAL SEX: Sex Determined During Pregnancy and at Birth by Genetic and Developmental Factors; 3.GENDER IDENTITY: Inherent Personal Sense of Being Male or Female 3
4 4. 4. GENDER NONCONFORMITY: The extent to which a person s gender identity, gender role or gender expression differs from cultural norms of the person s natal sex; 5. Transgenderism: Persons who identify, to varying degrees, with the opposite sex, not the natal sex; 6. Transsexualism: Individuals who seek physical transition (hormonal and/or surgical) to the gender opposite that of the natal sex. Gender Dysphoria Gender Dysphoria is a psychological condition, usually appearing in childhood, that causes varying degrees of distress based upon discrepancies between biological characteristics and role expectations AND perceptions of gender. This distress gets worse when the physical manifestations of puberty begin, enhancing social dissonance. When adaptive measures allow assumption of the gender of natal sex into adulthood, associated with hetero- or homosexual roles, persistent Gender Dysphoria may exacerbate distress at any time. 4
5 Differential Brain Processing of Audiovisual Sexual Stimuli in men: Comparison positron emission tomography study of the initiation and Maintenance of penile erection during sexual arousal. Miyagawa, et al. J.NeuroImage 2007; 3: WHY DO PEOPLE HAVE GENDER DYSPHORIA? rcbf Regional Cerebral Blood Flow Oxygen-15 Water Given During Pet Scan Ventral Right Putamen ASK NEUROSCIENTISTS 5
6 Differential Brain Processing of Audiovisual Sexual Stimuli in men: Comparison positron emission tomography study of the initiation and Maintenance of penile erection during sexual arousal. Miyagawa, et al. J.NeuroImage 2007; 3: rcbf Regional Cerebral Blood Flow Ventral Right Putamen Oxygen-15 Water Given During Pet Scan 6
7 Daniel Levitin ie AUDITORY EVENT SEGMENTATION ODD BALL DEFAULT MODE COGNITIVE NEUROSCIENCE NETWORKS Genes Social Dev Environ Hormones Natal Gender Pu Hormones Sex ber Relationships Prefer ty Traditions 7
8 COGNITIVE NEUROSCIENCE NETWORKS Genes Social Dev Environ Hormones Natal Gender Pu Hormones Sex ber Relationships Prefer ty Traditions GENDER DYSPHORIA: 1.SEX: Biological LESS and COMPLEX Physiological Characteristics that Define Persons as men and women without regard to one s specific identity; 2.NATAL SEX: Sex Determined During Pregnancy and at Birth by Genetic and Developmental Factors; 3.GENDER IDENTITY: Inherent Personal Sense of Being Male or Female 8
9 4. 4. GENDER NONCONFORMITY: The extent to which a person s gender identity, gender role or gender expression differs from cultural norms of the person s natal sex; 5. Transgenderism: Persons who identify, to varying degrees, with the opposite sex, not the natal sex; 6. Transsexualism: Individuals who seek physical transition (hormonal and/or surgical) to the gender opposite that of the natal sex. Gender Dysphoria Gender Dysphoria is a psychological condition, usually appearing in childhood, that causes varying degrees of distress based upon discrepancies between biological characteristics and role expectations AND perceptions of gender. This distress gets worse when the physical manifestations of puberty begin, enhancing social dissonance. When adaptive measures allow assumption of the gender of natal sex into adulthood, with hetero- or homosexual roles, persistent Gender Dysphoria may exacerbate distress at any time. 9
10 PROTOCOL (Dutch, French, Greek) A Dictionary of the English Language A History of the Language and an English Grammar By Samuel Johnson A.M. The original copy of any writing An original is stiled the protocol, scriptura matrix; And if the Protocol, which is the root and the foundation of the instrument, does not appear, the instrument is not valid. NOW GUIDELINES PROTOCOLS OF THE TWENTY-FIRST CENTURY
11 2003 Endocrine Treatment of Male-to-Female Transsexuals Using Gonadotropin- Releasing Hormone Agonist Dittrich R, et al Exp Clin Endocrinol Diabetes 113: , 2005 Erlangen, Germany Medications a. Estrogens b. Testosterone c. (Anti-Androgens) d. Progestins (GnRH agonist), e. GnRH Agonists 11
12
13 Why Two Phases? Why not just initiate cross-gender Hormones? Hormone Therapy for Adolescents Goal: Arrest pubertal development of unwanted characteristics of anatomic (natal) sex 13
14 GENDER DYSPHORIA: CONTROVERSY Drummond KD, SJ Bradley, M Peterson-Badali, KJ Zucker Univ. of Toronto Boys (40) with GID 20% GID Persists as adult Girls (25) with GID 12% GID Persists as adult For adolescents and adults: 70% persist (Cohen-Kettenis) Bisexual/homosexual: Boys 42.5% Girls 32% TRANS ADOLESCENTS Why Two Phases? Why not just initiate cross-gender Hormones? 14
15 Treatment Plan* Diagnostic evaluation PHASE ONE Begin pubertal delay with GnRH blocker Females at Tanner breast stage 2-3 Males at testicular size 6-8 ml Triptorelin Therapy for Adolescents 3.75 mg IM monthly, after 2 weeks PHASE TWO Age 16 begin cross sex hormones Age 18+ consider for surgery 15
16 TRANS MEN Why Two Phases? Why not just initiate cross-gender Hormones? Outcomes TRANS MEN 16
17 ADULT PROTOCOL TRANS MEN Testosterone Dose Response Curve WOMEN Dose Outcomes Protocol: Transition Female to Male Phase 1 (Infrequent) Cessation of Menses SOC Medroxyprogesterone Cyproterone Acetate + GnRH Agonist Testosterone Phase 2 Testosterone (Gradual) Transdermal Testosterone Weekly IM Testosterone Testosterone Undecanoate q 3 months (Europe) Testosterone pellets implant GOAL: Testosterone ng/dl 17
18 Protocol: Transition Female to Male 1. Testosterone Undecanoate 1000 mg IM q 12 weeks 2. Increase BP: 129/81 to 134/84 p= All patients reported one additional menses; none thereafter 4. Acne ( troublesome ) 14.3% 5. Shaving in 12 months - 77% The dose of Testosterone required to achieve average male levels, free and total, will vary over time due to changes in metabolism, SHBG binding and aromatase activity. In addition, transdermal absorption changes with time. The Dose should be adjusted based on serum levels. TRANS WOMEN Why Two Phases? Why not just initiate cross-gender Hormones? 18
19 Testosterone Suppression by Estradiol #5 #6 #7 #8 #9 #10 Estradiol Testo LH ADULT PROTOCOL NATAL MEN Testosterone Dose Response Curve TRANS WOMEN Dose Outcomes 19
20 Outcomes TRANS WOMEN Protocol: Transition Male to Female Phase 1 (OR Simultaneously) Two Three (12) Months Androgen Suppression 1. Cyproterone Acetate 50 mg/day 2. Spironolactone mg/day 3. GnRH Analog 4. Medroxyprogesterone + GnRH Agonist Gradual Increase MP mg/day GnRH Agonist Monthly x2 5. Finasteride -? Anti-Androgen; Hair Loss GOAL: Testosterone < 50 ng/dl 20
21 Protocol: Transition Male to Female Phase 1 Long Term Suppression Progestin/Anti-androgen GnRHa (Europe) Histrelin Implant (Adolescent) Phase 2 Gradual Addition of Estradiol Oral, IM, Patches GOAL: Estradiol pg/ml Maintain Testosterone Suppression Protocol: Transition Male to Female Androgen Suppression 3.8 mg goserelin + Administration of Estrogen 6 mg E2 Val Monitored 24 months Testosterone 540 ng/dl to 15 ng/dl & 16 ng/dl Estradiol 21 pgml to 188 pg/ml & 205 pg/ml 21
22 Protocol: Transition Male to Female Two Three Months Medroxyprogesterone Gradual Increase MP mg/day GnRHa x 2 months Gradual Addition of Estradiol Oral, IM, Patches Check LH and Testo 6-8 weeks After GnRHa agonist MedroxyProgesterone LEUPROLIDE Testo Est Cort Prolactin 0 Sept 03 Oct 03 Feb 04 Mar 04 Apr 04 May 04 Jul 04 Sep 04 Oct 04 22
23 MedroxyProgesterone LEUPROLIDE LEUPROLIDE MEDROXYPROGESTERONE ESTRADIOL 23
24 PHASE/STEP TWO PHASE/STEP ONE PROGESTINS GnRH ANALOGS CONTROVERIES 1. Certainty of Diagnosis 2. Role of Mental Health Professional 3. Age of Pubertal Suppression 4. Protocol Strategies a. Endogenous Hormones b. Hormone Dose c. Use of Progestins d. Complications MTF FTM 5. Surgery Age & Hormones 6. Transsexual vs. Transgender 24
25 QUESTIONS 25
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