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 WHAT IS GENDER DYSPHORIA? NOT GENDER IDENTITY DISORDER NOT TRANSSEXUALISM NOT GENDER NONCONFORMING PEOPLE 2
3 DISCOMFORT WITH THE GENDER PRESCRIBED BY THE NATAL SEX AND THE RESULTING BODY DEVELOPMENT, ESPECIALLY AT PUBERTY 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 3
4 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 4
5 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 5
6 COGNITIVE NEUROSCIENCE NETWORKS Genes Social Dev Environ Hormones Natal Gender Pu Hormones Sex ber Relationships Prefer ty Traditions 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. 6
7 NOW GUIDELINES PROTOCOLS OF THE TWENTY-FIRST CENTURY Endocrine Treatment of Male-to-Female Transsexuals Using Gonadotropin- Releasing Hormone Agonist Dittrich R, et al Exp Clin Endocrinol Diabetes 113: , 2005 Erlangen, Germany
8 5. Medications a. Estrogens b. Testosterone c. (Anti-Androgens) d. Progestins (GnRH agonist), e. GnRH Agonists Two Phases? WHY? Why not just initiate cross-gender Hormones? 8
9 Treatment Plan for Adolescents TRANS ADOLESCENTS 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 TRANS MEN Why Two Phases? Why not just initiate cross-gender Hormones? 9
10 Outcomes TRANS MEN ADULT PROTOCOL TRANS MEN Testosterone Dose Response Curve NATAL WOMEN Dose Outcomes 10
11 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 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. 11
12 TRANS WOMEN Why Two Phases? Why not just initiate cross-gender Hormones? ADULT PROTOCOL NATAL MEN Testosterone Dose Response Curve TRANS WOMEN Dose Outcomes 12
13 Outcomes TRANS WOMEN Testosterone Suppression by Estradiol #5 #6 #7 #8 #9 #10 Estradiol Testo LH 13
14 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 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 14
15 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 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 15
16 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 MedroxyProgesterone LEUPROLIDE 16
17 LEUPROLIDE MEDROXYPROGESTERONE ESTRADIOL PHASE/STEP TWO PHASE/STEP ONE PROGESTINS GnRH ANALOGS 17
18 QUESTIONS 18
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