Transgender Health Cases from the Transgender and Intersex Specialty Care Clinic Caroline Davidge-Pitts, MD Todd B Nippoldt, MD Department of Endocrinology, Diabetes, Nutrition Mayo Clinic, Rochester 2017 MFMER slide-1
No Financial relationships to disclose All cross hormone therapy is off-label use 2017 MFMER slide-2
Objectives Understand the reason and modalities for medical management of transgender people Identify the risks of cross hormone therapy Discuss some challenges in management 2017 MFMER slide-3
Case 1 GM, 45 year old biological male Since a child, has felt in the wrong body He cross-dressed secretly as an adolescent and felt more comfortable this way. He was hoping to lose these feelings, therefore got married and had two kids but this did not change how we felt. Finally, by 2013 he had to tell someone or he might hurt himself. He had told no one about these feelings prior to that. He told his wife and she was very supportive and feels that she will stay with him throughout this endeavor. They have support from their religious community and church and pastor as well. He has not yet talked to his children about this. 2017 MFMER slide-4
Case 1 In April of 2013 he started taking herbal phytoestrogens and with this noted that he did have a sense of being calmer, less irritable. He could "identify his emotions" and was able to cry and generally felt better. Eventually he started taking estradiol tablets that he got on the internet. With this he has had more positive effects mood-wise. He has noted some mild breast enlargement and minimal tenderness. He feels the testicles may be smaller, and he has noted finer hair on his legs and chest. He has decided that the best approach would be to continue his transition fully under medical direction and therefore presents to your clinic. 2017 MFMER slide-5
Etiology Genetics Monozygotic twin (23 pairs) 39.1 % concordance Dizygotic twins (28 pairs) 0% concordance Hormones 46 XX CAH raised female n=250 5.2 % gender dysphoria Brain structure Sexually dimorphic Gray and white matter studies Imaging studies Heylens G et al J Sex Med 2012 Dessens AB et al Arch Sex Behav 2005 Joel D et al PNAS 2015 2017 MFMER slide-6
Supporting Evidence anxiety, depression, improves social functioning and quality of life Surgery improves global functioning and quality of life. Low regret rates Newfield E Quality of Life Research 2006 Gomez-Gil E et al Psychoneuroendocrinology 2011 Meier SLC et al J Gay and Lesbian Health 2011 Wierckx J Sex Med 2014 2017 MFMER slide-7
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Criteria for Hormone Therapy Persistent, well documented gender dysphoria Capacity to make a fully informed decision and to consent to treatment Age of majority Reasonable control of significant medical or mental health concerns 2017 MFMER slide-9
Typical Hormone Regimens Feminizing hormone therapy Anti androgen Spironolactone 200-300 mg per day Finasteride 5 mg daily Flutamide 125 mg daily Cyproterone acetate outside of US Estradiol Oral: estradiol 2-12 mg per day IM 2 20 mg (usually weekly) Patches 0.05 0.2 mg/day Gels Progestogen Prometrium 100 mg daily 2017 MFMER slide-10
Case 2 MM is a 15-year-old, birth sex female. He remembers being different as of 7 to 8 years of age. He would occasionally force himself to dress as a girl. He started feeling down and more depressed as he got older. He had pubic hair development between the ages of 7 and 8. He had breast development at age 9 and menarche at age 10-1/2. He has been diagnosed with polycystic ovarian syndrome. He is quite distressed when he has his menses. He has a diagnosis of autism. He carries a diagnosis of depression and has had hospital admissions for this. His short-term goal is to start hormone therapy. He is currently doing online schooling, starting January 2015. He feels that his dad is not supportive. Mother has sole custody. Prior to having done online schooling, he was subjected to bullying in school. 2017 MFMER slide-11
Considerations in Children and Adolescents Persistence and desistence Mental health support School concerns Parental support Custody Self-harm Transition Steensma TD J Am Acad Child and Adolesc Psych 2013 Endocrine Society Guidelines WPATH Standards of Care 2017 MFMER slide-12
Mental Health of Transgender Children Supported in their Identities 73 prepubescent children age 3-12 years Socially transitioned transgender children supported in their gender identity normative levels of depression and only minimal elevations in anxiety Socially transitioned transgender children have lower rates of internalizing psychopathology than previously reported among children with GD living as their natal sex. Olson K et al Pediatrics 2016 2017 MFMER slide-13
Considerations in Children and Adolescents 2017 MFMER slide-14
Hormone therapy Pubertal blockers (GnRH agonists most common) Puberty induction age 16 (controversial) Very slow if first puberty Surgical therapy Age 18 2017 MFMER slide-15
6 year follow up 22 MtF 33 FtM Blockers (avg age 14.8 yrs) Cross sex hormones (avg age 16.7 yrs) Gender confirmation surgery (avg age 20.7 yrs) Outcomes Gender dysphoria resolved (after CSH) Improved psychological functioning No regret Well being same as general population De Vries et al Pediatrics 2014 2017 MFMER slide-16
Considerations in Children and Adolescents Bone n = 34 15 MtF 19 FtM Klink et al JCEM 2015 2017 MFMER slide-17
Considerations in Children and Adolescents Brain No detriment on executive functioning Fertility Compromised oocyte maturation and spermatogenesis Staphorsius AS Psychoneuroendocrinology 2015 Rosenthal S JCEM 2014 2017 MFMER slide-18
Case 3 28 year old trans woman Hormone therapy 1 year ago Estradiol 4 mg daily sublingual Spironolactone 100 mg BID 8 months later, spontaneous pain and swelling right upper arm No family history of blood clots Dx: right basilar vein thrombosis 2017 MFMER slide-19
Risk Discussion Venous Thromboembolism (VTE) Cancer Cardiovascular disease 2017 MFMER slide-20
Ethinyl estradiol 17β estradiol (Cyproterone acetate) 2017 MFMER slide-21
VTE in Transgender Women 45-fold increase in VTE in older studies No increase in VTE among 2236 transwomen on estradiol Gooren 2008 5% 214 transwomen VTE within 3 years of estrogen therapy (10/11 women had one other risk factor) Wierckx 2013 2017 MFMER slide-22
Treatment Options Transdermal / IM preferred? Sublingual >40 years Smokers Thrombophilia GnRH analogs Orchiectomy Lower estradiol dose Avoid conjugated estrogens (CEE) cardiac events and thrombosis, difficult to monitor Concomitant use of anticoagulant 2017 MFMER slide-23
Cancer n= 352 (214 MtF 138 FtM) Cross sex hormones avg 7.4 yrs No increased risk of cancer compared to general population n=5117 transgender veterans, no increased risk of breast cancer compared to general population Wierckx et al Eur J Endocrinol 2013 Brown LGBT Health 2017 MFMER slide-24
Vascular Risk n= 352 (214 MtF 138 FtM) Cross sex hormones avg 7.4 yrs Trans women: Increased cerebrovascular disease compared to control men Similar prevalence of MI compared to control men > 50 years?timing hypothesis Risk calculators Trans men: No increased risk Wierckx et al Eur J Endocrinol 2013 2017 MFMER slide-25
Case 4 62 year old trans woman, pilot for commercial airline Began hormone therapy in January 2007 Surgeries: bilateral orchiectomy 2008, and then a vaginoplasty 2012 Climara patch 0.2 mg weekly Bone density normal. Mammogram normal Previous abnormal stress test but CTA coronary showed no significant coronary disease, and her stress test in February 2015 was negative. Meds: Atorvastatin 40 mg daily : total cholesterol of 109, triglycerides 55, HDL 64, and LDL 34 mg/dl. A1c is 5.5%. 2017 MFMER slide-26
Organ-specific screening Transgender men: Pap smears: Not to be forgotten! Mammograms: Residual breast tissue Bone density: No guidelines. BMD preserved with testosterone. Transgender women Prostate screening: PSA may be unreliable Mammograms: age 40 with 5-10 years of hormones Bone density. Starts low, improves with hormones. Age 65 Both HPV vaccine Fertility discussion 2017 MFMER slide-27
Menopausal age in trans women No conclusive data or guidelines in this age group? Starting hormone therapy or continuing Evaluate risk factors and optimize Starting: Consider standard therapy for 2-3 years, then decrease. Transition complete: Minimize estrogen exposure, stop progestogen easier if removal of gonads has occurred. Monitor BMD, mammograms 2017 MFMER slide-28
Case 5 25 year old transgender man, on testosterone for 8 years Wishes to discuss fertility Comes to appointment with female partner Labs: AMH 3.56 ng/ml Estradiol 38 pg/ml 2017 MFMER slide-29
Masculinizing Hormone Therapy Testosterone SQ: testosterone cypionate/enanthate 25-200 mg Gels and patches Progestogen For menstrual irregularities or contraception IUD or Prometrium 2017 MFMER slide-30
Fertility in Transgender Men 54% desire children Wierckx 2012 Primordial follicle pool not depleted by androgens 41 transmen who experienced pregnancy after transition 61% had used testosterone 80% resumed menses within 6 months of stopping testosterone 88% used their own eggs 7% involved fertility medications Both prior testosterone users and non-users had similar complications. Light et al Obstet Gyn 2014 2017 MFMER slide-31
For trans men, the options are: Oocyte and/or embryo cryopreservation if partner or donor sperm is available Ovarian tissue cryopreservation (about 60 live births worldwide) (Experimental) In vitro oocyte maturation (Experimental) 2017 MFMER slide-32
Summary With expanding health coverage, patients will be seeking care more than ever Improved competence and confidence in transgender health needs to increase Further research is needed to expand our knowledge in this area as solid data is often scarce 2017 MFMER slide-33
Questions & Discussion 2017 MFMER slide-34