Disclosures. Current Concepts in Caring for Transgender Patients. 35 year old transgender woman wants to begin estrogen therapy

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1 Current Concepts in Caring for Transgender Patients Madeline B. Deutsch, MD, MPH Associate Professor of Clinical Family & Community Medicine Director, UCSF Transgender Care Center of Excellence for Transgender Health National Center of Excellence in Women s Health University of California San Francisco Disclosures Nothing relevant to disclose Will discuss off label use of FDA approved medications 46 y/o transgender man wants to begin testosterone therapy BMI 32 Hx oligomenorrhea Taking escitalopram for anxiety In a monogamous relationship with nontransgender (cisgender) male partner Has been living full time as a male for 3 years Interested in chest surgery 35 year old transgender woman wants to begin estrogen therapy History of borderline hyperlipidemia according to her prior physician ½ ppd smoker x 10 years, unwilling to quit Has been cross dressing for many years in secret Married to a heterosexual woman who is not accepting of pt desires, they have a 3 y/o son Has not yet spoken with coworkers/boss

2 19 year old person presents seeking primary care Name: Chase Gender ID: Genderqueer Pronouns: They/Them Birth assigned sex: Male Housing: Couch surfing Income: Occasional sex work, food stamps Substance abuse: Tobacco 2 3 cig/day, marijuana Polyamorous, some condomless receptive and insertive sex Transgender Gender identity which differs from birth sex Gender dysphoria Describes a state where the discordance between gender identity and birth sex causes distress Cisgender = non transgender Gender Identity & Sexual Orientation Gender Identity How one self identifies in the way they live and move through the world Mind Female? Male? Trans*? Genderqueer? Gender Expression How one does gender Feminine? Masculine? Androgynous? Sexual Orientation Multidimensional representation of sexuality Transgender Terminology Transgender (Trans) Man / Trans masculine Female to Male/FTM Female Assigned at Birth (FAAB) Transgender (Trans) Woman / Trans feminine Male to Female/MTF Male Assigned at Birth (MAAB) Genderqueer / non binary / non conforming Range of identities which lie outside binary

3 Sexuality intersections with gender Lesbian transgender woman Female identity, attracted to women Gay transgender man Male identity attracted to men Transgender prevalence studies clinic based Deutsch MB. Making it Count: Improving Estimates of the Size of the Transgender and Gender Nonconforming Populations. LGBT Health; In Press Transgender prevalence studies population based Gender Affirming Treatments and Procedures Hormone therapy Surgery Deutsch MB. Making it Count: Improving Estimates of the Size of the Transgender and Gender Nonconforming Populations. LGBT Health; In Press Other procedures Hair removal Speech therapy for voice feminization or masculinization Tucking/packing/binding

4 Why offer gender affirming care? Hormone therapy reduces anxiety, depression and improves social functioning & QOL Newfield E, Hart S, Dibble S, Kohler L. Quality of Life Research Jun 7;15(9): Gómez Gil E, Zubiaurre Elorza L, Esteva I, Guillamon A, Godás T, Cruz Almaraz M, et al. Psychoneuroendocrinology [Internet] [cited 2012 Dec 10]; Meier SLC, Fitzgerald KM, Pardo ST, Babcock J. Journal of Gay & Lesbian Mental Health. 2011;15(3): Gorin Lazard A, et al. J Sex Med Feb;9(2): Gender Affirming Hormones Supporting Evidence Regret rates & MedMal risk are extremely low Value added when bundling with other services Surgery improves global functioning, sexual functioning, family and interpersonal relationships, body image, and quality of life Eur Psychiatry 2002; 17: Archives of Sexual Behavior, Vol. 32, No. 4, August 2003, pp (2003) DSM V Gender Dysphoria Diagnosing Gender World Profl. Assn. for Transgender Health WPATH Standards of Care (SOC v7, Sept 2011) Focus on assessing readiness/appropriateness for various treatments & procedures Diagnosing Gender ICD 10 F64.1 Gender Dysphoria (mental health section) No code for medical care of someone with a history of gender transition) ICD 11 Work in process

5 Evidence for providing a respectful and appropriate transgender care setting Improved patient satisfaction Improved patient retention Patient safety Improved care Patients may be more comfortable with sensitive exams when they feel their identity is being respected Patients may be more likely to come in for other needed preventive and primary care, if they feel the clinic offers an accepting and gender affirming environment Kosenko K, Rintamaki L, Raney S, Maness K. Transgender patient perceptions of stigma in health care contexts. Med Care Sep;51(9): Melendez RM, Pinto RM. HIV prevention and primary care for transgender women in a community based clinic. J Assoc Nurses AIDS Care. 2009;20: What is A Respectful and Culturally Appropriate Care Setting? Bathrooms what bathrooms are transgender people allowed to use? Are there safety issues (for example, transgender women in the men s room may be at risk of assault) Waiting room materials and atmosphere are there any pamphlets, posters etc which make transgender people feel comfortable? Medical Records, including Electronic Medical Records is there a way to note patient s chosen name and pronoun, if they differ from that on legal documents? BMC Pediatr. 2015; 15: Improving transgender health by building safe clinical environments that promote existing resilience: Results from a qualitative analysis of providers Environments of Care With Transgender Communities Journal of the Association of Nurses in AIDS Care Volume 21, Issue 3, May June 2010, Pages What is A Respectful and Culturally Appropriate Care Setting? Front desk, nurse and provider staff are clinic staff trained in basic transgender cultural competency? Do they understand the importance of using the chosen name and pronoun, even if they differ from that which is on legal ID? Do they understand how to record and access this information in the medical record? Engage the community both in the development of clinical services oriented towards transgender people, as well as for dissemination of awareness about the services. Insurance Landscape WPATH defines gender affirming hormones, surgery, social transition, legal document changes all as medically necessary Many major insurance companies have developed internal guidelines Medi Caid covers care in some states (CA) Medicare recently removed long standing exclusion US Military (?) and TriCare now providing coverage

6 Early Adopter San Francisco Is transition care coverage cost effective? $8655/QALY cost Compared to other procedures where costs as high as $100,000 per QALY is acceptable Cost of coverage is $0.016 per member permonth Feminizing Hormones Goals Development of feminine secondary sex characteristics Suppression/minimization of masculine secondary sex characteristics Breast development Feminizing hormones physical effects Feminine redistribution of sub Q facial and body fat. Reduced muscle mass Reduced body and (to a lesser extent) facial hair Changes in perspiration and odors Arrest (and possible reversal) of scalp hair loss

7 Feminizing hormones other effects Reduced libido and erectile function Reduced size of testes, reduced or absent ejaculatory fluid and sperm count Changes in emotional and social functioning Effects vary from person to person Avoid projecting stereotypes Estrogen Feminizing hormones general approach Androgen blocker usually spironolactone (Sometimes) a progestagen Tobacco Smoking in the setting of any estrogen use is a risk factor for venous thromboembolism (VTE) What if unwilling or unable to quit? Harm reduction approach Transdermal estradiol (lower VTE risk) Aspirin 81mg/day Risk/benefit ratio for gastrointestinal hemorrhage is unknown Pituitary adenoma Several cases have been reported in transgender women(19) However, Endocrine Society guidelines recommend watchful waiting only in cases of assymptomatic prolactinomas (20) Therefore in the absence of visual disturbances, galactorrhea, or headache syndromes, routine monitoring of prolactin not likely of clinical value

8 Migraines Migraines have a clear hormonal component Patients with hx of complex/severe migraines should begin at low dose and titrate slowly Oral or transdermal routes may be preferred to avoid cyclic levels seen with injected estrogen (24) Unclear if the known increased risk of stroke in patients using oral contraceptives with a history of aura applies to transgender patients using 17 beta estradiol Use of estrogens in the perioperative period No clear evidence that transgender women at average risk of VTE should stop estrogen in the perioperative period Lowering dose or changing to transdermal route may be advisable (27) Studies of risks of perioperative oral contraceptives (ethinyl estradiol) have mixed results and methodological limitations (28) Stopping hormones abruptly in the setting of major surgery and gonadectomy can have negative impact Venous thromboembolism data from menopause literature Menopausal studies suggest no increased risk when transdermal estradiol used (29) Menopausal data on oral 17 beta estradiol is mixed, with risks as high as 2.5 4x increase (10,29) With a background rate of 1:1,000 to 1:10,000 in general population, absolute increase is small (4) Venous thromboembolism data in transgender women Studies > 10 years old showing 20 to 40 fold increase involved use of up to 200mcg/day of ethinyl estradiol, and did not control for tobacco use (30,31) These studies are not applicable to modern 17 beta estradiol regimens used in an average risk, nonsmoking population No increased risk has been observed in a large retrospective sample of Dutch transgender women using 17 beta estradiol (5)

9 Primary and secondary prevention of VTE Insufficient evidence to guide the use of estrogen therapy, anticoagulation, or antiplatelet therapy in transgender women with risk factors or personal history of DVT Masculinizing Hormones Case series of 11 transgender women with activated protein C resistance using transdermal estradiol without anticoagulation or antiplatelet therapy found no VTE after mean 64 months (32) Goals of therapy Development/emphasis of masculine secondary sex characteristics Elimination/minimization of feminine secondary sex characteristics Masculinizing hormones physical effects Development of facial and body hair Redistribution of body fat Increased muscle mass Deepened/masculine voice Increased perspiration, change in urine and body odors Frontal and temporal hairline recession, possible male pattern baldness/crown recession Clitoral growth

10 Masculinizing hormones other effects Increased libido Vaginal dryness and atrophy Cessation of menses Infertility/anovulatory state Possible changes in emotional and social functioning Masculinizing hormones general approach Use of one of several forms of parenteral testosterone Dose for complete replacement, not supplementation of low testosterone Other adjuncts may include progestagens, 5 alpha reductase inhibitors or aromatase inhibitors Coexisting metabolic disorders Metabolic syndrome Obesity Hyperlipidemia Impaired glucose tolerance Polycystic ovarian syndrome (PCOS) Coexisting metabolic disorders PCOS is not a contraindication to testosterone therapy Do maintain higher index of suspicion for hyperlipidemia and diabetes Amenorrhea in the presence of testosterone generally indicates endometrial atrophy (18,19) rather than hyperplasia

11 Coexisting metabolic disorders Psychosocial benefits of testosterone may include positive lifestyle changes which can reduce obesity and glucose and lipid disorders These benefits likely outweigh any potential increased metabolic risks Acne Approach is similar to that in non transgender people Acne tends to peak in 1 st year of therapy, then declines (20) Avoiding supraphysiologic levels, and avoiding excessive peaks associated with prolong (2 4 week) dosing intervals may help minimize acne Individualized approach Approach each patient individually, to assess their goals and expectations Avoid making guarantees of specific effects and time frames General expect major changes in 1 st 1 2 years, but can continue for as many as 5 years (11) Age at start, body habitus/shape, and genetics all play a role in extent and rate of changes Common Surgeries Hysterectomy / oopherectomy Vaginoplasty Phalloplasty Metaoidioplasty Breast augmentation Mastectomy Orchiectomy Facial feminization Tracheal shaving Other cosmetic procedures Cosmetic in quotes, since many of these procedures are not at all cosmetic, but instead therapeutic in transgender people

12 Vaginal Flora in the Neovagina Lack of lactobacilli and presence of BV No association between symptoms and a particular species

13 Fertility Fertility Transgender women Sperm storage Transgender men Oocyte / embryo preservation Reproductive Health Post hormones Sperm preservation. Stop hormones? HCG? Impact of T on ovarian structure/function Cumulative T exposure? Time since d/c T? Pregnancy and Transgender Men 41 FTM, mean age 28 20% conceived while still amenorrheic Role of contraception

14 Cancer & Screening Trans women Breast CA if > 5 yrs lifetime estrogen AND > 50 y/o Prostate CA? (tx for prostate CA is E + anti andr) Osteoporosis as with non trans or sooner if prolonged period without hormones < age 50 Trans men Breast CA as with non trans women if no surg Chest wall exam/mri/utz if post surg? No evidence of risk of Ov/Ut CA Osteoporosis as with non trans or sooner if prolonged period without hormones < age 50 Health outcomes?

15 Bibliography Feminizing Hormones 1. Shifren JL, Rifai N, Desindes S, McIlwain M, Doros G, Mazer NA. A comparison of the short term effects of oral conjugated equine estrogens versus transdermal estradiol on C reactive protein, other serum markers of inflammation, and other hepatic proteins in naturally menopausal women. J Clin Endocrinol Metab May;93(5): Ho JY P, Chen M J, Sheu WH H, Yi Y C, Tsai AC W, Guu H F, et al. Differential effects of oral conjugated equine estrogen and transdermal estrogen on atherosclerotic vascular disease risk markers and endothelial function in healthy postmenopausal women. Hum Reprod Oxf Engl Oct;21(10): Contraceptives TF on O, Koetsawang S, Mandlekar AV, Krishna UR, Purandare VN, Deshpande CK, et al. A randomized, double blind study of two combined oral contraceptives containing the same progestogen, but different estrogens. Contraception May;21(5): Hugon Rodin J, Gompel A, Plu Bureau G. MECHANISMS IN ENDOCRINOLOGY: Epidemiology of hormonal contraceptives related venous thromboembolism. Eur J Endocrinol Dec 1;171(6):R Asscheman H, Giltay EJ, Megens JAJ, de Ronde W, van Trotsenburg MAA, Gooren LJG. A long term follow up study of mortality in transsexuals receiving treatment with cross sex hormones. Eur J Endocrinol Jan 25;164(4): Bibliography Feminizing Hormones 6. Wolf Gould CS, Wolf Gould CH. A Transgender Woman with Testicular Cancer: A New Twist on an Old Problem. LGBT Health Dec 24; 7. Wierckx K, Gooren L, T Sjoen G. Clinical review: Breast development in trans women receiving cross sex hormones. J Sex Med May;11(5): Orentreich N, Durr NP. Proceedings: Mammogenesis in transsexuals. J Invest Dermatol Jul;63(1): Writing Group for the Women s Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: Principal results from the women s health initiative randomized controlled trial. JAMA Jul 17;288(3): Canonico M, Oger E, Plu Bureau G, Conard J, Meyer G, Levesque H, et al. Hormone Therapy and Venous Thromboembolism Among Postmenopausal Women: Impact of the Route of Estrogen Administration and Progestogens: The ESTHER Study. Circulation Feb;115(7): Sierra Ramírez JA, Lara Ricalde R, Lujan M, Velázquez Ramírez N, Godínez Victoria M, Hernádez Munguía IA, et al. Comparative pharmacokinetics and pharmacodynamics after subcutaneous and intramuscular administration of medroxyprogesterone acetate (25 mg) and estradiol cypionate (5 mg). Contraception Dec;84(6):

16 Bibliography Feminizing Hormones 12. Hembree WC, Cohen Kettenis P, Delemarre van de Waal HA, Gooren LJ, Meyer WJ, Spack NP, et al. Endocrine Treatment of Transsexual Persons:An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab Jun 9;94(9): Coleman E, Bockting W, Botzer M, Cohen Kettenis P, DeCuypere G, Feldman J, et al. Standards of Care for the Health of Transsexual, Transgender, and Gender Nonconforming People, Version 7. Int J Transgenderism. 2012;13(4): Thurman A, Kimble T, Hall P, Schwartz JL, Archer DF. Medroxyprogesterone acetate and estradiol cypionate injectable suspension (Cyclofem) monthly contraceptive injection: steady state pharmacokinetics. Contraception Jun;87(6): MD IE, PhD, MD RY, MD GC, MD FG, PhD, et al. Evolution of Gonadal Axis After Sex Reassignment Surgery in Transsexual Patients in the Spanish Public Health System. Int J Transgenderism Jun 1;9(2): Wierckx K, Elaut E, Van Hoorde B, Heylens G, De Cuypere G, Monstrey S, et al. Sexual desire in trans persons: associations with sex reassignment treatment. J Sex Med Jan;11(1): Bibliography Feminizing Hormones 17. Elaut E, De Cuypere G, De Sutter P, Gijs L, Van Trotsenburg M, Heylens G, et al. Hypoactive sexual desire in transsexual women: prevalence and association with testosterone levels. Eur J Endocrinol Eur Fed Endocr Soc Mar;158(3): Gooren L, Lips P. Conjectures concerning cross sex hormone treatment of aging transsexual persons. J Sex Med Aug;11(8): Goh HH, Li XF, Ratnam SS. Effects of cross gender steroid hormone treatment on prolactin concentrations in humans. Gynecol Endocrinol Off J Int SocGynecol Endocrinol Jun;6(2): Freda PU, Beckers AM, Katznelson L, Molitch ME, Montori VM, Post KD, et al. Pituitary incidentaloma: an endocrine society clinical practice guideline. J Clin Endocrinol Metab Apr;96(4): Gold SM, Voskuhl RR. Estrogen and testosterone therapies in multiple sclerosis. In: Progress in Brain Research [Internet]. Elsevier; 2009 [cited 2015 Nov 21]. p Available from: Trigunaite A, Dimo J, Jørgensen TN. Suppressive effects of androgens on the immune system. Cell Immunol Apr;294(2): Bibliography Feminizing Hormones 23. Labrie F. DHEA, important source of sex steroids in men and even more in women. Prog Brain Res. 2010;182: Chai NC, Peterlin BL, Calhoun AH. Migraine and estrogen. Curr Opin Neurol Jun;27(3): Gómez Gil E, Zubiaurre Elorza L, Esteva I, Guillamon A, Godás T, Cruz Almaraz M, et al. Hormone treated transsexuals report less social distress, anxiety and depression. Psychoneuroendocrinology May;37(5): Misawa A, Inoue S. Estrogen Related Receptors in Breast Cancer and Prostate Cancer. Front Endocrinol. 2015;6: Brighouse D. Hormone replacement therapy (HRT) and anaesthesia. Br J Anaesth May 1;86(5): Whitehead EM, Whitehead MI. The pill, HRT and postoperative thromboembolism: cause for concern? Anaesthesia Jul 1;46(7): Canonico M, Plu Bureau G, Lowe G, Scarabin PY. Hormone replacement therapy and risk of venous thromboembolism in postmenopausal women: systematic review and meta analysis. Bmj. 2008;336(7655):1227. Bibliography Feminizing Hormones 30. Asscheman H, Gooren LJG, Eklund PLE. Mortality and morbidity in transsexual patients with cross gender hormone treatment. Metabolism. 1989;38(9): van Kesteren PJ, Asscheman H, Megens JA, Gooren LJ. Mortality and morbidity in transsexual subjects treated with cross sex hormones. Clin Endocrinol (Oxf) Sep;47(3): Ott J, Kaufmann U, Bentz EK, Huber JC, Tempfer CB. Incidence of thrombophilia and venous thrombosis in transsexuals under cross sex hormone therapy. Fertil Steril. 2010;93(4):

17 Bibliography Masculinizing Hormones 1. Jacobeit JW, Gooren LJ, Schulte HM. Safety aspects of 36 months of administration of long acting intramuscular testosterone undecanoate for treatment of female tomale transgender individuals. Eur J Endocrinol Nov 1;161(5): Mueller A, Kiesewetter F, Binder H, Beckmann MW, Dittrich R. Long Term Administration of Testosterone Undecanoate Every 3 Months for Testosterone Supplementation in Female to Male Transsexuals. J Clin Endocrinol Amp Metab Sep;92(9): Olson J, Schrager SM, Clark LF, Dunlap SL, Belzer M. Subcutaneous Testosterone: An Effective Delivery Mechanism for Masculinizing Young Transgender Men. LGBT Health [Internet] Jun 26 [cited 2014 Jul 18]; Available from: 4. Subcutaneous Administration of Testsosterone A Pilot Study Report. Saudi Med J. 2006;27(12): Rosner W, Auchus RJ, Azziz R, Sluss PM, Raff H. Position statement: Utility, limitations, and pitfalls in measuring testosterone: an Endocrine Society position statement. J Clin Endocrinol Metab Feb;92(2): Bibliography Masculinizing Hormones 6. Carnegie C. Diagnosis of Hypogonadism: Clinical Assessments and Laboratory Tests. Rev Urol. 2004;6(Suppl 6):S Serin IS, Ozçelik B, Başbuğ M, Aygen E, Kula M, Erez R. Long term effects of continuous oral and transdermal estrogen replacement therapy on sex hormone binding globulin and free testosterone levels. Eur J Obstet Gynecol Reprod Biol Dec 1;99(2): Bui HN, Schagen SEE, Klink DT, Delemarre van de Waal HA, Blankenstein MA, Heijboer AC. Salivary testosterone in female to male transgender adolescents during treatment with intra muscular injectable testosterone esters. Steroids Jan;78(1): Dobs AS, Meikle AW, Arver S, Sanders SW, Caramelli KE, Mazer NA. Pharmacokinetics, efficacy, and safety of a permeation enhanced testosterone transdermal system in comparison with bi weekly injections of testosterone enanthate for the treatment of hypogonadal men. J Clin Endocrinol Metab Oct;84(10): Deutsch MB, Bhakri V, Kubicek K. Effects of cross sex hormone treatment on transgender women and men. Obstet Gynecol Mar;125(3): Bibliography Masculinizing Hormones 11. Coleman E, Bockting W, Botzer M, Cohen Kettenis P, DeCuypere G, Feldman J, et al. Standards of Care for the Health of Transsexual, Transgender, and Gender Nonconforming People, Version 7. Int J Transgenderism. 2012;13(4): Bhasin S, Cunningham GR, Hayes FJ, Matsumoto AM, Snyder PJ, Swerdloff RS, et al. Testosterone Therapy in Men with Androgen Deficiency Syndromes: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab Jun 1;95(6): Gold SM, Voskuhl RR. Estrogen and testosterone therapies in multiple sclerosis. In: Progress in Brain Research [Internet]. Elsevier; 2009 [cited 2015 Nov 21]. p Available from: Trigunaite A, Dimo J, Jørgensen TN. Suppressive effects of androgens on the immune system. Cell Immunol Apr;294(2): Chai NC, Peterlin BL, Calhoun AH. Migraine and estrogen. Curr Opin Neurol Jun;27(3): Bibliography Masculinizing Hormones 16. Gómez Gil E, Zubiaurre Elorza L, Esteva I, Guillamon A, Godás T, Cruz Almaraz M, et al. Hormone treated transsexuals report less social distress, anxiety and depression. Psychoneuroendocrinology [Internet] [cited 2012 Dec 10]; Available from: Meier SLC, Fitzgerald KM, Pardo ST, Babcock J. The effects of hormonal gender affirmation treatment on mental health in female to male transsexuals. J Gay Lesbian Ment Health. 2011;15(3): Grynberg M, Fanchin R, Dubost G, Colau J C, Brémont Weil C, Frydman R, et al. Histology of genital tract and breast tissue after long term testosterone administration in a female to male transsexual population. Reprod Biomed Online Apr;20(4): Perrone AM, Cerpolini S, Maria Salfi NC, Ceccarelli C, De Giorgi LB, Formelli G, et al. Effect of long term testosterone administration on the endometrium of female tomale (FtM) transsexuals. J Sex Med Nov;6(11): Wierckx K, Van de Peer F, Verhaeghe E, Dedecker D, Van Caenegem E, Toye K, et al. Short and long term clinical skin effects of testosterone treatment in trans men. J Sex Med Jan;11(1):