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Primary Care and Hormonal Treatments for Transgender Patients Nick Gorton, MD, DABEM

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1 Primary Care and Hormonal Treatments for Transgender Patients Nick Gorton, MD, DABEM

2 Definitions Sex – male, female, intersex, transsexual Sex – male, female, intersex, transsexual Gender – masculine, feminine, androgynous Gender – masculine, feminine, androgynous * Non Binary

3 Definitions Gender Identity Gender Identity Gender Expression Gender Expression

4 Definitions Transgender Transgender Transsexual Transsexual Cisgender/Cissexual Cisgender/Cissexual Cisgender Cissexual Transgender Transsexual

5 Definitions FTM MTF

6 The Two Commandments

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8 Primary Care and Hormone Therapy You already know 90% of what you need to know You already know 90% of what you need to know Most medical care of transgender patients has nothing to do with being transgender Most medical care of transgender patients has nothing to do with being transgender 100% of the medical treatments and most of the surgeries are used in cisgender patients 100% of the medical treatments and most of the surgeries are used in cisgender patients

9 The Handout

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13 How does this work? Typical Narrative... Accept your own trans identity and seek help Accept your own trans identity and seek help  Internet, local groups, organizations Find a therapist and receive a dx (and letter) Find a therapist and receive a dx (and letter)  3 month 'Real Life Experience' OR  Psychotherapy (duration TBD, usually 3+months) Find a medical provider Find a medical provider  Start hormone therapy  Non-genital surgery (same time as HRT)  1 year successful – genital surgery

14 Typical Narrative (following SOC) Does everyone do it this way? Does everyone do it this way? If they don't should you still treat them? If they don't should you still treat them?

15 Harm Reduction WPATH-SOC explicitly endorse harm reduction WPATH-SOC explicitly endorse harm reduction

16 Medical Treatments: Fundamentals Set realistic goals Set realistic goals  What will, might, and won't happen Emphasize primary and preventative care Emphasize primary and preventative care Use the simplest hormonal program that will achieve goals Use the simplest hormonal program that will achieve goals  Every option doesn't work for every patient  Cost, ease of use, safety

17 Medical Treatments: Fundamentals Patience is a virtue Patience is a virtue  Puberty comparison Side effects are in the eye of the beholder Side effects are in the eye of the beholder  Baldness

18 Medical Treatments: Fundamentals Hormone treatments are one of the easiest parts Hormone treatments are one of the easiest parts FTM – Testosterone up to normal male dose FTM – Testosterone up to normal male dose  Dose that masculinizes and stops menses is enough MTF – More difficult because must suppress testosterone production to get best results MTF – More difficult because must suppress testosterone production to get best results  Anti-androgen(s)  Estrogens

19 Medical Treatments: MTF Estrogens at high dose Estrogens at high dose  3-5x normal replacement doses  Estrogen Supresses Testosterone! Anti-Androgen Anti-Androgen  Spironolactone and others  Orchiectomy Results variable Results variable  Age at starting is important  Genetics plays a big part

20 The Special Case of Transgender Girls

21 Transgender Youth

22 Hormones: MTF - Estrogens Oral - $ Oral - $ $$$ Premarin 1.25 – 10mg/d (usual ) $$$ Premarin 1.25 – 10mg/d (usual ) $ Estradiol 1-5mg/d (usual 2-4) $ Estradiol 1-5mg/d (usual 2-4) IM – Delestrogen $$ IM – Delestrogen $$  10-40mg q2weeks (usual 20)  Can't easily 'stop' in an emergency when patient immobilized Transdermal – Estradiol patch $$$ Transdermal – Estradiol patch $$$ mg/day (1-3 patches/week – overlapped) mg/day (1-3 patches/week – overlapped) Probably the safest for transwomen predisposed to thrombo- embolic dz (age>40, smoking, FH, etc.) Probably the safest for transwomen predisposed to thrombo- embolic dz (age>40, smoking, FH, etc.) Patient's often wary of starting but some prefer after trying it Patient's often wary of starting but some prefer after trying it

23 Hormones: MTF - Estrogens Beneficial effects Beneficial effects  Breast growth  Suppress androgen production  Change of body habitus (muscle and fat)  Softening of skin Contraindications/Precautions Contraindications/Precautions  Same as in cisgender women  Individual risk/benefits (MTF get greater benefits r/t mental health than menopausal cisgender women.)  In transwomen with absolute CI – at least suppress testosterone fully

24 Hormones: Estrogens Adverse Effects THROMBOEMBOLIC DISEASE THROMBOEMBOLIC DISEASE Hepatotoxicity (especially ORAL) – incr TA, adenomas Hepatotoxicity (especially ORAL) – incr TA, adenomas  Medi-Cal will cover IM/TD (with TAR) if other Liver dz Prolactinoma (if dose is too high) Prolactinoma (if dose is too high) Decreased glucose tolerance Decreased glucose tolerance Lipid profile Lipid profile Gallbladder Disease Gallbladder Disease Worsening migraine/seizure control Worsening migraine/seizure control Breast Cancer Breast Cancer Mood Mood Decreased libido Decreased libido

25 Hormones: MTF - Anti-Androgens Antiandrogens - All Antiandrogens - All Decrease T production or activity Decrease T production or activity Slow/stop MPB, and decrease unwanted hair growth Slow/stop MPB, and decrease unwanted hair growth Decrease erections/libido Decrease erections/libido Improve BPH Improve BPH Spironolactone mg/d divided bid Spironolactone mg/d divided bid Cheap, reasonably safe Cheap, reasonably safe Hyper-K+, diuresis, changes in BP, 'just don't like it' Hyper-K+, diuresis, changes in BP, 'just don't like it' Decreased H/H (T erythropoetin) Decreased H/H (T erythropoetin) Cyproterone Cyproterone

26 Hormones: MTF - Anti-Androgens 5-α-reductase inhibitors 5-α-reductase inhibitors Finasteride, dutasteride, saw palmetto Finasteride, dutasteride, saw palmetto Finasteride (Proscar/Propecia) Finasteride (Proscar/Propecia) Stops conversion of T DHT Stops conversion of T DHT 5mg tabs = $20 for 30 at Costco 5mg tabs = $20 for 30 at Costco 1mg tabs = $74 for 30 at Costco 1mg tabs = $74 for 30 at Costco

27 Hormones: MTF - Anti-Androgens T DHT E not very active stuff 5-α-reductase aromatase Finasteride

28 Hormones: MTF - Monitoring Every Visit Every Visit BP, Weight, BMI BP, Weight, BMI Safety Safety Mental health Mental health General screening based on age, organ, gender, and sex appropriate norms General screening based on age, organ, gender, and sex appropriate norms Patient education Patient education S/Sx of TEDz S/Sx of TEDz Healthy Habits Healthy Habits Vision changes or lactation Vision changes or lactation

29 Hormones: MTF - Monitoring Clinical monitoring most important Clinical monitoring most important Same adverse events in cisgender pts w/ same meds (use what you know!) Same adverse events in cisgender pts w/ same meds (use what you know!) Labs Labs  0, 2, & 6 mo initially then (semi)annual or p changes  CBC, CMP, Lipids  PL and T CrK+K+ Glucose AST/ALT PL

30 Hormones: MTF - Efficacy What is adequate treatment? What is adequate treatment?  Pt outcomes – breast growth (peak 2-3 yrs), changes in skin, hair, fat/muscle, libido  The floor – testosterone levels ( female range)  The roof – prolactin level  >20 possibly too much 'extra' E use or other meds)  >25 probably too much  >30 definitely too much  >50 worry a great deal about PL-oma

31 Hormones: MTF - Monitoring Pituitary Adenoma Pituitary Adenoma 1 st Pass Metabolism 1 st Pass Metabolism AST/ASTPL

32 Hormones: MTF – Adverse effects Elevated PL: Stop Estrogens (not anti-androgen) Elevated PL: Stop Estrogens (not anti-androgen)  If levels normalize, resume E at lower dose  Consider changing meds that cause increase in PL  If levels remain high MRI to r/o PL-oma  Elevated LFTs  Look for other cause!  If due to E, lower dose or stop until LFT normal

33 Medical Treatments: FTM

34 Hormones: FTM Testosterone Injected Esters (cheapest) Testosterone Injected Esters (cheapest)  Cypionate  200mg/ml: 1-10ml vials  Cheapest - $ for 10ml (~4mos supply)  Enanthate  Biggest vial is 5ml  Slightly more expensive

35 Hormones: FTM Therapeutic Range 100 mg week 200 mg 2 weeks

36 Steady State Therapeutic Range Usually achieved after 3-5 T½ Usually achieved after 3-5 T½ T ½ of esters = 8-10 days T ½ of esters = 8-10 days

37 Hormones: FTM Transdermal Transdermal  Expensive: $7 day retail, $1/day compounded  Less variable levels  Daily administration  Risk of inadvertent transfer to others 5%, 1g QD 1%, 5g QD

38 Hormones: FTM - Monitoring Every Visit Every Visit BP, Weight, BMI BP, Weight, BMI Safety Safety Mental health Mental health General screening based on age, organ, gender, and sex appropriate norms General screening based on age, organ, gender, and sex appropriate norms Patient education Patient education Vaginal bleeding Vaginal bleeding Healthy habits Healthy habits Tx available for acne, MPB Tx available for acne, MPB

39 Medical Treatments: Fundamentals ALT Clinical monitoring most important Clinical monitoring most important Same adverse events in cisgender pts w/ same meds (use what you know!) Same adverse events in cisgender pts w/ same meds (use what you know!) Labs Labs  0, 2, & 6 mo initially then (semi)annual or p changes  CBC, CMP, Lipids  T (trough) in FTM Cr Glucose T Hgb Hct

40 Treatment Effects (any delivery...) Nearly immediate Nearly immediate  Increased sebum and resultant acne  Increased sex drive  Sometimes – amenorrhea  Metabolic changes start

41 Treatment Effects 1-6 months 1-6 months  Voice change starts – parallels adolescence  Hair growth (and loss) begins: parallels adolescence*  Clitoromegaly starts  Most amenorrhea (but E only decreases modestly)*  Fat and muscle distribution changes  Metabolic changes * Gooren, et al “Review of studies of androgen treatment of FTM transsexuals: Effects and risks of administration of androgens to females”.

42 Treatment Effects 1-5 Years 1-5 Years  Voice settles  Final fat and muscle redistribution  Clitoromegaly maxes  Length average 4-5cm (3-7 cm range) 1  Volume increases 4-8x 2  Greater change in younger patients 2 1 Meyer W, et al “Physical and hormonal evaluation of transsexual patients: a longitudinal study.” 2 Gooren, et al “Review of studies of androgen treatment of FTM transsexuals: Effects and risks of administration of androgens to females”.

43 Treatment Effects 5-10 years 5-10 years  Final hair growth  Androgenic alopecia can happen at any age – and does in 50% of FTMs by 13 years* * Gooren, et al “Review of studies of androgen treatment of FTM transsexuals: Effects and risks of administration of androgens to females”.

44 Androgenic Alopecia T DHT E not very active stuff 5-α-reductase aromatase Finasteride

45 Hormones: FTM – Adverse effects Acne – MC side effect (chest/back) Acne – MC side effect (chest/back) CV - worsening of surrogate endpoints - lipids, glucose metabolism, BP CV - worsening of surrogate endpoints - lipids, glucose metabolism, BP Polycythemia (normals for males) Polycythemia (normals for males) Unmask or worsen OSA Unmask or worsen OSA Enhanced Libido Enhanced Libido Androgenic alopecia Androgenic alopecia 'Other' hair growth 'Other' hair growth

46 Hormonal Treatments: Is this safe? Van Kesteren P, et al. “Mortality and morbidity in TS subjects treated with cross-sex hormones.” Clin Endo (Oxf). 47(3): Van Kesteren P, et al. “Mortality and morbidity in TS subjects treated with cross-sex hormones.” Clin Endo (Oxf). 47(3):  DESIGN: Retrospective, descriptive university teaching hospital that is the national referral center for the Netherlands (serving 16 million people)  SUBJECTS: 816 MTF & 293 FTM on HRT for total of 10,152 pt-years  OUTCOMES: Mortality and morbidity incidence ratios calculated from the general Dutch population (age and gender-adjusted)

47 Hormonal Treatments: Is this safe? Van Kesteren P, et al. “Mortality and morbidity in TS subjects treated with cross-sex hormones.” Clin Endo (Oxf). 47(3): Van Kesteren P, et al. “Mortality and morbidity in TS subjects treated with cross-sex hormones.” Clin Endo (Oxf). 47(3): FTMs 816 MTFs 10,152 pt years ???? c/w ♂ c/w ♀

48 Hormonal Treatments: Is this safe? Van Kesteren P, et al. “Mortality and morbidity in TS subjects treated with cross-sex hormones.” Clin Endo (Oxf). 47(3): Van Kesteren P, et al. “Mortality and morbidity in TS subjects treated with cross-sex hormones.” Clin Endo (Oxf). 47(3):  MTF/FTM total mortality no higher than general popl'n  Largely, observed mortality not r/t hormone treatment  VTE was the major complication in MTFs. Fewer cases after the introduction of transdermal E in MTFs over 40  In MTFs increased morbidity from VTE and HIV and increased proportion of mortality due to HIV HIVVTE

49 Hormonal Treatments: Is this safe? Van Kesteren P, et al. “Mortality and morbidity in TS subjects treated with cross-sex hormones.” Clin Endo (Oxf). 47(3): Van Kesteren P, et al. “Mortality and morbidity in TS subjects treated with cross-sex hormones.” Clin Endo (Oxf). 47(3): FTMs 816 MTFs 10,152 pt years c/w ♂ c/w ♀ No Increase Morbidity or Mortality No Increase Mortality Increase morbidity r/t HIV/VTE

50 Hormonal Treatments: Is this safe? Van Kesteren P, et al. “Mortality and morbidity in TS subjects treated with cross-sex hormones.” Clin Endo (Oxf). 47(3): Van Kesteren P, et al. “Mortality and morbidity in TS subjects treated with cross-sex hormones.” Clin Endo (Oxf). 47(3): The absence of evidence is not evidence of absence

51 Hormonal Treatments: Is this safe? Gooren L, et al. “Long term treatment of TSs with hormones: Extensive personal experience.” J Clin Endo & Metab. 93(1): Gooren L, et al. “Long term treatment of TSs with hormones: Extensive personal experience.” J Clin Endo & Metab. 93(1):  Same clinic group as 1997 paper – now 2236 MTF, 876 FTM ( )  Outcome M&M Data, data assessing risks of osteoporosis and cardiovascular disease, cases of hormone sensitive tumors and potential risks

52 Hormonal Treatments: Is this safe? Gooren L, et al. Cardiovascular Risks Gooren L, et al. Cardiovascular Risks  Analyzed studies of surrogate markers for CVDz in MTF/FTM: Body composition, lipids, insulin sensitivity, vasc function, hemostasis/fibrinolysis, others (HC CRP)  Some worsen, some improve, some are unchanged – much of the worsening seems likely d/t weight  MTF do worse than FTM  Hard clinical endpoints show no difference  Counsel patients about modifying CV risk

53 Hormonal Treatments: Is this safe? Gooren L, et al. Hormone Dependent Tumors Gooren L, et al. Hormone Dependent Tumors  Lactotroph Adenoma  Rare  Check PL!  Prostate Cancer  Prostatectomy is not a part of SRS  Screen based on the organs present  Withdrawal of testosterone may decrease but doesn't eliminate the risk of BPH and malignancy  May falsely lower PSA

54 Hormonal Treatments: Is this safe? DRE is a little different DRE is a little different

55 Hormonal Treatments: Is this safe? Gooren L, et al. Hormone Dependent Tumors Gooren L, et al. Hormone Dependent Tumors  Breast cancer  MTF - Estrogen exposure: dose and duration  Conservative: screen as cisgender women of same age/risk  Progesterone increases risk (esp if cyclic)  Other risk factors: obesity, FH, HRT >5 years  FTM  Reported in 1 case 10 years after mastectomy  Mastectomy reduces but doesn't eliminate risk  Some injected T is aromatized to estrogen  Family history

56 Hormonal Treatments: Is this safe? Gooren L, et al. Gynecologic Tumors Gooren L, et al. Gynecologic Tumors  Gynecologic Tumors  Cervical  Ovarian  Endometrial

57 Gynecologic Cancer risks in FTMs 6 + ??? ???

58 Gynecologic Cancer risks in FTMs Normal Hyperplasia Dysplasia Cancer FTMFTM PCOSPCOS ??? If infrequent periods ENDOMETRIAL CANCER

59 Gynecologic Cancer risks in FTMs Grynberg et al Histology of genital tract and breast tissue after long-term testosterone administration in a female-to-male transsexual population. Reproductive BioMedicine (2010) 20, Hysterectomies: Atrophy in 50, 54 Proliferative, 4 polyps, 8 hyperplasia, 1 with dysplasia with a small foci of carcinoma in situ.

60 Gynecologic Cancer risks in FTMs

61 IARC Working Group on Evaluation of Cervical Cancer Screening Programmes. Screening for squamous cervical cancer: duration of low risk after negative results of cervical cytology and its implication for screening policies. Br Med J. 1986;293:

62 Gynecologic Cancer risks in FTMs

63

64 Is it effective?

65 Of 28 studies 23 included Psych/HRT/Surgery Of 28 studies 23 included Psych/HRT/Surgery Five were Psych/HRT only Five were Psych/HRT only Pre-tx suicidality 30%, 8% post treatment Pre-tx suicidality 30%, 8% post treatment Significant improvements in SCL-90 and MMPI and in measures of gender dysphoria Significant improvements in SCL-90 and MMPI and in measures of gender dysphoria One study of Psych/HRT/Surgery showed long term SCL-90 scores were in non-clinical range One study of Psych/HRT/Surgery showed long term SCL-90 scores were in non-clinical range Five studies assessed employment and financial status and all improved Five studies assessed employment and financial status and all improved

66 What about regret ??? Pfäfflin, F., & Junge, A. (1998). Sex reassignment – Thirty years of international follow-up studies; SRS: A comprehensive review, Düsseldorf, Germany: Symposion Publishing. Pfäfflin, F., & Junge, A. (1998). Sex reassignment – Thirty years of international follow-up studies; SRS: A comprehensive review, Düsseldorf, Germany: Symposion Publishing.  74 f/u studies and 8 reviews published b/w  Less than 1% long term regret in over 400 FTMs  1.5% regret in over 1000 MTFs Compare with regret rates for gastric bypass, breast recon after mastectomy, surgical sterilization Compare with regret rates for gastric bypass, breast recon after mastectomy, surgical sterilization Studies after 1991 show lower rates of regret (and found risk of regret correlates well with surgical success.) Studies after 1991 show lower rates of regret (and found risk of regret correlates well with surgical success.)

67 Making Things Official

68 Identity Document Changes Part of the medical treatment for GID Part of the medical treatment for GID Lack of appropriate ID Lack of appropriate ID  Vulnerability to interpersonal violence  Inability to Get a job Get a job Make a purchase with a credit card Make a purchase with a credit card Board a plane Board a plane Enter a federal building Enter a federal building  Voluntary withdrawal from activities

69 Identity Document Changes Differing Standards Differing Standards  Surgical  Any treatment Examples Examples  CA DMV: Physician approval (restricted Psychologist)  US Dept of State: Physician approval  US Social Security Administration: Surgical  TX (Birth Cert): Any state court order  AK (BC): Letter from a surgeon  NY (BC): Letter from a surgeon and specific surgeries  OH, ID, MS, SC, TN (BC): Screw off  Physician approval  Patient request

70 What can you get in CA w/o SRS? Drivers License/State ID - DL328 Drivers License/State ID - DL328 Passport Passport Court Ordered Name and Gender Change Court Ordered Name and Gender Change CA Birth Certificate (possibly other states as well) CA Birth Certificate (possibly other states as well) Social Security NAME Social Security NAME Social Security GENDER MARKER Social Security GENDER MARKER

71 Supportive Letters There are no gender cops There are no gender cops Its not your job to enforce bad policy Its not your job to enforce bad policy Your job Your job  Advocate for your patients needs  Don't lie  Give your true medical opinion  Don't write something if you don't have experience

72 Supportive Letters: a thought experiment You are a doctor in NC in An 18 year old young man who is your patient asks you for help. He is white, but his great grandfather was African American. He was accepted to attend UNC-CH, but an anonymous letter to the school revealed his heritage. He was told he must provide a letter from a teacher, doctor, or minister verifying he is white to be allowed to enter UNC. You are a doctor in NC in An 18 year old young man who is your patient asks you for help. He is white, but his great grandfather was African American. He was accepted to attend UNC-CH, but an anonymous letter to the school revealed his heritage. He was told he must provide a letter from a teacher, doctor, or minister verifying he is white to be allowed to enter UNC.

73 Supportive Letters: a thought experiment You are a doctor in NC in An 18 year old young man who is your patient asks you for help. He is white, but his great grandfather was African American. He was accepted to attend UNC-CH, but an anonymous letter to the school revealed his heritage. He was told he must provide a letter from a teacher, doctor, or minister verifying he is white to be allowed to enter UNC. You are a doctor in NC in An 18 year old young man who is your patient asks you for help. He is white, but his great grandfather was African American. He was accepted to attend UNC-CH, but an anonymous letter to the school revealed his heritage. He was told he must provide a letter from a teacher, doctor, or minister verifying he is white to be allowed to enter UNC. You're pretty advanced for the 50's and understand race as a social construct and believe he really is 'white'.... but know that UNCs policies and understanding of race would exclude him. You're pretty advanced for the 50's and understand race as a social construct and believe he really is 'white'.... but know that UNCs policies and understanding of race would exclude him. Do you write the letter? Do you write the letter?

74 Supportive Letters There are no gender cops There are no gender cops Its not your job to enforce bad policy Its not your job to enforce bad policy Your job Your job  Advocate for your patients needs  Don't lie  Give your true medical opinion  Don't write something if you don't have experience

75 Supportive Letters I am a physician licensed to practice medicine and surgery in the state of California. I am a physician licensed to practice medicine and surgery in the state of California. John Smith is a patient in my care at LMHS John Smith is a patient in my care at LMHS In my medical opinion Mr Smith is a transsexual man. In my medical opinion Mr Smith is a transsexual man. I have determined that his male gender predominates and have provided him with appropriate and irreversible sex reassignment treatments. I have determined that his male gender predominates and have provided him with appropriate and irreversible sex reassignment treatments. (In addition, he has undergone irreversible sex reassignment surgery that I have verified by my own examination.) (In addition, he has undergone irreversible sex reassignment surgery that I have verified by my own examination.)

76 Supportive Letters As a result Mr Smith has completed all necessary medical (and surgical) procedures to fully transition from female to male. As a result Mr Smith has completed all necessary medical (and surgical) procedures to fully transition from female to male. He should be considered male for all legal and documentation purposes – including drivers license, birth certificate, passport, and social security records. He should be considered male for all legal and documentation purposes – including drivers license, birth certificate, passport, and social security records. Indicating his gender as male is accurate and will eliminate the considerable confusion and bias Mr Smith encounters when using identification that does not reflect his current true gender. Indicating his gender as male is accurate and will eliminate the considerable confusion and bias Mr Smith encounters when using identification that does not reflect his current true gender.

77 Resources

78 Resources Two page clinical protocol Two page clinical protocol Informed consent forms Informed consent forms This talk This talk project-health.org/transline project-health.org/transline


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