Masculinizing Options Swedish Hospital LGBTQ Symposium 4/13/2018 Kevin Hatfield MD The Polyclinic - Seattle WA

1 Laith Ashley Benjamin Melzer Gena Rocero

2 GOALS & OBJECTIVES

 Getting Started with patients  Introduction, First visits and discussion points  to consider  Androgens

 5a-reductase Inhibitors, Aromatase Inhibitors  Estrogen  SERMS (selective estrogen receptor modulators)  Progestin-only contraceptives  PrEP (Pre Exposure Prophylaxis against HIV)  Cases

3 Getting Started

 Meet the patient, Clarify Name, Pronouns, Gender Terminology

 Take full histories – Past and Current Medical, Surgical, Psychosocial, Sexual, Family, Medications

 Physical Exam

 “Tell me about your gender journey?”

 When did you first feel your gender was different than how others labeled you?

 When did you first discover a name for what you were experiencing?

 Where are you now in the process?

 What terms feel comfortable to describe your gender?

 What are your goals for today?

 Are you working with a skilled therapist?

 Patient role – “Captain of your own ship.”- Captain Kirk

 My Role – “safety monitor - fixer,” - Scotty

4 Approach to Masculinization What to Choose? Cross Hormone Protocol? Testosterones Aromatase inhibitors 5a-reductase inhibitors Estrogens Progestins

5 • Anastrazole (Arimidex) • Letrozole (Femara) • Finasteride (Proscar) • Exemastane • Dutasteride (Avodart) (Aromasin)

6 7 8 • Anastrazole (Arimidex) • Letrozole (Femara) • Finasteride (Proscar) • Exemastane • Dutasteride (Avodart) (Aromasin)

9 Timeline for Medicines Medicine When to Start Timeline Notes (T) Immediately Every 3-6 months Acne, Weight gain, Mood changes Aromatase inhibitors If ongoing menses/ Titrate to effect 0.5 mg BIW/TIW? High E with slow D 5-a Reductase If androgenic alopecia Set by patient Reduced phallus inhibitor is notable, growth Contraceptives ASAP if penetration by Set by patient Choose non-hormonal sex partner with penis or progestin only method Estrogen (E) Excessive dryness/skin Set by patient Therapy discussion weakness/coital with patient, go over topicals/orals spotting options. ASAP if sexual activity Set by patient, based Q3 month BMP, HIV, RPR, increases risk of HIV on personal risk Oral/Front & Back Hole PrEP* GC/CT-NAAT if exposure. activities applicable * Pre Exposure Prophylaxis Against HIV exposure

10 Testosterone Options

 Oral – Striant BID adhesive trans-buccal tabs

 Topical - Patch and Gel – Androgel, Testoderm, Testim, Axiron etc

 Topical compounds – Customized - creams, ointments, gels

 Injectable Testosterone - Enanthate, Cypionate, Undecanoate

 Implantable – Testopel

 Topical – (Europe only) - Andractim gel (DHT)

11 Testosterone Promotes

 Drop in vocal pitch Cartilage thickening Frontalis muscle hypertrophy  Change in body odor

 Amenorrhea within first 3-6 months  Acne – face and back  Muscle development: encourage routine exercise & stretching

 Increased appetite/weight gain  Increase in body hair  Facial hair – often much later

 Scalp hair loss and balding  Clitoromegaly

 Increased libido  Mood changes: Irritability is possible BUT most feel Contentment  Lab changes: Hct, lipids, sCr, AlkPhos

12 Testosterone Options

“T” Type Low Usual Dose Max Cost Dosing Notes Transbuccal 15 mg BID 30 mg BID 60 mg BID >$650/m BID Buccal adhesive

Patch 1-2 mg 4 mg 8 mg >$530/m Daily Peel-off, linty halo

Gel 1% or 1.62% 12.5 mg 50 mg 100 mg >$120/m Daily Pump or packet Transfer to partner? 2% Axillary Gel 30 mg 60 mg 120 mg $600/m Daily Messy/Sticky

Custom Cream 2.5 % 5 % 20% $15-$80/m Daily Specialty Pharmacy (vehicle matters!!!) Cypionate or 20 mg 60 mg 200 mg $5-$20/ Weekly Home SQ Injection Enanthate SQ month Undecanoate 750 mg 750 mg 750 mg $800/10w Q10 Weeks One size fits all IM Injection OFFICE ONLY - IM injection Testo/Stearic 75 mg 375 mg 1125 mg $800-$1200 Q3-4 Office ONLY- Trochar acid pellets /3-4months Months Assisted Insertion

13 Testosterone ½ Life by Type Bio Enanthate Cypionate Undecanoate

Type of Half-Life Dose LFT Cancer Risk Lab / Mood Testosterone Frequency D Changes Bio-identical 4-6 hours N/A Rare NOT Observed N/A

Enanthate 4.5 days Q7 Days Rare NOT Observed Likely/Possible

Cypionate 8 days Q7 Days Rare NOT Observed Likely/Possible

Undecanoate 20 days Q70 Days Rare NOT Observed Likely/Possible

14 Testosterone Level by Decade

15 Timeline of Testosterone Changes Site of Change Time of Onset Completion Time Reversible? Skin Oiliness/Acne 1-6 months 1-2 years YES Voice Deepening 2-4 months 1-2 years NO Facial Hair/Body Hair 3-6 months 3-5 years NO Muscle Mass Increase 6-12 months 2-5 years YES Amenorrhea 2-6 months N/A YES Fat Redistribution 3-6 months 2-5 years YES Libido Increase 1-3 months 1-2 years YES

Vaginal Atrophy/Dryness 3-6 months 1-2 years YES Clitoral Enlargement 3-6 months 1-2 years NO Androgenic Alopecia 6-12 months 3-5 years NO Fertility Reduction 3-6 months N/A PROBABLY

16 Other Half Life (Consider Flexible Dosing)

Medication / Half-Life Dose/ Cash Cost Purpose Action strength Frequency #90 tablets Finasteride 5-7 hours 1 - 2.5 mg $14-$20 Prevent 5a-Reductase 1 mg, 5 mg Daily Alopecia Inhibitor tab (Block DHT) Dutasteride 28 days 0.5 mg $35 Prevent 5a-Reductase 0.5 mg cap Daily - Alopecia Inhibitor Weekly (Block DHT)

Anastrazole 2 days 0.5 mg TIW $21 Lower E2 if Blocks T 1 mg tab too high conversion to E

Letrozole 2 days Daily $22 Lower E2 if Blocks T 2.5 mg tab too high conversion to E

Exemestane 1 day Daily $350 Lower E2 if Blocks T 25 mg tab too high conversion to E

17 Other Medications ( for particular needs )

Medication / Half-Life Dose/ Cash Cost Purpose Action strength Frequency #90 tablets Prasterone / 38 minutes 6.5 mg $540 Reduces Local conversion DHEA 6.5 mg (DHEAS 15 Inserted Daily dryness / into Estrogens/ insert hours) fragility Androgens Ospemifene 26 hours 60 mg daily $620 Reduces SERM acivity on 60 mg oral tab dryness / mucosal tissue fragility Estrogen ring n/a 2 mg Q 90 days $450 Reduces Local release of 2 mg insert dryness / Estrogen to fragility mucosa Etonorgestrel n/a 1 implant Q 3 $900 Contraception Prevents 68 mg implant years Ovulation IUD options n/a Q 3 or more $900+ Contraception Prevents progestin/Cu years Conception

18 Testosterone Induced Lab Value and Risk Changes

Probability Observation / Possible Risks Likely Increase of these Lab Values Higher LDL & Triglycerides (Lower HDL) Hematocrit Creatinine Alkaline Phosphatase

Possible Increased Risk Polycythemia (Sleep Apnea induced Hypoxemia) Possible Increased Risk if Other Heart Disease Factors Present Type 2 Diabetes (weight gain) No increase Breast/Uterine/Ovarian Cancer

19 20 Typical SQ Testosterone Injection Supplies  Testosterone Cypionate 200mg/ml 10 ml vial $45 3-5 month supply 18G 21G 1mL Slip Tip Luer-Lok Syringe 25G 30G

21 Testosterone Dosing and Escalation Treat Patient NOT Protocol

 Use patient’s age & desired rate of change

 Consider body habitus and menstrual regularity/dysphoria

 Start with 20-60 mg SQ weekly (0.1 mL – 0.3 mL of 200mg/mL T Cypionate)

 Check Total Testosterone and at nadir in 5-6+ weeks

 Look for T nadir between 450-650 and Estradiol <50

 IF T <650 consider increase by 20 mg and recheck T in 3-6 months

 Maintain high range T nadir for 3-5 years to complete changes

 If Estradiol >60 AND Pelvic complaints, ongoing menses or slow observed changes add 0.5 mg Anastrazole BIW-TIW and look for Estradiol to fall back to normal male range

22 Remember to discuss Sexually Transmitted Infections Some patients may ask about precautions but … Please be proactive – inform and educate, offer 3 site testing “An ounce of prevention…” My mantra – “Leave no ‘active’ orifice untested!”

23 Case 1 - Martin - February 2017

Martin, 18 yo AFAB headed to WSU in Fall. “100% guy” ; he/him pronouns. “I have known since 3rd grade.”  Medical history; Vaccine Hx, Surg Hx.  Social history – “parents not on board”  Working part time for college money  (-)Tobacco, (+)THC, (+)Dating  No prior HPV vaccine (#1 today)  Dates only vagina-bodied people  Would like to get a counselor  Binder is effective but rigidly inelastic  Baseline labs Total T 39 ng/dL, E 215 pg/mL, HCT 35.6%

What can we do for him?

24 Martin – April 2017 ; 2 month follow up/lab visit Prior labs T 39 ng/dL E 215 pg/mL  Nadir labs prior to visit Total T 270, E 142, HCT 37 HCT 35.6%  Medication started – decided to pay cash, ongoing counseling to improve parental relationship  Needle phobia is improving (great! HPV#2 today!)  Noting some changes from T  New binder is “ok, but not great”  Dating life is “busier”, Still using THC – “but less than before”  Wants Male gender in EPIC & Driver License form  Surgical consult information (top surgery)

25 Martin – August 2017, 4 month follow up/lab visit Prior Labs T 270  Nadir Labs done a week prior to visit E 142  Total Testosterone 490, Estradiol 46, HCT 45.6 HCT 37%  Physical exam  Voice deeper  Facial hair  Acne – manageable  No bleeding for 7 weeks – “very happy”  Sexual activity – “Still dating and doing fine”  Joint counseling sessions with parents went well!  Wants all legal gender forms prior to college (in 2 weeks)  HPV #3 today  Outline next visits during college breaks  Then you get Email in November 2017 about changes in his dating life…

26 Case #2 – Max - July 2016

 32 yo Max has known about personal gender nonconformity since gradeschool.

 Came out to parents & friends as Bisexual in 9th grade.

 Parent’s voiced “concerns about sexuality”

 Married to cis-female partner, has 2 yo child. Gender talk with spouse earlier this year – “Went pretty well”

 They/them pronouns; Identifies as “Non-binary - Transmasculine”

 PMHx : Obesity, Asthma, Elevated Triglycerides SurgHx : C-section

 FamHx: Dad HTN, OSA; Mom Obesity, DM2 @44; Brother OSA

 SocHx: Moved to Seattle 2 months ago from Ames Iowa; Works at Big tech company with wife; 7-10 drinks per week, (-) Tobacco, (-) THC, Committed non-monogamous.

 Goal for first visit: “Starting T Today since… I’ve wanted to start T since 10th grade” Data from Visit: BP 134/86, BMI 32.2 TChol 178, LDL 87, HDL 42, TG 245 Total T 28 ng/dL, E 310 pg/dL, HCT 38.2 %

What should we do for Max?

27 Items for Max

 More health history discussed, Medical record request for more detail… Vaccines?

 Physical exam: Vitals, Affect, HEENT, Heart, Lungs, Abd, etc.

 Need for healthful food choices and routine exercise on T and preparing for pregnancy

 Fertility discussion, They desire pregnancy in next 18 months – Timing of Testosterone and preconception planning. Ob/Gyn referral given.

 Testosterone consent forms given, DOL paperwork given. STI/PrEP discussed

 Importance of counseling and support during transition reviewed.

 Agenda setting and their timeline reviewed “voice deeper & more hair ASAP”

 Testosterone injection education materials, Youtube video, Rx (cost coaching)

 First 60 mg Testosterone training session – able to self inject with coaching only!

 Lab value recheck planned at 10-12 week nadir (they are traveling) with next day office visit.

28 Prior Labs Max – October 2016, 3 month f/u & lab visit T 28 E 310  Vitals BP 130/89, BMI 33.1 HCT 38.2  Nadir Labs done a day prior to visit LDL 87 HDL 42  Total Testosterone 320 ng/dL, Estradiol 156 pg/mL, HCT 47.6%, TG 245 T Chol 192, LDL 84, HDL 35, TG 365

 Still having monthly cycle – “tiny bit shorter and lighter” BP 134/86 BMI 32.2  Physical exam

 Voice is a little deeper, minimal hair on face.  “Changes seem too slow Doc, How much can we raise the dose?”

What do you do?

29 Prior Labs Max – February 2018, 20 month f/u visit T 320 E 156  Have been back on SQ T for 6 months since delivery of 2nd child. HCT 47.6 Bottle feeding. LDL 84  Exercising routinely and committed to healthy food choices HDL 35  Vitals BP 123/82, BMI 28.7 TG 365  Nadir Labs Total Testosterone 580 ng/dL, Estradiol 18 pg/mL, HCT 50.6%, TChol 208 LDL 112, HDL 49, TG 235 BP 130/89 BMI 33.1  Physical exam – deeper voice, some facial hair, androgenic alopecia noted

 No bleeding for 3 months

 Complaints today: “Dryness and bleeding with sex and the wife says, ‘You snore too much.’”

How can we help Max now?

30 Thank you!

[email protected]

31