Transgender Medicine in Primary Care John-Paul Bettencourt, D.O., M.P.H., AAHIVS jbettencourt@fenwayhealth.org
Conflict of Interest Disclosure There are no conflicts of interest or financial relationships with a commercial entity producing healthcare-related products and/or services. The use of medications discussed in this presentation for gender affirming hormone therapy are off-label, however, their use follows current best practices and are evidencebased when possible.
http://tinyurl.com/2017unecom tinyurl.com/ 2017UNECOM
Transgender Patient Refers to a person who is born with the genetic traits of one gender but has the internalized identity of another gender This is an umbrella term that can encompass a wide range of gender identities Hill, Mel Reiff, and Jay Maya. 2011. The Gender Book
Etiology of Transgender Identity There has been research into genetics, brain anatomy and function, hormonal influences But the fact is, we just don t know. Twin studies show: ~ 30% concordance in MtF monozygotic twins ~ 23% concordance in FtM monozygotic twins (Diamond, 2013)
Transgender Demographics 1 in 11,900 natal males 1 in 30,400 natal females Some researchers estimate that the prevalence is closer to 1 in 500 (Data from the Netherlands)
Transgender Demographics Massachusetts Behavioral Risk Factor Surveillance Survey (2016) 0.4% of population identified as transgender
Why discuss this topic?
Risk Mitigation Herbst, et al. Estimating HIV Prevalence and Risk Behaviors of Transgender Persons in the United States: A Systematic Review. AIDS and Behavior Jan 2008: 12 (1): 1-17 Average HIV infection rate in MtF populations was 27.7% African American transwomen the rate was 56.3% Death rate due to AIDS was 30x higher then the general population.
Depression and Suicide Suicidal ideation rates as high as 64% 40% of transgender/gender variant individuals report having attempted suicide Suicide death rate is 600% general population 40% ATTEMPT SUICIDE (Dutch cohort) 12
One or More Negative Experiences with a Health Care Provider in the Past Year Did Not Seek Care This Past Year Due To Fear of Mistreatment
To find health should be the object of the doctor. Anyone can find disease. - A.T. Still
Lecture Goal Provide an introduction to Gender Affirming Medicine by reviewing the basics of treatment and model of care. Resulting in a better understanding and increased comfort by the medical provider when treating patients who are transgender.
OBJECTIVES 1. Discuss terminology of transgender and nonbinary gender community 2. Review Informed Consent Model of Care including team approach 3. Review common medical and surgical treatments in transgender medicine 4. Review ongoing treatment and lab work, and best practices for transgender medicine
DSM 5 December 2012: American Psychiatric Association formally replaced the diagnosis of Gender Identity Disorder with Gender Dysphoria
Gender Dysphoria The discomfort or distress that is caused by a discrepancy between a person s gender identity and that person s sex assigned at birth (and the associated gender role and secondary sex characteristics) - Coleman, SOC, V 7 p168 The focus of health care engagement is alleviating the distress.
Gender Dysphoria The goal of treatment for a transgender patient is to improve their quality of life by facilitating their transition to a physical state that more closely represents their sense of self.
Gender Affirming Medical Care
Transgender Standards of Care
WPATH Standards of Care Criteria for hormone therapy Persistent, well-documented gender dysphoria Capacity to make fully informed decisions and consent for treatment Age of majority (other WPATH SOCs for minors) If significant medical or mental health concerns are present, they must be reasonably well controlled.
Standard vs. Informed Consent Model (WPATH SOC7) Standard Model of Care: Initiation of hormone Rx after psychosocial assessment by qualified mental health professional Recommendation for team care or collaborative model Psychotherapy not required (but available) Medical provider experienced with hormone treatment Informed consent
Informed Consent Model (Deutsch, 2012) Requires the healthcare provider to effectively communicate benefits, risks and alternatives of treatment to patient Requires the healthcare provider to judge that the patient is able to understand and consent to the treatment Informed consent model does not preclude mental health care Recognizes that prescribing decision ultimately rests with clinical judgment of provider working together with the patient Informed consent is not equivalent to treatment on demand
A Continuation of Care many transgender patients have already taken self-prescribed hormones 2013 Ontario survey: 25% had ever used and 6.4% were currently using 2009 NYC study: 23% of transwomen currently using 2007 Virginia Trans Health Initiative Survey: 60% of transwomen & 23% of transmen had ever used
Transgender Health Program
The Crew Patient Captain You determine the goals, rate, and method of transition Dr. Bettencourt Navigator Monitors medical course with labs/physical exam/etc., and determines medically appropriate route to travel (prescribes treatment only when medically appropriate) Team Nurse Assists with medical questions Transhealth Patient Advocate Assists with non-medical questions including insurance options Team Behavioral Health Specialist Assists with Behavioral Health aspects of transitioning Team Medical Case Manager Assists with paperwork (name/gender change forms, etc.) Support Groups (See Fenway Health webpage for complete list) Support for Non-transgender Partners of Transgender People Drop-In Night for Parents and Guardians of Transgender Young People Fenway Health Drop-In Transgender Peer Support Group
Initial Visits Review history of gender experience Document prior hormone use Obtain sexual history Review patient goals Address safety concerns Assess social support system Assess readiness for gender transition Review risks and benefits of hormone therapy Obtain informed consent Order screening laboratory studies Provide referrals
Follow-up Visits Assess masculinization/feminization Review medication use Monitor mood cycles and adjust medication as indicated Discuss social impact of transition Counsel regarding sexual activity Review surgical options Plan change of name and gender marker on legal forms Review risk factors ASSESS SAFETY
Response to Hormone Therapy Heredity and age limit the tissue response to hormones More is not always better
Transgender Men Treatment Options Aydian Dowling is the first Trans Person on Men's Health Cover.
Female to Male Treatment Options Injectable Testosterone Testosterone Enanthate or Cypionate IM or SC q 1 or 2 weeks, standard dose is 50 100 mg weekly Testosterone undeconoate (Aveed) 750 mg initial, 4 weeks, then q 10 weeks Transdermal Testosterone Androderm (2 and 4 mg patches) 2-8mg daily Gels (packets/pumps), 50 100 mg daily, Androgel pump 1.62% gives 20.25 mg /pump, Androgel or Testim packets provide 25 mg (2.5 gm) or 50 mg (5 gm) Axiron 2% pump gel for axillary application 1 pump (30 mg) to each axilla daily Testosterone Pellet Testopel- implant 6-10 pellets q 3 to 6 months Striant 30 mg buccal system q 12 hours Buccal Testosterone
Other Tx Considerations for FtM Testosterone cream in aquaphor for clitoral enlargement Estrogen vaginal cream for atrophy Rogaine or Finasteride for male pattern baldness Use of Progesterone may help to reduce estrogen levels and aid in cessation of menses before or after starting testosterone therapy.
Masculinizing Effects of Testosterone Onset Maximum Effect (months) (years) Skin oiliness/acne 1-6 1-2 Fat redistribution 1-6 2-5 Cessation of Menses 2-6? Vaginal atrophy 3-6 1-2 Clitoral enlargement Permanent change 3-6 1-2 Deepening of voice Permanent change 3-12 1-2 Facial/Body Hair Growth Permanent change 6-12 4-5 Scalp Hair Loss Permanent change 6-12? Increased Muscle Mass & Strength 6-12 2-5 Emotional changes Increased sex drive Coarser Skin/ Increased Sweating Weight Gain/Fluid Retention Mild Breast Atrophy Weakening of Tendons
Selected Drug Interactions - Testosterone Increases the anticoagulant effect of warfarin Increases clearance of propranolol Increases the effects of sulfonylureas
Risks of Testosterone Therapy Lower HDL and Elevated triglycerides Increased homocysteine levels Polycythemia Possible worsened migraine Variable effects on mood / Mental health? Increased risk of sleep apnea Chronic pelvic pain (Hepatotoxicity) Infertility Male pattern baldness Unknown effects on breast, endometrial, ovarian tissues
FtM Health Considerations Bone Health Most studies show no change or an increase in bone mass after initiating testosterone therapy Increased muscle mass / mechanical loading Role of aromatization of testosterone to estrogen Diabetes Higher prevalence compared to control group of natal men and women. About half the cases diagnosed BEFORE starting hormone therapy (Wierckx 2013) Lifestyle? PCOS High rates reported in transgender men Unclear how testosterone therapy impacts this
Clinical Risks for Transmale Patient Gooren, et al (2008): Despite changes in CAD risk factors, NO increase in cardiovascular morbidity and mortality in 876 FtM patients. Asscherman, et al (2011): 365 FtM, 18 years median follow-up. No difference in overall or cause-specific mortality Only 1 MI in 72 y/o patient on T for 42 years No increase in over-all cancer mortality, no breast CA 1 death by illicit drug use
Recommended Laboratory Monitoring These are recommended tests and do not substitute for the clinical judgment of the physician.
Laboratory Monitoring for FtM Patients on Testosterone CBC (Hgb/Hct) Baseline Lipid Profile, only as clinically indicated Liver Enzymes, only if evidence of underlying liver disease Fasting Glucose, only if clinically indicated? Screen for PCOS
Laboratory Monitoring for FtM Patients on Testosterone After 3-6 months, then every 6-12 months CBC Every 6-12 months Lipid Profile, as indicated HgbA1c, as indicated Serum Testosterone Goal: Serum Estradiol Goal: Serum testosterone levels 6-12 wk after dosage change, At 6-12 months, Then as indicated 350-700 ng/dl (<50 pg/ml) Estradiol levels?
Primary Care for Transmasculine Individuals Pap smears As per guidelines for ciswomen Testosterone can cause atrophy of the cervical epithelium mimicking dysplasia Increase in unsatisfactory samples 10x higher than in natal women)) Longer latency to follow-up testing (Potter, 2014) Endometrial hyperplasia Hysterectomy for 1 prevention of endometrial cancer is not recommended nor routine screening with ultrasound Unexplained bleeding should be explored / patients need to inform providers Mammograms and CBE As per natal females, if no chest reconstruction If post-op no reliable screening recommendations - yearly chest exams?
Transgender Men Treatment Options
Male to Female Treatment Options Oral Estrogens Estradiol (estrace) 2-8 mg PO or SL daily (can be divided into BID dosing) Premarin (conjugated estrogens) 1.25-10mg PO daily (can be divided into BID dosing) Transdermal Estrogens Estradiol patch 0.1-0.4mg total weekly dose (some patches are twice weekly application) May start lower in patients at risk of side effects. Maximum single dose patch available is 0.1 mg Injectable Estrogens Estradiol valerate 5-20mg IM q 2 weeks Estradiol cypionate 2-10mg IM weekly Antiandrogens Spironolactone (aldactone) 50-400mg PO daily (can be divided into BID dosing) Finasteride (Proscar) 2.5-5mg PO daily
Other (Not Used) MtF Options Cyproterone Acetate (not available in US) GnRH agonist: Goserelin Acetate, Leuprolide Flutamide an androgen receptor blocker, associated with severe liver toxicity Bicalutamide (Casodex), used in treatment of prostate CA,? Less liver toxicity, still with anecdotal reports of severe liver toxicity
Male to Female Treatment Options Progestins: Questionable benefit on breast development, mood, sexual function associated with increased risk of cardiovascular events and breast cancer in WHI as well as increased risk of weight gain and depression. Wierckx K, Gooren L, and T Sjoen G. (2014) Clinical review: Breast development in trans women receiving cross-sex hormones. J Sex Med 2014;11:1240 1247.
Male to Female Treatment Options Hydroquinone Topical treatment for pigmentation caused by estrogen therapy Hair Removal Eflornithine (Vaniqa) cream Electrolysis Laser hair removal
Feminizing Effects of Estrogens & Antiandrogens Effect Onset (months) Maximum (months) Decreased Libido 1-3 3-6 Decreased Spontaneous Erections?? Breast Growth Permanent Change 3-6 24-36 Decreased Testicular Volume Permanent Change 3-6 24-36 Decreased Sperm Production Permanent Change Unknown Unknown Redistribution of Body Fat 3-6 24-36 Decrease in Muscle Mass 3-6 12-24 Softening of Skin 3-6 Unknown Decreased Terminal Hair 6-12 >36 NOTE: Possible slowing or cessation of scalp hair loss, but no regrowth No change in voice from hormone therapy
Risks of Estrogen Therapy Venous thrombosis/ thromboembolism Increased risk of cardiovascular disease Weight gain Decreased libido Hypertriglyceridemia Elevated blood pressure Decreased glucose tolerance Gallbladder disease Benign pituitary prolactinoma Mental health effects? Breast cancer Infertility
Risks of Spironolactone Therapy Increased urinary frequency Hyperkalemia Hypotension Renal insufficiency
Drug Interactions Estradiol, Ethinyl Estradiol, Testosterone levels are INCREASED by: Nefazodone Fluvoxamine Indinavir Sertraline Diltiazem Cimetidine Itraconazole Fluconazole Clarithromycin Grapefruit Isoniazid Fluoxetine Efavirenz Paroxetine Verapamil Astemizole Ketoconazole Miconazole Erythromycin Triacetyloleandomycin Estradiol, Ethinyl Estradiol, Testosterone levels are DECREASED by: Lopinavir Rifampin Phenytoin Carbamazepine Progesterone Phenobarbital Dexamethasone Phenylbutazone Naphthoflavone Benzoflavone Sulfamide Sulfinpyrazone
Drug Interactions Estrogen levels are DECREASED by: Smoking cigarettes Nelfinavir Nevirapine Ritonavir Estrogen levels are INCREASED by: Vitamin C
Clinical Risks for Transfemale Patient Venous ThromboEmbolism In the Dutch cohorts: Annual VTE rates of 2.6% in first year, falling to 0.4% thereafter 1-2% risk of death from PE All but 1 of these patients was using oral ethinyl estradiol Belgian cohorts also showed increased incidence of VT (6-8%) also associated with ethinyl estradiol Asschemann (2014) (9 centers) showed increase in risk of about 18/10,000 patient-years 54
Clinical Risks for Transfemale Patient Diabetes Studies have shown decreased insulin sensitivity in transwomen treated with estrogen (Elbers 2003) Higher prevalence of DM compared to controls, but almost all diagnoses made BEFORE starting estrogen therapy (Wierckx 2013) Retrospective Dutch Study: All-cause mortality was 51% higher than in the general population Overwhelming majority of the difference due to HIV, drug overdose and suicide a 64% increased risk in cardiovascular mortality, however no significant difference was seen for cerebrovascular mortality (Asscheman, 2011)
Clinical Risks for Transfemale Patient Prolactinoma 5 cases of prolactinomas have been found in MTF patients 10mo, 14, 18, 20, and 30 years after initiation of hormone tx So, unclear when and how long to monitor, since this is quite rare (Bunck 2009, Cunha 2015) 56
Lab Monitoring for MtF Patients Baseline: Renal panel, if on spironolactone Lipids, if indicated clinically Fasting Glucose, if indicated clinically Testosterone level, if suspicion for hypogonadism Prolactin level, if on medication or sx of prolactinoma Liver Enzymes, if suspicion for underlying liver disease
Lab Monitoring for MtF Patients If on spironolactone, serum electrolytes 1 to 6 weeks after start/dosage change, then every 3 months in first year, then yearly Lipids, glucose, LFTs only as clinically indicated Prolactin level?? Hgb/Hct will often drop into the lab-normal female range Serum testosterone level (at 6 to 12 months) Goal <55 ng/dl Serum Estradiol Levels (?) Goal 100 to 200 pg/ml)
Primary Care for Transfeminine Individuals Pelvic exam Pelvic exam to assess surgical site, and then follow ups for general genital issues or concerns No cervix = no Pap ( Agenesis of cervix ) The ph and microflora of the neo-vagina differs significantly from a natal vagina Lack of lactobacilli Alkaline environment Mixed microflora of aerobe and anaerobe species More complex BV specifically presence of anaerobes difficult to treat (Consider clindamycin) NO candida seen No formal recommendation on optimal vaginal hygiene, but some speculate best to douche with warm water alone, if anything at all
Primary Care for Transfeminine Individuals Mammography and CBE Patients age >50 who have been on feminizing endocrine agents over 5 years -? 1 or 2yr intervals NO increase in incidence of malignancy compared with cismen, BUT patients had cancers that were the detected late with poorer outcomes (Brown 2014) WHI: Progestin, with estrogen, increases risk of breast cancer Prostate cancer screening As per cismen Androgen antagonists may falsely decrease serum PSA levels Feminizing hormonal therapy appears to decrease prostate volume and the risk of prostate cancer but to an unknown degree 3 reported cases of prostate cancer in the Dutch cohort (2011). All had started hormone therapy AFTER age 40.
Primary Care for Transfeminine Individuals Bone Scan: Consider >age 65 and/or having stopped estrogen therapy for longer than 5 years not routinely indicated prior to orchiectomy
Use only estradiol Recommendations for Transfemale Patient Consider transdermal or low-dose oral estradiol in patients >40yrs old (and daily ASA) Attention to lifestyle factors: healthy diet, smoking cessation, exercise can reduce cardiovascular risk! https://www.kidney.org/atoz/content/potassium
Surgical Treatments Masculinizing phalloplasty/scrotoplasty Metaoidioplasty (clitoral release/enlargement, may include urethral lengthening) Masculinizing chest surgery ("top" surgery) Voice surgery Hysterectomy/oopherectomy Vaginectomy Voice modification Facial hair removal Feminizing vaginoplasty Orchiectomy Augmentation mammoplasty Facial feminization procedures Reduction thyrochondroplasty (tracheal cartilege shave) Genital tucking and packing Chest binding
De-Transitioning 2015 US Trans Survey: 8% of respondents reported having de-transitioned at some point in time 5%: gender transition was not for them 4%: initial transition did not reflect the complexity of their gender identity 2%: for medical reasons Most common reason - pressure from other persons or issues connected with social transition
Is cross-sex hormone therapy effective? 94% of trans individuals reported an improvement in their quality of life 96% answered that their sense of wellbeing improved 85% described their emotional stability as improved and 11% reported no change Close, Colin, Affirming Gender, Affirming lives: A report of the 2011 Transition Survey. Santa Rosa, CA: GATE, 2012.
Additional Resources http://www.lgbthealtheducation.org http://www.wpath.org Endocrine Society Clinical guidelines Published: September 2017 https://doi.org/10.1210/jc.2017-01658 UCSF Center of Excellence for Transgender Health http://transhealth.ucsf.edu/
Fenway Health Trans Health Program Tim Cavanaugh, MD Fenway Health Transgender Health Program Medical Director Ruben Hopwood, PhD Fenway Health Transgender Health Program Coordinator Cei Lambert Fenway Health Transgender Health Program Patient Advocate http://fenwayhealth.org/care/medical/transgender-health/ 857-313-6589 transhealth@fenwayhealth.org
Thank you The Person is a unit of Mind, Body, and Spirit