Treatment modalities for Gender transitioning in people living with HIV

Transcription

1 Treatment modalities for Gender transitioning in people living with HIV LAURA BEAUCHAMPS, MD ASSISTANT PROFESSOR, DIVISION OF INFECTIOUS DISEASE UNIVERSITY OF MISSISSIPPI MEDICAL CENTER MEDICAL DIRECTOR OPEN ARM HEALTHCARE CENTER

2 The term: Transgender describes persons whose current gender identity differs from their sex at birth

3 Basic GenderTerminology SEX refers to a person s physical body, it s chromosomal and anatomical characteristics; male/female. GENDER describes a person s feeling of being male or female, regardless of biology (what s in the brain vs the genitals). SELF-IDENTITY a process of how one view s oneself. Develops over lifetime, more rapid formation from childhood to young adulthood. Shaped by social interactions and cognitive processing of experiences and feelings. GENDER IDENTITY is the sense of oneself as girl/woman, boy/ man. Refers to actions, ways of interacting, how one feels about oneself. GENDER ROLE the roles, attitudes and feelings that society considers appropriate for being a male or female.

4 Alternative Constructs of Gender Identity: Terminology Follows Concept Identity Begins Here Identity Begins Here Medical Construct: Gender Reassignment Or Transitioning Patient Centered Construct: Gender Affirmation

5 Basic gender terminology TRANSGENDER an umbrella term feelings or behaviors do not match assigned gender MALE TO FEMALE TRANSGENDER = transwoman FEMALE TO MALE TRANSGENDER = transman CROSSDRESSER (for entertainment, sexual gratification) DRAG QUEEN/KING GENDERQUEER gender is fluid, not male or female

6 Cultural perspectives Cross gendered behaviors documented from beginning of time. Varying societal reaction/acceptance. Native American respect for gender fluidity. The Two Spirit people---both male and female spirits within one person. The mahu of Hawaii Hirjas of modern India Castrati of Europe

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9 Why are HIV providers caring for transgender persons? Fully transitioned person may no longer identify as TG, but as the reassigned sex Trans-inclusive data collection proposed asks sex assigned at birth and current gender The transgender population of the US is estimated at High rates of HIV in transgender persons in US 1 in 5 being hardest hit by HIV (CDC) HIV is not a contraindication for gender transitioning treatments While drug-drug interaction may occur, non are dangerous Treatment with hormones is an incentive for patients to address HIV disease

10 Health Disparities -Lifetime prevalence of suicide attempts among transgender adults is estimated to be as high as 41% o compared to less than 9% among the general U.S. population o and approximately 10-20% among lesbian, gay, and bisexual (LGB) adults. -From recent meta-analysis HIV prevalence among transgender women across 15 countries was 19.1% o In high income countries: 21.6% o In low-income and middle-income countries: 17.7% Stefan D Baral, Tonia Poteat, Worldwide burden of HIV in transgender women: a systematic review and meta-analysis, 2012, The Lancet

11 Barriers to care No safe way to identify TG status Assumed under LGBT umbrella Lack of TG in population based research Lack of provider knowledge ( around 50% have to teach provider) If no ID, can t get care, job, insurance Refusal to provide hormones Previous negative experiences

12 Health care staff competency on transgender issues TG friendly practice environment Unisex restrooms Frequent Transgender 101 trainings for all staff including front desk personnel Awareness on handling depression and suicidal calls. Including knowledge of transgender suicide hotline phone number EHR and nickname or AKA Simple addition of 1-hour lecture to the standard medical school curriculum at Boston University School of Medicine increased student s willingness to treat transgender patients (Safer et al Endocrine Pract 2013)

13 Open Arms Health Care Center Community Health Care Organization caring for LGBT community, HIV prevention and care Located in Jackson, Mississippi (only on in the state) Academic-Community relationship with UMMC Opened February NP, 2 MDs, 2 nurses, 1 Mental Health Provider, 2 case managers Cares for 96 transgender individuals. 50 MTF and 46 FTM. From these 13 are living with HIV 22% of MTF are on PrEP (8) HIV Ryan White Clinic opened July Also provide HIV care for insured patients.

14 Percent Demographic Characteristics (n=20) MTF / FTM (Gender Identity) AA / White (Race) Yes / No (Current Employment) Yes / No (Current Insurance) HIV + / HIV - diagnosis) (HIV Mean age 25.5 years and ranging from 18 to 49 years

15 Case 1 43 y/o HIV-positive transgender woman has approached you regarding hormonal feminization. She wants to go all the way with feminization but she desires to continue having erectile function until she can have surgery. She has been feeling more hungry lately and she is also concerned about gain weight gain on hormones PMH: Hypertension Hyperlipidemia Type II DM HIV diagnosed 5 years ago, no hx of OI, CD4 nadir 250 cells/ul Anemia

16 Case 1 BP: 125/75 HR: 80 T: 98.6 WT: 160lbs HT: 5 9 RR:16 CD4: 400 HIV RNA: <20 Hgb: 12 Plt: 150 Glu: 134 (fasting) Medications: HCTZ 25mg PO Qdaily Benazepril 5mg PO dialy Pravastatin 40mg PO QHS Glipizide 5mg PO BID Truvada, atazanavir 300mg and norvir 100mg daily Social hx: Smokes tobacco 0.5 packs/day, 1 bowl of MJ QHS Occ ETOH (1 beer 3x week) with occasional binge drinking (1 weekend/3 months) Not in a relationship currently, has both male and female sex partners, occasional condom use but not consistent

17 Case 1: answers??

18 When with provider 10 things transgender people should discuss with their provider 9 : 1. Access to healthcare 2. Health history 3. Hormones 4. Cardiovascular health 5. Cancer 6. HIV, STDs, and safer sex 7. Alcohol and tobacco 8. Depression/anxiety 9. Injectable silicone 10. Fitness (diet & exercise)

19 What the protocols say Hormone therapy best given in the context of primary/hiv care Psychotherapy not required TG experienced therapist available as needed---adjustment to physical and psychosocial changes Hormones can be Rx d by family MD/NP/PA with experience Not necessary to refer to endocrine More is not better or faster: effects may not be evident until 2 years of continuous tx. Hereditary limits the tissue response and cannot be overcome by increasing dose The Harry Benjamin International Gender Dysphoria Association s Standards of Care For Gender Identity Disorders

20 Basic Primary Care Principles Patient s decide gender identity Use their preferred name/pronoun What to do if unsure? If you have it, check it Affirmed woman will still have a prostate gland Does an affirmed man still have his uterus and ovaries? When guidelines conflict in regard to gender or anatomy, use the more conservative guideline

21 Follow up and Health Maintenance If there is an organ there, screen it. Prostate exam for transwoman (DRE) If neovagina from colon mucosa, screen for colon cancer Pap smear as for natal female if glans penis used to construct vagina (especially if hx of HPV) Screening mammogram for >50 years of age, >5 years of estrogen use, positive family hx, BMI >35. Cross-sex hormones do not increase the risk of breast cancer development in either MTF or FTM Generally the follow up schedule for visits and labs for HIV are sufficient Every visit screen for adverse effects of hormones Stop all estrogens 2 weeks prior to any major surgery or immobilizing event and resume one week after resumption of mobility Add ASA mg for all patients at risk for thromboembolism (tobacco, >40 y/o, obese, cardiac risk factors

22 Clinical care Nonoperative 80% never able to have surgery Choice-- Cost prohibitive In U.S., insurance does not cover, but this is changing Some insurance plans in CA deem surgery as medically necessary Preoperative planning surgery a little or a lot Castration reduces need for hormones. The only surgery for some. Postoperative can decrease hormones by half

23 Spectrum of transitioning Dressing in the preferred gender Hormones without surgery Hormones and surgery Castration, penectomy, neovagina, labiaplasty, breast augmentation, tracheal shave, facial feminization Other Hair removal (electrolysis only permanent option), voice training, fat transfer

24 Sex Reassignment Surgery (SRS) HIV not a contraindication to surgery CD4>400, viral load undetectable (Bowers) Breast augmentation after 18 months on hormones to achieve max hormonal development Genital surgery one year of real life experience Letter from mental health professional attesting to readiness

25 Informed consent Mental health counselors Is there a sound sense of gender identity? Mental stability to make major decisions? Uncontrolled mental health issues? Can understand risks/benefits to make informed choice? Coping skills? Support system?

26 Progress on the road to better medical care for transgender patients. Gardner, Ivy; Safer, Joshua Current Opinion in Endocrinology, Diabetes & Obesity. 20(6): , December DOI: /01.med d Box 1. no caption available 2013 Wolters Kluwer Health Lippincott Williams & Wilkins. Published by Lippincott Williams & Wilkins, Inc. 2

27 Female hormones: changes Breast development Softening of the skin Body fat redistribution Decreased muscle mass, especially upper extremities Cessation of male pattern baldness Atrophy of genitals, especially testicles Decreased body hair Decreased libido Decreased/loss of fertility Feeling of well being

28 Estrogens: What to use Try to avoid first pass through liver effect: sublingual, transdermal or injection. (not done with PO formulations like conjugated estrogens like Premarin: >depression) PO estradiol 2-4 mg per day can be given SL and it s cheap. (eg, Estrace) Transdermal 0.1 to 0.2 mg/24 hr applied 2x/week (eg, Estradot): Estradiol valerate 20 to 40 mg every 2 week IM (least preferred due to high and low levels) (eg, Delestrogen) Precautions: hyperlipidemia, DM, tobacco use, hepatitis, alcoholic liver disease, renal insufficiency, migraine, seizure disorder, retinopathy, strong family history of breast cancer or any other estrogen dependent tumor Ethinyl estradiol (PO) is not safe: longer action, increase risk for complications. SHOULD not be considered for males over 40 y/o or those with clotting abnormalities or hx of DVT

29 Progestins Use is controversial Allows full nipple development, +/- Adverse effects profile concerning (CAD, lipid changes, pulmonary embolism, stroke, breast cancer) Increases libido (for some, a descreased libido is desired) Provera 5-30 mg/day. Depo-provera 200 mg IM q 3 months

30 Androgen antagonists Testosterone blocker Those wanting an androgynous appearance may use this alone Most often used along with estrogen Allows for lower estrogen dose (when adverse estrogen side effects anticipated) Helpful in decreasing body hair Caution with renal problems, if on ACE-I or ARB due to hyperkalemia potential Spironolactone 100 to 200 mg/day (eg, Aldactone) avoid use with digoxin Finasteride: Propecia or Proscar conversion of testosterone to DHT. 5-10mg daily GnRn agonists: nafarelin acetate, goserelin acetate and leunrorelin acetate: desensitize pituitary fully reversible effects (good for adolescence to stall changes of puberty) No signs of demasculinization: Testosterone level at 6 months

31 Table 2 Progress on the road to better medical care for transgender patients. Gardner, Ivy; Safer, Joshua Current Opinion in Endocrinology, Diabetes & Obesity. 20(6): , December DOI: /01.med d Table 2 Hormone regimes for transgender women (MTF) 2013 Wolters Kluwer Health Lippincott Williams & Wilkins. Published by Lippincott Williams & Wilkins, Inc. 4

32 Contraindications to use of female hormones Estrogen-dependent cancer Pituitary tumor Severe cardiomyopathy, hypertension, uncontrolled History of thromboembolic event History of CVA Severe mental problems Assessment of cardiovascular risk: lower doses of estrogen (more not better) Bilateral nonarteritic ischemic optic neuropathy due to excessive estrogen dosage Wierckx et al, Arch sexual behavior 2014

33 Bilateral Orchiectomy For intolerant of other anti-androgen therapy Less anti-androgen Tx, since 90% come from testosterone come from testicles Irreversibility and potential scarring (sometimes scrotal tissue is used to create labia and give depth to neovagina) After orchiectomy a maintenance dose of Estrogen is needed also to prevent osteoporosis Estrogen doses in post-orchiectomy can often be reduced by 1/3 to ½ and still maintain feminization

34 Laboratory MTF: Pre treatment free testosterone level, fasting glucose, LFT, CBC, lipid panel, prolactin level, Hepatitis screen, RPR, Testosterone and estrogen levels Recheck 1-2 months after starting, 3 months after changing dose Patients are seen quarterly include STD screening with extragenital NAAT swabs for GC/CT Prolactin level at 1, 2 and 3 years: prolactin level will be significantly elevated for 1 year before an adenoma become autonomous and enlarged FTM: LFT, CBC, Yearly Testosterone level used selectively and rarely but can be ordered if not showing masculinization after 6-12 months on maximum dose

35 Gender conforming Hormones with HAART Little has been reported on interactions Testosterone has been used relatively safely for hypogonadal natal males on HAART without evidence of drug interaction Estradiol: Studies in HIV natal females taking contraceptive (at a much lower dose than a TW would take) show significant changes in estradiol levels when used in combination with NNRTI s and PI s but not with other HAART classes.

36 Contraceptive Patch/Implanon in HIV positive women ACTG trial Lopinavir/ritonavir and transdermal contraceptive patch (EE/NGM) Compared with women not taking PI demonstrated a 45% decrease in AUC of EE (P= 0.064) 83% increase in AUC of norelgestromin in treatment with PI arm. Numerous case reports of contraceptive failure in women taking efavirenz who have the ENG implant Data on DMPA Depot and Levonorgestrel IUS are reassuring effective contraceptive methods in conjunction with ARV s. Robinson et al, Contraception for HIV-positive woman: A review of Interactions between Hormonal Contraception and Antiretroviral Therapy. Infectious Diseases in Obstetrics and Gynecology, 2012

37 Hormones and HAART Decrease estrogen level with nevirapine, and efavirenz Etravirine and rilpivirine are safe to use with HRT Atazanavir increases estrogen levels All PI boosted with ritonavir decrease ethinyl estradiol level by 37-48% (attributed to cytochrome P-450 enzymes induction) Atazanavir can be given with 35ug No significant effects with CCR5 inhibitors or Integrase inhibitors. Elvitegravir +COBI: give with at least 30ug (concentration of hormone can be reduced) Oral contraceptives are not known to induce or inhibit UGT1A1 or CYP3A4

38 Pharmacokinetic Effects of Seleccted ARVs on Oral Contraceptives Antiretroviral Class Ritonavir-boosted PIs Non-boosted PIs NNRTI Boosted integrase inhibitors Some combination regimens including a PI and a NNRTI Observed drugs in class Fosamprenavir/ritonavir Lopinavir/ritonavir Atazanavir/ritonavir Darunavir/ritonavir Tipranavir/ritonavir Atazanavir Fosamprenavir Nevirapine Etravirine Rilpivirine Elvitegravir/cobicistat Observed impact on pharmacokinetics of coadministered oral contraceptive Decreased ethinyl estradiol by up to 48% Increases ethinyl estradiol up to 48% Can show decreased or increased plasma concentrations of ethinyl estradiol estrogen or norethindrone. norgestimate ethinyl estradiol Can yield complicated pharmacokinetic impact.

39 Dolutegravir has no effect on PK of oral contraceptives with Norgestimate and Ethinyl Estradiol No Cytochrome P450 Randomized, 2 period, double blind, placebo-controlled, 16 women enrolled. NGM0.25mg/EE0.035mg Days 1-10 BID Dolutegravir 50mg or matching placebo and switched to other treatment during days AUC, maximum plasma concentration and concentration at the end of the dosage interval for both NGM and EE were same in both groups. DTG had no effect with the PK and PD Also No significant differences in luteinizing hormone, follicle-stimulating hormone and progesterone seen Song et al, Annals of pharmacotherapy, 2015

40 STD risk reduction for Transwomen Transwomen engage in unprotected anal receptive sex (in urban areas like San Francisco) Clements-Noelle, 2008 Men will pay more for commercial sex workers who don t use condoms Employment discrimination, need for validation, unconscious re-enactment of previous sexual trauma can result in sex work and survival sex/sex drug exchanges Referrals can help ongoing risk reduction interventions: Employment assistance Substance abuse treatments Psychological counseling

41 Case 1 A/P Diet Exercise Medication adherence Switch HAART regimen: add integrase inhibitor Counsel on STD screening: genital, extragenital and Hep C infection (sexually transmitted/iv drug use) Follow HRT lab monitoring and review side effects quarterly

42 Case 2 32 y/o transman comes to your office with a list of concerns. On testosterone x 10 months, female partner for 4 years, no tobacco or alcohol. His list is as follows: 1. New attraction to men-why? 2. Vaginal bleeding after vaginal penetration by female partner 3. Feeling depressed 4. low back pain from testosterone 5. Chest surgery next week-letter 6. My other doctor told me my blood is too thick and I need to stop it

43 Case 2 cont Weight: 158 GU: enlarged clitoris, vaginal wall smooth, cervix with stenotic os/nonfriable. Back- tender paraspinal muscles in lumbar region, no bony tenderness HCT: 49, Tot Chol-209, LDL-155, HDL-32

44 Transman treated with Testosterone Deepening of the voice Clitoral enlargement Mild breast atrophy Increased facial and body hair Male pattern baldness Cessation of menses Erythrocytosis Potentiation of warfarin, dec blood sugars Reversible changes: increased upper body strength, weight gain, increased social and sexual interest and arousability and decreased hip fat Transdermal testosterone is an option if no injectable desired Testosterone doses post-oophorectomy should be considered, taking into account the risks of osteoporosis

45 Table 1 Progress on the road to better medical care for transgender patients. Gardner, Ivy; Safer, Joshua Current Opinion in Endocrinology, Diabetes & Obesity. 20(6): , December DOI: /01.med d Table 1 Hormone regimes for transgender men (female to men) 2013 Wolters Kluwer Health Lippincott Williams & Wilkins. Published by Lippincott Williams & Wilkins, Inc. 3

46 STD risk reduction for transmen FTM who have sex with women do not see themselves at risk May place themselves at risk: not using condoms or latex barriers fearing lack of acceptance by women, gay or bi men mean of compensating for body image to avoid rejection In response to survivor guilt for not being exposed to HIV/AIDS due to not being OUT in gay community in the earlier periods of AIDS pandemic Testosterone causes vaginal dryness and with intercourse can create more viable host for STD transmission

47 Cardiovascular disease in transsexual persons treated with cross-sex hormones Reversal of the traditional sex difference in cardiovascular disease pattern Exposure of testosterone in transmen not associated with a strong increase in cardiovascular events Aging and pre-existing cardiovascular pathology contributes to the CV risk in Transwomen Use of synthetic biopotent ethinyl estradiol in a dose 2-4 times of OCP increases CV risk substantially The route of administration of estrogens (oral vs transdermal ) impacts on the risks Gooren et al, European Journal of Endocrinology, 2014

48 HIV Diagnoses and Care Among Transgender Persons and Comparison With Men Who Have Sex With Men: New York City, transgender persons among all persons newly diagnosed with HIV in NYC between January 2006 and December 2011 Representing 1% of all new diagnoses Most were transgender women, and most reported sex with males Compared with MSM newly diagnosed in the same interval, transgender women were equally likely to be diagnosed with AIDS concurrently and to have timely linkage to care but less likely to achieve viral suppression (1) 1. Wiewel et al, ajph Dec 2015

49 Bone Health Endogenous estrogens and androgens protect against osteoporosis Maintain physiologic levels BMD for post orchiectomy on no hormones BMD screening before starting on feminizing hormones for patients AT RISK for osteoporosis only, Otherwise start screening at age 60 or earlier if sex hormones levels are consistently low Tom Waddel Health Center. Protocols for Hormonal Reassignment of Gender, 2013 Gardner and Safer, Progress in medical care for transgender patients, 2013

50 Risk Behavior and Sexually Transmitted Infections Among Transgender Women and Men Undergoing Community-Based Screening for Acute and Early HIV Infection in San Diego 151 individual transgender women and 30 individual transgender men undergoing community based, voluntary screening for acute and early HIV infection (AEH) in San Diego, California between April 2008 and July 2014 HIV positivity rate was low for both, transgender women (2%) and transgender men (3%) undergoing AEH screening Although transgender women appeared to engage in higher rates of risk behavior overall, with 69% engaged in condomless receptive anal intercourse (CRAI) and 11% engaged in sex work, it is important to note that 91% of transgender women reported recent sexual intercourse, 73% had more than 1 sexual partner, 63% reported intercourse with males, 37% intercourse with males and females, and 30% had CRAI rates of HIV infection, as well as rates of reported STIs and sexual risk behavior in transgender men may resemble those found in transgender women. support the need for comprehensive HIV prevention in both, transgender women and men. Green et al, Medicine Baltimore 2015

51 HIV prevention in Transgender population Transgender specific intervention are scarce Consistent condom use with appropriate lubricants: essential Female condom. Can it be an alternative for transgender woman? PrEP: iprex include transgender participants (Thailand, Peru and Brazil), rectal microbicide More social and behavioral research clarify link between efficacy in biomedical studied and realworld effectiveness of prevention

52 Black transwomen and HIV risk Table 1. Comparison of Site-Specific Prevalence of Selected Sexually Transmitted Infections By Identification as Transwomen (TW), Among Young Black MSM Infection Prevalence TW Prevalence Non-TW RR 1 P Urethral Chlamydia 1/29 (3.4%) 31/485 (6.4%) Pharyngeal Chlamydia 5/28 (17.9%) 20/469 (4.3%) Rectal Chlamydia 8/28 (28.6) 79/457 (17.3%) Urethral Gonorrhea 1/29 (3.4%) 26/485 (5.4%) Pharyngeal Gonorrhea 6/28 (21.4%) 44/469 (9.4%) Rectal Gonorrhea 3/28 (10.7%) 63/456 (13.8%) Syphilis 7/29 (24.1%) 69/482 (14.3%)

53 Table 3. Comparison of Measures Representing Who Study Volunteers Had Sex With and Socio-economic Marginalization, By Identification as Transwomen (TW), Among Young Black MSM Infection Prevalence TW Prevalence Non-TW RR 1 P Who sex partners have been (past 90 days) Had anal sex for money/drugs 9/30 (30.0%) 36/566 (6.4%) 4.69 <.001 Had anal sex for money 9/32 (28.1%) 36/577 (6.2%) 4.53 <.001 Depend on sex partner for money, food, etc. 11/30 (36.7%) 69/562 (12.3%) 2.98 <.001 Sex partner recently released from prison 8/32 (26.7%) 10/566 (1.8%) 14.8 <.001 Had sex with a guy without knowing his name 16/30 (53.3%) 142/566 (25.1%) 2.12 <.001 Had sex once with a guy and never saw him again 17/30 (56.7%) 177/566 (31.3%) Had sex with females 8/32 (25.0%) 112/577 (19.4%) Socio-economic Marginalization (past 12 months) 2 Missed meals due to lack of money 13/32 (40.6%) 124/577 (21.5%) Had to borrow money just to get by 18/32 (56.3%) 239/577 (39.7%) Received food stamps 13/32 (40.6%) 152/577 (26.3%) No cell phone 9/32 (28.1%) 125/577 (21.7%) Ever been incarcerated 15/32 (46.9%) 149/577 (25.8%) Rate Ratio (TW Prevalence/Non-TW Prevalence) 2 With the exception of the last table entry (ever been incarcerated)

54 Case 2 A/P Discuss vaginal health Recommend yearly pap smears Diet, exercise Lower dose of testosterone bi-weekly. Follow HCT Follow hormone levels Bone scan for lower back pain

55 Resources Vancouver Coastal Health, Transcend Transgender Support and Education Society, & the Canadian Rainbow Health Coalition. (2006). Endocrine therapy for transgender adults in British Columbia: Suggested guidelines. Retrieved from Tom Waddell Health Center Transgender Team. (2013). Protocols for hormonal reassignment of gender. Retrieved from Fenway Health. (2014). Transgender health. Retrieved from World Professional Association of Transgender Health

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