Caring for Pediatric Transgender and Gender Diverse Patients

Home , Femminiello, Gender dysphoria, Lhamana, Winkte

CARING FOR PEDIATRIC TRANSGENDER AND GENDER DIVERSE PATIENTS

Rhamy Magid, MD – Department of Pediatrics Courtney LeClair, PhD – Department of Child and Adolescent Psychiatry OBJECTIVES

• Development of gender identity in children

• Diagnosis of gender dysphoria in children and the rationale for gender- affirming treatment

• Options available to children at various ages and developmental stages

• Questions we most often hear from parents HISTORY HISTORY

• Gender diverse people have existed throughout history, on every continent. HISTORY

• Gender diverse people have existed throughout history, on every continent. • Gender diversity is not a new phenomenon. • Various Native American tribes recognize and honor two-spirit persons • Zuni (Lhamana), Lakota (Winkte) • Pre-colonial Incas (Peru) worshipped a dual-gender god, and rituals honoring them were performed by third-gender shamans (Quariwarmi) • Mashoga (Kenya) includes a range of gender identities on a continuum, including gay men, but also biological men who identify as women. They often assume female gender roles and serve a crucial role in weddings. • Hijra (South Asia) consider themselves a third gender • Femminiello (Italy), kocek (Ottoman empire), sistergirls & brotherboys (Aboriginal Australia), Chuckchi (Russia) HISTORY

• In the US, understanding of gender is evolving • 2015 Fusion Millenial poll of adults age 18-34 found that the majority see gender as a spectrum, rather than as a man/woman binary TERMINOLOGY TERMINOLOGY

• Gender Identity • Internal sense of self. The gender I know I am. TERMINOLOGY

• Gender Identity • Internal sense of self. The gender I know I am. • Gender Expression • What my appearance or behavior communicates about my gender. TERMINOLOGY

• Gender Identity • Internal sense of self. The gender I know I am. • Gender Expression • What my appearance or behavior communicates about my gender. • Natal Sex/Assigned Gender • The sex assigned at birth (typically based on genitals or chromosomes). • Transgender or non-binary • When gender identity differs from gender assigned at birth. TERMINOLOGY

DEVELOPMENT OF GENDER IDENTITY IN CHILDREN

DEVELOPMENT OF GENDER IDENTITY

• By age 2-3, • Gender identity begins to emerge • Child can recognize most stereotypical gender expressions (eg, clothes, toys, appearance) • By age 3-4, • Child has a sense of their own gender identity & can use language to express it • They are aware of anatomical differences between sexes. • May start to segregate by gender • By age 4-6, • Child may associate gender with specific behaviors (“girls wear makeup”) but can modify this through exposure • Children often expressing their gender through behavior (dress, play) • By age 5-7 • Gender constancy develops • Child may develop behavior concerns if they feel their gender expression is limited or outside the “norm” DEVELOPMENT OF GENDER IDENTITY

• Age 9-12 • Puberty leads to continued gender exploration • Some gender diverse kids may begin to engage in more stereotypical masculine/feminine behaviors • Some kids may begin to express a transgender identity or explore their gender for the first time • The start of puberty can lead to significant MH concerns for transgender kids • Age 12-18 • Gender identity becomes fully developed • With hormonal/body changes, some teens realize they are transgender for the first time • Some transgender teens may have known when they were younger, but are just able to express it now • Some felt “different” as children but understand that difference better now GENDER DYSPHORIA/GENDER INCONGRUENCE GENDER DYSPHORIA

So….what is gender dysphoria? GENDER DYSPHORIA

So….what is gender dysphoria? • Distress experienced due to a conflict between the sex assigned at birth and one’s gender identity GENDER DYSPHORIA

Being transgender or gender expansive is NOT a diagnosis or disorder, but rather an identity factor.

The distress of gender dysphoria IS a concern that might be diagnosable and for which treatment exists, according to DSM-5 criteria. GENDER DYSPHORIA

PREVALENCE • Broad range of estimated prevalence(0.5% - 1.3%) • Older data based on who presented to clinics for treatment of gender dysphoria • Newer data based on population sampling • May be influenced by perceived safety of respondent • Minnesota survey of teens in 2016: 2.7% HS students identify as transgender or GNC • 2017 Harris poll of millennials found that 12% identify as transgender or gender nonconforming. GENDER DYSPHORIA

• Increased risk of depression, anxiety, behavior problems, drug abuse, alcohol abuse, self injury, suicide • 54% of TGNB youth considered suicide in the last year • 29% made an attempt RATIONALE FOR TREATMENT OF GD

• Increased risk of depression, anxiety, behavior problems, drug abuse, alcohol abuse, self injury, suicide • 54% of TGNB youth considered suicide in the last year • 29% made an attempt

• These risks are due to the chronic discrimination and stigmatization experienced by the individual, not inherent to the TGNB identity RATIONALE FOR TREATMENT OF GD

• Providing gender-affirming care improves mental and physical health • What constitutes gender-affirming care? • Medical interventions • Social transition • Family support • Legal and educational support RATIONALE FOR GENDER AFFIRMATIVE CARE

• Gender-affirming care reduces suicidal ideation and suicide attempts • Family acceptance is associated with positive mental health and reduced suicide attempts • Socially transitioned youth have similar rates of depression and anxiety as cisgender siblings and peers • Usage of youth’s chosen name reduces suicidal ideation RATIONALE FOR TREATMENT OF GD

• Puberty suppression is associated with improvement in behavior problems and overall psychological functioning, as well as lower lifetime suicidal ideation • Hormone therapy is associated with reduced emotional and behavioral problems and decreased suicidality TREATMENT OPTIONS TREATMENT OPTIONS

• Guidelines and Standards • WPATH Standards of Care (currently v7; v8 in the works) • Endocrine Society Guidelines (updated 2017) TREATMENT OPTIONS

• Pre-adolescent (Tanner stage 1) • No medical treatment indicated • Support, support, support • Social transition • social transition does not have to be permanent • You can also express gender-variant behavior without fully socially transitioning TREATMENT OPTIONS

• Early adolescent (>= Tanner stage 2) • Puberty suppression with a GnRH agonist Fully reversible • Leuprolide • Histrelin • spironolactone TREATMENT OPTIONS

• Early adolescent (>= Tanner stage 2) • Puberty suppression with a GnRH agonist Fully reversible • Leuprolide • Histrelin • spironolactone

• Adolescent • Hormone therapy Partially reversible • Estradiol • Testosterone 222 PUBERTY SUPPRESSIONRev Endocr Metab Disord (2018) 19:221–225 Table 1 unwanted sexual characteristics and their typical age of presentation

Unwanted male secondary sexual characteristics Unwanted female secondary sexual characteristics

Type Tanner stage of development Type Tanner stage of development (Typical age in years) (Typical age in years)

Lower pitch voice T3 (13–14) Breast enlargement (requiring compression clothing) T3–5(11–14) Adam’sapple T4(14–16) Female body habitus T4–5(12–14) Prominent jaw T4–5(15–18) Menstruation T5 (12–13) Larger hands and feet Broadened shoulders Coarser facial and body hair

such as approach. In the recent past, successful early puberty Current treatment with parenteral GnRH agonists is offered blockage has been demonstrated to allow time for the proper in a variety of ways, from yearly surgically implanted subcu- psychological evaluation of patients as they first present to taneous device, to injectable versions given either monthly or medical care [21], improve functioning in several cognitive every 3 months or twice a year [37–39]. Benefits of the intra- and social domains in gender dysphoric adolescents undergo- muscular (IM) injectable GnRH agonists compared to the sur- ing treatment [22], and facilitate achieving more desirable gically implanted one include ease of administration, avoid- cosmetic results after full physical transition [23]. ance of anesthesia complications, as well as relatively quick recovery of the Hypothalamic Pituitary Gonadal (HPG) axis upon discontinuation. The advantages of the implantable 2 Treatment options GnRH agonists are the avoidance of repeated IM injections, less frequent need for administration, and the extended sup- Treatment for puberty suppression should start as early as one pression of the HPG axis past the licensed approved duration achieves Tanner 2 staging on pubertal exam (i.e. breast bud- of 1 year (reports suggest one implant can inhibit the axis for ding for natal females and testicular enlargement more than up to 2 years) [40]. It is noteworthy that a newer version of an 4 cm in natal males) and detectable LH levels [24]. First line intramuscular depot GnRH agonist given twice a year has treatment for pubertal suppression are GnRH analogs [24, 25], been FDA approved for use in central precocious puberty much due to their success in treating gonadotropin-dependent [41]. The efficacy of this dose has not yet been compared with precocious puberty [26]. Initiation of therapy produces a de- the monthly or three-monthly depot preparations, and to-date crease in gonadotropins (Luteinizing Hormone and Follicle there have been no published data regarding its use in the Stimulating Hormone) and eventually endogenous sex steroid transgender population. Table 2 is listing typically prescribed levels [27], an effect that is reversible upon discontinuation of regiments of GnRH agonists [37–39]. treatment [28]. An alternative approach involves the use of Monitoring of therapy while on GnRH agonists includes a GnRH antagonists. Despite their more rapid effect on decreas- careful monitoring of anthropometric measurements, clinical ing gonadotropin levels [29], they are not commonly chosen pubertal staging and measurement of LH and natal sex ste- due to the need for much higher dosage [30], which contrib- roids [27, 42]. Although early pubertal changes have been utes to the most impactful obstacle in using them: their cost noted to reverse with treatment, in children that have more [31]. A different and the most cost effective option is the use mature pubertal characteristics the aim is to stop further of progestins, similarly to how they were used prior to the progression rather than induce regression of Tanner staging development of GnRH analogues for precocious puberty [42]. Biochemically suppressing LH level to undetectable [32–34]. There have been only two recent studies investigat- or at least <0.60 IU/L seems to be sufficient to halt puberty ing the use of progestins for endogenous puberty blockage in in its tracks [27]. transgender youth, with participants having been enrolled at a late-pubertal stage [35, 36]. The efficacy of gonadotropin reduction was not as good as that seen with GnRH analogues, 3 Side effects of pubertal suppression but progestins were suggested to be a cost-effective alternative for patients presenting at pubertal Tanner 4 stage or beyond. It Pubertal suppression in precocious puberty is a relatively safe is unknown how effective progestins might be in stopping medical intervention with little acute and chronic side effects puberty at its earlier phases (Tanner 2 or 3) in younger trans- [41, 43, 44]. Most frequently, adverse effects involve prob- gender individuals. lems with the injection site itself. Redness and swelling can be The Standards of Care 7TH VERSION

evaluating this approach only included children who were at least 12 years of age (Cohen-Kettenis, Schagen, Steensma, de Vries, & Delemarre-van de Waal, 2011; de Vries, Steensma et al., 2010; Delemarre-van de Waal, van Weissenbruch, & Cohen Kettenis, 2004; Delemarre-van de Waal & Cohen-Kettenis, 2006).

Two goals justify intervention with puberty suppressing hormones: (i) their use gives adolescents more time to explore their gender nonconformity and other developmental issues; and (ii) their use may facilitate transition by preventing the development of sex characteristics that are difﬁcult or impossible to reverse if adolescents continue on to pursue sex reassignment.

Puberty suppression may continue for a few years, at which time a decision is made to either discontinue all hormone therapy or transition to a feminizing/masculinizing hormone regimen. Pubertal suppression does not inevitably lead to social transition or to sex reassignment.

Criteria for puberty suppressing hormones PUBERTY SUPPRESSION

In order for adolescents to receive puberty suppressing hormones, the following minimum criteria must be met:

1. The adolescent has demonstrated a long-lasting and intense pattern of gender nonconformity or gender dysphoria (whether suppressed or expressed);

2. Gender dysphoria emerged or worsened with the onset of puberty;

3 . Any co-existing psychological, medical, or social problems that could interfere with treatment (e.g., that may compromise treatment adherence) have been addressed, such that the adolescent’s situation and functioning are stable enough to start treatment;

4. The adolescent has given informed consent and, particularly when the adolescent has not reached the age of medical consent, the parents or other caretakers or guardians have con- sented to the treatment and are involved in supporting the adolescent throughout the treatment process.

Regimens, monitoring, and risks for puberty suppression

For puberty suppression, adolescents with male genitalia should be treated with GnRH analogues, which stop luteinizing hormone secretion and therefore testosterone secretion. Alternatively, they may be treated with progestins (such as medroxyprogesterone) or with other medications that block testosterone secretion and/or neutralize testosterone action. Adolescents with female genitalia should be treated with GnRH analogues, which stop the production of estrogens and

World Professional Association for Transgender Health 19

Standards of Care_1c.indd 19 9/20/11 9:43 PM PUBERTY SUPPRESSION

• GnRH agonists • Leuprolide (Lupron) – intramuscular injection monthly, q3 months, q6 months • Histrelin (Vantas) – subcutaneous implant; effective for up to 2 years • Suppress LH production and thereby testosterone/estrogen production • Stops virilization in natal males • Stops menses in natal females and may cause some atrophy of existing breast tissue PUBERTY SUPPRESSION

• Benefits • Reduction in distress around physical changes • Potential reduction in future surgical intervention • Fully reversible PUBERTY SUPPRESSION

• Benefits • Reduction in distress around physical changes • Potential reduction in future surgical intervention • Fully reversible

• Risks • Compromised bone mineralization • Varying data on catch-up • Fertility implications • ? Brain development doi: 10.1210/jc.2017-01658 https://academic.oup.com/jcem 3883

want to preserve fertility, which may be otherwise Remarks compromised if puberty is suppressed at an early stage Measurements of gonadotropin and sex steroid levels and the individual completes phenotypic transition with give precise information about gonadal axis suppression, the use of sex hormones. although there is insufficient evidence for any specific Limited data are available regarding the effects of short-term monitoring scheme in children treated with GnRH analogs on brain development. A single cross- GnRH analogs (88). If the gonadal axis is not completely sectional study demonstrated no compromise of execu- suppressed—as evidenced by (for example) menses, erec- tive function (107), but animal data suggest there may be tions, or progressive hair growth—the interval of GnRH an effect of GnRH analogs on cognitive function (108). analog treatment can be shortened or the dose increased. During treatment, adolescents should be monitored for Values and preferences negative effects of delaying puberty, including a halted Our recommendation of GnRH analogs places a higher growth spurt and impaired bone mineral accretion. Table 7 value on the superior efficacy, safety, and reversibility of illustrates a suggested clinical protocol. the pubertal hormone suppression achieved (as compared Anthropometric measurements and X-rays of the left with the alternatives) and a relatively lower value on hand to monitor bone age are informative for evaluating limiting the cost of therapy. Of the available alternatives, growth. To assess BMD, clinicians can perform dual- depot and oral progestin preparations are effective. Ex- energy X-ray absorptiometry scans. perience with this treatment dates back prior to the emergence of GnRH analogs for treating precocious pu- 2.4. In adolescents who request sex hormone treat- berty in papers from the 1960s and early 1970s (109–112). ment (given this is a partly irreversible treatment), These compounds are usually safe, but some side effects we recommend initiating treatment using a have been reported (113–115). Only two recent studies gradually increasing dose schedule (see Table 8) involved transgender youth (116, 117). One of these after a multidisciplinary team of medical and studies described the use of oral lynestrenol monotherapy MHPs has confirmed the persistence of GD/ followed by the addition of testosterone treatment in gender incongruence and sufficient mental ca- transgender boys who were at Tanner stage B4 or further pacity to give informed consent, which most at the start of treatment (117). They found lynestrenol safe, adolescents have by age 16 years (Table 5). but gonadotropins were not fully suppressed. The study (1 | ss) ÈÈ reported metrorrhagia in approximately half of the in- 2.5. We recognize that there may be compelling dividuals, mainly in the first 6 months. Acne, headache, reasons to initiate sex hormone treatment prior to hot flashes, and fatigue were other frequent side effects. the age of 16 years in some adolescents with GD/ Another progestin that has been studied in the United gender incongruence, even though there are States is medroxyprogesterone. This agent is not as ef- minimal published studies of gender-affirming fective as GnRH analogs in lowering endogenous sex hormone treatments administered before age hormones either and may be associated with other side 13.5 to 14 years. As with the care of adolescents effects (116). Progestin preparations may be an acceptable $16 years of age, we recommend that an expert treatment for persons without access to GnRH analogs or multidisciplinary team of medical and MHPs with a needle phobia. If GnRH analog treatment is not manage this treatment. (1 | sss) È available (insurance denial, prohibitive cost, or other PUBERTY2.6. We suggest monitoringSUPPRESSION clinical pubertal devel- reasons), postpubertal, transgender female adolescents opment every 3 to 6 months and laboratory may be treated with an antiandrogen that directly sup- parameters every 6 to 12 months during sex presses androgen synthesis or action (see adult section). hormone treatment (Table 9). (2 | ss) ÈÈ

Table 7. Baseline and Follow-Up Protocol During Suppression of Puberty

Every 3–6 mo Anthropometry: height, weight, sitting height, blood pressure, Tanner stages Every 6–12 mo Laboratory: LH, FSH, E2/T, 25OH vitamin D Every 1–2y Bone density using DXA Bone age on X-ray of the left hand (if clinically indicated)

Adapted from Hembree et al. (118). Abbreviations: DXA, dual-energy X-ray absorptiometry; E2, estradiol; FSH, follicle stimulating hormone; LH, luteinizing hormone; T, testosterone;

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• When can you start? • 16? 14? 13? 3884 Hembree et al Guidelines on Gender-Dysphoric/Gender-Incongruent Persons J Clin Endocrinol Metab, November 2017, 102(11):3869–3903

Table 8. Protocol Induction of Puberty

Induction of female puberty with oral 17b-estradiol, increasing the dose every 6 mo: 5 mg/kg/d 10 mg/kg/d 15 mg/kg/d 20 mg/kg/d Adult dose = 2–6 mg/d In postpubertal transgender female adolescents, the dose of 17 b-estradiol can be increased more rapidly: 1 mg/d for 6 mo 2 mg/d Induction of female puberty with transdermal 17b-estradiol, increasing the dose every 6 mo (new patch is placed every 3.5 d): 6.25–12.5 mg/24 h (cut 25-mg patch into quarters, then halves) 25 mg/24 h 37.5 mg/24 h Adult dose 5 50–200 mg/24 h For alternatives once at adult dose, see Table 11. Adjust maintenance dose to mimic physiological estradiol levels (see Table 15).

Induction of male puberty with testosterone esters increasing the dose every 6 mo (IM or SC): 25 mg/m2/2 wk (or alternatively, half this dose weekly, or double the dose every 4 wk) 50 mg/m2/2 wk 75 mg/m2/2 wk 100 mg/m2/2 wk Adult dose = 100–200 mg every 2 wk In postpubertal transgender male adolescents the dose of testosterone esters can be increased more rapidly: 75 mg/2 wk for 6 mo 125 mg/2 wk For alternatives once at adult dose, see Table 11. Adjust maintenance dose to mimic physiological testosterone levels (see Table 14).

Adapted from Hembree et al. (118). Abbreviations: IM, intramuscularly; SC, subcutaneously.

Evidence assessment) do not develop until well after 18 years (121). Adolescents develop competence in decision making at They suggest that health care procedures should be di- their own pace. Ideally, the supervising medical pro- vided along a matrix of relative risk, so that younger fessionals should individually assess this competence, adolescents can be allowed to decide about low-risk although no objective tools to make such an assessment procedures, such as most diagnostic tests and common are currently available. therapies, but not about high-risk procedures, such as Many adolescents have achieved a reasonable level of most surgical procedures (121). competence by age 15 to 16 years (119), and in many Currently available data from transgender adolescents countries 16-year-olds are legally competent with regard support treatment with sex hormones starting at age 16 to medical decision making (120). However, others be- years (63, 122). However, some patients may incur po- lieve that although some capacities are generally achieved tential risks by waiting until age 16 years. These include before age 16 years, other abilities (such as good risk the potential risk to bone health if puberty is suppressed

Table 9. Baseline and Follow-up Protocol During Induction of Puberty

Every 3–6 mo Anthropometry: height, weight, sitting height, blood pressure, Tanner stages Every· 6–12 mo In transgender males: hemoglobin/hematocrit, lipids, testosterone, 25OH vitamin D ·In transgender females: prolactin, estradiol, 25OH vitamin D Every· 1–2y BMD using DXA ·Bone age on X-ray of the left hand (if clinically indicated) BMD· should be monitored into adulthood (until the age of 25–30 y or until peak bone mass has been reached). For recommendations on monitoring once pubertal induction has been completed, see Tables 14 and 15.

Adapted from Hembree et al. (118). Abbreviation: DXA, dual-energy X-ray absorptiometry.

Downloaded from https://academic.oup.com/jcem/article-abstract/102/11/3869/4157558 by guest on 22 July 2018 3888 Hembree et al Guidelines on Gender-Dysphoric/Gender-Incongruent Persons J Clin Endocrinol Metab, November 2017, 102(11):3869–3903 estrogen may benefit from avoiding the first pass effect, cessation of menses, increased sexual desire, increased but they can result in more rapid peaks with greater facial and body hair, increased oiliness of skin, increased overall periodicity and thus are more difficult to monitor muscle, and redistribution of fat mass. Changes that (147, 148). However, there are no data demonstrating occur within the first year of testosterone therapy include that increased periodicity is harmful otherwise. deepening of the voice (152, 153), clitoromegaly, and Clinicians can use serum estradiol levels to monitor male pattern hair loss (in some cases) (114, 144, 154, oral, transdermal, and intramuscular estradiol. Blood 155) (Table 12). tests cannot monitor conjugated estrogens or synthetic estrogen use. Clinicians should measure serum estra- Transgender females diol and serum testosterone and maintain them at the Physical changes that may occur in transgender fe- level for premenopausal females (100 to 200 pg/mL males in the first 3 to 12 months of estrogen and anti- and ,50 ng/dL, respectively). The transdermal preparations androgen therapy include decreased sexual desire, and injectable estradiol cypionate or valerate preparations decreased spontaneous erections, decreased facial and may confer an advantage in oldertransgenderfemaleswho body hair (usually mild), decreased oiliness of skin, in- may be at higher risk for thromboembolic disease (149). creased breast tissue growth, and redistribution of fat mass (114, 139, 149, 154, 155, 161) (Table 13). Breast Values development is generally maximal at 2 years after initi- Our recommendation to maintain levels of gender- ating hormones (114, 139, 149, 155). Over a long affirming hormones in the normal adult range places a period of time, the prostate gland and testicles will high value on the avoidance of the long-term complica- undergo atrophy. tions of pharmacologic doses. Those patients receiving Although the time course of breast development in endocrine treatment who have relative contraindications transgender females has been studied (150), precise in- to hormones should have an in-depth discussion with their formation about other changes induced by sex hormones physician to balance the risks and benefits of therapy. is lacking (141). There is a great deal of variability among individuals, as evidenced during pubertal development. Remarks We all know that a major concern for transgender fe- Clinicians should inform all endocrine-treated in- males is breast development. If we work with estro- dividuals of all risks and benefits of gender-affirming gens, the result will be often not what the transgender hormones prior to initiating therapy. Clinicians should female expects. strongly encourage tobacco use cessation in transgender Alternatively, there are transgender females who re- females to avoid increased risk of VTE and cardiovas- port an anecdotal improved breast development, mood, cular complications. We strongly discourage the un- or sexual desire with the use of progestogens. However, supervised use of hormone therapy (150). there have been no well-designed studies of the role of Not all individuals with GD/gender incongruence seek progestogens in feminizing hormone regimens, so the treatment as described (e.g., male-to-eunuchs and in- question is still open. dividuals seeking partial transition). Tailoring current Our knowledge concerning the natural history and protocols to the individual may be done within the effects of different cross-sex hormone therapies on breast context of accepted safety guidelines using a multidisciplinary approach including mental health. No evidence- Table 12. Masculinizing Effects in Transgender based protocols are available for these groups (151). We Males need prospective studies to better understand treatment options for these persons. Effect Onset Maximum Skin oiliness/acne 1–6 mo 1–2y 3.4. We suggest that endocrinologists provide edu- Facial/body hair growth 6–12 mo 4–5y cation to transgender individuals undergoing Scalp hair loss 6–12 mo —a treatment about the onset and time course of Increased muscle mass/strength 6–12 mo 2–5y – – physical changes induced by sex hormone Fat redistribution 1 6 mo 2 5y Cessation of menses 1–6 mo —b treatment. (2 | sss) Clitoral enlargement 1–6 mo 1–2y È Vaginal atrophy 1–6 mo 1–2y Deepening of voice 6–12 mo 1–2y Evidence Estimates represent clinical observations: Toorians et al. (149), Assche- Transgender males man et al. (156), Gooren et al. (157), Wierckx et al. (158). Physical changes that are expected to occur during aPrevention and treatment as recommended for biological men. the first 1 to 6 months of testosterone therapy include b Menorrhagia requires diagnosis and treatment by a gynecologist.

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Table 13. Feminizing Effects in Transgender 3 months during the first year of hormone Females therapy for transgender males and females and then once or twice yearly. (2 | ss) Effect Onset Maximum ÈÈ Redistribution of body fat 3–6 mo 2–3y Decrease in muscle mass and strength 3–6 mo 1–2y Evidence Softening of skin/decreased oiliness 3–6 mo Unknown Pretreatment screening and appropriate regular Decreased sexual desire 1–3 mo 3–6 mo medical monitoring are recommended for both trans- Decreased spontaneous erections 1–3 mo 3–6 mo Male sexual dysfunction Variable Variable gender males and females during the endocrine transition Breast growth 3–6 mo 2–3y and periodically thereafter (26, 155). Clinicians should Decreased testicular volume 3–6 mo 2–3y monitor weight and blood pressure, conduct physical Decreased sperm production Unknown .3y exams, and assess routine health questions, such as to- Decreased terminal hair growth 6–12 mo .3ya Scalp hair Variable —b bacco use, symptoms of depression, and risk of adverse Voice changes None —c events such as deep vein thrombosis/pulmonary embo-

Estimates represent clinical observations: Toorians et al. (149), lism and other adverse effects of sex steroids. Asscheman et al. (156), Gooren et al. (157). aComplete removal of male sexual hair requires electrolysis or laser Transgender males treatment or both. Table 14 contains a standard monitoring plan for b Familial scalp hair loss may occur if estrogens are stopped. transgender males on testosterone therapy (154, 159). cTreatment by speech pathologists for voice training is most effective. Key issues include maintaining testosterone levels in the physiologic normal male range and avoiding adverse development in transgender females is extremely sparse events resulting from excess testosterone therapy, par- and based on the low quality of evidence. Current evi- ticularly erythrocytosis, sleep apnea, hypertension, ex- dence does not indicate that progestogens enhance breast cessive weight gain, salt retention, lipid changes, and development in transgender females, nor does evidence excessive or cystic acne (135). prove the absence of such an effect. This prevents us from Because oral 17-alkylated testosterone is not recom- drawing any firm conclusion at this moment and dem- mended, serious hepatic toxicity is not anticipated with onstrates the need for further research to clarify these parenteral or transdermal testosterone use (163, 164). important clinical questions (162). Past concerns regarding liver toxicity with testosterone have been alleviated with subsequent reports that indicate Values and preferences the risk of serious liver disease is minimal (144, 165, 166). Transgender persons have very high expectations re- Transgender females garding the physical changes of hormone treatment and Table 15 contains a standard monitoring plan for are aware that body changes can be enhanced by sur- transgender females on estrogens, gonadotropin suppres- gical procedures (e.g.,breast,face,andbodyhabitus). sion, or antiandrogens (160). Key issues include avoiding Clear expectations for the extent and timing of sex supraphysiologic doses or blood levels of estrogen that may hormone–induced changes may prevent the potential lead to increased risk for thromboembolic disease, liver harm and expense of unnecessary procedures. dysfunction, and hypertension. Clinicians should monitor serum estradiol levels using laboratories participating in 4.0 Adverse Outcome Prevention and external quality control, as measurements of estradiol in Long-Term Care blood can be very challenging (167). VTE may be a serious complication. A study re- Hormone therapy for transgender males and females ported a 20-fold increase in venous thromboembolic confers many of the same risks associated with sex disease in a large cohort of Dutch transgender subjects hormone replacement therapy in nontransgender per- (161). This increase may have been associated with the use sons. The risks arise from and are worsened by in- of the synthetic estrogen, ethinyl estradiol (149). The in- advertent or intentional use of supraphysiologic doses of cidence decreased when clinicians stopped administering sex hormones, as well as use of inadequate doses of sex ethinyl estradiol (161). Thus, the use of synthetic estrogens hormones to maintain normal physiology (131, 139). and conjugated estrogens is undesirable because of the 4.1. We suggest regular clinical evaluation for phys- inability to regulate doses by measuring serum levels and ical changes and potential adverse changes in the risk of thromboembolic disease. In a German gender response to sex steroid hormones and laboratory clinic, deep vein thrombosis occurred in 1 of 60 of monitoring of sex steroid hormone levels every transgender females treated with a GnRH analog and oral

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Table 8. Protocol Induction of Puberty

Adapted from Hembree et al. (118). Abbreviations: IM, intramuscularly; SC, subcutaneously.

Table 9. Baseline and Follow-up Protocol During Induction of Puberty

Adapted from Hembree et al. (118). Abbreviation: DXA, dual-energy X-ray absorptiometry.

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the secondary sex characteristics of the individual’s Evidence designated gender, and (2)toreplaceendogenoussex It is the responsibility of the treating clinician to hormone levels consistent with the individual’sgender confirm that the person fulfills criteria for treatment. identity by using the principles of hormone re- The treating clinician should become familiar with the placement treatment of hypogonadal patients. The terms and criteria presented in Tables 1–5andtakea timing of these two goals and the age at which to begin thorough history from the patient in collaboration with treatment with the sex hormones of the chosen gender the other members of the treatment team. The treating is codetermined in collaboration with both the person clinician must ensure that the desire for transition is pursuing transition and the health care providers. The appropriate; the consequences, risks, and benefits of treatment team should include a medical provider treatment are well understood; and the desire for knowledgeable in transgender hormone therapy, an transition persists. They also need to discuss fertil- MHP knowledgeable in GD/gender incongruence and ity preservation options (see recommendation 1.3) the mental health concerns oftransition,andaprimary (67, 68). care provider able to provide care appropriate for Transgender males transgender individuals. The physical changes in- Clinical studies have demonstrated the efficacy of duced by this sex hormone transition are usually ac- several different androgen preparations to induce mas- companied by an improvement in mental well-being culinization in transgender males (Appendix A) (113, (129, 130). 114, 131–134). Regimens to change secondary sex 3.1. We recommend that clinicians confirm the di- characteristics follow the general principle of hormone agnostic criteria of GD/gender incongruence replacement treatment of male hypogonadism (135). and the criteria for the endocrine phase of Clinicians can use either parenteral or transdermal gender transition before beginning treatment. preparations to achieve testosterone values in the normal (1 | s) male range (this is dependent on the specific assay, but is 3.2. WeÈÈÈ recommend that clinicians evaluate and ad- typically 320 to 1000 ng/dL) (Table 11) (136). Sustained dress medical conditions that can be exacerbated supraphysiologic levels of testosterone increase the risk by hormone depletion and treatment with sex of adverse reactions (see section 4.0 “Adverse Out- hormones of the affirmed gender before begin- come Prevention and Long-Term Care”) and should ning treatment (Table 10). (1 | s) be avoided. ÈÈÈ 3.3. We suggest that clinicians measure hormone Similar to androgen therapy in hypogonadal men, levels during treatment to ensure that endogenous testosterone treatment in transgender males results in sex steroids are suppressed and administered sex increased muscle mass and decreased fat mass, increased steroids are maintained in the normal physiologic facial hair and acne, male pattern baldness in those ge- range for the affirmed gender. (2 | ss) netically predisposed, and increased sexual desire (137). ÈÈ

Table 10. Medical Risks Associated With Sex Hormone Therapy

Transgender female: estrogen Very high risk of adverse outcomes: Thromboembolic disease Moderate· risk of adverse outcomes: ·Macroprolactinoma ·Breast cancer ·Coronary artery disease ·Cerebrovascular disease ·Cholelithiasis ·Hypertriglyceridemia Transgender male: testosterone Very high risk of adverse outcomes: Erythrocytosis (hematocrit . 50%) Moderate· risk of adverse outcomes: ·Severe liver dysfunction (transaminases . threefold upper limit of normal) ·Coronary artery disease ·Cerebrovascular disease ·Hypertension ·Breast or uterine cancer Downloaded from https://academic.oup.com/jcem/article-abstract/102/11/3869/4157558 by guest on 22 July 2018 PEDIATRIC STANDARDS OF CARE FOR GENDER AFFIRMING THERAPY (WPATH, V.7)

• Psychological interventions for children and adolescents: • Help families to accept and nurture their child • Facilitate social support within the community • Reduce child’s distress related to gender dysphoria or psychosocial difficulties • Help youth develop positive self-concept • Support families in managing anxiety about child’s psychosexual outcomes • Avoid imposing binary view of gender; Support options for exploring gender expression/identity • Support families and child in deciding how/when to socially transition • Serve as an advocate to schools, courts, community, etc. ABOUT OUR CLINIC • Located within the outpatient Pediatrics Clinic (CSC, 3rd floor) • Meets on Thursdays, AM session and PM session • Staffed by Dr. Rhamy Magid (pediatrician), Dr. Courtney LeClair (psychologist), Ka Powell (psychology intern), Kari Abraham (nurse), Gina Davis (social worker) • Devoted admin support (Lola Dee) and medical assistant (Maria Gayles) • Affiliated psychologists and psychiatrists available for referral and consultation • Serves children and teens ages 3 -18 +

• Primary care (e.g. well child checks, vaccinations) • Mental health care (individual and family therapy, diagnostic assessment, and psychological evaluation) • Pubertal suppression • Gender-affirming hormone therapy • Social work support • Referrals to surgeons or subspecialists (e.g., reproductive health) as needed • Referral to community supports or resources as needed Intake appointments • Meet initially with both psychologist and pediatrician • Later, time alone with each of them, as well as with SW, Gina Davis, as needed • If needed/desired – physical exam, labs, xray Follow up appointments • Meet with psychologist and/or pediatrician, as needed • Labs, if needed • Coordination of care may involve: • Referrals to surgeons, speech and language pathologists, therapists, etc. • Communication with schools, religious organizations, other community orgs • Communication with primary care doctors, other docs involved in care • Communication with therapists, case managers • Assistance with name change/gender marker change process QUESTIONS WE HEAR FROM PARENTS Is medical treatment safe? Is medical treatment safe? • Yes, gender affirming hormone therapy is generally regarded as safe, both in adults and adolescents. Is medical treatment safe? • Yes, gender affirming hormone therapy is generally regarded as safe, both in adults and adolescents. • Study of 116 youth, mean age 14-25 • Testosterone: • Increase in BMI, Hct, cholesterol. Decrease in HDL. • No change in liver enzymes, BUN, Cr, prolactin, TG, HbA1c, BP • Estradiol: • Decrease in ALT (still wnl). Increase in prolactin (still wnl). • No change in BMI, BP, AST, cholesterol, TG Is medical treatment safe? • Puberty blockers are also a safe and fully reversible treatment Is medical treatment safe? • Puberty blockers are also a safe and fully reversible treatment • The Endocrine Society recommends treating adolescents with GD with puberty blocking medication • Extends the gender exploration period • Leads to improved physical and mental health outcomes Is medical treatment safe? • Puberty blockers are also a safe and fully reversible treatment • The Endocrine Society recommends treating adolescents with GD with puberty blocking medication • Extends the gender exploration period • Leads to improved physical and mental health outcomes • Long history of use in children with precocious puberty Is medical treatment safe? • Puberty blockers are also a safe and fully reversible treatment • The Endocrine Society recommends treating adolescents with GD with puberty blocking medication • Extends the gender exploration period • Leads to improved physical and mental health outcomes • Long history of use in children with precocious puberty • Biggest long term considerations are bone mineral density (BMD) and fertility. • BMD compromise appears to reverse with stopping blocker or starting hormone • Puberty blockade alone does not appear to interfere with fertility How do children know their gender identity? How do children know their gender identity? • "Gender is an innate part of a person and it is not “decided” upon; rather, it is known or comes to be known." (Gender Identity Workbook for Children) • Why do we only question how transgender children know their gender identity? Why don't we question how cisgender children know their gender identity? • How did YOU know?

"If we believe and affirm a child when they are cisgender and stereotypical in their gender expression, what good reason is there to chronically reject a child’s persistent assertion of their gender or their expressions of their gender simply because we aren’t used to the diversity?" (Gender Identity Workbook for Children) Are adolescents being influenced by their peers, media, etc, to have a transgender/gender diverse identity? Are adolescents being influenced by their peers, media, etc, to have a transgender/gender diverse identity? • Most teens explore various facets of their identity, and gender identity is no exception. It is normal and healthy to explore one's gender expression or identity, as teens figure out who they are. • Part of our mental health assessment explores how a teen began thinking about their gender identity and how they continue to explore/view their identity. We assess this in order to ensure that a teen is not being unduly influenced by others. • Often, a teen who is interested in exploring their gender identity is drawn to other teens who are interested in this as well. • Sometimes seeing their peers who are further along in their gender exploration helps teens put the pieces together about who they are. RESOURCES STRATEGIES FOR ADULTS TO PROMOTE HEALTHY GENDER DEVELOPMENT IN CHILDREN (ADAPTED FROM NACCHO WEBSITE: HTTP://ESSENTIALELEMENTS.NACCHO.ORG/ARCHIVES/9103)

• Learn the key terminology related to gender (e.g., identity, expression), understand that gender is a spectrum rather than binary, and understand that gender identity is distinct from sexuality. • Pay attention to the world through a "gender lens". Notice how gender is described in media, how behaviors/clothes/activities are gendered, how expectations vary based on gender. Decide whether you want these messages passed to children, and give deliberate information to contradict these messages if not. • Explore your own gender to better understand your biases and stereotypes. Questions to ask yourself include (but are not limited to): • Growing up, did you think of yourself as a boy, a girl, both, neither or something different? How did you come to that recognition? When? • What messages did you receive from those around you about gender? Did those messages make sense to you? • How were kids who did not fit into expectations about gender treated by others (teachers, family, faith community, etc.)? By you? • How have your race, ethnicity, faith, class, community/sense of place influenced your gender? • How has your understanding of gender influenced how you parent your children? • Create a family/clinic/school environment conducive to gender exploration. Allow access to varied types of clothing, hair styles, accessories, activities, etc, without pressure to choose. • Talk with children about gender. Communicate openness and acceptance of gender diversity through your words and actions. Transforming Families is a community where transgender, gender non-conforming, and questioning youth and their families come together to support each other in a safe, welcoming space. At our monthly gatherings, separate breakout groups for parents, kids, siblings, and teens provide the opportunity to meet and learn from other people traveling the same path.

TRANSGENDER, NON-BINARY AND GENDER EXPANSIVE

CHILDREN (AND ANIMALS) IN DIVERSE PICTURE BOOKS

10,000 Dresses. Marcus Ewert. (1 – 3) A modern fairy tale about becoming the person you feel you are inside. While Bailey dreams of beautiful dresses, no one wants to hear about it because he is a boy. Then an older girl comes along who is inspired by Bailey and they make beautiful dresses together.

The Adventures of Tulip, Birthday Wish Fairy. S. Bear Bergman. (K – 2) Follow Tulip as he helps out with birthday wishes. When Tulip receives a wish from a child known as David who wishes to live as Daniela, he seeks the wise counsel of the Wish Fairy Captain.

Annie’s Plaid Shirt. Stacy B. Davids. (Pre-K – 2) Annie loves her plaid shirt and wears it everywhere. One day her mom tells her that she must wear a dress to her uncle's wedding. While Annie protests, her mom insists. Annie is miserable. She feels weird in dresses. Why can't her mom understand? Annie has an idea. But will her mom agree?

Are You A Boy Or Are You A Girl? Sarah Savage. (Pre-K – 1) Follow Tiny, a non-binary child who prefers gender-neutral pronouns and loves dressing up and playing football (soccer). When they start school, the other kids ask, “Are you a boy or are you a girl?” Tiny’s graceful answer introduces kids (and adults) to gender diversity and respecting those around you.

Backwards Day. S. Bear Bergman. (K – 1) Andrea looks eagerly forward to Backwards Day every year, so she can turn into a boy for one day. But one year she doesn't turn along with everyone else. She's miserable. The next day, however, she turns into a boy and stays that way!

The Boy & the Bindi. Vivek Shraya. (Pre-K – 2) A five-year-old South Asian boy becomes fascinated with his mother’s bindi, the red dot commonly worn by Hindu women and wishes to have one of his own. Rather than chastise her son, she agrees to it, giving him permission to be more fully himself.

Bunnybear. Andrea J. Loney. (Pre-K – 1) Although Bunnybear was born a bear, he feels more like a bunny. The other bears don't understand him, and neither do the bunnies. Will Bunnybear ever find a friend who likes him just the way he is?

www.welcomingschools.org BACKGROUND

1. A growing number of youth are realizing that they are THINGS TO SAY TO YOUR CHILD transgender — a person whose gender is diferent from their birth sex (often called the sex that they were 1. I don’t understand this yet, but I am trying, and, “assigned at birth.”) I love you. 2. For some parents/guardians, it is a big surprise to learn 2. What name do you want me to call you? What that a child is transgender, while for others, it makes gender pronouns do you use (he/him/his, she/ sense right away. her/hers, they/them/theirs or another pronoun)? I might mess up sometimes, but I will try. 3. Some parents/guardians feel confused, sad, or disconnected when they first learn that a child is 3. You deserve to be loved and respected; I love and transgender and feel that they need to get to know respect you. If anyone hurts or disrespects you, their child again. come to me and we will figure it out together. 4. You deserve to feel good about yourself, and I 4. Even when parents/guardians are not surprised or sad, support you. If you feel sad or worried, come to many feel worried about their child’s safety, happiness, me and we will figure it out together. and future. Most parents/guardians feel unprepared to help their child navigate life as a diferent gender, 5. You will always have a place to live, even if particularly in relation to peers, siblings, school we argue. administrators, family, and faith communities. 6. How do you feel the same? How do you feel diferent? What worries do you have? 5. You, your child, and your family deserve love and support. Many families are uncertain about how to 7. You may have known for a while that you are find knowledgeable, afrming health care, counseling transgender, and you may be in a rush to start resources, friends and role models for their child, and living as your true gender, but this is new for me. support for themselves — especially early on after Please try to be patient while I catch up because I learning that a child is transgender. Many families find want to and I will. that the beginning of this journey is the hardest and 8. Let’s remember to have fun together even when that, with time and support, life gets easier. things are hard. What things would you like to QUESTIONS?