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miércoles, 6 de febrero de 2013


Clinical Crossroads
Conferences With Patients and Doctors
February 6, 2013
Clinician's Corner
Management of Transgenderism
Norman P. Spack, MD

Author Affiliations:Dr Spack is Associate in the Endocrine Division of Boston Children's Hospital and Cofounder/Codirector of the hospital's Gender Management Service and is Assistant Professor of Pediatrics at Harvard Medical School, Boston, Massachusetts.

JAMA. 2013;309(5):478-484. doi:10.1001/jama.2012.165234.

Gender identity disorder (transgenderism) is poorly understood from both mechanistic and clinical standpoints. Awareness of the condition appears to be increasing, probably because of greater societal acceptance and available hormonal treatment. Therapeutic options include hormone and surgical treatments but may be limited by insurance coverage because costs are high. For patients seeking male-to-female (MTF) change, hormone treatment includes estrogens, finasteride, spironolactone, and gonadotropin-releasing hormone (GnRH) analogs. Surgical options include feminizing genital and facial surgery, breast augmentation, and various fat transplantations. For patients seeking a female-to-male (FTM) gender change, medical therapy includes testosterone and GnRH analogs and surgical therapy includes mammoplasty and phalloplasty. Medical therapy for both FTM and MTF can be started in early puberty, although long-term effects are not known. All patients considering treatment need counseling and medical monitoring.
.DR TESS:Ms L is a 54-year-old biological male who self-identifies as a woman and is considering surgical removal of her penis and construction of a vagina. Ms L lived her early life as a boy and as a heterosexual male adult.
.Around age 10 years, Ms L realized that despite being a boy, he enjoyed dressing in women's underwear and clothing. As a young man, Ms L married and fathered a child. Ms L married again as a heterosexual male but sought psychotherapy to address relationship issues. After 3 years, Ms L's therapy was centered around issues of cross-dressing; he came to understand, with the help of a therapist and cross-dressing and transgender support groups, that she is actually a woman. She sought hormone treatment to begin to change her appearance and match gender identity. She is happy with the effects of hormone therapy but is considering surgical treatment.
.Ms L's medical history is significant for benign prostatic hyperplasia, borderline hypertension, migraine headaches, and a vasectomy. Her current medications include intramuscular estradiol valerate, 10 mg every 2 weeks; oral spironolactone, 75 mg/d; oral estradiol, 1 mg twice a day; and oral finasteride, 5 mg/d. Her mother died of postmenopausal breast cancer and her father had prostate cancer and died at age 61 years of heart disease. Ms L's daughter has been diagnosed as having depression and attention-deficit/hyperactivity disorder.
.Ms L has only had sexual intercourse with women (when she self-identified as a heterosexual male). Ms L has not had problems with drugs or alcohol. She is self-employed, and she does not have health insurance.
.Ms L is white, is 70 in tall, and weighs 161 lb. She has male-pattern baldness with mild to moderate hair loss around the edges of her crown. Her breasts did not show any masses and she has no axillary lymphadenopathy. Her testicles are atrophied. Her prostate is very mildly and symmetrically enlarged.
.With estrogen therapy, her free testosterone level is nearly undetectable, prolactin and thyrotropin levels are within normal limits, and estradiol level is 66 pg/mL (reference range for adult men, 8-43 pg/mL). Her total cholesterol is 117 mg/dL (3.03 mmol/L); low-density lipoprotein cholesterol, 51 mg/dL (1.32 mmol/L); and high-density lipoprotein cholesterol, 51 mg/dL (1.32 mmol/L).
...I actually had issues all my life around my gender identity. As a child, I wanted things a neighbor friend used to tell me were incorrect; I wanted to play house and wanted to have a baby when I got older.
.I identified as a cross-dresser from an early age until my late 40s. While in therapy, I realized that I am not a cross-dresser but what I call “transgender.” Before I started hormones, I realized, I don't really have 2 genders. I really have 1. I’m really female.
.The first people I told were close friends; they were very understanding. There has been some rejection and loss, but the acceptance and the strengthening of relationships, certainly with women, has been tremendous. My social circle has increased. Within my own family, it has been a hard aspect for them to accept.
.I started with spironolactone without estrogen. The effect for me was a lack of drive or energy. But when the estrogen started, it was wonderful; it just felt like it was more and more me. I’m extremely happy. A lot of wonderful feelings and changes accompany it, not just on the physical level, but emotionally and mentally.
.My hopes are actually just to have the female genitalia, for both a social and a sexual life. I’m looking forward to that very much—being able to have identification that matches who I am. And I look forward to having a sexual relationship as a female.
.I’m a little bit nervous about complications if I were to pursue surgery. My understanding is that it takes about 3 to 6 months to start to feel yourself, and anywhere from 6 months to a year to have a complete recovery. So those are things that I’m not really looking forward to.
...How often and when do patients seek to affirm an identity of the opposite gender? What is the current understanding of the mechanism by which patients identify with the opposite gender? What are the medical options for male-to-female (MTF) therapy in adolescence and adulthood? What are the medical options for female-to-male (FTM) therapy in adolescence and adulthood? What surgical options exist for transgender patients and what are the costs? What are the important unanswered questions about transgender individuals? What do you recommend for Ms L?
.DR SPACK: Ms L's situation is similar to many but not all who have an adult presentation, having cross-dressed as a child, married as a man, and fathered a child while feeling uncomfortable beinga man. She is taking customary high-dose estrogen to suppress testosterone production and using potentially high-risk estrogen injections despite a family history of early coronary artery disease and breast cancer. She is contemplating feminizing genitoplastic surgery, although she has no specific plan and uncertain resources. Although she began to seek counseling only in her 40s in spite of conflicts about her gender throughout her life, 3 years of psychotherapy facilitated her physical and social transition.
The basic nomenclature around gender identity and patients' desire to affirm the identity of the opposite gender can be confusing (Box 1). Quiz Ref IDTransgenderism refers to an informal diagnosis that describes individuals like Ms L, whose gender identity (the inherent sense of being male or female) differs from their biologic sex.
.Box 1. Definitions
.Sex: Refers to the physical genotype and phenotype, without regard to the sense of self.
.Gender identity: Inherent sense of being male or female regardless of genotypic, phenotypic, or biochemical sex. Also referred to as affirmed gender.
.Transgender:An informal diagnosis to describe those whose gender identity is different from their biologic sex.
.Transsexual:Term typically ascribed to adults committed to making their bodies congruent with their gender identity.
.Gender identity disorder: Formal diagnosis for the above conditions, according to the Diagnostic and Statistical Manual of Mental Disorders(Fourth Edition). This is a psychiatric diagnosis, so medical/surgical treatment is often not covered by health insurance.
.Cross-dresser (transvestite):An individual who derives pleasure from dressing in clothes of the opposite sex (usually a genotypic male wearing female attire). Cross-dressers usually retain a gender identity consistent with genotypic sex and have no wish for anatomical change.
.Sexual orientation:The sex that a person is physically attracted to, without regard to gender identity. In their affirmed gender, transgender individuals may be straight, gay, bisexual, or asexual.
.An accurate assessment of the prevalence of transgenderism in the United States is limited by the lack of case registries or a single national health insurance plan. In the Netherlands, the prevalence of transsexualism is 1 in 11 900 genotypic men and 1 in 30 400 women.1Former data in the United States were unfortunately based on prevalence of feminizing genitoplastic surgeries (sex reassignment surgery). These are expensive and not covered by insurance; many patients forgo it. Therefore, these studies may have underrepresented the true prevalence of transgenderism.
.About 66% of adult transsexuals report an onset of gender dysphoria in childhood, as was the case for Ms L; for the remainder, dysphoria develops later in life.2Virtually every program for under-21-year-olds finds an equal MTF-FTM sex ratio, yet adult clinics typically record 3 to 1 in favor of MTF. Many circumstances, however, may bias the data.3- 4Male-to-female adolescents are at extreme risk of bullying and violence, which may delay “coming out.” Because androgyny in females is more accepted in US society, younger patients may be less aware whether they are lesbian, androgynous, or truly FTM and eventually desirous of mastectomy and testosterone treatment.
.There is a perceptible increase in the number of people in the United States coming forward as transgender, and at younger ages. Statistics are limited by variability in the services available that facilitate identification of transgender youth and by cultural factors that inhibit people in some subpopulations from being identified prior to adulthood.5Some early school-aged children's parents insist that their offspring affirm the gender identity of their genetic sex from the very first gender-specific behaviors and preferences.6Although 80% of such gender-nonconforming children may not be transgender at the onset of puberty, many are homosexual or “gender2 queer” as adolescents and adults (gender queer individuals see themselves within a continuum between male and female; some reject the concept of gender identity as binary). The 20% who persist as transgender become increasingly gender-dysphoric at the onset of Tanner stage 2 puberty (in genetic girls, ages 10-12 years, with breast development; in genetic boys, ages 12-14 years, with doubling/tripling of testicular size) and almost never desist from being transgender.3,7Greater openness to and acceptance of sexual orientation and gender variance and positive depictions of transgender people in the media contribute to patients expressing their gender identity and/or role at an earlier age. Parental and public awareness of medical treatments, such as gonadotropin-releasing hormone (GnRH) analog therapy to block the onset of genetic puberty, give the impression that the incidence of transgender children is increasing.8 Increasingly, colleges and universities are providing counseling and hormone therapy and a few offer the full array of surgeries with university health insurance. A list of websites relating to transgenderism education and treatment is given in the eBox.
.The diagnosis of gender identity disorder (according to the Diagnostic and Statistical Manual of Mental Disorders[Fourth Edition]) requires a series of evaluations by mental health care professionals (Box 2). At the Gender Management Services Clinic at Boston Children's Hospital, patients must provide a letter of referral from a mental health care clinician who has seen the patient for at least 6 months and complete approximately 6 hours of psychological evaluation, including family member participation, before beginning any hormone therapy.
.Box 2. Current Recommendations for Treatment of Transgender Adults1
.Initial diagnosis: Mental health care professionals should follow the World Professionals Association for Transgender Health's standards of care9 to accurately diagnose gender identity disorder.
.Psychotherapy: Individuals with gender identity disorder often have other psychosocial or psychiatric issues. Psychotherapy should assess the influence of these conditions on an individual's diagnosis as well as allocate appropriate treatment for all diagnoses.
.Real-life experience: Individuals seeking medical treatment should first live in the desired gender role for 12 months before beginning medical, irreversible treatment.
.Hormone therapy:Once the diagnostic criteria have been met, the treating endocrinologist can begin the proper cross-sex hormone treatment and/or hormone depletion. The endocrinologist should monitor the physical changes of the patient.
.Surgery:Endocrine guidelines recommend that after 1 year of hormone treatment, the transsexual individual, the attending endocrinologist, and the mental health care professional may consider sex reassignment surgery.
.Because the presentation of adults is idiosyncratic, academic psychologists have also developed subcategories for their diagnoses. These classifications may be extremely important to the therapists working with them, but the main relevance to their medical and surgical clinicians is whether a mental health care clinician has referred the patient as a candidate who meets the standards for hormone and/or surgical intervention.9
Biologic mechanisms remain elusive. The phenomenon, like homosexuality, is not limited by geography or era; there are reports of people living in the opposite gender throughout history.
.No studies have documented a relationship between transgenderism and maternal-fetal hormonal milieu. Female infants with congenital adrenal hyperplasia who are exposed to the highest continuous fetal androgen concentrations may be profoundly genitally affected, yet the overwhelming majority retain a female gender identity throughout life.10Some infant genetic males with disorders of sex development with hormonally functional testes in utero have undergone gonadectomy and sex reversal shortly after birth because of a lack of genital anlage to form male genitals. Many of these children remain in their female identity, suggesting that gender identity may be malleable in some cases and for a finite time.11
.Quiz Ref IDRecent pathologic and nuclear magnetic resonance imaging studies suggest that transgenderism may be linked to alterations in the brain. A sexually dimorphic area in the hypothalamic bed nucleus of the stria terminalis is typically twice as large in biological males. In stained autopsy slices from 30- to 40-year-old MTF transsexuals, the nucleus is female sized. Change in size may not be attributable to estrogen use—in nontranssexual men taking estrogen for years who died of prostate cancer, similar slides showed no change. Similar concordance with genetic sex rather than environmental hormone exposure has been seen in virilized women who died of adrenal cancer.12A recent nuclear magnetic resonance imaging study described 4 sex-specific areas of the human brain. Transgender individuals studied before the administration of any hormones had brain regions consistent with their affirmed gender, not their genotypic sex.13Studies of identical twins, who share the transgender diagnosis far more than fraternal twins or siblings, suggest that genetics play a major role in the etiology of transgenderism.14
Transgender patients choose a variety of approaches to feel comfortable with their outward appearance. Some adult patients are content or feel coerced to remain in the gender role of their natal sex because of family or social circumstances. Others, such as genotypic males with a slim frame, a height less than 73 in, soft facial features and vocal pitch, a relatively nonprominent “Adam's apple,” relatively sparse and light facial hair, and no male-pattern balding have major cosmetic advantages. Some may only take cross-gender sex steroids but dress in a natal or androgynous style. For those who desire medical therapy, options include estrogens, finasteride, spironolactone, and GnRH analogs for MTF patients. Quiz Ref IDHormone therapy for adults has permanent effects and should be preceded by at least 1 year of counseling and living full-time in the gender role of the affirmed sex.15Results of use of hormone agents are highly variable for fully mature genetic male adults. The overall goal is to achieve phenotypic feminization and decrease the virilizing effects of endogenous testosterone.Endocrinologists should continuously monitor the health effects of these therapies (Table and Box 3).

Male-to-Female Treatmenta
1. Evaluate patient every 2 to 3 months in the first year and then 1 to 2 times per year to monitor for appropriate signs of feminization and for development of adverse reactions.
.2. Measure serum testosterone and estradiol levels every 3 months. Serum testosterone levels should be less than 55 ng/dL. Serum estradiol level should not exceed the peak physiologic range for young, healthy females, with ideal levels of approximately 100 to 200 pg/mL. Dosages of estrogen should be adjusted according to the serum levels of estradiol.
.3. For individuals taking spironolactone, serum electrolytes, particularly potassium, should be monitored every 2 to 3 months in the first year.
.4. Routine cancer screening (eg, breast, colon, prostate) is recommended as for nontranssexual individuals.
Female-to-Male Treatmenta
.1. Evaluate patient every 2 to 3 months in the first year and then 1 to 2 times per year to monitor for appropriate signs of virilization and for development of adverse reactions.
.2. Measure serum testosterone every 2 to 3 months until levels are in the normal physiologic range for males. For testosterone enanthate/cypionate injections, the testosterone level should be measured midway between injections. If level is higher than 800 ng/dL or lower than 320 ng/dL, adjust dosage accordingly. For transdermal testosterone, the testosterone level can be measured at any time after 1 week. During the first 3 to 9 months of testosterone treatment, total levels may be high although free testosterone levels are normal because of high sex hormone binding globulin levels in some biological women.
.3. Measure estradiol levels during the first 6 months of testosterone treatment or until there has been no uterine bleeding for 6 months. Estradiol levels should be less than 50 pg/mL.
.4. Make complete blood count and liver function measurements at baseline and every 3 months for the first year and then 1 to 2 times a year. Monitor weight, blood pressure, lipids, fasting blood glucose (if there is a family history of diabetes), and hemoglobin A1c (if patient has diabetes) at regular visits.
.5. If cervical tissue is present, an annual Papanicolaou test is recommended by the American Congress of Obstetricians and Gynecologists.
.6. If mastectomy is not performed, consider mammograms as recommended by the American Cancer Society.

.aConsider bone mineral density testing at baseline if risk factors for osteoporotic fracture are present (eg, previous fracture, family history, glucocorticoid use, prolonged hypogonadism). In individuals at low risk, screening for osteoporosis should be conducted at age 60 years or in those who are not adherent to hormone therapy.
.Estrogen is used to achieve feminization (eg, breast development, softening of skin, a more female fat distribution and alteration in mood) via negative feedback on the hypothalamus; estrogen also down-regulates gonadotrophins to lower serum testosterone levels. This reduces the rate of growth of male-pattern hair, erections, and libido while enhancing the effect of estrogen on breast growth. Quiz Ref IDIn an MTF patient who has not had the testes removed, the dosage of estrogen required to suppress testosterone levels to the negligible range and to maximize feminization is 4 to 8 times greater than any nontransgender woman would be given. The risk of thromboembolism at these high dosages is a concern.To achieve these high levels, intramuscular estrogen can be given, as in the case of Ms L, as 10 mg weekly of estradiol valerate. This formulation results in serum levels of estrogen of more than 1800 pg/mL. Intramuscular injections spare the patient's liver a “first-pass” exposure via the enterohepatic circulation that could otherwise stimulate hepatic clotting factors. However, the high serum levels can overexpose the liver via the systemic circulation and the hepatic artery and lead to potentially carcinogenic liver neoplasia and growth.16Many laboratories cannot reliably measure estradiol levels other than 17β-estradiol. Because of increased risk of venous thrombosis and cardiovascular risk compared with 17β-beta estradiol, oral ethinyl estradiol and conjugated estrogens should be avoided.16- 19There are very infrequent reports of prolactinomas (estrogen treatment routinely doubles or triples the baseline prolactin level), breast cancer, and even prostate cancer in MTF patients. In the latter case, the cancer was probably in situ at the initiation of estrogen therapy.20
.The main purpose of spironolactone is to inhibit androgen binding to its receptor to diminish the rate of growth and thickness of male-pattern hair; this reduces the heavy financial burden of electrolysis, which can cost $120/week (Table).
.Finasteride blocks the enzyme 5α-reductase, inhibiting the conversion of testosterone to dihydrotestosterone (DHT) and is usually given to reduce prostatic size from benign prostatic hypertrophy. Lower dosages have been shown to reduce the involvement of dihydrotestosterone in early male-pattern balding. Interestingly, treating Ms L's benign prostatic hypertrophy may not be necessary because it may be partially treated by the estrogen-induced suppression of serum testosterone and dihydrotestosterone (Table).
.Gonadotrophin-releasing hormone analog is used frequently in MTF individuals in Europe who have not undergone gonadectomy and following at least 6 months of counseling. In adolescents, extensive psychological evaluation is also required. These drugs are available in the United States as leuprolide, nafarelin, or histrelin. They inhibit the release of gonadotrophins and thereby the stimulus for secretion of testosterone from the testes. The suppression of testosterone that is achieved rivals that of a bilateral gonadectomy and only 1 to 2 mg of daily oral estradiol is required for feminization. The rate of male-pattern hair growth slows, breasts increase, and erections virtually cease. Libido is also suppressed. The Dutch have made this treatment the core of their adolescent program, blocking puberty at its onset and providing several years of continuing counseling until a definitive decision can be made regarding taking estrogen at about age 16 years.21- 24 The results are dramatic: gender dysphoria is reduced and social and academic performance improves.7,25- 26Estrogen reduces stature to a more appropriate female height, voice never deepens, facial hair never grows, facial bone structure is less male-angular, and breast development is normal. Unfortunately, these drugs are prohibitively expensive regardless of age at use and are rarely covered by insurance in the United States for transgenderism (Table).
.Although Ms L started hormone therapy late, she does have the advantage of a relatively thin frame, normal height for a woman, and light hair, which minimizes facial hair removal. Her regimen of high-dose estrogen and spironolactone can certainly suppress erections, diminish libido, and improve mood. Breast development in an adult of this build is highly variable and may not be adequate to the patient despite use of estrogen (Table).
Hormone treatments for FTM patients include testosterone, GnRH analogs, and progestin. The best option and order in which to treat depends on the age of the patient at presentation.
.Treating FTM individuals hormonally is relatively easy when they are aged 14 to 16 years. Young FTM individuals who are at Tanner stage 2 and experiencing an increase in gender dysphoria should be counseled and treated with a GnRH analog. Pubertal suppression via a GnRH analog prevents full biological puberty and, specifically, menses. Around age 16 years, the patient may begin cross-hormone therapy. Testosterone cypionate or enanthate given subcutaneously or intramuscularly weekly (50-75 mg per dose) suppresses menses and virilizes the body, face, and hair. Reversible pubertal suppression prevents changes such as breast development that would later need surgical removal.
.For adults, parenteral or transdermal preparations are used to achieve normal male testosterone value ranges (320-800 ng/dL). Despite the differences in treatment, both adolescents and adults must have 6 months of experience living in the desired gender role before beginning hormone treatment.9As with MTF patients, endocrinologists should continuously monitor for normal and adverse health effects (Box 3).9

...Because most insurance companies in the United States consider surgical therapy cosmetic and typically do not cover costs, the exact number of patients seeking surgical therapy is unknown.
.Quiz Ref IDMale-to-female transgender individuals who have not had pubertal suppression early in life may seek facial feminizing surgery, breast augmentation, and various fat transplants as either adults or adolescents. Male-to-female surgical techniques include penile inversion or creation of a vagina from sections of the colon.27Depilated scrotal skin is used to create the labia.Two decades ago, much of the literature on postoperative MTF patients described considerable dissatisfaction concerning sensation and orgasm in the genitoplasty. More recent nerve-sparing techniques have rendered remarkable improvements.27- 29 In Thailand, where the price is lower than in the United States, these types of procedures can range between $9000 and $20 000. The estimated cost of vaginoplasty surgery (1 stage with penile inversion, clitoroplasty, and labioplasty) plus hospital stay in a Philadelphia, Pennsylvania, transgender center is $19 500. Breast implants are approximately $8100 and additional facial and body augmentation surgeries range from $3500 to $10 600 (Philadelphia).
.Female-to-male adolescents or adults who have not had pubertal suppression may seek mammoplastic surgery as soon as it can be done, usually around age 16 years. A small-breasted individual can have an excellent, nearly scar-free result with a simple subareolar incision and excision of breast tissue. For those with an inframammary fold, the procedure is similar to a reduction mammoplasty except that a flat chest is the ultimate goal, so the subcostal scars are obvious.30- 31 The prices of subcutaneous mastectomies/mammoplasty range from just under $5000 to $7900 (Philadelphia).32

...Definitively determining the mechanism by which some individuals are transgender will be a major future achievement. In addition to validating transgender patients' experiences, their conditions will no longer be regarded as primarily psychiatric disorders. It will enable social adjustment and suppression of the natal undesired puberty. Treatment as a primary medical condition would result in insurance coverage, including surgery.
.Follow-up studies of transgender youth whose puberty was suppressed are needed to assess long-term effects. Areas for research include bone mineral density, other unexpected medical effects, and long-term psychological and social functioning.33Issues of long-term reproductive health and preservation of ova and sperm for patients even if their puberty is suppressed should be investigated.34
.How to manage this population of patients as they mature and expand within our health care system is yet to be determined. Primary care physicians need to make their own “transitions” to care for transgender patients, as many have done in caring for those who are gay or lesbian. Training needs to be enhanced to manage the psychological issues, medications, and associated risks.35Medical schools need to include the care of gender variance in all of its forms in their curricula, and training programs for mental health clinicians need to incorporate such information.
.Transgender people are among the last patients to be excluded from the US health care system and universal protection from discrimination. Yet we have much to learn from them about the neurobiology and social psychology of gender. These patients strain our usual constructs about nature and nurture. Yet we also learn, as we did when homosexuality was removed from being listed as a mental illness in 1973, about the negative effects on patients of describing a condition as a mental illness when it appears to be secondary to medical treatment delayed or denied. There is no greater gift to patients than to respect them for who they believe they are and to enable them to refashion their bodies to match their affirmed gender.

Ms L has some unique risks from the current treatment as a middle-aged MTF person and her options may unfortunately be limited by insurance issues.
.She has a worrisome family history of early cardiovascular disease and breast cancer. Based on the high dose of estrogen being taken and the thromboembolic risk of taking so much estradiol via injection, she should consider doing whatever she can to lower her estrogen dose to a normative level.36Optimal treatment would be a feminizing genitoplasty because only 1 to 2 mg of estradiol would be needed. However, surgery may not yield patient satisfaction and is a $25 000 undertaking not covered by insurance. Other surgical options include feminizing surgery to the facial bones, tracheal shaves to remove the Adam's apple, brow plastic surgery to bring the hairline forward, and augmentation mammoplasties.37For patients whose bodies cannot align with their gender, physicians should not underestimate the influence of circulating hormones that do match the patient's gender. Ms L does require reevaluation and potential counseling from a mental health gender specialist to reassess her candidacy for genitoplastic surgery and to provide support regardless of her decision, even if it is based solely on financial grounds.
.The next best option, especially if genitoplasty is not likely to occur, would be bilateral gonadectomies, which would be affordable and have the same hormonal benefits. Postoperatively, spironolactone can usually be reduced but not necessarily discontinued because male-pattern hair loss often continues. If surgical gonadectomy is not possible, a “medical gonadectomy” could be possible with a GnRH analog via 1- or 3-month depot injection, daily nasal spray, or small subcutaneous implant in the underside of the upper arm that releases drug for up to 2 years. She also would need to take 1 to 2 mg of estradiol.36
.To minimize her long-term risks, she requires annual mammograms as would any estrogen-taking MTF individual her age.36She needs to be mindful of all risk factors for cardiovascular disease and receive prompt and proper treatment should she develop hyperlipidemia, hypertension, or diabetes.

QUESTION:What do you see is the role of psychiatry and mental health clinicians in managing these patients?
.DR SPACK:The role of mental health clinicians in managing these patients through their self-discovery and treatment is critical. In my practice, patients need to be in counseling for at least 6 months to be treated. They need to remain in counseling throughout treatment and transition. In my practice, families benefit too. Mental health intervention should persist for the long term, even after surgery, as patients continue to be at mental health risk, including for suicide.36While the causes of suicide are multifactorial, the possibility cannot be ruled out that some patients unrealistically believe that surgery(ies) solves their psychological distress. Early intervention in young adolescents, including pubertal suppression, has been initiated only in the past 10 to 15 years; long-term follow-up is awaited to determine whether the outcomes are more favorable.21,25
.QUESTION: To what extent is gender dysphoria universal? Can you tell us if it is worldwide and if it is cross-cultural?
.DR SPACK:The degree to which patients express themselves has to do with cultural acceptance. The data about the actual incidence is very difficult to obtain. Initial studies in the United States, based on surgical data, are likely to be inaccurate.


..Corresponding Author:Norman P. Spack, MD, Endocrine Division, Children's Hospital, 300 Longwood Ave, Boston, MA 02115 (
Additional Contributions:We thank the patient for sharing her story and providing permission to publish it, and Amy Tishelman, PhD, Gender Management Service, Boston Children's Hospital, for assistance with the manuscript. No compensation was received.
The conference on which this article is based took place at the Psychiatry Grand Rounds at Beth Israel Deaconess Medical Center, Boston, Massachusetts, on February 24, 2011.
Clinical Crossroads at Beth Israel Deaconess Medical Center is produced and edited by Risa B. Burns, MD, series editor; Tom Delbanco, MD, Howard Libman, MD, Eileen E. Reynolds, MD, Marc Schermerhorn, MD, Amy N. Ship, MD, and Anjala V. Tess, MD.
.Clinical Crossroads Section Editor: Edward H. Livingston, MD, Deputy Editor, JAMA.

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.2 +Cohen-Kettenis PT, Pfäfflin F. The DSMdiagnostic criteria for gender identity disorder in adolescents and adults. Arch Sex Behav. 2010;39(2):499-513
.3 +Cohen-Kettenis PT, Delemarre-van de Waal HA, Gooren LJ. The treatment of adolescent transsexuals: changing insights. J Sex Med. 2008;5(8):1892-1897
.4 +Wallien MS, Cohen-Kettenis PT. Psychosexual outcome of gender-dysphoric children. J Am Acad Child Adolesc Psychiatry. 2008;47(12):1413-1423
.5 +Zucker K, Lawrence A. Epidemiology of gender identity disorder: recommendations for the standards of care of the World Professional Association for Transgender Health. Int J Transgenderism. 2009;118-18
.6 +Zucker KJ. Gender identity disorder in children and adolescents. Annu Rev Clin Psychol. 2005;1467-492
.7 +Smith YL, Van Goozen SH, Kuiper AJ, Cohen-Kettenis PT. Sex reassignment: outcomes and predictors of treatment for adolescent and adult transsexuals. Psychol Med. 2005;35(1):89-99

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