Pubertal Suppression in Transgender Youth

Courtney Finlayson

• Publisher: Elsevier
• Year: 2018
• ISBN:
  9780323569644
• Topic: Medicine
• Subtopic: Endocrinology & Metabolism

Offering current guidelines on the relatively new practice of puberty suppression for gender-dysphoric adolescents, Pubertal Suppression in Transgender Youth provides a succinct, easy-to-digest overview of this timely topic. This concise, clinically-focused resource by Dr. Courtney Finlayson covers all relevant topics, from a brief history of medical care of transgender youth to emerging developments in the field.

Chapter 1

History of Care of Transgender Youth

Norman Spack, MD

Abstract

Over the past 40 years, care for transgender youth has evolved from essentially nonexistent to being the standard of care. Pioneering work in the Netherlands led to the Dutch Protocol, using gonadotropin analogues to suppress puberty. The first program for youth in the United States was started by this author. Now there are society guidelines for care, multidisciplinary programs throughout the country and even options like summer camp for gender nonconforming youth. This chapter, a very personal narrative, describes this evolution.

Keywords

Dutch protocol; Gender non-conforming; Guidelines; Pubertal suppression; Transgender

To write about “endocrine treatment” of transgender/gender nonconforming juveniles younger than 16 years is an oxymoronic act. Prior to the past decade, gender dysphoria, like homosexuality until 1973, was considered a psychiatric disease codified in the Diagnostic and Statistical Manual of Mental Disorders. It was unthinkable that a physician would prescribe cross-sex steroids to a gender dysphoric juvenile and risk stunted growth and induce precocious puberty. The only alternative then was psychiatric referral despite the prevalence of reparative therapy and its negative attitude toward any cross-gender behavior.¹ Efficacy of reparative therapy, which has been called into question, is based on the experience of a few investigators. They posit that only a minority of dysphoric juveniles will persist as transgender at puberty, with many who desist becoming gay. These data, like most studies on prepubertal gender nonconforming youth, were skewed by the nature of the institution in which they were seen, which in the case above was a psychiatric clinic. From the perspective of transgender individuals who seek treatment for the first time as adults, the overwhelming majority recall cross-gender feelings before the age of 10 years and many before the age of 5 years.² However, few parents supported their child living in a cross-gender social role in public, and the price was being bullied and rejected, which contributed to self-harm and sometimes even suicide.³

While some care for transgender adults has historically been provided in the United States, its fragmented nature and the lack of long-term longitudinal care and insurance coverage make outcome studies challenging. The Dutch, however, have a unique ability to perform such studies: they have one treatment center in a small country with one national insurer covering 100% care, including medical, surgical, pharmaceutical, and counseling in a country that is open minded about sexuality and gender. Despite all these favorable supports, the Dutch have considered starting treatment in adults a gigantic failure. In Louis Gooren's study of 3500 patients over 20 years, the finding that 1200 had already died was staggering. This is 51% higher than the general population, and they didn't die of hormonal causes. They succumbed to “psychosocial deaths”: suicide, substance abuse, alcoholism, homelessness, underemployment, and homicide.^4,5

Faced with these terrible outcomes for so many transgender adults, Gooren and his associates at the VU University Medical Center Amsterdam reasoned that a totally different paradigm was necessary, one that would spare carefully screened transgender adolescents the indignity of going through their genetic puberty and live as adults with a body that would not match their affirmed gender identity. They reasoned that merely starting cross-gender steroids early in puberty would have inherent difficulties. Growth would likely be stunted and the steroids would have irreversible side effects, such as infertility, and that it would be too difficult for a 10- to 12-year-old girl or a 12- to 14-year-old boy to make a knowledgeable mature judgment about these effects. The logical alternative was pubertal blockade, as had been used for decades for children with idiopathic central precocious puberty (CPP). Before the advent of GnRH analogues (GnRHa), before 1990, the treatment was 40–60 mg high-dose progesterone daily to suppress the hypothalamic-pituitary-gonadal axis. This regimen is far from perfect, with a Cushingoid appearance due to the high-dose progesterone binding to the cortisol receptor. Thus, stress dosing for illness could be necessary, and the skeletal bone age was often inadequately suppressed, limiting height potential (personal communication, John F. Crigler, Jr., MD).

The alternative treatment for CPP was begun by a collaboration between the pediatric endocrine departments of the Boston Children's Hospital and Massachusetts General Hospitals. They used GnRHa which were successful and became the standard of care.⁶ The patients stopped the GnRHa at an appropriate pubertal age, went on to fully experience full pubertal development, menstruate, ovulate, and give birth. The initial cohort has been followed for 30 years.

In a seminal moment, the Amsterdam group tried GnRHa in a few transgender early adolescents (Tanner 2) on the assumption that their puberty was acting as if it were precocious and noxious. When they later added cross-sex steroids, around the age of 15 years, while the endogenous hormones were still suppressed, the physical and psychological effects were remarkably positive.⁴ Their first paper outlining their treatment evaluation and protocol for patients younger than 18 years was published in the European Journal of Endocrinology in 2006.⁷ Inclusion of GnRHa into the therapeutic “mix” over a 22-year period was published by the same authors in 2011.⁸ They also reported no net loss of bone density in patients treated with GnRH after the addition of sex hormones. This was highly significant because suppressing puberty is known to reduce bone mass acquisition. Previous data, from the younger CPP patients who took GnRH for twice as long as the transgender patients, were skewed by the fact that CPP is associated with advanced bone age and bone mineral density at the time of diagnosis, and the transgender patients are not advanced in either. Although bone mass acquisition in transgender patients continues at a prepubertal rate while only on GnRH, after 2 years of added treatment with cross-sex steroids, they normalized for age and affirmed sex. However, a more recent Dutch study suggested that bone mineral density might be compromised.⁹ Conceivably, the Dutch protocol which raises cross-sex steroid dose relatively slowly could be responsible, and this is a fertile area for future investigation.

In evaluation of psychosocial functioning, virtually all programs that treat using pubertal suppression have noted a marked reduction in self-harm compared to the pretreatment era. Equally important, is the remarkable outcome in psychosocial well-being for patients treated with all components of the Dutch protocol: GnRHa treatment in early puberty, gender-affirming hormones added around the age of 15 years, and all surgeries completed at the age of 18 years.⁸ When individuals were studied again at the age of 20–22 years, living in the complete social role of their affirmed gender, their psychosocial well-being not only compared favorably with age-matched nontransgender Dutch peers but was also often better.¹⁰

Awakening the American pediatric endocrine audience to their potentially pivotal role in the care of transgender youth was no easy matter. With its designation as a psychiatric disease, many endocrine division and pediatric department leaders would have preferred that these patients remain in the psychiatric clinics. Multidisciplinary care was expensive and the probability of funding for clinical care in a medical clinic for a psychiatric disorder was questionable. Furthermore, insurance coverage for GnRHa, that cost hundreds to thousands of dollars, was invariably not covered. In the late 1990s, two conferences were held for combined European and American physicians and mental health professionals interested in becoming involved with transgender youth. At the first, in London, the Dutch team presented their plan for what became known as the “Dutch Protocol” of pubertal suppression. Shortly after, at a working group conference at VU University Medical Center Amsterdam (VUMC), Peggy Cohen-Kettenis offered to share her psychological testing materials to confirm severe gender dysphoria with the then Boston Children's Hospital psychologist Laura Edwards-Leeper, PhD. In 1998, Henriette Delemarre, MD, from VUMC presented her preliminary findings on the Dutch cohort of pubertally suppressed adolescents at an endocrine division conference at the Boston Children's Hospital and gave special attention to their preliminary studies, showing that 2 years of cross-sex hormones protected against diminished bone mineral density.

Also in 1998, this author began to bring older teens on cross-sex hormones into the Endocrine Teaching Clinic, inspiring several of the Boston Children's Hospital's endocrine fellows and some rotating internal medicine fellows to get involved. Within a decade, many of these physicians would have transgender patients of their own. In the final analysis, interacting with transgender patients and their parents convinced other physicians, mental health staff, nurses, and administrators that transgender adolescents were not mentally ill, yet were in profound danger of suicide and bullying. The patient numbers were not large enough to guarantee that they would ever knowingly see a transgender patient. Yet, many departments heard about the number of patients we were seeing and wanted to be better informed. A decision was made to let the patients do the talking, and indeed, they captured the hearts and minds of the hospital community. The hospital administration was so proud of being the first such clinic in North America that a semiannual glossy magazine sent out by the development office featured the clinic we named “GeMS,” the Gender Management Service.

By 2005, the Boston clinic had an endocrinologist, a psychologist skilled in testing, and a social worker and was ready to open the doors to new patients who were gender dysphoric and between Tanner 2 and 18 years of age. To make full use of the clinic space and broaden the range of patients to be seen, half the patients were not transgender but had disorders of sex development and were cared for collaboratively by urologists and endocrinologists. Regrettably, the clinic was not yet able to provide counseling and support groups for younger or prepubertal children, and for the immediate high demand for the new services provided.

The clinic was a favorite for observation by medical students and residents from a variety of disciplines. Since the clinic session lasted a whole day, cases of the day were discussed with the entire team during a lunch conference including the medical “visitors.” Several of the attendees at the clinic, like Stanley Vance, MD, have made their marks as leaders of new programs for transgender adolescents around the continent. Vance began coming to our clinic as a first-year Harvard Medical student and is now on the adolescent medicine staff of the University of California, San Francisco (UCSF), and a key figure in that Center's gender team. He spent a year with the Amsterdam group on a Fulbright grant while in medical school and coauthored papers with us.

Our 2012 Pediatrics publication described our first 100 consecutive patients.² Noteworthy findings were the advanced age and degree of pubertal advancement in genotypic females, averaging 15 years of age. Most patients described feelings of being in the wrong body as early as the age of 5 years. Forty-four percent had significant psychiatric histories, 20% reported self-mutilation and 9% had made suicide attempts. For the past 5 years, the GeMS program has sponsored one weekend day annually for each of the three groups: families, health professionals, and school personnel. Since 2015, with additional staff, prepubertal children are being seen. Perhaps the most significant impact of the GeMS clinic is the encouragement provided to other clinicians across the nation who wished to create a similar clinic of their own. In 2007, GeMS was the sole clinic in any pediatric academic center on the continent. A decade later, there are approximately 60 programs, and the GeMS provided advice to most of them.

In 2008 a task force led by Wylie Hembree, MD, was appointed by the P...