Long-term Puberty Suppression for a Nonbinary Teenager Ken C. Pang, FRACP, PhD,a,b,c,d Lauren Notini, PhD,a,e Rosalind McDougall, PhD,f Lynn Gillam, PhD,f,g Julian Savulescu, PhD,a,h Dominic Wilkinson, FRACP, PhD,h Beth A. Clark, PhD, HEC-C, RCC,i Johanna Olson-Kennedy, MD,j Michelle M. Telfer, FRACP,a,b John D. Lantos, MDk

Many transgender and gender-diverse people have a gender identity that abstract does not conform to the binary categories of male or female; they have a nonbinary gender. Some nonbinary individuals are most comfortable with an androgynous gender expression. For those who have not yet fully progressed through puberty, puberty suppression with gonadotrophin- aMurdoch Children’s Research Institute, Melbourne, Victoria, releasing hormone agonists can support an androgynous appearance. Australia; bDepartment of Adolescent Medicine and Although such treatment is shown to ameliorate the gender dysphoria and gChildren’s Bioethics Centre, The Royal Children’s Hospital, Melbourne, Victoria, Australia; cDepartments of Paediatrics serious mental health issues commonly seen in transgender and gender- and dPsychiatry, eMelbourne Law School, and fSchool of diverse young people, long-term use of puberty-suppressing medications Population and Global Health, The University of Melbourne, h carries physical health risks and raises various ethical dilemmas. In this Melbourne, Victoria, Australia; Uehiro Centre for Practical Bioethics, Oxford University, Oxford, United Kingdom; iThe Ethics Rounds, we analyze a case that raised issues about prolonged pubertal University of British Columbia, Vancouver, Canada; suppression for a patient with a nonbinary gender. jUniversity of Southern California, Los Angeles, California; and kBioethics Center, Children’s Mercy Hospital, Kansas City, Missouri

Dr Pang conceived this article and contributed to the design, drafting, and review of the manuscript; Drs Referrals of transgender and gender- various ethical dilemmas. In this Ethics Notini, McDougall, Gillam, Savulescu, Wilkinson, diverse (TGD) children and adolescents Rounds, we present a case that Clark, Olsen-Kennedy, and Lantos and Ms Telfer to gender clinics worldwide have combines features of several real cases contributed to the design, drafting, and review of the grown dramatically in the past decade that raised issues about prolonged manuscript; and all authors approved the final as societal awareness of gender pubertal suppression for a patient with manuscript as submitted. diversity has increased and relevant a nonbinary gender. We then ask DOI: https://doi.org/10.1542/peds.2019-1606 clinical services have become clinicians and experts in bioethics from Accepted for publication May 28, 2019 1,2 available. At the same time, it has The Royal Children’s Hospital in Address correspondence to John D. Lantos, MD, become apparent that many TGD young Melbourne, Australia; the Uehiro Centre Children’s Mercy Kansas City, 2401 Gillham Rd, people have a gender identity that does for Practical Ethics at Oxford University Kansas City, MO 64108. E-mail: [email protected] not conform to the binary categories of in the United Kingdom; and The PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, male or female; that is, they have University of British Columbia to 1098-4275). a nonbinary gender identity.3–5 Some comment on the case. Copyright © 2020 by the American Academy of Pediatrics nonbinary individuals are most comfortable with an androgynous FINANCIAL DISCLOSURE: The authors have indicated THE CASE they have no financial relationships relevant to this gender expression. For those who article to disclose. have yet to fully progress through EF is a physically well, academically FUNDING: Funded by the Government of Victoria puberty, puberty suppression with bright 15-year-old. EF was assigned male at birth but has for many years through the Operational Infrastructure Support gonadotrophin-releasing hormone Program (Drs Savalescu and Wilkinson) and The had a nonbinary gender identity and agonists (GnRHa) can support an Royal Children’s Hospital Foundation (Dr Pang). preferred the use of gender-neutral androgynous appearance. Although POTENTIAL CONFLICT OF INTEREST: The authors have “they” and “them” pronouns. such treatment is shown to ameliorate indicated they have no potential conflicts of interest the gender dysphoria and serious As a preschooler, EF displayed gender- to disclose. mental health issues commonly seen in diverse behaviors and struggled to TGD young people, long-term use of identify with being exclusively male or To cite: Pang KC, Notini L, McDougall R, et al. puberty-suppressing medications also female. At primary school, they initially Long-term Puberty Suppression for a Nonbinary Teenager. Pediatrics. 2020;145(2):e20191606 carries physical health risks and raises presented as male, but this did not feel

Downloaded from www.aappublications.org/news by guest on September 25, 2021 PEDIATRICS Volume 145, number 2, February 2020:e20191606 ETHICS ROUNDS right. During this time, with parental least 18 years old under the care of EF’s bone density has already fallen support, they identified and dressed their gender service. Their clinicians to the lowest 2.5 percentile. It can be as a girl at home. This did not feel contact the clinical ethics consultation expected to continue falling. Although right either. EF became increasingly team to ask, “Is that appropriate?” EF is at increased risk of fractures, unhappy, prompting a referral to their this needs to be put into perspective. local gender service, where they Lauren Notini, PhD, Rosalind According to 1 calculator, a 50-year- received a diagnosis of gender McDougall, PhD, and Lynn Gillam, old birth-assigned male with a bone dysphoria and have had ongoing PhD, Comment density in the lowest 2.5 percentile psychiatric and pediatric support. The key question in this case is has a 0.2% to 0.3% risk of sustaining whether it is ethically justifiable for a hip fracture and a 1% to 2% risk of Soon after attending the gender clinicians to offer puberty blockers other fractures in the next 5 to service, EF began to identify as long-term to EF. 10 years compared with a control agender (ie, they saw themselves as with normal bone density (0% risk of neither male nor female). With the In many health care situations hip fracture and 0.7%–1% risk of support of their family, friends, and involving young people, questions of other fractures in the next 5–10 the school community, they have lived capacity arise. The issue of whether years).1 This calculator is based on full-time as such ever since, although EF has the capacity to consent to data from older adults who have gone with their long hair and tendency to puberty blockers on their own behalf through puberty; hence, how low wear dresses, they are often regarded is 1 element of this case. However, in bone density affects EF’s actual risk of ’ as female by strangers. EF s mental our view, it is not the most ethically fractures is unknown. Nevertheless, health had been good with only minor important nor the most ethically even if EF’s risk of fractures is higher discomfort associated with their male complex aspect of this situation. The than these statistics, EF and/or their genitalia. capacity question is relevant only parents may still decide that these insofar as it determines who can The onset of puberty at age 11 was risks are outweighed by the potential provide consent to the intervention. fi associated with worsening gender psychosocial bene ts of EF having The more ethically complex aspect of fi dysphoria and increased anxiety a body that ts their nonbinary this case is whether the intervention about possible voice deepening and identity. should be provided even with the facial and body hair growth. EF consent of EF or their parents. We regarded these masculinizing changes Alternatively, EF could discontinue will therefore assume that EF’s as inconsistent with their agender blockers and recommence male parents will consent to long-term identity and was therefore keen to puberty. Or they could begin estrogen blockers if EF is not capable of commence GnRHa to suppress further and a transition to a female providing their own consent. We pubertal development. Relevant phenotype. These options could focus, then, on the question of counseling with their pediatrician and address the bone density concerns whether offering blockers long-term psychiatrist included discussion of described above to some degree. is justified. the possible benefits and harms of Although adolescents who have received puberty suppression commencing GnRHa therapy. In this case, there is the range of experience an increase in bone Eventually, both EF and their parents possible pathways for EF’s care with density after estrogen or testosterone provided assent and consent to substantial uncertainty about the therapy, their bone density is still commence GnRHa. Treatment was risks and benefits of each approach. below that of age-matched peers.2 It started at age 12 while EF was at There is currently a lack of evidence is not known whether their bone Tanner stage 2. about the impact of using puberty density catches up later. An ethical blockers long-term. But we can At age 15, EF remains on regular problem with this approach is that EF speculate. GnRHa treatment. The dysphoria and would develop unwanted secondary anxiety have diminished. Annual If EF does use blockers long-term, sexual characteristics. Their gender dual-energy radiograph absorption there seem to be 2 main risks: dysphoria and anxiety will likely scan monitoring has shown that their impaired fertility in the future and return, potentially increasing their bone mineral density has regularly low bone density. There is 1 primary risk of self-harm or suicide.3 The fallen and is now in the lowest 2.5 benefit: treatment could continue to trade-off here is thus between EF percentile, although there have been alleviate EF’s gender dysphoria and maintaining normal bone density no fractures. EF, whose desire for anxiety. How that should be weighed with increasing gender dysphoria and biological children in the future against the risks depends on the EF using medication to relieve gender remains unclear, wishes to continue magnitude and seriousness of the dysphoria but increasing the risk of puberty suppression until they are at harms that could result. bone fractures.

Downloaded from www.aappublications.org/news by guest on September 25, 2021 2 PANG et al A third option is that EF could remain which we have framed the Biologically, it is not. Continuing on blockers for another year or 2 only ethical issue. puberty suppression poses some to give EF more time to consider their significant health risks. The issue is gender identity and future options. Dealing with the straightforward whether the psychosocial benefits This presents less risk to bone concern about bone density allows outweigh the biological harms. This density than if EF remained on other, deeper ethical questions to requires a deep exploration of the fi blockers long-term and so would be emerge. Is it ethically justi able to patient’s psychology, conscious and more ethically justifiable. However, it use medical interventions to support unconscious motivations, values, may not resolve the issue. EF may nonbinary gender identity on capacity for psychological change and continue to identify as nonbinary and a permanent basis? Or is there some adaptation, and the nature of their fi not be willing to discontinue blockers ethically signi cant difference social relationships. at a later stage. between nonbinary gender identity and binary transgender identity? For Philosophy can contribute to the There is another option that appears example, critics might argue that analysis of such a case through to avoid the trade-off between bone nonbinary bodily appearance in theories of the meaning of well-being. health and psychological well-being. adults is just too different from what There are 3 main theories of well- “ ” fi EF could remain on blockers long- is natural and that creating such an being: hedonistic, desire ful llment, term while receiving medication appearance does not fall within the and objective list. According to known as selective estrogen receptor proper goals of medicine. In contrast, hedonistic theories, what matters is modulators (SERMs). Because SERMs on this view, binary transgender happiness and pleasure. For desire fi have estrogenlike actions in certain identity does involve a desire for ful llment, the good of a person lies “ ” tissues (eg, bone) but not others (eg, a natural bodily appearance (albeit in that person satisfying their deepest breasts),4 they could theoretically not the 1 that matches the bodily and strongest desires. According promote improved bone density appearance at birth) and so can be to objective list theories or while preventing the development regarded as consistent with the perfectionistic theories, what is good of unwanted secondary sexual proper goals of medicine. We do not for a human being is to be engaged in fi characteristics, allowing EF to nd this argument convincing, but we certain meaningful activities, like continue to psychosocially benefit do see that there is as important deep personal relationships, having from blockers. On the other hand, question to answer. But that question and raising children, being creative, SERMs are typically only used in is beyond the scope of this essay. or being morally good. much older patients to treat breast Overall, then, using SERMs to support A person’s psychology places certain cancer, osteoporosis, and menopausal EF in their nonbinary gender identity boundaries on what can be good for symptoms, although they have been long-term looks to be the most them. For example, if a person deeply occasionally used to treat boys who ethically justifiable option, although it does not wish to be a parent, then develop gynecomastia during having children could be bad for that 5 is not without its own ethical puberty. They have not been used in complications. person and their children. For conjunction with puberty blockers in another person, having children could young patients such as EF. SERMs are be good. also associated with side effects of Julian Savulescu, PhD, and Dominic Wilkinson, FRACP, PhD, Comment their own, including hot flashes and However, it is not merely present increased risk of blood clots.4 There is The basic ethical principle of medical psychology and a person’s occurrent also some evidence that tamoxifen, ethics is that doctors should offer wishes that determine their well- a type of SERM, can be associated patients treatments that are in their being. Psychological development with cognitive impairment in women best interest. Best interest clearly may open new possibilities for being treated for breast cancer.6 This includes not just the treatment of greater well-being. In this regard, risk could potentially be exacerbated disease but the psychosocial well- extensive psychological analysis and in the developing adolescent brain. being of the person. Doctors are not counseling is necessary. Lemma7 under an ethical or legal obligation to notes that some transgender cases Notwithstanding these potential risks, offer interventions that are not in the represent deep conflicts about the possibility of using SERMs to best interest of the patient. So, the identity and other unconscious achieve the body shape that EF wants, central ethical question in this case is conflicts. A psychological assessment while avoiding the problem with bone whether continued hormonal can assist in identifying whether density, is attractive. It seems to have suppression of puberty for EF, with transitioning to another gender or, in mostly ethical pros and minimal an increasing risk of osteoporosis and this case, delaying puberty is best for ethical cons, according to the terms in fractures, is in their best interest. this patient.

Downloaded from www.aappublications.org/news by guest on September 25, 2021 PEDIATRICS Volume 145, number 2, February 2020 3 In many cases, it will not be clear deep uncertainty around the question for EF, their family, and their care what is in the best interest of the of whether continued puberty team.10 8 patient. Because of pluralism in suppression is in their best interest Step 1: Identify ethical concerns. value and different valuing of risk, it and whether their desire for this is Continuation of pubertal can be ambiguous as to which course autonomous. What should we do suppression, although beneficial of action is best. The second principle then? When either the implications of for alleviating distress, preventing of medical ethics is that patients a medical intervention for well-being secondary sex characteristic should make their own autonomous are unclear or the extent of the development, and providing time decisions about the medical autonomy of the patient is not fully for decision-making about fertility treatments offered to them. When it is determined, we contend that there is and family creation, may be fi uncertain whether a course of action is a moral obligation to scienti cally inappropriate because of in the interest of the patient, doctors study such interventions to diminishing bone density. should defer to the autonomous determine their impact on well-being Step 2: Gather relevant information. evaluations of the patient. or the degree of autonomy. That is, EF has received care consistent the intervention should be as Autonomy is self-determination. It is with current guidelines, including rigorously studied as possible. about forming one’s own values and assessment of needs and pubertal choosing from a range of options The gold standard for scientific suppression. This has improved what one believes will make one’s research is the randomized placebo- their quality of life, and EF’s stated own life best (or acting morally). It is controlled trial. A controlled trial preference is to continue pubertal not mere choice: many of our choices would be preferable to either suppression. Discontinuing do not promote our values. Values are uniformly providing or denying this puberty blockers without other what we rationally endorse: what we treatment. It would promote the interventions would result in the believe is valuable when we have all interests of young people with gender development of a testosterone- the facts, are thinking logically, and dysphoria, both now and in the directed puberty (eg, lower voice, are vividly imagining the alternatives. future, through generating evidence facial hair, and larger stature) that Importantly, autonomy requires about the benefits and harms of is either permanent or would a concept and understanding of the treatment. But such trials are not require surgical intervention to self, the being whom choice will always feasible. If EF did not wish to change. It is well understood that affect. Autonomy involves the enter a trial, a case-control design the development of secondary sex matching of the world to that self. might be employed. Research would characteristics that are not aligned reduce uncertainties about whether with gender identity causes EF is 15 years old, and it is not clear such interventions are in the best suffering for many transgender what their level of cognitive interest of the patient. Without good individuals.11 Potential effects of development is. Moreover, full outcome data, we leave EF’s fate to long-term pubertal suppression autonomy, even for adults, requires guesswork. This approach would monotherapy on bone density are a deep understanding of both almost certainly result in harm to unclear; however, with shorter- conscious and unconscious desires some patients, now and in the future. term use (2 years), bone density and motivations. It requires not only increases significantly once sex understanding of the world (in this Some people analyze dilemmas such hormones are introduced.12 Some case, the medical options and their as this by relying on a distinction clinicians recommend limiting consequences) but of oneself. The between “treatment” and suppression to 2 years to promote importance of psychological analysis “enhancement.” We reject that optimal bone density.13 Although is again central to such cases. approach. Even if gender dysphoria is fi not a disease in the strict medical the bene ts of pubertal Just as it may not be clear whether sense, the use of puberty blockers suppression are clearly a choice is in the best interest of the 14 might be an instance of an established, EF will need to patient, it may not be clear whether enhancement that promotes well- experience sex hormones at that choice is fully autonomous. In being.9 some point. such cases, we should defer to the Autonomy is supported through desires of a competent patient or, if Beth A. Clark, PhD, HEC-C, RCC, and timely access to information that is they are incompetent, their Johanna Olson-Kennedy, MD, necessary for informed decision- competent surrogate (in this case, the Comment making.15 EF likely has the capacity to parents). We provide an analysis using make decisions regarding their care Where does that leave us? In cases a clinical ethical decision-making and should be supported in this by like EF’s, we suggest that there is framework to identify a path forward their parents and care team. It is

Downloaded from www.aappublications.org/news by guest on September 25, 2021 4 PANG et al unknown whether EF and their until age 18, or (3) make a decision a narrative ethics approach, EF can parents have received adequate about sex hormones now. be supported in envisioning information regarding known and Step 4: Consider consequences. First, a range of possibilities and feeling unknown implications of extended a unilateral decision by the team to empowered to author their unique 20 pubertal suppression and the immediately halt pubertal gender journey. temporary nature of this intervention suppression without a clear and John D. Lantos, MD, Comments and whether they have been engaged imminent health risk carries in fertility and family-creation potential for both triggering The case and comments illustrate the 1,13,16,17 counseling. a mental health crisis and neglect complexity of providing medical care fi of fiduciary duties. We also find the in the absence of a strong scienti c Decisions about EF’s care are being second option, continuation of evidence base for making choices. made in a societal context of pubertal suppression as Ideally, we would know the long- increasing affirmation of transgender a monotherapy until age 18, term physical and psychological experiences and availability of insupportable because “kicking the consequences of various gender-affirming care. However, interventions and their can down the road” (ie, delaying gender-affirming care remains largely corresponding noninterventions. inevitable decision-making) is focused on binary experiences, Then, at least, we could base a risk- likely to have detrimental effects contributing to excessive barriers and benefit assessment based on facts. In and may not yield significant long- health inequities for nonbinary this case, uncertainties abound. 15,18 term benefits. Third, making (including agender) youth. Experts must make recommendations a decision about sex hormones in Decision-making may be impacted by on the basis of speculation and the short-term could result in a lack of information regarding extrapolation. Furthermore, the benefits for bone density, access to gender-affirming care options for nature of treatment options in cases decisional support from family and nonbinary people. Care planning that like this are such that randomized familiar care providers, validates nonbinary experiences and trials are likely infeasible. All we can minimization of harms, and explores a range of options, including hope for are cautious clinical promotion of fidelity. not taking exogenous hormones judgments, shared decision-making, (known as “noho”) and low-dose Step 5: Make, implement, and and careful evaluation and reporting hormone regimes (known as “loho”), evaluate a choice. We support of outcomes after different choices is essential for promoting justice. a gender-affirmative approach with are made. a care plan that involves the It is vitally important to respect EF’s following: creating space to explore experience of gender and goals of the complexities of gender and the ABBREVIATIONS care because only EF can know their full range of appropriate medical GnRHa: gonadotrophin-releasing own gender. However, although and nonmedical options, making hormone agonists patients generally have a negative a decision about sex hormones (ie, SERM: selective estrogen receptor right to refuse unwanted endogenous or exogenous; alone or modulators interventions, they do not have in combination with pubertal TGD: transgender and gender a positive right to demand suppression), and ceasing pubertal 19 diverse unreasonable treatment. EF’s suppression as a monotherapy in clinicians must consider whether the a supportive manner. 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Downloaded from www.aappublications.org/news by guest on September 25, 2021 Long-term Puberty Suppression for a Nonbinary Teenager Ken C. Pang, Lauren Notini, Rosalind McDougall, Lynn Gillam, Julian Savulescu, Dominic Wilkinson, Beth A. Clark, Johanna Olson-Kennedy, Michelle M. Telfer and John D. Lantos Pediatrics 2020;145; DOI: 10.1542/peds.2019-1606 originally published online January 23, 2020;

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