Advances and New Perspectives

#### **Chapter 6**

## Standards Developments for Improving Care for Transgender People

*Kelly Davison*

#### **Abstract**

Outdated GSSO information practices contribute to institutional and interpersonal stigma for transgender people in healthcare. Poorly defined data elements, conflated sex and gender concepts, constrained representation of gender variation, and lack of cultural understanding on the part of health information professionals and clinicians are contributing to healthcare environments and interactions that stigmatize transgender people and that drive health inequities. In this chapter, I will review recent developments in standards oriented toward addressing gender bias in the technical structures that support healthcare institutions. I will focus on the international work of Canada Health Infoway's Sex and Gender Working Group and the Health Level Seven International Gender Harmony Project. The intent is to provide an overview of these efforts and garner further interest, participation and adoption standards that support safe and gender-affirming healthcare for all people.

**Keywords:** GSSO information practices, Canada Health Infoway, Sex and Gender Working Group, HL7 International, Gender Harmony Model, health equity

#### **1. Introduction**

An estimated 1–3% of people in Canada are transgender, and just over 7% of Canadians identify as lesbian, gay or bisexual [1]. Approximately 32% of them report having unmet healthcare needs [2]. In the United States, there are over 1,000,000 transgender people, a third of which report avoiding healthcare for fear of discrimination [3]. Transgender people and sex and gender minorities (SGM) experience unnecessary and preventable health inequities including higher rates of mortality, depression, anxiety, substance use, chronic disease and suicidality which are, in part, the summary result of atrocious experiences of discrimination and stigmatization on the part of healthcare staff and institutions [1, 4–6]. Institutionalized cisheteronormativity, a term which refers to the culturally-driven normalization of cisgender, heterosexual status and the invisibilization of non-cis, non-heterosexual people [7, 8], is a primary social bias encoded into digital health structures and care cultures that prevents meaningful knowledge development about the health status

and needs of this population [1, 6, 7]. Poorly defined data elements, conflated sex and gender concepts, constrained representation of gender variation, and lack of cultural understanding on the part of health information professionals and clinicians are all conditions contributing to healthcare systems, environments and interactions that stigmatize transgender people, and that drive health inequities [1, 6–10]. Since 2019, technical, data and messaging standards development organizations (SDOs) have been working to modernize gender, sex and sexual orientation (GSSO) information practices in electronic health records (EHRs) to enable inclusive and affirming care for transgender people and SGM [1, 8, 11]. In this chapter, I will provide an overview of these recent innovations, including work of Canada Health Infoway's Sex and Gender Working Group and the HL7 Gender Harmony Model.

#### **1.1 Health is a human right**

The global population of transgender people and SGM live with higher burdens of disease and lower health than many other populations, especially cisgender people [12, 13]. Despite of the fact that the human rights of transgender people are protected by national and internal law [14], transgender people continue to face severe discrimination. The experiences of transgender people in healthcare, at the hands of healthcare staff, are atrocious [1], and ought to be a central concern to healthcare decision makers, policy makers and legal supports, and to society at large [15, 16]. Healthcare, as an organizational, regional, national and global social system with a specific ethical orientation that ought to adhere to, uphold, and advocate for the Universal Human Rights of transgender people, and *Health for All* [17]. Health is a human right [18]. Modernization of outdated gender, sex and sexual orientation information practices is a foundational step to creating healthcare institutions that are gender-affirming [9, 10, 12, 13].

#### **2. Outdated GSSO information practices**

Modernization of outdated GSSO information practices is an equity-oriented endeavor [19] intended to address the technical conditions that enable structural and institutional bias and that contribute to health inequities for transgender people and SGM [16]. Information practices include the definition, collection, organization, sharing and use of health information [17]. The term "Gender, Sex and Sexual Orientation" or "GSSO" was coined by C. Kronk, PhD of Yale University, who has created and published a Queer Ontology to facilitate increased awareness and improved understanding and consistency of use of GSSO terms [14, 20]. Outdated GSSO information practices include:


#### **3. Modernizing GSSO information practices**

Building on the momentum of the work of such expert agencies as the Fenway Institute, Trans Care BC and Rainbow Health Ontario, there has been a recent increase in activity related to raising the critical awareness about the importance of diversity, equity, and the role of healthcare in creating the conditions for the well health of transgender people and SGM in North America and beyond [11, 12]. A diverse international community of people and organizations, including expert agencies, SDOs, researchers, EHR and solutions vendors, healthcare professionals and health information professionals, have dedicated their time and expertise to making healthcare more inclusive. In this section, I will discuss key developments within this community and key activities in relation to the healthcare of transgender people and SGM beginning with my own country, Canada.

#### **3.1 Canada Health Infoway**

Heading up the co-development, maintenance and support of technical and interoperability standards that support healthcare in the country, Canada Health Infoway (Infoway) has been a key organization enabling digital health in Canada since 2001. As Canada's National Release Center for such technical standards as the HL7 International information exchange standards, the Systematized Nomenclature of Medicine—Clinical Terms (SNOMED CT) and Logical Observation Identifiers, Names and Codes (LOINC), Infoway's mandate includes bringing a Canadian perspective to international standards development with SDOs such as HL7 International, SNOMED International, and the Regenstrief Institute. At the national level, Infoway collaborates with a network of pan-Canadian Healthcare Organizations, provinces, jurisdictions, vendors and governance bodies to support the implementation of technical standards in the Canadian digital health ecosystem and develops, maintains and publishes pan-Canadian and jurisdictional subsets via

the Terminology Gateway service. Infoway convenes stakeholders by establishing communities for collaboration and working groups on a central information sharing and engagement platform, InfoCentral. One such working group is Infoway's Sex and Gender Working Group (SGWG).

#### **3.2 Canada Health Infoway's sex and gender working group**

Infoway's SGWG was established in 2019 with the primary aim of modernizing outdated GSSO information practices in Canadian electronic health records [17] to support the health of all Canadians. Since then, this international community of researchers, pan-Canadian Health Organizations, healthcare agency representatives, subject matter experts, and people with lived experience have been convening monthly to share recent and relevant research, discuss the process of modernization [17] and lead modernization by taking evidence-informed action.

#### **3.3 A proposed action plan to modernize GSSO information practices**

After 2 years of convening, Infoway's Sex-Gender Working Group produced *A Proposed Action Plan to Modernize GSSO Information Practices in Canadian Electronic Health Records* (the Action Plan) in early 2021 [17]. This visionary work, led by Dr. Francis Lau of the University of Victoria and supported by a network of people and agencies participating in the SGWG including Health Canada, the Canadian Institutes of Health Research Institute of Gender and Health, Canada Health Infoway, the Canadian Institute for Health Information, the Canadian Health Information Management Association, the University of Victoria GSSO research team and more, provides a comprehensive summary of existing research and proposes a plan to modernize the outdated GSSO information practices that stigmatize transgender people and SGM [21]. Although grounded in the grassroots of Canadian healthcare, the vision, recommendations and research knowledge outlined the Action Plan could be applied internationally. There are seven primary aims of the GSSO Action Plan produced by the Infoway SGWG:


Although there remains much work to do, members of Infoway's SGWG are using the Action Plan and its aims as a guide to specify and cultivate adoption of modern, consensus-based data, technical and exchange standards that address structural cisheternormativity in Canadian healthcare. The community continues to meet on a monthly basis and drive new research, insights, and the development of modern approaches and practices to realize the aims outlined in the Action Plan.

The continued support of standards organizations such as Canada Health Infoway will play a foundational role in the ongoing process of modernization of healthcare. More information about Canada Health Infoway and Infoway Communities can be found on InfoCentral.

#### **4. HL7 International**

The beliefs, attitudes and organizational practices required to create culturally and psychologically safe, quality healthcare for transgender people will be adopted by individual health organizations. However, meaningful change will not happen unless the standards that we use to communicate health information from one service to another—the standards we use to connect a continuum of care services are also modernized such that they are inclusive of transgender people and SGM and are designed to address the problems related to outdated information practices. Health information exchange standards (sometimes referred to as messaging standards) are powerful drivers of systemic change. As a world-leading exchange standard development organization, HL7 International plays an important role in the specification and implementation of health information exchange standards that support *Health for All.*

#### **4.1 The HL7 International gender harmony project**

In 2019, HL7 International created the Gender Harmony Project as an open, international collaboration of volunteers and experts from international agencies and SDOs dedicated to creating gender-inclusive standards in healthcare, and to addressing harms associated with biased exchange standards [11]. Members of this group have been meeting regularly to define, specify, model and explicate the Gender Harmony Logical Model since its establishment.

#### **4.2 The HL7 International gender harmony logical model**

In early 2021, the Gender Harmony Project produced the informative-ballot-forcomment that outlines the Gender Harmony Logical Model. Input on the document was collected from international stakeholders, and the first release of the informative document was published by the HL7 International Vocabulary Working Group in August of 2021: *Gender Harmony*—*Modeling Sex and Gender Representation, Release 1* [22]. The Gender Harmony Logical Model is a model that can be applied in the design of inclusive digital health systems and messaging standards such as HL7 version 2 (HL7v2), Version 3 (V3), Clinical Document Architecture (CDA®) and Fast Health Interoperability Resources (FHIR®) used to exchange health information between digital health systems [11]. The Gender Harmony Logical Model supports modernized design of interoperable EHRs and related standards, and is designed to enable:

#### *4.2.1 Improved definition of gender and sex information*

	- Explicit description of model concept and element attributes means that organization of administrative and clinical GSSO information is clearly defined, streamlining GSSO data collection use cases.

#### *4.2.3 Clear organization of gender and sex information*


#### *4.2.4 Semantic sharing and exchange*


#### *4.2.5 Reduced risk of use of outdated information practices*

1.Reduces unconscious bias and unchecked assumptions related to sex and gender.


The consistent application of the Gender Harmony Model in the design of joined-up health information systems is a shift in paradigms—from outdated GSSO information practices to modern ones, and a shift that enables quality healthcare for transgender people and SGM.

#### **4.3 The gender harmony paradigm**

The Gender Harmony Paradigm in healthcare is implementing systems design that addresses conditions resulting in health inequities for SGM. It involves meaningful integration of the HL7 Gender Harmony Logical Model, modern GSSO information practices and associated standards enabling culturally safer institutional policies and practices that support inclusive healthcare for transgender and SGM people. The Gender Harmony Model reduces real and latent harms associated with current gender constructs in health by: (1) decoupling administrative and clinical concepts in digital health systems; (2) addressing the conditions that lead to negative clinical interactions that deter transgender people from seeking care (e.g. being misgendered, misnamed or outed); and finally (3) by addressing conditions that make transgender people and people with nonbinary gender identities invisible to clinicians, policy makers, analysts and researchers who use health information for system improvement. At the patient level, the Gender Harmony Model enables clinicians' use of person-centred language in clinical interactions and provides them with the information necessary for objective and appropriate preventive screening, treatment and referral options based on unambiguous sex and gender health information. At the organizational level, implementation of the Gender Harmony Model involves the adoption and use of logical, technical and data standards necessary to support gender affirming care cultures and practices. At the health system level, implementation of the model orients clinical and institutional healthcare toward gender equity by addressing problems associated with the omission of data elements required to generate knowledge for health system improvement.

#### **4.4 HL7 International gender harmony model overview**

The Gender Harmony Logical Model, which I will call 'the Model' throughout the remainder of this chapter for ease of reading, does not exclusively benefit transgender and nonbinary people. All patients benefit from higher quality care and analytics enabled by the Model. Application of the Model can broadly be considered a step toward personalized medicine and more person-centred care since it enables more granular use and understanding of complex social and medical phenomena. The data elements of the Model [22] are designed to address the conditions that are currently leading to health inequities for transgender people such as problems associated with omission of data elements required for affirming care (i.e. Name to Use, Pronouns), conflation of administrative sex and gender concepts (i.e. Gender Identity, Recorded Sex or Gender) and by creating opportunities for clinicians to provide care by specifying care needs, rather than making assumptions related to outdated binary

constructs (i.e. Sex for Clinical Use) [11]. In this section, I will provide an overview of each data element and its specific attributes that support design and implementation decisions in digital health systems such as EHRs. Model data elements will be capitalized to improve readability.

#### *4.4.1 Gender identity*

In healthcare, knowing a patient's gender identity allows clinicians to provide informed and affirming, quality care, without misgendering them based on assumptions or pre-existing and out of date information in the patient record. All people have a gender identity. Gender Identity is a person or patient's personal sense of being a man, woman, boy, girl or something else [22]. Gender identity must be declared by the person or patient, rather than them being labeled with it. Gender identity is fluid and can change, and so must be collected routinely [23]. People can identify with none, one, or many genders, and can set time constraints on specific gender identities. Gender Identity should be used in conjunction with the other Model data elements to support gender-affirming, quality healthcare and should be validated privately with the patient to avoid outing them. Outing is when information about a person's gender or sexual identity is made known to specific people without permission. If this is done by a clerk or a clinician in the context of an emergency room or a waiting room, it may be directly harmful to the person being outed or lead to harm. As with all EHR data, informed consent about collection, sharing and use of Gender Identity information should be acquired before it is entered in the patient chart.

In order to ensure international applicability of the Model, the terms *male gender identity* and *female gender identity* have been used to represent gender identities associated with binary male and female sexes. The term nonbinary gender identity is proposed as a value option to represent code value options that are not accurately represented within the binary male/female construct [22].

Gender Identity is included in the Canadian Institute for Health Information CIHI Reference Data Model [24] (CRDM) and the United States Core Data for Interoperability Version 2 [25] (USCDIv2).

#### *4.4.2 Name to use*

Name to Use is the name that the person accessing healthcare services uses and wishes the care team to use. Importantly, Name to Use may not simply be a person's preferred name. Name to Use may be a name associated with the person's gender identity, and so should be used in healthcare interactions to avoid misnaming or outing people. Name to Use may or may not be consistent with a person's legal name. Misnaming people based on legal records can be harmful, so it is best to ensure that the name the patient uses is validated privately, and that this validated information is updated in the patient record routinely and promptly upon patient arrival to prevent misnaming or outing in subsequent care interactions. Use of the Name to Use may be time-limited [22].

#### *4.4.3 Pronouns*

Pronouns (also called third person pronouns, personal pronouns and incorrectly often called preferred pronouns) and possessives are language tools used to communicate with and about people. They include such options as he/him/his, she/her/

#### *Standards Developments for Improving Care for Transgender People DOI: http://dx.doi.org/10.5772/intechopen.101907*

hers, and they/them/theirs, among many options [7]. Pronouns come in sets. The most common pronouns used are gendered, and so by validating pronouns used by a patient and updating the care record before clinical interactions occur, intake staff can help ensure that patients are not misgendered by clinicians in subsequent interactions by the use of incorrect pronouns, and maintain the integrity of the therapeutic relationship. The Pronouns data element of the Model complements Gender Identity and Name to Use to ensure that communications with and about a patient are personcentred and affirming of their gender [21]. A useful rule of thumb is that until pronouns are confirmed by the patient, the gender-neutral options they/them/theirs can be used in interpersonal interactions to avoid misgendering. Like Name to Use and Gender Identity, patients may use more than one pronoun or set of pronouns, and their use of specific pronouns may be time delimited.

#### *4.4.4 Recorded sex or gender*

One of the primary problems associated with outdated GSSO information practices is that sex and gender concepts, the code values that represent them, the labels on the data fields they occupy and their distinct meanings, are conflated and used as though they are synonymous [6]. Administrative values cannot be used for clinical decision making with 100% reliability, particularly when used in the care of people whose sex at birth does not align with their gender identity and people who identify as transgender. Separating the sex or gender value that has been recorded on identification and other administrative or legal artifacts from clinical sex and gender identity helps to reduce unchecked assumptions about anatomy based on inaccurate recorded sex or gender information. The Model data element called Recorded Sex or Gender does just this: it separates administrative sex and gender information from the clinical sex and gender information, and is necessary to provide safe, quality, and genderaffirming clinical interactions.

Because there are so many different possibilities in the documentation that patients can present to support identification, it may be important to know the provenance of the Recorded Sex or Gender information. Provenance includes details about the jurisdiction that issued the record, its acquisition date, its validity period, and information about the source record including the name and definition of the field name and definition. Sex or gender information that is displayed on drivers' licenses, government IDs, birth certificates and other documents are Recorded Sex or Gender information. In many cases, this information is acquired through active interfaces between health information systems and government administrative databases via exchange standards. Inconsistencies between Recorded Sex or Gender data values and Gender Identity should not automatically be regarded as erroneous and should be validated with the patient.

Birth sex, or sex assigned at birth, as an example of recorded sex or gender that is present in most care records, is included in the CRDM [24] and the USCDIv2 [25].

#### *4.4.5 Sex for clinical use*

Sex for Clinical Use is a novel clinical data element that supports person-centred care by enabling clinicians to specify clinical sex beyond binary options based on different observations. Much like the explicit inclusion of a patient-declared Gender Identity, the key value of Sex for Clinical Use is that it enables the removal of unchecked assumptions about a person's sex that may be present in administrative binary male/female constructs. To achieve this, a provider may refer to an anatomic inventory, a surgical history, a hormonal inventory or other artifacts that inform the context for the observation. Four such examples include:


Full transition is not always required to address gender dysphoria [10], but the ability for providers to reduce unchecked assumptions based on recorded sex or gender, and provide agile, appropriate and quality care to all people is an important feature that the model supports. Value options that are proposed for the model include 'male,' 'female' and 'specified' sex for clinical use. The term 'specified' was chosen for the Model to eliminate stigma associated with a value options of 'complex' (not all patients who may benefit from the use of this element are particularly complex), to align with the use case where an option is specified by the provider, and to enable backwards compatibility with (and avoid use) of the stigmatizing term 'other,' as is so commonly used in health information systems [8].

#### **5. Stigma, encoded**

When used together, the five data elements of the Gender Harmony Logical Model facilitate the tight alignment between social concepts, code systems, health terminology standards, exchange standards, EHR design and healthcare practices required to address stigma and drive health equity through the provision of gender-affirming care. However, code systems and health terminology standards are dynamic in nature and remain prone to the inappropriate codification of stigmatizing or pathologizing terms, codes or concepts [4]. As society becomes more complex and technology become more ubiquitous, the importance of remaining vigilant for standards that exclude marginalized populations and intersectional patient identities will become increasingly important. Primary care providers, in particular, are instrumental to the implementation of changes that will close the equity gap for transgender people because they provide the bulk of preventive screening and treatment related care and serve as a primary coordination point for patients. Modernized GSSO information practices help primary care providers to ensure that patients are appropriately matched to their care needs, and that assumptions related to conflated sex and gender concepts are avoided [13]. However, regulated health information professionals that have healthcare-specific training and awareness of healthcare models, ethics and practice will play a critical role in supporting modernization efforts. Certified Terminology Standards Specialists (CTSS), Certified Classification and Coding Specialist (CCCS), Certified Healthcare Information Management (CHIM) professional credentials, signal professional adherence to a base set of demonstrated

#### *Standards Developments for Improving Care for Transgender People DOI: http://dx.doi.org/10.5772/intechopen.101907*

competencies and ethics, and professionals with health information credentials such as these are more likely to have knowledge about the importance of the therapeutic relationship and downstream impacts of technical design on patient care [26]. A major responsibility of certified health information professionals is to align technical design with clinical requirements such that the integrity of this most sacred and fundamental component of healthcare—the therapeutic relationship—is protected. Like credentialed and regulated clinicians, certified health information professionals are accountable for upholding the core evidence-based values and ethics that support healthcare (i.e., person-centred care, trauma-informed care, the Gender Harmony Logical Model). The Digital Health Revolution has arrived [27], and the ongoing datafication of healthcare and society means that informatics professionals must regularly visit their ethics to ensure they are aligned with healthcare values, develop critical awareness of the impact of structural bias in data and technical design and standards on social justice, cultivate ethical communities around the design and analysis of information systems and standards, and evaluate the impact of their work on the lives of the patients they serve [28].

#### **6. Conclusion**

Transgender people experience unnecessary and preventable health inequities that are, in part, the result of social bias encoded into the technical and data structures that connect systems in the digital health ecosystem. Poorly defined data elements, conflated sex and gender concepts, constrained representation of gender variation in code systems, outdated terminology standards and health information exchange standards contribute to this harm. Canada Health Infoway's Sex and Gender Working Group is an international, transdisciplinary community of people and agencies with an Action Plan to modernize gender, sex and sexual orientation information practices in healthcare. The HL7 International Gender Harmony Project has recently published the first release of the informative document for the Gender Harmony Logical Model, a consensus-based, evidence-informed logical model developed to address outdated information practices and support the modernization of healthcare for sex and gender minorities. Though there remains much work to do, this dedicated international community of professionals, researchers and people with lived experience are undertaking actions that enable inclusive and affirming care for transgender people and SGM.

#### **Acknowledgements**

I gratefully acknowledge the ongoing support of these efforts by Health Canada, Canada Health Infoway, all the members, agencies and presenters participating in Infoway's Sex-Gender Working Group, the Canadian Institute of Health Information, the Canadian Health Information Management Association, the Office of the National Coordinator, HL7 Canada, HL7 International and the University of Victoria GSSO Research Team, the Canadian Institutes for Health Research, Michael Smith Health Research BC, the Community-Based Research Centre, and the large community of people, providers and agencies dedicated to equitable health for transgender people and sex and gender minorities for their continued work toward a better humanity, and a better future.

### **Conflict of interest**

The author(s) declare no conflict of interest.

#### **Notes/thanks/other declarations**

My thanks to Dr. Francis Lau for his review of this chapter as I was drafting it. The information provided in this chapter has been derived from my participation as Co-Chair in Infoway's Sex and Gender Working Group and participation in the HL7 Gender Harmony Project. Please report any mistakes or inconsistencies to me at kdaviso@uvic.ca

### **Author details**

Kelly Davison University of Victoria, Victoria, British Columbia, Canada

\*Address all correspondence to: kdaviso@uvic.ca

© 2022 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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#### **Chapter 7**

## Phalloplasty in Transgender Men with and without Urethral Lengthening

*Christopher Salgado, Kerstin Yu, Stefan Kenel-Pierre, Edward Gheiler and Tony Shao*

#### **Abstract**

Our goal in trans man phalloplasty is to decrease the patient's level of gender incongruence, obviate the use of an external prosthesis, be able to orgasm, and give the patient the ability to urinate standing (if desired), while also attempting to decrease urinary complications. The decision to undergo urethral lengthening is considered early in this surgical process. However, urethral complications are among the most common problems we see in phalloplasty, and surgical techniques have evolved to decrease these complications. We have developed an advanced two-stage mucosa-only prelaminated neourethra phalloplasty technique to address these issues. Our surgical technique is detailed in addition to providing patient demographics, co-morbidities, flap complications, and urinary sequelae. We also discuss the perineal urethroplasty in patients opting for no urethral lengthening in phalloplasty. All options should be given and risks considered in trans men undergoing soft tissue phalloplasty, and these will be discussed in detail.

**Keywords:** phalloplasty, sex reassignment surgery, transition, transgender, urethroplasty

#### **1. Introduction**

The radial forearm flap is the most commonly used technique for phalloplasty. The goals of penile construction in a transgender man are to decrease the patient's gender incongruence, obviate the use of an external prosthesis, give the patient the ability to orgasm, and to urinate through the constructed phallus if desired. Urethral strictures and fistulas are common complications following a phalloplasty with urethral lengthening that may be mitigated with a two-stage technique that utilizes a mucosa-only prelaminated neourethra. Sources of the mucosa may include vaginal and oral mucosa and less commonly, uterine, bladder, and colonic mucosa.

Transition of the trans man genitalia is commonly performed in multiple stages including a hysterectomy and oophorectomy primarily and if desired, followed by a vaginectomy with urethral diversion to the perineum or lengthening with a phalloplasty, scrotoplasty, and glansplasty. The ovaries may be preserved at the time of hysterectomy

for possible egg preservation. If the decision is made to preserve the ovaries, it is crucial for the patient to be monitored for abnormalities through yearly routine surveillance.

First stage surgery may consist of a hysterectomy and oophorectomy (if not done prior) along with a vaginectomy with urethra lengthening using an anteriorly based vaginal flap with labia minora tissues along with prelamination of the nondominant radial forearm flap using vaginal mucosa, buccal mucosa, and less common skin grafts.

Second stage surgery, which commonly occurs 2–3 months following the first stage, consists of tubularization of the radial forearm tissue with free flap transfer, microvascular anastomosis, neurotization, urethroplasty, scrotoplasty, and glansplasty.

#### **2. Justification for the radial forearm free flap**

Given the large cutaneous surface of a native male phallus, autologous construction of a neophallus commonly will necessitate a large cutaneous donor site. Flaps, such as the tube-in-tube radial forearm flap, latissimus dorsi flap, scapular flap, deltoid flap, abdominal pedicled flap, and anterolateral thigh (ALT) flaps have all been used for phalloplasty [1]. Though many techniques have been described, the radial forearm free flap (RFFF) remains the most common for phalloplasty due to its long, reliable vascular pedicle, multiple nerve innervations for anastomosis to the recipient site, and pliability of the tissue facilitating eventual implant placement [2]. In addition, the radial forearm flap has a lower urethral and flap loss complication rate compared to the anterolateral thigh flap [3]. Harvest allows for simultaneous operative sites at the pelvis, upper extremity, and oral region if buccal mucosa is needed. This ability allows for decreased operative time, which can last from 5–12 hours. The RFFF technique makes it possible for patients to fulfill their desires of standing micturition, aesthetic acceptability, and erogenous and tactile sensation.

Erectile rigidity is another commonly reported goal of phalloplasty. To achieve an erection, radial bone can be utilized as an osteocutaneous flap at the time of neophallus creation, or a patient can opt to undergo insertion of a semirigid or hydraulic prosthesis at least 1 year after phalloplasty. It should be noted, however, that our practice prefers to no longer perform the osteocutaneous RFFF due to dyspareunia experienced by the patient post-surgery. This is due to the anchoring of the radius bone at the pubic symphysis. Additionally, most centers report a 30%+ extrusion rate necessitating implant removal at 2–3 years, and reoperation rates reach 100% at 5 years (**Figure 1**) [4]. There is a significant risk of complications following placement of penile prosthesis including mechanical failure, infection, and mal-positioning. It is critical to have a plastic surgeon trained in microvascular surgery present during the placement of the penile implant as the vascular pedicle may be readily injured during the dissection and subsequent dilation process required for placement of the cylinders. It is critical to avoid multiple passing of the dilators so that devascularization of the phallus does not ensue.

Adding to the complexity of phalloplasty is the creation of a functional penile urethra. The urethra after neophallus construction can be divided into distinct segments, from proximal to distal: native (female) urethra, fixed or lengthened urethra, the anastomotic urethra, penile shaft urethra, and external meatus. The fixed urethra is the portion of the urethra formed after lengthening the native urethra via local vaginal or labial flaps, extragenital flaps, and grafts of skin or mucosa (**Figure 2**). The phallic urethra can be constructed by prelamination, tube-in-tube techniques, or pedicle flaps [2].

*Phalloplasty in Transgender Men with and without Urethral Lengthening DOI: http://dx.doi.org/10.5772/intechopen.102437*

**Figure 1.** *Radius bone exposure following radial forearm osteocutaneous flap phalloplasty.*

**Figure 2.** *Patient 3 months following urethral lengthening using labia minora and anterior vaginal wall flaps.*

#### **2.1 Inflow for phalloplasty: preoperative assessment**

The preoperative assessment begins with a physical examination. The patient is assessed for adequate perfusion to the lower extremities. Ideally, the patient should have a palpable pedal pulse bilaterally. If perfusion is in question especially when dealing with patients with peripheral arterial disease, one can obtain noninvasive studies such as arterial duplex or plethysmography to determine which side to use. Preoperative vein mapping can be performed to assess for deep venous thrombosis as well as the caliber and quality of the great saphenous vein. Ideally, the great saphenous vein should be 2.5–3 mm and free of sclerosis.

#### **2.2 Branch of profunda femoris artery**

A branch of the profunda femoris artery is an option for inflow. The perfusion to the thigh is robust thus a branch of the profunda femoris artery can typically be sacrificed without significantly affecting thigh perfusion. To expose the profunda femoris artery, a longitudinal skin incision is made in the thigh overlying the femoral arteries. The femoral bifurcation is identified and the superficial femoral artery is preserved. The main trunk of the profunda femoris artery is identified and preserved. There are tributary branches of the profunda femoris vein that are ligated to facilitate exposure and hemostasis. The branches of the profunda femoris artery are identified and circumferentially dissected. Typically, the ascending branch is of adequate caliber and length to be used for the inflow. If this branch is not long enough or the caliber is too small, the remaining branches of the profunda can be explored.

#### **2.3 Great saphenous vein to femoral artery transposition in a loop configuration (loop graft)**

An alternative source of inflow can be the superficial femoral artery or the common femoral artery. The great saphenous vein can be used as a conduit. An oblique incision is made in the medial groin overlying the femoral artery bifurcation as well as the saphenofemoral junction. The saphenous vein is identified first and preserved. The superficial femoral artery is then exposed that lies medial to the femoral vein. The artery is sequentially dissected and controlled, and the skin incision is extended distally along the course of the saphenous vein. The length of the vein needed to perform the loop transposition varies by patient. The length required can be estimated with a free tie. Ideally, the loop graft needs to be able to reach the pubis when is oriented medially. Once the saphenous vein is exposed, it is circumferentially dissected and its tributary branches are ligated and divided. Careful attention needs to be made when ligating the branches too close to the vein as it may cause stenosis. The saphenous vein is then transected distally, and the distal end is ligated. The vein is then cannulated and distended with heparinized saline solution. Any defects are identified and repaired. When the vein is distended, it is marked for orientation. To perform the loop configuration, the distal end of the vein is swung in a counterclockwise fashion toward the femoral artery. The patient is systemically heparinized. The femoral artery was clamped proximally and distally and an arteriotomy is made using 11 blades and then lengthened with Potts scissors. Alternatively, an aortic punch device can be used to enlarge the arteriotomy to the desired size. The anastomosis should be approximately 4 mm. An end-to-side anastomosis was performed between the femoral artery and the saphenous vein paying careful attention to maintaining

#### *Phalloplasty in Transgender Men with and without Urethral Lengthening DOI: http://dx.doi.org/10.5772/intechopen.102437*

the orientation of the vein to avoid twisting and kinking. Just prior to completing the last few sutures of the anastomosis, the femoral artery is forward and back-bled. The lumen of the artery and vein are flushed with heparinized saline solution to flush any thrombus. Once the anastomosis is completed, the clamps are released. The loop graft is assessed for orientation and flow. The patient's leg and foot also need to be assessed to ensure there are no changes to baseline perfusion. One can expect a weak pulse and a thrill when palpating the graft. A Doppler can also be used to assess the presence of flow. If the loop graft is kinked or twisted, it may thrombose. When the loop graft is ready to be used, it is transected in the middle; the proximal end is the arterial inflow and the distal end is the venous outflow.

#### **2.4 Complications of urinary stricture and fistula**

Complications of urinary stricture and fistula are prevalent. Variations of urethral lengthening techniques among centers have resulted from attempts to improve upon urologic complication rates, which range from 33 to 77% in large case series [5]. Urethral cutaneous fistulas following surgery may range from 22 to 75% [6]. Fistulas occur most commonly at or just proximal to the anastomosis between the phallic urethra and fixed urethra due to vascular insufficiency of the flap and decreased lumen of the phallic urethra. Rates of urethral strictures in female-to-male phalloplasty recipients range from 11 to 74% [7–9]. Since the plastic surgeon alone is not trained in the management of urethral strictures or fistulas, we believe it is essential to have a qualified reconstructive urologist involved in the management of these complications to optimize patient care.

The radial forearm flap may allow the patient to have penetrative sexual intercourse, has minimal donor site scarring, results in a cosmetically acceptable phallus, has tactile and erogenous sensitivity, and potentially creates a competent neourethra that allows for standing urination. These ideal characteristics, described by Hage et al, are mostly met by the RFFF (radial forearm free flap) [10].

Recognizing that urethral strictures and fistulas remain the most challenging complication we face, we have been able to decrease their occurrence with a staged technique. We have found that the radial forearm tube-within-a-tube technique not only requires electrolysis of the forearm to avoid hair growth within the urethra—a common cause of stricture—but also requires a larger donor site since flap skin is used to create the urethra. Minimizing the donor site and decreasing stricture rates

#### **Figure 3.**

*Cystoscopy of prelaminated neourethra prior to stage 2 phalloplasty revealing mucosa which mimics that of native urethral mucosa.*

have encouraged us to continue the two-stage technique with mucosal prelamination, which more closely mimics native urethra mucosa (**Figure 3**).

#### **3. Patient evaluation**

Given the potential morbidity associated with the complex phalloplasty procedure, an adequate preoperative evaluation is essential. The need for gender dysphoria evaluation and medical clearance is unique to this patient population. Gender identity disorder or gender incongruence is classified by the International Classification of Disease Manual as ICD-10-CM F64.9. The DSM-5 defines gender dysphoria as an incongruity between the patient's experienced and expressed gender and their assigned gender, which causes clinically significant distress lasting at least 6 months, however, this has often lasted nearly the individual's entire life [11]. According to the World Professional Association for Transgender Health (WPATH), a psychological evaluation and two letters recommending gender affirmation surgery from two psychiatrists or licensed mental health therapists, who independently assessed the patient, are required for the removal of reproductive organs and/or phalloplasty [12]. In addition, the patient must have taken hormone replacement therapy and lived as their true gender for at least 1 year. These prerequisites are not only required by most insurance companies for authorization of the procedure but also ensure that patients have a realistic understanding of the procedure and serve to minimize disappointment and patient regret.

The importance of a thorough preoperative psychosocial evaluation cannot be overstated. Adequate social support is encouraged to facilitate a successful recovery. The patient should be informed to expect frequent postoperative visits 1–2 months following surgery and should understand that the operation will impact their ability to work for 4–6 weeks. The surgeon should remain involved in all stages of the preoperative evaluation by corresponding with the patient's mental health provider and urogynecologist.

A clear and candid discussion regarding the patient's desired goals from surgery, including the length and circumference of the neophallus, allows the surgeon to determine whether expectations are realistic given the patient's anatomy. The limitations, functional outcomes, recovery, risk of complications, timing of procedures, and cost of each surgery should be honestly discussed with the patient.

It is critical to accurately document current medications, including antiplatelet agents and hormones, in addition to the patient's smoking history. Androgens such as testosterone must be discontinued 2 weeks prior to surgery to reduce the risk of thrombosis, and smoking cessation is required 4 weeks prior to surgery and up to 4 weeks after to ensure proper healing. Specific information regarding prior infections helps in selecting postoperative antibiotics, as postsurgical infection will delay healing and increase morbidity.

The microsurgical component of RFFF phalloplasty requires additional preoperative evaluation. Adequate recipient vessels will be needed for the microsurgical construction. If arterial inflow from the thigh will be used then pedal vessels should be assessed for adequate inflow. The abdominal wall should be examined for prior incisions particularly if the inferior epigastric vessels will be used as recipient's vessels. We have used the inferior epigastric artery, descending branch of the lateral femoral circumflex or on occasion arterio-venous loops for recipient arteries and the inferior epigastric vein or saphenous veins for recipient venous outflow.

#### *Phalloplasty in Transgender Men with and without Urethral Lengthening DOI: http://dx.doi.org/10.5772/intechopen.102437*

Allen's test of the patient's nondominant hand confirms that harvest of the RFFF flap will not compromise the blood supply to the hand. If the results of Allen's test are poor, that is, the hand remains cool and pale after the release of ulnar artery occlusion, using another donor site should be considered or the dominant forearm. In addition, sensitive tattoos of the proposed forearm should be evaluated. Patients who live in cold climates may need reconstitution of their arterial anatomy with vein grafts after flap harvest.

**Figure 4.** *Clitoral nerves are exposed as recipient's nerves at stage 2 RFFF phalloplasty.*

Prior to surgery, it is also vital to assess patient sensation to determine if orgasm can be achieved through clitoral stimulation. The dorsal clitoral nerve (**Figure 4**), ilioinguinal nerve, and genitofemoral nerve co-apted to the medial and lateral antebrachial cutaneous nerves will provide both erogenous and protective sensation to the neophallus. If a patient has difficulty achieving orgasm prior to surgery, it is unlikely that the patient will be able to after surgery.

It should also be noted that part of the patient population has forearm tattoos that will affect the cosmesis of the neophallus. Patient preference will dictate whether the presence of forearm tattoos on the neophallus is acceptable. Clear expectations should be set with the patient regarding the forearm donor site scar, which may be perceived as a stigma, however, we argue the scar is more acceptable than the anterolateral thigh flap scar (**Figure 5**).

#### **3.1 Preoperative preparation**

In our practice, we construct the penile urethra by forearm prelamination with mucosa, which obviates the need for forearm depilation (as would be the case in a tube-within-a-tube technique). The native urethra is a fibromuscular tube lined by urothelium, columnar epithelium, and nonkeratinizing squamous epithelium. Mucosal grafts have greater homology to the native urethra as they are also composed of nonkeratinized epithelium, which has led to less scar contracture and subsequent urethral strictures and fistulas following neourethral construction [1].

*Phalloplasty in Transgender Men with and without Urethral Lengthening DOI: http://dx.doi.org/10.5772/intechopen.102437*

Prior to phalloplasty, a patient should have had a hysterectomy and oophorectomy. If he has not yet had these procedures, it is possible to have them performed during the first stage of our approach to staged phalloplasty. We have found that uterine mucosa is readily available if the patient is undergoing hysterectomy in the same operative setting as phalloplasty, and can be used to construct a patent, functional penile urethra [1]. If a patient is interested in egg harvesting prior to oophorectomy, this is performed before definitive and irreversible hysterectomy and oophorectomy.

The current sequence of surgery in our practice is first a subcutaneous mastectomy, followed by a hysterectomy and oophorectomy combined with a vaginectomy, scrotoplasty, and reconstruction of the horizontal part of the urethra, and later the actual phalloplasty.

#### **3.2 Surgical technique**

We have found our two-stage technique allows for a urethral conduit which mimics that of a native urethra with no hair growth while minimizing the donor site on the forearm. Our decreased stricture rate has encouraged us to continue the use of this technique in patients pursuing phalloplasty with urethral lengthening.

#### **3.3 Stage 1: prelamination technique**

The main procedures are as follows:


IV antibiotics against gram-positive, gram-negative organisms and anaerobes are administered to the patient 1 hour prior to incision.

The first stage entails flap prelamination during which the radial forearm flap is designed and the neourethra is formed using autologous tissue; mucosa is preferentially used in our practice. The markings for the planned flap are determined preoperatively following a normal Allen's test on the patient's nondominant upper extremity, ensuring that the patient's hand can be perfused with the ulnar artery alone. The flap is elevated from the ulnar to radial direction in the supra-fascial plane to allow placement of the neourethra.

Prelamination of the patient's eventual penile urethra is performed by grafting vaginal, and/or buccal mucosa in a suprafascial plane of the donor volar and ulnar forearm. The vaginal mucosa is harvested during the vaginectomy for the creation of the neourethra. We lengthen the native female urethra using labia minora tissues and an anterior pedicled vaginal flap. If a hysterectomy has not already been performed, it can be performed during this stage to provide additional mucosal tissue for the neourethra. The buccal mucosa is also harvested at this time if necessary (**Figures 6** and **7**). To allow

#### **Figure 6.** *Markings of buccal mucosal graft. Avoid injury to Stenson's duct.*

for irrigation of the entire prelaminated neourethra, holes are cut into a 24-French Foley. After mucosal harvest, the mucosal grafts are cleansed with a betadine and normal saline solution and then sewed around the holed catheter construct, exteriorizing the sub-mucosal surface using a running, locking suture. Placing this construct lengthwise in the subcutaneous forearm (suprafascial plane) allows for the creation of a tubular graft, which will become the penile neourethra of the eventual phalloplasty. The patient is then immobilized in a splint for several days. Irrigation of the prelaminated flap is then performed twice daily beginning 1 week after surgery, a practice continued until flap transfer to prevent infection.

Creating the urethra with mucosal tissue and not using forearm tissue decreases the width of the flap skin paddle compared to the traditional tube-within-a-tube urethra and yields a more aesthetically acceptable donor site scar. With this method, the patient can place his upper extremity across his chest with the flexor aspect against the chest and the scar will not be visible (**Figure 8**). Furthermore, with this technique, the patient does not need to undergo costly depilation treatments as there will be no hair growth within the urethra. Prelamination can also be completed with a skin graft from the thigh or abdomen when mucosal tissue is inadequate in patients who have undergone metoidioplasty with vaginectomy, however, this may lead to increased stricture rates.

#### **3.4 Stage 2: radial forearm free flap transfer**

Approximately 8–12 weeks after the first stage flap prelamination, creation of the neophallus can be performed. Although allowing more time between stages may be

*Phalloplasty in Transgender Men with and without Urethral Lengthening DOI: http://dx.doi.org/10.5772/intechopen.102437*

#### **Figure 7.**

*Vaginal and buccal mucosa with mucosal surface toward the foley catheter in preparation for tubularization around the catheter.*

favorable, we have found that 8 weeks is long enough to achieve successful wound healing and favorable results and is a time frame that is tolerable for our patients [1].

One hour before incision is made, antibiotics against gram-positive, gram-negative, and anaerobic organisms should be intravenously administered to the patient. A tourniquet is used for flap harvest, in addition to a hand table. Separate surgical set-ups are used for the pelvic area and upper extremity to avoid cross-contamination. Two surgical teams can work simultaneously—one team performs the RFFF harvest and the second team performs the dissection of the recipient's vessels (inferior epigastric artery and vein and/or descending branch of the lateral circumflex artery and saphenous vein), recipient nerves, preparation of the urethra for anastomosis and scrotoplasty.

The design of the radial forearm flap was defined in the first stage. A marking pen is used to delineate the dimensions of the flap, which will commonly measure 5.5–7.5 inches in length and 5.5–6.5 inches in width. Whereas the flap was elevated in the suprafascial plane for prelamination at Stage I, the flap is now elevated in the subfascial plane to avoid injury to the neourethra. The dissection begins on the ulnar side of

#### **Figure 8.**

*Patient following staged radial forearm flap harvest revealing limited donor site secondary due to prelamination of the urethra.*

the forearm and proceeds to the flexor carpi radialis and brachioradialis tendons for the RFFF harvest. The medial and lateral antebrachial cutaneous nerves are preserved during dissection of the radial forearm flap for coaptation to one dorsal nerve of the clitoris end-to-side for erogenous sensation and the ilioinguinal or genitofemoral nerve for tactile sensation. The radial artery and venae comitantes are ligated distally and proximally dissected for vascular anastomosis. Prior to distal ligation, the artery may be temporarily clamped to ensure blood flow to the hand. The basilic and/or cephalic veins are preserved and dissected with the flap. While the RFFF remains connected to its inherent blood supply, the flap is tubed into a phallus and sutured so that the neourethra is buried within the tubed phallus (**Figure 9**).

Using a modification of Monstrey's scrotoplasty technique, the clitoris is dissected free from the lengthened urethra and denuded of skin [13]. The clitoral hood skin is removed and used for the coronaplasty using a technique described by Gottlieb [14] (**Figure 10**). The recipient arteries harvested for the vascular anastomoses are either the inferior epigastric artery or the descending branch of the lateral femoral circumflex

#### **Figure 9.** *Tubed radial forearm flap at the donor site with the prelaminated urethra.*

*Phalloplasty in Transgender Men with and without Urethral Lengthening DOI: http://dx.doi.org/10.5772/intechopen.102437*

#### **Figure 10.**

*Trans male patient during the harvest of clitoral (or T-dick) hood skin for coronaplasty using Gottlieb technique.*

#### **Figure 11.**

*Descending branch of the lateral femoral circumflex artery as recipient artery and saphenous vein as recipient artery in preparation for free flap phalloplasty.*

artery. Of note, once we switched to using the descending branch of the lateral femoral circumflex artery as our recipient artery, we no longer had re-open procedures due to vascular compromise [2]. The thigh incision made for the lateral femoral circumflex is also used for the harvest of the great saphenous vein (**Figure 11**). Since we use the greater saphenous veins as recipient veins for the radial forearm flap, the proximal incision made to harvest the greater saphenous vein is also used for the gracilis muscle harvest. The distal free end of the muscle, harvested via a separate distal incision, is delivered through the proximal incision. Undermining of the soft tissues is performed from the proximal thigh incision to the level of the midline groin defect where the urethral anastomosis is to be performed.

After vessel preparation with a microscope and confirming adequate outflow from the descending branch of the lateral femoral circumflex artery and inflow from the great saphenous vein, the RFFF is transferred to the pubic area. The forearm donor site can be covered with either an autologous split-thickness skin graft or the surgeon can apply a dermal substitute that can be grafted later. The first maneuver is to place the foley catheter, which is located in the neourethra, directly into the patient's bladder. Absorbable sutures are used for the urethral anastomosis in two layers, which is the first anastomosis performed (**Figure 12**).

The arterial, venous, and neural anastomoses are performed next in that order and are all hand-sewn using 9-0 nylon suture with the aid of an operative microscope. The radial artery is connected end-to-end to the descending branch of the lateral circumflex artery. The venous anastomosis is performed between the cephalic or basilic vein and the greater saphenous vein. A second venous anastomosis can be performed between a radial venous comitante vein with the contralateral greater saphenous vein. Two to three nerve anastomoses may also be performed. The medial and lateral antebrachial cutaneous nerves are anastomosed end-to-end to the ilioinguinal nerves

**Figure 12.** *First of two-layered urethral anastomosis in staged radial forearm flap phalloplasty.*

#### *Phalloplasty in Transgender Men with and without Urethral Lengthening DOI: http://dx.doi.org/10.5772/intechopen.102437*

and to one of the dorsal clitoral nerves end-to-side. The ilioinguinal nerve is commonly found exiting the external inguinal ring. A cadaver nerve graft may be used as an interposition nerve graft when needed.

The gracilis muscle may be harvested in a minimally invasive fashion and wrapped around the urethral anastomosis, avoiding compression of the vascular pedicle, to provide vascularity to a minimally vascular urethral anastomosis (**Figure 13**). This maneuver also provides bulk to the neo-scrotum often obviating the need for scrotal implants. At our institution, we have been able to minimize urethral fistula rates using a gracliis muscle flap to augment the urethral anastomosis [15].

A suprapubic tube is placed and used for urinary diversion if needed during urinary training of the neo-phallus.

Upon closure of all incisions, a Norfolk coronaplasty is performed with either a skin graft or labial graft obtained from the clitoral hood region by denuding the clitoris before transposition (**Figure 10**) [16].

Following surgery, patients are transferred to the intensive care unit for flap monitoring and will remain on strict bed rest for a minimum of 3 days. An implantable Doppler device has been very helpful in flap monitoring. Prophylaxis for microvascular thrombosis is typically subcutaneous heparin and aspirin. Strict monitoring of the free tissue transfer is performed by the intensive care unit and resident staff [17]. Patients whose forearm donor site was first covered with a dermal substitute are taken back to the operating room for definitive coverage with a skin graft after 2 weeks. Several days later the patient may be discharged home with both a penile catheter and suprapubic catheter (**Figure 14**). A pericatheter retrograde cystourethrogram can be planned 12 weeks postsurgery. If there is no extravasation of dye, indicating that there is no urinary fistula, the foley catheter can be removed and the suprapubic catheter can be clamped (**Figure 15**). Patients are encouraged to urinate through their neophallus with the suprapubic catheter clamped. We then check for residual urine in the bladder using a bladder scan if necessary. If the patient is successfully able to urinate from the phallus and adequately empty the bladder for several days the suprapubic tube can be discontinued.

If the patient desires, he can tattoo the glans and shaft of the neophallus for aesthetic enhancement, which is ideally performed before full tactile sensation has been achieved

#### **Figure 13.**

*Gracilis muscle harvest via minimally invasive approach prior to alpha wrap around the urethral anastomosis.*

#### **Figure 14.**

*Trans man following Stage II phalloplasty revealing suprapubic tube and penile foley catheter.*

#### **Figure 15.**

*Pericatheter retrograde cystourethrogram 8 weeks following second stage phalloplasty operation in trans man. The study reveals no contrast extravasation indicating no fistula and no stricture noted.*

(typically 1-year postop). Similarly, the donor site can be tattooed to avoid the stigmata of a skin graft (**Figure 16**).

Since the RFFF phalloplasty lacks bone, it may be too soft to allow for penetrative intercourse. Implantation of an erectile prosthesis is a definitive procedure, that may be performed after 8–12 months when tactile sensation is achieved at least ¾ distally of the penile shaft. A simple Tinel sign is often used to assess postoperative tactile sensation in the neo-phallus postoperatively. Both malleable dual or single cylinder

*Phalloplasty in Transgender Men with and without Urethral Lengthening DOI: http://dx.doi.org/10.5772/intechopen.102437*

**Figure 16.** *RFFF donor site with tattoo concealment.*

penile prostheses or inflatable prostheses may be used for the erectile device commonly anchored to the ischial tuberosities. We strongly recommend plastic surgery involvement in placement of the prosthesis since knowledge of the location and preservation of the neo-phallus vascular supply is critical to successful placement. More technical details of the neo-phallus implant placement will be discussed in a separate chapter. Prior to implant placement, as the patient is awaiting neural sensation, patients may have successful penetrative intercourse by using an elastic 3M Coban wrap and a condom.

#### **4. Postoperative sequelae/complications**

It is important that the patient is aware of the potential complications that may occur following surgery, included in the informed consent. Some complications may include partial or total flap loss, hematoma at the donor or recipient site, an insensate flap, anorgasmia, skin graft loss, chronic pain, numbness, urinary complications, hypertrophic scarring, infection, cold intolerance, vascular compromise, abdominal wall weakness or hernia, implant infection or malfunction, dyspareunia, tendon exposure, limited hand function, and persistent gender dysphoria.

Urethral fistulas and strictures are common untoward events following phalloplasty in the transgender male and may prevent the patient from voiding while standing. A meta-analysis of 665 patients drawn from 11 studies found that an average of 0.51 strictures and/or fistulas can be expected per free forearm flap phalloplasty [17]. The published rate of urologic complications following penile reconstruction ranges from 23 to 75% [18, 19]. The subsequent management of urethral fistulas and strictures can be challenging. Initially, conservative measures such as periodic urethral dilatation or internal urethrotomy can be employed as temporizing measures prior to definitive surgical management.

Most urethral fistulas occur at the anastomosis between the fixed urethra and phallic urethra, and often can occur proximal to a concomitant stricture. The techniques for fistula repair described are the simple fistula repair, the use of local tissue transfer, two-stage procedures with use of mesh graft, bladder, or buccal mucosa [20]. When the fistula is small with substantial overlying tissue, spontaneous resolution is likely. However, when a urethrocutaneous fistula is large and superficial, the abovementioned surgical repair is necessary.

Urethral strictures also primarily occur at the anastomotic urethra. The keystone surgical procedures for urethral stricture include urethroplasty (excision and primary anastomosis) and staged Johanson-type urethroplasty with additional skin grafts, preferentially buccal mucosa [21]. Surgical approaches are customized to the length of the stricture. A patient who has both a urethral fistula and stricture should have both problems addressed at the same time.

There are many variations of urethroplasty available owing to the considerable heterogeneity of phallic and neourethral construction techniques. Well-vascularized local flaps are utilized when available, as well as buccal mucosal grafts. A patient who has undergone several urethral fistula and/or stricture repair attempts will have progressively fewer options for reconstruction. At our institution, we have significantly decreased our fistula rates in transgender male phalloplasty by augmenting the paucity of vascularized tissue at this anastomosis using a pedicled gracilis flap at the time of flap transfer [15]. Prelamination with mucosal grafts may also decrease urethral stenosis and fistula formation [2].

#### **5. Conclusion**

The goals of phalloplasty include a sensate, cosmetically acceptable phallus with an incorporated neourethra, and the ability to place an implantable penile prosthesis to allow rigidity for penetrative intercourse. In the majority of cases, phalloplasty is the final stage of treatment for gender dysphoria.

While other donor sites may be used, the radial forearm free flap is a favorable technique due to its high vascularity, adequate sensation, sufficient tissue pliability,

#### *Phalloplasty in Transgender Men with and without Urethral Lengthening DOI: http://dx.doi.org/10.5772/intechopen.102437*

and good cosmetic outcome. We have found that our two-stage technique allows for a neourethra, which mimics a native urethra with no hair growth, while minimizing the donor site on the forearm compared to the previously used skin for a tube-within-atube radial forearm flap technique. Using a pre-laminated urethra our patients do not need to undergo electrolysis since the urethra is not created from forearm tissue, so we do not have the risk of hair growth in the urethra and its associated complications. Our decreased stricture rate has encouraged us to continue the use of this technique in patients pursuing phalloplasty with urethral lengthening. Although there have not been any blinded, randomized controlled trials comparing single-stage to two-stage phalloplasty, we believe that prelamination using mucosa for the construction of the trans male phallus urethra is a worthwhile technique that has demonstrated a reduction in the prevalence of complications with this already very challenging procedure.

### **Conflict of interest**

The authors declare no conflict of interest.

### **Author details**

Christopher Salgado1 \*, Kerstin Yu1 , Stefan Kenel-Pierre1 , Edward Gheiler1 and Tony Shao2

1 Constructive Surgery Associates, Miami, FL, USA

2 Division of Vascular and Endovascular Surgery, University of Miami, Miami, FL, USA

\*Address all correspondence to: miamiplasticsurgeon@hotmail.com

© 2022 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

### **References**

[1] Salgado CJ, Fein LA, Chim J, Medina CA, Demaso S, Gomez C. Prelamination of neourethra with uterine mucosa in radial forearm osteocutaneous free flap phalloplasty in the female-tomale transgender patient. Case Reports in Urology. 2016;**2016**:8742531. DOI: 10.1155/2016/8742531. [Epub: 16 Mar 2016].

[2] Salgado CJ, Nugent A, Hadeed J, Lalama M, Rey J, Medina C. Two-stage prelaminated mucosal neourethra radial forearm flap phalloplasty for transgender men. Global Journal of Medical Research. 2021;**1**(1):1-13

[3] Xu KY, Watt AJ. The pedicled anterolateral thigh phalloplasty. Clinics in Plastic Surgery. 2018;**45**(3):399-406

[4] Hoebeke PB, Decaestecker K, Beysens M, Opdenakker Y, Lumen N, Monstrey SM. Erectile implants in femaleto-male transsexuals: Our experience in 129 patients. European Urology. 2010;**57**(2):334-341

[5] Monstrey S, Hoebeke P, Selvaggi G, Ceulemans P, Van Landuyt K, Blondeel P, et al. Penile reconstruction: Is the radial forearm flap really the standard technique? Plastic and Reconstructive Surgery. 2009;**124**(2):510-518

[6] Al-Tamimi M, Pigot GL, van der Sluis WB, van de Grift TC, Mullender MG, Groenman F, et al. Colpectomy significantly reduces the risk of urethral fistula formation after urethral lengthening in transgender men undergoing genital gender affirming surgery. The Journal of Urology. 2018;**200**(6):1315-1322

[7] Rohrmann D, Jakse G. Urethroplasty in female-to-male transsexuals. European Urology. 2003;**44**(5):611-614

[8] Leriche A, Timsit MO, Morel-Journel N, Bouillot A, Dembele D, Ruffion A. Long-term outcome of forearm flee-flap phalloplasty in the treatment of transsexualism. BJU International. 2008;**101**(10):1297-1300

[9] Kim SK, Moon JB, Heo J, Kwon YS, Lee KC. A new method of urethroplasty for prevention of fistula in female-to-male gender reassignment surgery. Annals of Plastic Surgery. 2010;**64**(6):759-764

[10] Joris Hage J, De Graaf FH. Addressing the ideal requirements by free flap phalloplasty: Some reflections on refinements of technique. Microsurgery. 1993;**14**(9):592-598

[11] Edition F. Diagnostic and statistical manual of mental disorders. American Psychiatric Association. 2013;**21**:591-643

[12] Coleman E, Bockting W, Botzer M, Cohen-Kettenis P, DeCuypere G, Feldman J, et al. Standards of care for the health of transsexual, transgender, and gender-nonconforming people, version 7. International Journal of Transgenderism. 2012;**13**(4):165-232

[13] Selvaggi G, Hoebeke P, Ceulemans P, Hamdi M, Van Landuyt K, Blondeel P, et al. Scrotal reconstruction in female-tomale transsexuals: A novel scrotoplasty. Plastic and Reconstructive Surgery. 2009;**123**(6):1710-1718

[14] Gottlieb LJ, Levine LA. A new design for the radial forearm free-flap phallic construction. Plastic and Reconstructive Surgery. 1993;**92**(2):276-283

[15] Salgado CJ, Nugent AG, Moody AM, Chim H, Paz AM, Chen HC. Immediate pedicled gracilis flap in radial forearm flap phalloplasty for transgender male

*Phalloplasty in Transgender Men with and without Urethral Lengthening DOI: http://dx.doi.org/10.5772/intechopen.102437*

patients to reduce urinary fistula. Journal of Plastic, Reconstructive & Aesthetic Surgery. 2016;**69**(11):1551-1557

[16] Gilbert DA, Jordan GH, Devine CJ Jr, Winslow BH. Microsurgical forearm "cricket bat-transformer" phalloplasty. Plastic and Reconstructive Surgery. 1992;**90**(4):711-716

[17] Frey JD, Poudrier G, Chiodo MV, Hazen A. A systematic review of metoidioplasty and radial forearm flap phalloplasty in female-to-male transgender genital reconstruction: Is the "ideal" neophallus an achievable goal? Plastic and Reconstructive Surgery Global Open. 2016 Dec;**4**(12):e1131. DOI: 10.1097/gox.0000000000001131

[18] Santucci RA. Urethral complications after transgender phalloplasty: Strategies to treat them and minimize their occurrence. Clinical Anatomy. 2018;**31**(2):187-190

[19] Kim SK, Moon JB, Heo J, Kwon YS, Lee KC. A new method of urethroplasty for prevention of fistula in femaleto-male gender reassignment surgery. Annals of Plastic Surgery. 2010;**64**(6):759-764

[20] Levine LA, Elterman L. Urethroplasty following total phallic reconstruction. The Journal of Urology. 1998;**160**(2):378-382

[21] Jun MS, Santucci RA. Urethral stricture after phalloplasty. Translational Andrology and Urology. 2019;**8**(3):266

#### **Chapter 8**

## Effects of Hypothalamic Blockers in the Treatment of Gender Dysphoria in Preadolescence: Medical and Psychological Implications of Taking Care

*Massimo Di Grazia and Camilla Taverna*

#### **Abstract**

Gender identity does not always develop in line with biological sex. Gender dysphoria at young age implies a strong incongruence between gender identity and the assigned sex; the rejection of one's sexual attributes and the desire to belong to the opposite sex; and a significant clinical suffering or impaired individual functioning in life spheres. The purpose of this chapter is a narrative review of the literature available on puberty suppression therapy through GnRH analogues. Biological puberty provides intense suffering to the adolescent with gender dysphoria who does not recognize himself in his own body. These drugs suppress the production of endogenous gametes and sex hormones. Although the effects of therapy are reversible, and biological development resumes spontaneously once the medication is stopped, the administration of GnRH analogues at a young age has fueled a scientific debate on the matter of the ethics of pharmacological intervention with minors. In conclusion, the studies considered show that GnRH analogues do not have long-term harmful effects on the body; prevent the negative psychosocial consequences associated with gender dysphoria in adolescence (suicidal ideation and attempts, self-medication, prostitution, self-harm); improve the psychological functioning of young transsexuals; and are diagnostic tools that allow adolescents to buy time to explore their gender identities.

**Keywords:** gender dysphoria, puberty suppression, GnRH analogues, preadolescence, AMAB, AFAB

#### **1. Introduction**

Gender identity was first defined by Stoller as "a complex system of beliefs that everyone has about himself, that is, his own sense of masculinity or femininity" [1]. According to the current binary system, which rigidly distinguishes male and female, the common expectation is that gender identity in children and adolescents develops in line with biological sex [2]. However, the developmental trajectories of gender identity are manifold. Only recently has a theorization of gender identity begun as a fluid dimension of the self, in which the boundaries between masculine and feminine are blurred, and of which diversified manifestations are possible [2]. In the case of young gender variants, interests and attitudes do not conform to the social stereotypes of masculinity and femininity [3]. If the gender variance is associated with clinically significant suffering, for which the young person shows a rejection of their sexual attributes and the desire to belong to the other gender, then it is gender dysphoria [4]. Gender dysphoria is a clinical condition and requires specialist intervention, which includes psychological care of the young person and the family, associated with targeted medical and pharmacological treatment [5]. Biological puberty generates severe suffering for adolescents with gender dysphoria who do not recognize themselves in their bodies and can interfere with psychological functioning and individual well-being. Drug therapies are currently available to alleviate the psychological distress associated with gender dysphoria. Suppression of biological puberty involves the administration of gonadotropin-releasing hormone (GnRH) analogues that disrupt the endogenous production of gametes and sex hormones, arresting the development of secondary sexual attributes [5–7]. However, the question of early pharmacological intervention with adolescents with gender dysphoria is still the subject of debate among professionals in the field, and further investigations are needed to better understand the benefits and risks associated with the therapy.

#### **2. Puberty suppression**

Hypothalamic blockers have been used in the treatment of children and adolescents with central precocious puberty since 1981. Empirical studies demonstrate the efficacy and long-term safety of similar drugs, such as gonadotropin-releasing hormone (GnRH) [8]. In 2009, the Endocrine Society published guidelines for the treatment of adolescents with gender dysphoria, recommending suppression of puberty with hypothalamic blocking drugs for patients who have reached Tanner stages 2–3 (Table 6 and Table 7 in the appendix) and who meet the eligibility criteria (further detailed below), assigning pediatricians to care for children with gender dysphoria [6]. The World Professional Association for Transgender Health also follows the Endocrine Society guidelines for the treatment of children and adolescents, and published the seventh edition of the Standards of Care [7]. Adolescents with gender dysphoria often consider the physical changes associated with puberty to be unsustainable [6, 9]. Girls experience breast appearance, followed by an increase in breast volume and fat mass. Breast growth is also associated with accelerated height development, with menarche usually occurring 2 years later. In boys, the first physical change is the growth of the testicles that reach a volume of at least 4 ml. Starting from a testicular volume of 10 ml, daily testosterone levels increase, resulting in virilization of the physical appearance. Physical changes in pubertal development are the consequence of the maturation of the hypothalamus-pituitary-gonadal axis and the development of secondary sexual characteristics [10]. According to clinical practice guidelines, transgender and gender non-conforming (TGNC) young people can undergo puberty suspension procedures, with the administration of the synthetic hormones GnRH analogues that have the effect of suppressing the endogenous production of sex hormones [6, 7, 11, 12]. The suppression of the functioning of the gonads can be effectively achieved with the inhibition of gonadotropic secretion with

*Effects of Hypothalamic Blockers in the Treatment of Gender Dysphoria in Preadolescence… DOI: http://dx.doi.org/10.5772/intechopen.101812*

GnRH analogues and antagonists [6]. While similar drugs achieve this effect after a short period of administration, the antagonists immediately block pituitary secretions. Since long-acting antagonists are not available for use in pharmacotherapy, long-acting agonist analogues are the best treatment option.

#### **2.1 Eligibility criteria for treatment with gonadotropin-releasing hormone GnRH analogues**

According to the indications provided in the Standards of Care, withdrawal therapy can only be started at the beginning of puberty, which coincides with Tanner stages 2–3 [7], and a detectable presence of steroid sex hormones in the blood [5]. The treatment eligibility criteria proposed in the Standards of Care are shown in **Table 1** [7].

#### **2.2 Pharmacology of GnRH analogues**

GnRH is a decapeptide produced by the GnRH-secreting neuronal system, located in the preoptic area of the anterior hypothalamus and the mid-basal hypothalamus [13]. The axons of GnRH secreting neurons send projections to different areas of the nervous system. Some of these terminate in a ganglion of vascular buttons in the median eminence of the primary portal vessel, which releases GnRH into gonadotropic cells. GnRH reaches the anterior pituitary via the portal system and activates specific receptors, stimulating the production of gonadotropins, such as luteinizing hormone (LH) and follicle-stimulating hormone (FSH). The gonadotropins thus synthesized regulate the activity of the gonads (reproductive organs), responsible for the production of gametes and female and male steroids. If GnRH is administered it results in rapid production of LH and less secretion of FSH. Since GnRH is a decapeptide, it is made up of a chain of 10 amino acids, joined together by a peptide bond. The amino acids of GnRH with crucial functions are found at positions 1, 2, 3, 6, and 10. A large number of analogues with agonistic or antagonistic properties have been synthesized, obtained by modifications of the amino acid chain. Triptorelin in GnRH analogue is mostly used to treat adolescents with gender dysphoria.

#### **2.3 Pharmacodynamics**

The single administration of GnRH agonists causes the secretion of LH and FSH in the pituitary cells, with the consequent regulation of the activity of the gonads


• The adolescent has provided informed consent, and especially when the patient has not reached the age to consent to medical procedures, the parents, or other caregivers or guardians, have consented to the treatment and/or are committed to offering support throughout the duration of the treatment process.

#### **Table 1.**

*Eligibility criteria for treatment with GnRH analogues [7].*

<sup>•</sup> The adolescent showed an intense and lasting pattern of gender non-compliance, or gender dysphoria (repressed or expressed);

(stimulating or flare-up effect), [13]. Repeated administrations, on the other hand, result in the desensitization of gonadotropic cells and a reduction in the number of GnRH receptors on the membranes (down-regulation), with the effect of inhibiting the production of the hormones LH and FSH. The result is the blocking of the synthesis of androgens, estrogens, and male and female gametes. The mechanism of action of the antagonists is different since they act by blocking the pituitary receptors for endogenous GnRH and exogenous agonists, blocking access. Levels of LH and FSH decrease rapidly a few hours after administration. The drugs are effective in suppressing gonadotropic production, however, long-acting formulations have not yet been synthesized.

#### **3. Criticism of pharmacological therapy**

There are potential risks concerning the use of similar GnRH drugs, in relation to the effects that they can generate in the critical time interval for the development of the adolescent brain and bone mass. Although the therapy is safe in patients with central precocious puberty, these data are not generalizable to transsexual adolescents. For them, the treatment, in addition to starting later in development and continuing until the age of 15–16, is not followed by a process of inducing puberty of the biological sex, but of the opposite sex to that of birth [11]. These practices may also expose individuals to greater psychosocial difficulties as they remain physically prepubertal as peers reach puberty [5]. Therapy can thus contribute to more and more socially isolating transsexual adolescents, further increasing the risk of being victims of discrimination and bullying. Furthermore, adolescents could interpret the administration of hypothalamic blockers as a guarantee for future surgical sex reassignment, without engaging in other reflections on the matter [14]. They may risk feeling trapped in a certain life trajectory once puberty suppression therapy has begun, because family members and healthcare professionals, albeit in a benevolent way, may inadvertently reinforce a specific gender identity [12]. Furthermore, GnRH analogues are very expensive and not always reimbursed by health insurers [6, 9]. Progestins represent a less effective but more affordable alternative: they suppress gonadotropic secretion and exert a mild peripheral anti-androgen effect in boys; in girls, they suppress ovulation and progesterone production for long periods of time, with variable estrogen residues [15]. However, side effects such as disruption of adrenal functioning and bone growth are frequent at these doses of administration [6]. Therefore, when the patient can bear the costs of the therapy, the guidelines recommend proceeding with the administration of GnRH analogues, as they are safer and more effective [7].

#### **4. Benefits of treatment with GnRH analogues**

Empirical studies demonstrate the efficacy of GnRH analogue therapy in suppressing puberty in transgender adolescents. Schagen and colleagues found the efficacy of GnRH analogue therapy in suppressing puberty in trans adolescents: after 12 months of therapy, in 49 trans assigned female at birth (AFAB, mean age 13.6 years) adolescents, testicular development was halted with a reduction in volume, in 67 trans assigned male at birth (AMAB) adolescents, (mean age 14.2 years), menstruation was blocked and breast development regressed [16]. They share the belief that therapy is a way to allow patients to buy time in which they can mature

#### *Effects of Hypothalamic Blockers in the Treatment of Gender Dysphoria in Preadolescence… DOI: http://dx.doi.org/10.5772/intechopen.101812*

cognitively and emotionally, in order to better manage gender variance [17]. In addition, the timeliness of the intervention is fundamental: hypothalamic blockers are less effective in reducing secondary sexual attributes when taken when puberty is already advanced (Tanner stage 4 or 5), [18]. If administered in prepuberty, drugs reduce the number of operations required in the future for gender reassignment, including breast removal in MtoF transsexual individuals, facial and voice feminization procedures in FtoM individuals [9, 19]. The cartilage of the nose, jaw, and larynx (Adam's apple) is also less developed after treatment [9, 20]. Those who are in favor of early treatment emphasize the suffering of patients who have been treated as adults, the advantage of buying time in the diagnostic phase, and having a physical appearance more conforming to that of the desired gender [11]. Also in Italy, a group of psychologists and endocrinologists expert in gender identity issues has begun to question the use of analogous GnRH drugs, coming to the conclusion that they do not cause any sex change, which temporarily suspends the formation of secondary sexual characteristics and have reversible effects [21]. Early therapy does not initiate the transition phase, but allows the adolescent to explore their gender identity, preventing, in the case of "desistant" young people in whom gender dysphoria would tend to regress naturally, the possibility of undergoing treatments more irreversible such as therapies with gender-affirming hormones (GAH) [9, 18, 19]. Adolescents have the opportunity to explore their gender identity in greater tranquility, without having to worry about the development of secondary sexual attributes [22]. Therapy with hypothalamic blockers can be considered a diagnostic tool since it allows a greater understanding of the degree and persistence of adolescent distress [23] and improves the accuracy of the diagnosis itself [20].

Another advantage of the use of GnRH analogues is the reversibility of the treatment: when the patient, after having explored the role consistent with gender identity, no longer wishes to undergo sex reassignment therapies, therapy with GnRH analogues can be interrupted and normal pubertal physiological development resumes [6, 19]. Furthermore, in adolescents who are already biologically mature but are undecided about cross-sex hormone therapy, hypothalamic blockers can inhibit those physiological functions that are perceived as unpleasant, such as menstruation in girls and erections in boys, in the intervening period, until the actual decision [11]. Regarding the efficacy of the drugs, the suppression of the activation of the hypothalamic–pituitary-gonadal axis has been demonstrated, with a reduction in testicular volume, in the levels of gonadotropins and prepubertal steroid sex hormones [23].

#### **4.1 Psychological effects of the drug**

Some international scientific societies, such as the World Professional Association for Transgender Health-WPATH; the European Society of Endocrinology-ESE; the European Society for Pediatric Endocrinology-ESPE; and the Lawson Wilkins Pediatric Endocrine Society-LWPES, recommend treatment with blockers that can improve children's quality of life and social relationships since gender-variant adolescents can experience severe distress that can lead to suicide [21]. Studies showing an association between the suspension of puberty and a reduction in depression and anxiety are encouraging in this regard [11, 12]. A better psychosocial adaptation seems to be related to early intervention, as the physical aspect more conforming to that of the experienced gender, allows one to be better accepted as a member of the other sex than those who start treatment in adulthood [20, 24]. Two longitudinal

studies conducted by researchers from the medical centre of VU University in Amsterdam investigated the effectiveness of drug therapy with similar GnRH, in terms of psychological effects and drug tolerance. The first survey involved 70 transsexual adolescents [25]. The initiation of treatment was associated with reduced emotional and behavioral problems and an improvement in general functioning. However, the feelings of anger and anxiety remained stable even in a second measurement time before the start of cross-sex hormone therapy. The second research with 55 young transsexuals evaluated the long-term efficacy of the treatment protocol in subsequent times: before the start of therapy with GnRH analogues, at the time of induction of puberty with cross-sex hormones, 1 year after gender reassignment surgery [26]. By investigating psychological functioning and general well-being in areas such as social interactions and education or quality of life, the researchers showed that among young adults, gender dysphoria was attenuated, with improved psychological functioning following the beginning of gender-affirming medical interventions. Greater satisfaction with one's physical appearance was noted: the therapy had allowed an anatomical development that conformed to and not in contrast with one's gender identity. Furthermore, the psychological well-being level of the population was equal to or greater than that of the general population [26]. The results suggest that the origin of psychiatric symptoms may not be primarily psychiatric, but secondary to gender dysphoria, in particular, due to the development of secondary sexual attributes in the pubertal phase [26]. These results were replicated by a study conducted with young patients with gender dysphoria at Boston hospital [18]. Costa and colleagues [27] have evaluated the psychological functioning, measured with CGAS, in a sample of adolescents with gender dysphoria at different stages of care: after 6 months of psychological support; after 12 months of psychological support and six of treatment with similar GnRH; after 18 months of psychological support and 12 months of treatment with GnRH analogues using the Children's Global Assessment Scale (CGAS). The sample was divided into a group immediately eligible for treatment, and a group not immediately eligible for treatment. Young people immediately eligible for treatment had higher psychological functioning scores at the start of management and showed no significant improvement after 6 months of psychological support. Psychological functioning improved significantly after 12 months of treatment with GnRH analogues in young people immediately eligible for treatment, with results similar to those found in a sample of adolescents without psychological or psychiatric symptoms. On the other hand, in the group not immediately eligible for treatment, there was an improvement in functioning already after 6 months of psychological support. A 2011 study by the Dutch group evaluated psychological functioning by administering the Minnesota Multiphasic Inventory-2 (MMPI-2) and Minnesota Multiphasic Inventory-Adolescent (MMPI-A) in a group of adults and adolescents requiring reassignment of type. Compared to adolescents, a higher percentage of adults were in the clinically significant range of scores on the Paranoia scale (49.8% vs. 18. 1%, χ<sup>2</sup> (1) = 26.641, pb0.001) and the Psychasthenia scale (36.9% vs. 13.3%, χ<sup>2</sup> (1) = 16.662, pb0.001), [28].

When adolescents and adults were compared for the number of total MMPI scales for which they achieved scores in the range of clinical significance, most adults (62.8%) had clinical relevance scores for two or more scales. Instead, most adolescents (67.5%) had clinical relevance scores for none or only one of the subscales (χ<sup>2</sup> (2) = 24.198, pb0.001). The authors speculate that the better functioning observed in adolescents compared to adults may also be associated with the timing of the assessment since they had not yet developed secondary sexual characteristics.

*Effects of Hypothalamic Blockers in the Treatment of Gender Dysphoria in Preadolescence… DOI: http://dx.doi.org/10.5772/intechopen.101812*

#### **4.2 Negative psychosocial outcomes of untreated gender dysphoria in adolescence**

Brain development patterns during puberty increase the likelihood of adopting risky behaviors, a typical characteristic of adolescents [29]. However, the decision to undertake a reassignment process is not immediate and usually derives from a deep-rooted desire already present years before the young person turns to specialized centres. Furthermore, given the presence of this variable of impulsivity, adolescents with gender dysphoria could react to the omission of care by adopting risky behaviors, such as prostitution [30] and self-harming behaviors, even going so far as to attempt suicide [31].

#### *4.2.1 Harm reduction model*

The Harm Reduction Model is configured as an alternative to the moral model and the disease model, focusing on the consequences of deviant behavior [30]. When it is no longer possible to work preventively and the young transsexual has already adopted risky behaviors, he is encouraged to reduce them by the mental health professional who provides him with information on the pros and cons of each type of conduct, in order to protect his health [30, 32].

#### *4.2.2 Autolesionism, suicides' ideations and attempts*

For many professionals who treat developmental gender dysphoria, the decision to administer GnRH analogues is based on the fear of a possible increased risk of suicide in untreated adolescents. In the literature, there is a greater risk of suicidal ideation and attempts among young transsexuals [31, 33–35]. Studies investigating suicidal risk factors in transgender and gender non-conforming youth (TGNC) have identified gender dysphoria, parental physical and verbal abuse, and body image concerns as predictors [36]. Research conducted in Europe and America shows that young people with gender dysphoria are more likely to have other coexisting mental health problems, resulting in anxiety, depression, and suicidal tendencies [12]. GnRH analogue therapy has been shown to reduce psychological distress in transsexual adolescents [25, 26], so it could be hypothesized that the administration of hypothalamic blockers can actually prevent the adoption of suicidal behaviors in the adolescent with gender dysphoria. Spack and colleagues (2012) examined a sample of 97 adolescents with gender dysphoria from the Gender Management Service (GeMS) between January 1998 and February 2010 [18]. The data collected indicate that among young people: 44.3% had a history of psychiatric diagnoses; 37.1% took psychiatric drugs; 21.6% had a history of self-injurious behavior. Specifically, 20 patients reported selfmutilation episodes, and nine had attempted suicide at least once. The authors found an improvement in psychological functioning after medical intervention, suggesting that the patient's psychiatric symptoms may be secondary to gender dysphoria. Grossman and D'Augelli investigated the ideas and suicide attempts in a group of 55 adolescents with gender dysphoria [31]. The results obtained indicate an association between suicidal risk and two aspects related to self-esteem: body weight and the perception of one's physical appearance by others. Transsexual people strive to change their bodies in order to be perceived externally in a way that is congruent with their gender identity [37]. The use of hypothalamic blockers to nullify the inconsistency between perceived gender and the development of secondary sexual attributes reduces the stress associated with gender role transition and provides the opportunity

to socially present oneself as a member of the opposite sex [38]. However, most adolescents with gender dysphoria do not have access to the care and resources to be able to achieve this state of self-congruence and satisfaction for their own bodies [31]. Therefore, age-appropriate medical treatment with GnRH analogues and hormones could prevent self-harming behaviors, ideas, and suicide attempts in young transsexuals. Indeed, when adequate treatment cannot be offered, some adolescents may react by making suicide attempts [30].

#### *4.2.3 Automedication*

Adolescents often prefer to buy hormones and blockers illegally rather than go to a specialized clinic, especially if the professional requires the fulfillment of many criteria to be able to administer the therapy [30]. If the doctor refuses to prescribe the therapy or to correct the dosage and way of taking it, young transsexuals will probably continue to obtain the drugs in unconventional ways. The risk of psychological, social, and behavioral complications is greater if the administration is not guided by a specialist [30]. The injection of potentially toxic, low-quality drugs without medical supervision could expose the adolescent to unsatisfactory physical outcomes and health-threatening medical conditions, such as HIV, AIDS, and hepatitis. Teens may also be given silicone injections, increasing the risk of infections or other complications (discolouration of surrounding tissues, inflammation and silicone-induced pulmonary embolism). Furthermore, involvement in illegal buying practices can have judicial consequences for young people, with repercussions in terms of social stigma and further involvement in the criminal justice system in adulthood [12, 39]. Those who come from geographic areas where gender adjustment treatments are not available often need to emigrate in order to receive appropriate medical treatment [39]. Often these are young illegal immigrants for whom prostitution remains the only option available to earn the money needed to pay for healthcare [40]. Baltieri and colleagues report two case reports of adolescents with gender dysphoria in Brazil who engaged in prostitution to obtain enough money to illegally buy cross-sex hormones, after being denied treatment because they were not reaching age, minimum sufficient [30]. Hormonal drugs were not given as there are no laws in Brazil regulating the medical treatment of young trans people.

#### *4.2.4 Psychological issues*

Denial of treatment has irreversible psychological effects on the psychosexual development of the adolescent since he will never be able to experience puberty in line with his own gender identity. Transsexual adolescents often suffer more from not being able to experience puberty of the desired sex than from the inability to experience puberty of the sex assigned at birth in case of treatment with similar GnRH [24]. Retrospective studies conducted with transsexual adults indicate that psychological problems, such as anxiety and depression, often emerge during puberty as a consequence of the distress associated with the development of secondary sexual attributes [24]. Psychopathologies secondary to gender dysphoria can, therefore, be prevented if we intervene in time [28]. Unfavorable outcomes of surgical gender reassignment in adults appear to be associated with late treatment rather than early intervention [41, 42]. Studies evaluating the psychological functioning of adults and transsexual adolescents from the same clinic also found improved functioning among adolescents who had been treated early with hormone therapy [28, 38, 43]. The poorer *Effects of Hypothalamic Blockers in the Treatment of Gender Dysphoria in Preadolescence… DOI: http://dx.doi.org/10.5772/intechopen.101812*

psychological functioning in adults may result in part from the constant and lasting distress they have experienced throughout their lives. In fact, the omission of treatment can result in long-term psychosocial outcomes such as stigmatization and social isolation [24].

#### **5. Atypical development with GnRH analogues**

Given the effects of drugs on the body during treatment, the guidelines recommend monitoring the adolescent with auxological clinical evaluations (weight, height, body mass index, blood pressure, and Tanner stage) every 3–6 months, and evaluation hormones (LH, FSH, estradiol, testosterone, prolactin, and 25-OH vitamin D) to be repeated every 6–12 months for the first year of therapy [5].

#### **5.1 Short-term collateral effects**

Hypothalamic blockers are generally well tolerated, with the exception of possible hot flashes [23], fatigue, migraine, mood changes, injection pain, and abscesses [5]. Some cases of arterial hypertension following the administration of Triptorelin were observed in three male transsexual adolescents in a sample of 138 subjects [5, 44]; and in two treated patients, with complications in one out of two patients related to increased intracranial pressure, which resulted in a temporary interruption of treatment [45]. The increase in intracranial pressure is a very rare side effect, usually associated only with the analogue GnRH drug Leuprolide [46]. The consequences that the use of similar GnRH drugs can have on blood pressure require further investigation [11].

#### **5.2 Long-term collateral effects**

#### *5.2.1 Fertility*

From the available literature, it is noted that treatment with analogous GnRH has no negative effects on the fertility of younger patients who are treated before the age of 7 [47], indeed it seems to have a protective effect in patients with central precocious puberty [48]. In young male (biological sex) adolescents with gender dysphoria undergoing GnRH analogue therapy, sperm production and development of the reproductive system is insufficient for sperm cryopreservation [6]. However, sperm production can be induced by a spontaneous recovery in gonadotropin production after cessation of GnRH analogues, or by gonadotropin-stimulating treatment (associated with physical manifestations of testosterone production), [6].

#### *5.2.2 Nervous system effects*

The physiological reorganization of the central nervous system occurs during puberty, in particular the executive functions located in the prefrontal cortex develop [49]. What emerges from the studies conducted so far is that there are no undesirable effects on brain development for adolescents undergoing therapy with GnRH analogues and GAF: the brain functioning of young patients seems to replicate that of the general population [24]. No negative effects on executive function emerged in research [50]. However, further long-term investigations are needed to arrive at more conclusive data [11].

#### *5.2.3 Effects on bones development*

During puberty, bone mass increases, reaching its maximum density around 20–30 years of age [11]. Suspension of puberty in adolescence is associated with reduced bone mineral density (BMD) in adult men [6]. Some studies do not detect changes in BMD values during the period of administration of GnRH analogues [6]. Other data report stable values of bone mineral density during therapy, but with a decrease in zeta scores, and a resumption of bone mass accumulation at the start of cross-sex hormone therapy [23]. When BMD was assessed in the same adult sample, a delay in reaching peak bone mass was detected, since the loss of zeta scores was still partially present at the age of 22. William Malone, an American endocrinologist interested in puberty blockers, affirms that the drugs seem to halt the rapid increase in bone density, the expected rise that takes place typically in adolescence is delayed [51]. Van Coverden and colleagues observed an increase in bone mass in the long-term treatment of adolescents with gender dysphoria: during the administration of gender-affirming hormones (GAF) there is a recovery in bone mass accumulation following normal physiological development [52]. Therapy with GnRH analogues appears to initially reduce BMD, with a future normalization after the induction of puberty with cross-sex hormones. Dutch studies report a reduction of BMD during puberty suppression, with a subsequent increase at the start of GAH therapy and achieving a final BMD no different than that observed before initiating analogue [44, 53].

#### *5.2.4 Metabolical effects*

The first data on early hormone therapy in adolescents with gender dysphoria revealed an increase in fat mass and a decrease in lean mass, only during the first year of treatment with Triptorelin, followed by a restoration of normal values with the administration of GAF [23]. Effects on lipid and carbohydrate metabolism were absent in the sample examined. Evidence shows an increase in body mass index (BMI) [54], an increase in fat mass, and a reduction in lean mass [16] in trans adolescents taking GnRH analogues.

#### *5.2.5 Effects on growth*

Suppression of puberty can impair growth in trans adolescents AFAB and AMAB [6, 55]. Schagen and colleagues found a reduction in the rate of growth rate in the sample of trans adolescents analyzed [16]. This can be an advantage for trans AMAB adolescents, who are more likely to reach a height similar to the average female population. Growth reduction can also have side effects on bone development and metabolism [56]. Subsequent therapy with cross-sex hormones allows for manipulation of growth and the achievement of an almost normal height [23]. Since the expected height for trans AMAB adolescents is greater than the female average, it is possible to increase the dose of estrogen administered during therapy with GAF, to reduce the final height. On the contrary, for trans AFAB adolescents, treatment with GnRH analogues must be longer, before being able to administer androgens at the age of 16 [55]. To achieve maximum height, a slow introduction of androgens mimics an acceleration of growth typical of puberty, or one can proceed with the administration of oxandrolone, a growth-stimulating anabolic steroid [6].

*Effects of Hypothalamic Blockers in the Treatment of Gender Dysphoria in Preadolescence… DOI: http://dx.doi.org/10.5772/intechopen.101812*

#### *5.2.6 Effects on venous circulation*

Despite the lack of clear results, venous thromboembolism can be a complication of drugs, so early screening for thrombophilia is appropriate for those with a personal or family history of venous thromboembolism [6].

#### **6. Ethical aspects**

The biomedical ethics model, theorized by Beauchamp and Childress, is the main point of reference for the management of ethical problems in the clinical setting [57]. According to the authors, there are four prerequisites that healthcare and health professionals must abide by in clinical practice, which are autonomy, non-maleficence, beneficence, and justice.

#### **6.1 Autonomy**

Hormonal treatment in puberty is justified as it aims to satisfy the desire of adolescents who want to align biological sex with their gender identity. Respect for the autonomy of the young person and the decision to undergo therapy should be emphasized, as the same results are not achievable if the drugs are administered in adulthood, except with invasive operations [20]. Furthermore, to fully respect the autonomy of the child, it is essential to educate him to know the different treatment options for gender dysphoria, in order to allow an informed decision, regardless of geographic location or socioeconomic status. The exercise of autonomy in the decision-making process is based on the recognition of children's rights and the informed consent expressed by the adolescent and the family [58].

#### **6.2 Non-maleficence**

The principle of non-maleficence imposes the obligation not to inflict harm on the patient. Hypothalamic blockers are classified as a reversible treatment since they appear to be free of long-term side effects. The doctor who respects the principle of non-maleficence adopts a more holistic approach and considers not only the possible damage to the body but also any negative consequences on the emotional, social, and spiritual values. For many adolescents, the ability to reduce the distress associated with developing secondary sexual attributes is far more important than druginduced fertility deprivation. In general, the arguments against the use of blockers are based on the concern that gender dysphoria in childhood may go into remission in adolescence [59, 60]; on the impossibility of making a certain diagnosis of gender dysphoria in developmental age given the variability of gender identity in childhood and adolescence [17, 33]; and on the lack of knowledge of the long-term effects on the organism and psychological functioning [60, 61]. Furthermore, therapy can inhibit the spontaneous formation of a compliant gender identity, which sometimes develops through the "gender crisis" [62], and reduce libido, negatively affecting the adolescent's sexual experiences and limiting exploration of one's sexual orientation [17, 33]. Finally, for trans adolescents AMAB, the arrest of the development of the penis and testicles reduces the amount of skin tissue needed to perform a better vaginoplasty [63]. According to Giordano, the ethics of puberty suppression therapy depend not only on the balance of risks and benefits of the treatment but also on the evaluation of the consequences of the omission of treatment [39]. Health professionals must consider the long-term implications on the body (invasiveness of surgery), and the psychological and social/relational risks (self-loathing, social integration, and suicide risk).

#### **6.3 Beneficence**

Given the variability in the persistence of gender dysphoria from childhood to adulthood, it is not easy to establish how the specialist can operate in such a way as to respect the principle of beneficence The health professional makes some choices also influenced by personal belief systems and theoretical orientation that can influence the future of the adolescent, in both cases of treatment with similar GnRH and abstention from therapy [64]. The Standards of Care authorizes specialists to adapt the guidelines according to the needs and wishes of the individual patient [7]. The choice of prescribing blockers is ethical when the doctor believes that the patient will benefit from the treatment. If, after conducting the appropriate assessments, the physician concludes that refusal of treatment is the riskiest option because gender dysphoria is likely to persist into adolescence and adulthood, then early treatment is found to be in the best interests of the patient. Child [19]. The doctor's responsibility is to help the child or adolescent consider the possible consequences of each choice.

#### **6.4 Justice**

According to the principle of justice of Beauchamp and Childress, health services must be equally distributed among the population. Gender-dysphoric young people seeking assistance face a variety of barriers due to socioeconomic status and geographic location. There are disparities in access to care between gender-variant adolescents and cisgender peers, due to the stigma that prevents them from seeking and obtaining adequate treatments [12]. The social and structural stigma experienced by gender non-conforming young people reduces accessibility to care from a structural, interpersonal, and individual point of view [65]. The structural stigma implies a reduction in available resources and health coverage; the medicalization of atypical expressions of gender identity; electronic registers with only two options for gender identification; the lack of knowledge and research on the health of trans people [65]. Stigma in social relationships at school and in the family also represents a barrier to access to specialized medical services for atypical gender identity [66]. Young people, inserted in a stigmatizing social context, are increasingly reluctant to reveal their atypical gender identity. The tendency to hide associated with the fear of being judged as different reduces the likelihood for young gender-variant people to seek and receive assistance [67]. Furthermore, the services are not equally distributed throughout the territory, so there are few clinics with specialized professionals who are used to treat problems related to gender identity, generating inequalities in access to care due to geographic location. The shortage of adequately trained and competent personnel can lead to inappropriate or even harmful medical care for patients [68]. Gender-variant young people often have difficulty accessing other forms of assistance [69].

*Effects of Hypothalamic Blockers in the Treatment of Gender Dysphoria in Preadolescence… DOI: http://dx.doi.org/10.5772/intechopen.101812*

#### **7. Conclusion**

The experience of biological puberty is an undesirable condition for adolescents with gender dysphoria who find themselves living in a body they do not recognize as their own. Actionable interventions for gender dysphoria are classified in the Standards of Care as fully reversible, partially reversible, and irreversible interventions [7]. Suppression of puberty is a reversible treatment that involves the administration of similar drugs of gonadotropin-releasing hormone (GnRH). The analogue agonist most frequently used with adolescents with gender dysphoria is Triptorelin, administered by the intramuscular or subcutaneous route. This intervenes to arrest the development of secondary sexual attributes and associated physiological functions in adolescents with gender dysphoria. After the suppression of puberty, if gender dysphoria persists, the induction of puberty of gender identification can be carried out by administering GAF [11]. Regarding drug safety, GnRH analogues appear to be well tolerated in the short term, with the exception of hot flashes [23], fatigue, migraine, mood swings, pain from injection, and abscesses [5]. Even in the long term, there do not seem to be any significant side effects on the body, but the knowledge is still uncertain [11]. The issue of fertility is particularly delicate, since, if the gender adjustment process is continued, it remains irremediably compromised for adolescents who have not resorted to the preservation of sexual gametes. This aspect represents an element to be evaluated when defining the decision-making capacity of the minor who chooses to undergo medical treatment for gender dysphoria [24]. When the young person has not yet reached the age of majority, the request for the gender adjustment process should be accompanied by parental approval. However, there is no agreement on the minimum age for adolescents to express consent. Furthermore, it seems useless to establish an age threshold: the International Covenant on the Rights of the Child focuses on the capacity for judgment, whereby the adolescent can express consent when he has reached sufficient emotional and cognitive maturity to understand the implications of therapy, including possible side effects and risks that may occur [12]. Since puberty suppression therapy is partly experimental, consent cannot be fully informed, because the professionals themselves are not aware of all the long-term outcomes of drugs on the body [19]. The candidate can undertake treatment if he meets the eligibility criteria for treatment, whereby the professional assesses whether the adolescent is able to understand and provide consent; and was informed of the expected outcomes, possible disadvantages, potential loss of fertility, and opportunities for preserving fertility [5].

Parents have the right to make decisions for their children only when they do not hinder the "best interests" of young people [12]. The choice of the clinician should not be based only on parental opinion, because parents do not always know what their children's wishes are, and there is a risk of limiting the child's right to autonomy [17]. Gender dysphoria implies a strong inconsistency between assigned sex and experienced gender, with a rejection of one's sexual attributes leading to clinically significant suffering and impaired individual functioning in daily life [4]. This condition is also associated with problems of a psychological and psychiatric nature, such as depression and anxiety [70]; suicide ideas and attempts [18, 31, 35]; an intense dissatisfaction with one's body image [71, 72].

The negative psychosocial consequences of untreated gender dysphoria in adolescence are now well known. First of all, the young person can experience the omission of treatment as psychological torture and interpret it as a denial of the possibility of experiencing puberty of the kind of identification. Faced with this suffering, the adolescent who reacts with impulsiveness can adopt behaviors that are risky to health [30]. The anguish can be so intense that it leads to suicidal ideas and attempts. Suicidal behaviors are more frequent in the transgender population than in the rest of the population [31, 33–35]. Unfavorable outcomes of surgical gender reassignment in adults appear to be associated with late treatment rather than early intervention [41]. Poorer psychological functioning in adults could be due to the distress experienced due to a prolonged inconsistency between gender identity and physical appearance that exposes to stigmatization and social isolation [24]. On the other hand, timely treatment with similar GnRH not only allows to prevent negative outcomes but also bring benefits to the young person. The same effects cannot be obtained if therapy is started later in puberty, as blockers are less effective in reducing secondary sexual attributes when they are already formed [18, 20], for which it will be necessary to expose themselves to invasive surgical removal operations in the future. Suppression of puberty can be considered a diagnostic tool, as it saves time for both the adolescent, who can explore their gender identity without worrying about the development of secondary sexual attributes [22], and to the clinician, who can better understand the nature and intensity of adolescent distress [23] to arrive at a more precise diagnosis [20]. Many studies have found an improvement in functioning and psychological well-being after treatment with GnRH analogues [25–38]. When, on the other hand, therapy is denied, and the adolescent resorts to self-medication, he is no longer followed by professionals in the sector, with the foreseeable physical and psychological repercussions that follow (wrong methods and dosages of administration, possible infections due to injections that do not comply with appropriate hygiene standards), [12, 39]. Involvement in prostitution exposes adolescents to situations that are risky for their life and sexual health since they could be victims of abuse or contract infections and diseases if they do not use the appropriate precautions [71]. The advantages that can be brought by GnRH analogue therapy cannot be underestimated, which are arresting in the development of secondary sexual attributes and greater satisfaction with body image; preventing a series of risky behaviors for health, in particular suicidal ideations and attempts. The right of the adolescent emerges to a future in which life opportunities are maximized, whereby the possibility of living the puberty experience of gender identification is offered, preventing the need to undergo invasive gender affirmation surgeries in future [73–75]. The importance of respecting the right of the child to exercise personal autonomy in the decision-making process is noted, so his/her opinion must be considered by the professional when making a therapeutic choice [17, 76, 77]. Whether parents not only deny consent but adopt abusive attitudes towards the gender-variant child, then the possibility of intervention to protect the minor is evaluated [78]. Since the prevalence of gender in adolescence is progressively increasing in the population [24], this issue cannot be underestimated, and it is important to convey the right therapeutic tools for young people afferent to health services [79]. It is clear that denial of therapy is not a neutral option, and the health professional cannot omit the intervention, thus thinking of not harming the patient. This type of action can harm young people in two ways: it does not respect the principle of non-maleficence as they can adopt risk behaviors that compromise their health; does not respect the principle of beneficence as it does not bring benefit. The studies cited highlight the importance of evaluating for each case which therapeutic option is that can improve the well-being and quality of life of the minor, without focusing on rigid and a priori beliefs, but keeping the multiple possibilities of treatment open.

*Effects of Hypothalamic Blockers in the Treatment of Gender Dysphoria in Preadolescence… DOI: http://dx.doi.org/10.5772/intechopen.101812*

#### **Author details**

Massimo Di Grazia1 and Camilla Taverna<sup>2</sup> \*

1 Hospital Infermi, AUSL Romagna, Rimini, Italy

2 University of Padova, Padova, Italy

\*Address all correspondence to: camillataverna5@gmail.com

© 2022 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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### *Edited by Carlos Miguel Rios-González*

Trans people suffer from significant health disparities in multiple areas, one of which is public health. Real or perceived stigma and discrimination within biomedicine and healthcare delivery, in general, can affect trans people's desire and ability to access appropriate care, thereby impacting their own health. The biggest barrier to both safe hormone therapy and adequate general medical care for transgender patients is the lack of access to care. Despite guidelines and data supporting the current transgender medicine treatment paradigm, trans patients report that a lack of providers experienced in trans medicine represents the single largest component inhibiting access. Transgender care is not taught in conventional medical training programs and very few doctors have the necessary knowledge and level of comfort. As such, this book provides up-to-date information on the health of transgender people. Chapters address such topics as standards for transgender care, the treatment of gender dysphoria, the lived experiences of transgender persons in Brazil and India, and much more.

Published in London, UK © 2022 IntechOpen © coffeekai / iStock

Transgender Health - Advances and New Perspectives

Transgender Health

Advances and New Perspectives

*Edited by Carlos Miguel Rios-González*