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Canisius University Access Provided by: Transgender and Gender Diverse Health Care: The Fenway Guide Chapter 7: Gender­Affirming Hormone Therapy for Adults Julie Thompson INTRODUCTION This chapter focuses on the recommended approach to prescribing gender­affirming hormone therapy (GAHT). It includes guidance for the health care professional in recognizing an individual’s appropriateness for hormone therapy, providing informed consent, and developing a patient­ centered, individualized approach to treatment. Various hormone therapy options are discussed, as is the rationale for decision making in choosing specific medications. Additionally, this chapter provides information on the importance of understanding patient goals and providing education on expectations, the wide­ranging effects of GAHT, and guidelines for monitoring treatment. Hormonal gender affirmation is still a relatively new field of study, with data on health outcomes and medication safety being actively researched, and recommendations for best practices modified frequently. The dynamic nature of this field is both exciting and challenging; this chapter presents current guidelines. BACKGROUND AND DEFINITION Gender affirmation for many transgender and gender diverse (TGD) individuals is a multidimensional process involving aspects of social, emotional, and physical affirmation to reduce gender dysphoria. Gender dysphoria refers to the range of emotional distress experienced when there is a misalignment of one’s physical body and perceived gender with the internal sense of self. GAHT refers to sex steroids (mainly testosterone or estrogen) administered in various forms to produce or enhance secondary sex characteristics that promote physical affirmation. Using GAHT can reduce the internal stress of gender dysphoria as one’s physical body begins to align with the desired sense of self. Physical affirmation may also allow some people to move more comfortably or safely through the world as their affirmed and authentic self. Several studies have shown significant reductions in mental health comorbidities (depression, suicidality, substance use) and an overall improvement in quality of life with the ability to access GAHT.1–4 As such, for many individuals, access to GAHT is an important and necessary part of their self­ actualization process. The goal of GAHT is to create the internal hormone environment that best aligns with one’s gender identity, with the aim of achieving physical characteristics that are culturally accepted and expected as a presentation of that gender. GAHT often involves taking hormone medications (exogenous hormones) that are affirming and suppressing the body’s production of hormones (endogenous hormones) that do not align with one’s gender identity. GAHT therapy is most often focused on increasing or decreasing estrogen and testosterone with various medication options to produce a combination of reversible and permanent changes to the body. Not all TGD­identified individuals seek hormonal therapy as part of their affirmation. There is a great diversity of gender identities and expressions, and health care professionals must assess each individual’s goal for accessing care in a nonjudgmental and supportive way. According to the 2015 U.S. Transgender Survey, 79% of TGD respondents desired hormone therapy as part of their gender affirmation (which corresponded to 95% of transgender men and women respondents and 49% of nonbinary respondents).5 The TGD population is a diverse group of individuals, and therefore creating a low­barrier, welcoming environment to discuss patients’ needs and goals for gender­affirming care can allow for an individualized approach to treatment, health education, and support. ESTABLISHING THE GOALS FOR HORMONE THERAPY For many individuals, the aim of initiating hormones is to achieve the maximum changes to their bodies that culturally represent a feminine or masculine identity. However, some people with nonbinary or genderqueer identities may desire a nuanced hormonal makeup to achieve a more androgynous appearance to decrease gender dysphoria. Understanding a patient’s goals prior to starting on hormone therapy can ensure proper expectation setting and allow for tailoring of individual treatment regimens to achieve these desired goals whenever possible and safe. Hormones can affect external appearance, leading to secondary sex characteristics of the affirmed gender—for example, testosterone can cause a deeper voice and facial hair growth, whereas estrogen may induce breast development. Additionally, GAHT can promote affirming changes in body function by Downloaded 2024­5­23 2:0 suppressing endogenous P Your for hormones, IP is 138.92.199.188 example, cessation of menses with testosterone or decreased spontaneous erections with estrogen. Chapter 7: Gender­Affirming Hormone Therapy for Adults, Julie Thompson Page 1 / 20 Hormones do have limitations. In individuals who have already experienced natal puberty, hormones do not alter bone structure, height, and other ©2024 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility changes that have occurred over time due to endogenous hormones. To reject the rigid concepts of binary identities, clinicians should consider moving away from classifying hormones as “feminizing” or “masculinizing” For many individuals, the aim of initiating hormones is to achieve the maximum changes to their bodies that culturally represent a feminine or masculine identity. However, some people with nonbinary or genderqueer identities may desire a nuanced hormonal makeup toCanisius achieve aUniversity more androgynous appearance to decrease gender dysphoria. Understanding a patient’s goals prior to starting on hormone therapy canAccess ensure proper Provided by: expectation setting and allow for tailoring of individual treatment regimens to achieve these desired goals whenever possible and safe. Hormones can affect external appearance, leading to secondary sex characteristics of the affirmed gender—for example, testosterone can cause a deeper voice and facial hair growth, whereas estrogen may induce breast development. Additionally, GAHT can promote affirming changes in body function by suppressing endogenous hormones, for example, cessation of menses with testosterone or decreased spontaneous erections with estrogen. Hormones do have limitations. In individuals who have already experienced natal puberty, hormones do not alter bone structure, height, and other changes that have occurred over time due to endogenous hormones. To reject the rigid concepts of binary identities, clinicians should consider moving away from classifying hormones as “feminizing” or “masculinizing” and referring to hormones by their generic names—testosterone, estrogen, androgen­blocker—and known physical effects. In this way, clinicians can be specific about the effects of the hormones without tying physical traits or body characteristics to a gender. INFORMED CONSENT Often, individual clinicians and health institutions have established protocols for evaluating appropriateness for initiating hormone therapy. The most commonly adopted and referenced guidelines were developed by the World Professional Association of Transgender Health (WPATH), an international, multidisciplinary organization comprised of medical and mental health care professionals, researchers, advocates, and policymakers with expertise in transgender health and policy. WPATH sets international standards of care for transgender health practices and health equity. WPATH recommends an informed consent approach before starting GAHT for assessment and education with the patient.6 The informed consent process can be performed by either a medical or mental health clinician experienced in transgender health. Informed consent refers to the conversation between a health care professional and patient that thoroughly explains the benefits and risks of and realistic expectations for the full range of treatment options available for that patient. It also includes the process of assessing the patient’s capacity to understand this explanation. There is no one structured or prescribed way to provide informed consent; rather, it should be individualized to a patient’s cognitive and emotional needs, age, and cultural context. It is critical to set clear expectations with patients regarding unknowns due to gaps in research, limitations of medications, and the long­term health outcomes of therapy. Patients should be given the opportunity to discuss how these limitations and outcomes may align with their current and future goals and expectations.7 Throughout this process, the individual’s sense of self and agency should be promoted and supported.8 For some patients, assessment for appropriateness of hormone therapy is straightforward, while for others, more time may be needed to understand goals or to ensure support for ongoing medical, behavioral health, or social issues. WPATH recommends consideration of the following four criteria during the assessment: 1. Persistent, well­documented gender dysphoria (of at least 6 months as assessed by either a medical or behavioral health professional). 2. Capacity to make a fully informed decision and consent to treatment. 3. Age of majority in a given country. 4. If significant medical or mental health concerns are present, they should be reasonably well controlled.6 The presence of co­occurring medical or mental health conditions should not necessarily contraindicate or delay access to GAHT. If an underlying medical or mental health condition is both poorly controlled and presents a risk specifically in the setting of GAHT, it is recommended that the condition is stabilized before initiating hormone therapy. This recommendation requires nuanced decision­making and an individualized approach, which should include assessment of the patient’s health history, baseline level of functioning, and current level of functioning. Finally, the role of the patient’s gender dysphoria or the impact of hormone therapy use on this health condition should be assessed to determine the potential positive or negative impact of starting or continuing hormone therapy. The decision to deny or delay care should not be taken lightly. In most cases, GAHT has significant positive protective mental health benefits, and denial of hormone therapy can worsen depression, anxiety, and suicidality. Additionally, blocking access to gender­affirming treatment can lead to procurement of nonmedically supervised hormones and disengagement from medical care.3,9,10 Therefore, practicing gender­affirming care with a harm reduction philosophy should be the standard of care. Harm reduction aims to minimize negative health, social, or legal impacts of a potential high­risk behavior without requiring the individual to stop the behavior or blaming them for engaging in the behavior.11,12 Whenever possible, an attempt to stabilize a condition should be made while initiating GAHT. Downloaded 2024­5­23 2:0 P Your IP is 138.92.199.188 GUIDING EXPECTATIONS Chapter 7: Gender­Affirming Hormone Therapy for Adults, Julie Thompson Page 2 / 20 ©2024 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility Before starting GAHT, patients should be able to demonstrate clear and realistic expectations of hormone therapy, while also understanding the unique and largely unpredictable responses of each individual to hormone therapy. The age at which therapy is started, body habitus, and genetics procurement of nonmedically supervised hormones and disengagement from medical care.3,9,10 Therefore, practicing gender­affirming care with a Canisius University harm reduction philosophy should be the standard of care. Harm reduction aims to minimize negative health, social, or legal impacts of a potential Access Provided by: high­risk behavior without requiring the individual to stop the behavior or blaming them for engaging in the behavior.11,12 Whenever possible, an attempt to stabilize a condition should be made while initiating GAHT. GUIDING EXPECTATIONS Before starting GAHT, patients should be able to demonstrate clear and realistic expectations of hormone therapy, while also understanding the unique and largely unpredictable responses of each individual to hormone therapy. The age at which therapy is started, body habitus, and genetics likely play a role in the degree and speed at which changes may occur. These aspects also tend to influence the potential for risk factors from GAHT. The clinician and patient should review the physical and behavioral changes that are expected, limitations of hormone therapy, and the general timeline of these changes to guide patient expectations. It is also necessary to discuss the potential risks of hormone therapy on the body that are known, as well as the unknowns that still exist in this field regarding these medications and their outcomes. This information should be discussed in the context of the individual’s goals and how these may, or may not, affirm their gender and meet their needs. Effects of Testosterone Therapy Testosterone therapy can cause lowering of the pitch of the voice, fat redistribution from the buttocks and hips to the abdomen, increased muscle mass, and growth of facial and body hair. For most individuals, testosterone also causes cessation of menses13,14 (Table 7­1). Testosterone is generally safe. Although testosterone has been associated with a negative effect on lipids (specifically an increase in low­density lipoprotein and decrease in high­density lipoprotein), elevation in hematocrit, and a small increase in blood pressure, research has not shown an increase in cardiovascular events in those taking gender­affirming testosterone when compared with the general population. However, longer­term follow­up studies are still lacking. More data on cardiovascular outcomes in older (65 years of age or older) individuals will be helpful to better understand this risk with longer use of testosterone and as individuals age.13,14 Additionally, testosterone does not appear to increase the risk of breast or other reproductive cancers.14–16 Effects of Estrogen and Antiandrogen Therapy Estrogen and antiandrogen therapy (medications that suppress the body’s production or response to testosterone and allow the effects of estrogen to be more apparent) often lead to breast growth, fat redistribution from the abdomen to the buttocks and hips, slowing of facial and body hair growth, and softening of skin. These medications may also decrease spontaneous erections, testicular size, and libido14,17 (Table 7­2). Estradiol therapy has been associated with an increase in cardiovascular events, such as venous thromboembolism and stroke.18,19 It is unclear about the extent to which the type of estrogen and other comorbidities (hyperlipidemia, tobacco use, hypertension) increases the likelihood of these events. However, it remains imperative to proactively manage cardiovascular health in anyone starting estrogen therapy. Estrogen and antiandrogens are not associated with an increased risk of breast cancer in transgender women compared with cisgender women.16,20,21 Finally, estradiol appears to protect bone, and data indicate decreased bone turnover markers in individuals on estradiol therapy. Additionally, there does not appear to be an increased fracture risk in those using gender­affirming estrogen therapy.22–24 Because GAHT suppresses endogenous hormone production, fertility may be affected. It remains unclear if these effects on the reproductive system are fully reversible in all adults who have undergone their natal puberty. Several studies suggest that stopping GAHT and allowing endogenous hormones to return to their prior physiologic levels may restore fertility; however, the age of the individual must be considered.25,26 Additional research is needed to counsel patients with more confidence and predictability about the effects of GAHT on fertility. At this time, it is still recommended to encourage individuals to consider cryopreservation of their gametes before starting hormone therapy if biological children are desired.27 It can also be beneficial to discuss family planning on an ongoing basis for those whose family planning goals are evolving or for whom cryopreservation before initiation of GAHT is not an option. TAKING AN APPROPRIATE HISTORY The clinician must attain relevant medical, behavioral health, and social history from the individual to guide safe and effective care.28 Assessment for medical safety should occur in the setting of underlying medical issues and family health history. Before initiating hormone therapy, baseline laboratory tests and a physical exam may also be warranted depending on the individual’s underlying medical conditions, age, and family medical history. A behavioral health history should also be performed to assess the patient’s need for supportive referrals as well as to ensure that any mental health conditions are relatively stable and that the individual can consent to treatment. Additionally, a social history can illuminate safety issues and support needs that the patient may have and experience throughout their affirmation. Finally, it can be Downloaded helpful to2:0 2024­5­23 obtain a gender P Your narrative, which is a history of experienced gender awareness and includes the development, IP is 138.92.199.188 exploration, Chapter acceptance or rejection, 7: Gender­Affirming Hormone identification, Therapy for and persistence Adults, of one’s gender, as well as any symptoms of gender dysphoria. There isPage Julie Thompson no one 3 / 20 ©2024 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility “right” story. Gender narratives often vary and may be nuanced and influenced by the intersectionality of identities and experiences of an individual.29 A gender narrative can help contextualize a patient’s experience and goals to help guide treatment and create a clearer understanding between the laboratory tests and a physical exam may also be warranted depending on the individual’s underlying medical conditions, age, and family medical Canisius University history. A behavioral health history should also be performed to assess the patient’s need for supportive referrals as well as to ensure that any mental Access Provided by: health conditions are relatively stable and that the individual can consent to treatment. Additionally, a social history can illuminate safety issues and support needs that the patient may have and experience throughout their affirmation. Finally, it can be helpful to obtain a gender narrative, which is a history of experienced gender awareness and includes the development, exploration, acceptance or rejection, identification, and persistence of one’s gender, as well as any symptoms of gender dysphoria. There is no one “right” story. Gender narratives often vary and may be nuanced and influenced by the intersectionality of identities and experiences of an individual.29 A gender narrative can help contextualize a patient’s experience and goals to help guide treatment and create a clearer understanding between the patient and clinician on how to provide individualized, affirming care for that patient. See Table 7­3 for a review of the various components of medical, behavioral health, family, and social histories that should be obtained before starting GAHT. TESTOSTERONE THERAPY There are several options for the administration of testosterone, including injectables, topical gels or patches, and implantable long­acting pellets. Choosing which formulation is best depends on patient preference, ability to self­inject, risks of medication transfer to others, response to hormone therapy, insurance coverage, and cost. Injectable Testosterone Formulations The most common form of testosterone is injectable due to its low cost and ability to increase testosterone levels quickly and efficiently. Testosterone can be injected subcutaneously (SC) or intramuscularly (IM). Injectable Testosterone Formulations Medication Testosterone cypionate (cottonseed oil) name Or Testosterone enanthate (sesame seed oil) Frequency Injected weekly or every 2 weeks, IM or SC Additional Dose recommendations are the same whether using IM or SC injections. SC injections use smaller needles than IM and tend to be less comments painful. IM injections may be preferred or necessary for larger volumes.30–33 Biweekly dosing reduces the number of injections but leads to greater fluctuations in testosterone levels that can be uncomfortable for some patients. Weekly dosing may be a better choice for those concerned about the impact of fluctuating hormone levels on mood or other medical conditions. IM, intramuscular; SC, subcutaneous. Transdermal Testosterone Formulations Because it is dosed daily, the effects of transdermal testosterone more closely parallel the natural physiologic fluctuations of testosterone than is true with other forms of testosterone. Transdermal formulations can be considered if there are concerns about the effects of significant fluctuations in hormone levels, if more gradual changes are desired, or both. Transdermal Testosterone Formulations Gels Medication Testosterone gel names Frequency Applied daily Downloaded 2024­5­23 2:0 P Your IP is 138.92.199.188 Chapter 7: Gender­Affirming Hormone Therapy for Adults, Julie Thompson Page 4 / 20 ©2024Additional McGraw Hill. All Patients Rights Reserved. Terms must use caution of Use to avoid Privacy skin­to­skin Policyat application contact Notice Accessibility area(s) with partners, children, or pets until the medication is comments completely absorbed. Hands should be washed immediately after application. If skin­to­skin contact is anticipated, the area should be washed with soap and water or covered. The majority of the dose is absorbed within 4 hours of application.34 Because it is dosed daily, the effects of transdermal testosterone more closely parallel the natural physiologic fluctuations of testosterone than is true with other forms of testosterone. Transdermal formulations can be considered if there are concerns about the effects of significantCanisius University fluctuations in hormone levels, if more gradual changes are desired, or both. Access Provided by: Transdermal Testosterone Formulations Gels Medication Testosterone gel names Frequency Applied daily Additional Patients must use caution to avoid skin­to­skin contact at application area(s) with partners, children, or pets until the medication is comments completely absorbed. Hands should be washed immediately after application. If skin­to­skin contact is anticipated, the area should be washed with soap and water or covered. The majority of the dose is absorbed within 4 hours of application.34 Recommended application site is the upper arms.35 Patches Medication 2 mg or 4 mg testosterone transdermal system name Frequency New patch(es) applied daily Additional Patches commonly cause skin irritation. They are not recommended for patients known to have sensitive skin. comments Long­Acting Testosterone Formulations Long­acting formulations can be good options for people who find regular injections difficult and who are not candidates for transdermal formulations. These injections and implantable pellets may provide more consistent levels of testosterone over longer periods. They tend to be more expensive and must be administered by a medical professional in the clinic. Typically, long­acting formulations are only recommended after other methods have been tried. Long­Acting Testosterone Formulations Implantable Pellets Medication Testosterone pellets name Frequency Implanted every 3–4 months Additional Requires minor surgical procedure to implant pellets under the skin in the upper, outer area of the buttock notes It is recommended that individuals initiate therapy with another form of testosterone prior to initiating testosterone pellets to ensure testosterone is tolerable and affirming. Long­Acting Injectables Medication Testosterone undecanoate name Downloaded 2024­5­23 2:0 P Your IP is 138.92.199.188 Chapter 7: Gender­Affirming Frequency Hormone Therapy for Adults, Julie Thompson Initial injection Page 5 / 20 ©2024 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility Injection at 4 weeks Injections every 10 weeks thereafter formulations. These injections and implantable pellets may provide more consistent levels of testosterone over longer periods. They tend to be more Canisius expensive and must be administered by a medical professional in the clinic. Typically, long­acting formulations are only recommended University after other methods have been tried. Access Provided by: Long­Acting Testosterone Formulations Implantable Pellets Medication Testosterone pellets name Frequency Implanted every 3–4 months Additional Requires minor surgical procedure to implant pellets under the skin in the upper, outer area of the buttock notes It is recommended that individuals initiate therapy with another form of testosterone prior to initiating testosterone pellets to ensure testosterone is tolerable and affirming. Long­Acting Injectables Medication Testosterone undecanoate name Frequency Initial injection Injection at 4 weeks Injections every 10 weeks thereafter Additional Potential for rare, adverse side effect of pulmonary oil microembolism, anaphylaxis, or both following injection. Therefore, patients notes must remain in the clinic for 30 minutes following injections for observation. Due to these unique risks, the FDA has approved this medication only under a restricted prescribing scheme. FDA, US Food and Drug Administration. Additional or Alternative Hormone Therapy Some trans masculine or nonbinary individuals may desire or require additional medications to reduce symptoms of dysphoria. For example, cessation of menses may be critical to gender affirmation, but testosterone and its effects may not be desired. In these cases, hormonal contraceptives can be used to reduce or stop menstrual bleeding. Additionally, these medications may also be used to prevent pregnancy when requested and warranted, as testosterone alone does not reliably prevent pregnancy.30 ESTROGEN AND ANTIANDROGEN THERAPY 17β­estradiol, more commonly known as estradiol, is the recommended medication for GAHT. It is molecularly identical to the estrogen that circulates in the body and is observed to have the lowest risk profile, while also being quite effective.31,32 Estrogen can suppress testosterone and its effects, but estrogen alone may not be enough to suppress testosterone sufficiently for some individuals. Antiandrogen therapy may be needed to allow the effects of estrogen to be more apparent. Estrogen Therapy Like testosterone, there are several options for administration. The choice is typically based on patient preference, accessibility, effectiveness, cost, and individual safety considerations. Oral Estrogen Formulations Oral estradiol2024­5­23 Downloaded is dosed daily 2:0and therefore P Your IP is provides steady levels of estrogen in the body. This formulation is relatively cheap, accessible, and easy to 138.92.199.188 administer. Chapter 7: Gender­Affirming Hormone Therapy for Adults, Julie Thompson Page 6 / 20 ©2024 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility Oral Estrogen Formulations Like testosterone, there are several options for administration. The choice is typically based on patient preference, accessibility, effectiveness, cost, Canisius University and individual safety considerations. Access Provided by: Oral Estrogen Formulations Oral estradiol is dosed daily and therefore provides steady levels of estrogen in the body. This formulation is relatively cheap, accessible, and easy to administer. Oral Estrogen Formulations Medication Estradiol tablets names Frequency By mouth daily Additional Dissolving these tablets under the tongue, called sublingual (SL) dosing, may decrease the potential for estradiol affecting the liver comments (and the liver affecting the medication). However, there are no data to support that SL dosing is any safer or more beneficial than swallowing the tablets. The amount absorbed under the tongue is likely to be variable and unpredictable. The benefits versus risks of this dosing method are largely unknown. There may be pharmacokinetic differences in serum levels produced by oral vs. sublingual dosing of the estradiol, but the average serum levels throughout the day are likely the same.39 Transdermal Estrogen Formulations Transdermal estradiol appears to be the safest formulation from a cardiovascular standpoint, showing little impact on lipids and a decreased risk of thromboembolic events (blood clots) compared with other formulations.33–36 Transdermal formulations may be more appropriate for those with a higher than average cardiovascular risk, such as patients who are hypertensive, diabetic, or smokers. Like oral formations, transdermal formulations also provide the benefit of steady estrogen levels as well as ease of use. Transdermal Estrogen Formulations Patches Medication names Estradiol transdermal system Frequency Patch(es) applied once or twice a week, depending on the brand Additional comments Patches formulated for twice­weekly use may be preferable for patients for whom adhesiveness is an issue. Gels Medication names Estradiol gel Frequency Applied daily Additional comments May be more expensive than other formulations. Less likely to cause a skin reaction (no adhesive as with the patch). Downloaded 2024­5­23 2:0 P Your IP is 138.92.199.188 Injectable Chapter Estrogen Formulations 7: Gender­Affirming Hormone Therapy for Adults, Julie Thompson Page 7 / 20 ©2024 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility Injectable estradiol is typically dosed intramuscularly (IM) every 2 weeks, although weekly dosing with smaller amounts is possible, with the benefit of decreasing the fluctuations between doses. Some patients believe that injectable dosing produces changes more rapidly than transdermal  Additional comments May be more expensive than other formulations. Canisius University Less likely to cause a skin reaction (no adhesive as with the patch). Access Provided by: Injectable Estrogen Formulations Injectable estradiol is typically dosed intramuscularly (IM) every 2 weeks, although weekly dosing with smaller amounts is possible, with the benefit of decreasing the fluctuations between doses. Some patients believe that injectable dosing produces changes more rapidly than transdermal preparations; however, there is no evidence to support this contention. Some avoid injectable formulations due to needle phobia, the inconvenience and timing of injections (whether self­injecting or by a medical professional), and the wider fluctuations in hormone levels from dose to dose. Injectable Estrogen Formulations Medication Estradiol valerate name Frequency Injected every week or every 2 weeks IM Additional Injectable estrogens have few applications outside of their use in gender affirmation, resulting in periodic shortages from the comments manufacturer and/or difficulty obtaining injectable estradiol. These shortages are likely to continue, and those with concerns about this may consider topical or oral formulations instead. Medication Estradiol cypionate name Frequency Injection every 2 weeks IM Additional If switching from the valerate to the cypionate formulation, dosage adjustment is needed. The dosage of estradiol cypionate should be comments lowered to about 1/3 to 1/4 of the valerate dose. Estradiol cypionate tends to produce a lower, later, and longer peak level when compared to estradiol valerate, but the average levels in the blood, and effects on the body, should be the same. IM, intramuscularly. Antiandrogen Therapy For many, androgen­blocker medications are needed or desired to decrease endogenous production of and response to testosterone, allowing the effects of estrogen to be more apparent. Estrogen alone can suppress testosterone, but for some patients, estrogen alone may not be enough to suppress testosterone sufficiently. Antiandrogen Formulations Medication Spironolactone name Frequency By mouth once or twice daily Additional Spironolactone is a potassium­sparing diuretic that can directly inhibit testosterone production and its effects, as well as potentially Comments having its own small estrogenic effect. Those who are smaller and thinner, have lower blood pressure, are on certain blood pressure medications, or have underlying kidney disease may be at increased risk of experiencing adverse side effects. Downloaded 2024­5­23It2:0 P Yourthe is currently IP antiandrogen is 138.92.199.188 of choice in the United States. Chapter 7: Gender­Affirming Hormone Therapy for Adults, Julie Thompson Page 8 / 20 ©2024 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility Medication Finasteride, dutasteride name For many, androgen­blocker medications are needed or desired to decrease endogenous production of and response to testosterone, allowing the Canisius effects of estrogen to be more apparent. Estrogen alone can suppress testosterone, but for some patients, estrogen alone may not be enoughUniversity to suppress testosterone sufficiently. Access Provided by: Antiandrogen Formulations Medication Spironolactone name Frequency By mouth once or twice daily Additional Spironolactone is a potassium­sparing diuretic that can directly inhibit testosterone production and its effects, as well as potentially Comments having its own small estrogenic effect. Those who are smaller and thinner, have lower blood pressure, are on certain blood pressure medications, or have underlying kidney disease may be at increased risk of experiencing adverse side effects. It is currently the antiandrogen of choice in the United States. Medication Finasteride, dutasteride name Frequency By mouth once daily Additional These medications block the conversion of testosterone to its more potent form, DHT. They do not inhibit the production of comments testosterone and therefore will not lower blood testosterone levels. May be most effective for those with androgenic hair loss/baldness, significant facial hair, or those who are unable to tolerate higher doses of spironolactone. Medication Leuprolide name Frequency Injected monthly or every 3 months, depending on the formulation. This injection is done by a medical professional. Additional Decreases endogenous production of sex hormones and is used to block gonadal (testicular or ovarian) function. In prepubertal comments individuals, it can also reversibly block pubertal development prior to starting on gender­affirming hormone therapy. Leuprolide can be an option for some adults as part of a hormone therapy regimen, but it may be cost­prohibitive and therefore is not a first­line therapy. The most common antiandrogen medication used in the United States is spironolactone, a potassium­sparing diuretic. At high doses, it directly inhibits both the production and binding of testosterone to the testosterone receptor and may also exert a small estrogenic effect of its own.37–39 Spironolactone is inexpensive and generally well tolerated. Recently, some have challenged the safety and effectiveness of spironolactone. One study questioned the effectiveness of spironolactone and its actual mechanism of action in the setting of estrogen therapy.40 Anecdotal reports from patients and clinicians have raised concerns about possible long­term effects on endogenous corticosteroid production and mental health.41,42 None of these issues has been explored in depth, and there is no proven clinical significance or relevance to these theories at this time. Despite these challenges, spironolactone remains one of the most studied, affordable, and safest antiandrogen medications available. As additional medications are evaluated for their effectiveness and safety in the context of gender­affirming care, these recommendations may change, and more desirable alternatives for testosterone suppression may emerge. Some individuals are able to achieve testosterone suppression without an antiandrogen, either with estrogen alone or post­post­gonadectomy. In these cases, no additional medication is indicated for the suppression of endogenous testosterone. Antiandrogens should be discontinued after a patient undergoes orchiectomy. Progesterone Therapy Downloaded 2024­5­23 2:0 P Your IP is 138.92.199.188 The benefit Chapter of progestins for gender 7: Gender­Affirming affirmation Hormone Therapyisfornot well established. Adults, Some patients and medical professionals report that progesteronePage Julie Thompson may 9help / 20 improve breast development, promote improvement in mood and libido, and have other positive ©2024 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility benefits. However, progesterone has also been known to cause weight gain, fatigue, irritability, and negative mood changes in other individuals. Progesterone is part of a cisgender female’s hormonal makeup and may be desired on this basis as part of a patient’s gender­affirming hormone therapy. It is important to weigh the benefits vs. Some individuals are able to achieve testosterone suppression without an antiandrogen, either with estrogen alone or post­post­gonadectomy. In Canisius University these cases, no additional medication is indicated for the suppression of endogenous testosterone. Antiandrogens should be discontinued after a Access Provided by: patient undergoes orchiectomy. Progesterone Therapy The benefit of progestins for gender affirmation is not well established. Some patients and medical professionals report that progesterone may help improve breast development, promote improvement in mood and libido, and have other positive benefits. However, progesterone has also been known to cause weight gain, fatigue, irritability, and negative mood changes in other individuals. Progesterone is part of a cisgender female’s hormonal makeup and may be desired on this basis as part of a patient’s gender­affirming hormone therapy. It is important to weigh the benefits vs. potential risks of starting progesterone. In a few studies, progesterone has been shown to play a role in suppressing testosterone production, which supports its use as supplemental, or alternative, antiandrogen medication when needed.43 Progesterone may be considered if estrogen alone or estrogen and spironolactone are not effective in adequately suppressing testosterone. Micronized progesterone (Prometrium) is the formulation that is molecularly identical to the progesterone produced in the body. It appears to be the safest option in terms of cardiovascular health. Progesterone Formulations Medication Micronized progesterone name Frequency By mouth once daily, or cyclical dosing (10 days every month) Additional Some patients may prefer cyclic dosing as its effects may mimic a menstrual cycle, which can be affirming for some. However, others comments may find the hormonal fluctuations with cyclic dosing troubling and may prefer to take this medication daily. Progesterone’s role in breast development has yet to be proven. Reported increases in breast size seem most likely due to general weight gain and fat deposition in the breasts as caused by progesterone and estrogen, and not the direct effect of progesterone on the breast tissue itself. So far, there is no evidence to show any specific benefit (or lack of benefit) regarding progesterone’s effect on breast development.44 Medication Depot medroxyprogesterone acetate (DMPA or Depo Provera) name Frequency Injected every 3 months Additional DMPA has been shown to have a slightly higher risk of side effects than micronized progesterone. DMPA is associated with bone loss in comments cisgender women and mood changes (irritability, depression). DMPA may also pose an increased risk of blood clotting events compared with the micronized progesterone, but this association needs to be studied further.45 The benefit may be in the 3­month injectable dosing, but the risks may outweigh the benefits in many individuals. GAHT FOR NONBINARY/GENDERQUEER INDIVIDUALS Some nonbinary or genderqueer individuals may desire sex hormone levels in a range midway between the physiologic cisgender male and female ranges or to use gender­affirming hormones for a limited amount of time. The decision to prescribe GAHT and the dosages used should be based on a discussion with the patient. A clear understanding of patient goals and ensuring realistic expectations are necessary, given the unique and often unpredictable responses of each individual to hormone therapy. “Microdosing” is a term that is sometimes used to describe using low doses or limited doses of testosterone or estrogen to affirm a gender identity. Most often, microdosing is requested by individuals identifying as nonbinary or genderqueer, but it may be requested by anyone for whom these alternative dosing options affirm their nuanced identity. There is no one Downloaded way to “microdose”; 2024­5­23 2:0 P Your rather, microdosing should be viewed as another example of an individualized approach to prescribing hormone IP is 138.92.199.188 Chapter 7: Gender­Affirming Hormone Therapy for Adults, therapy. Patients are often started on low doses, and changesJulie areThompson Page closely monitored to ensure that the medication continues to affirm their 10 / 20 identity ©2024 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility and that changes that are not desired do not occur. Patients should be counseled that it is not possible to predict the changes that may occur as a result of hormone therapy or how fast they may occur. It is imperative to discuss changes that may be permanent and that it may not be possible to unpredictable responses of each individual to hormone therapy. Canisius University “Microdosing” is a term that is sometimes used to describe using low doses or limited doses of testosterone or estrogen to affirm a gender identity. Access Provided by: Most often, microdosing is requested by individuals identifying as nonbinary or genderqueer, but it may be requested by anyone for whom these alternative dosing options affirm their nuanced identity. There is no one way to “microdose”; rather, microdosing should be viewed as another example of an individualized approach to prescribing hormone therapy. Patients are often started on low doses, and changes are closely monitored to ensure that the medication continues to affirm their identity and that changes that are not desired do not occur. Patients should be counseled that it is not possible to predict the changes that may occur as a result of hormone therapy or how fast they may occur. It is imperative to discuss changes that may be permanent and that it may not be possible to tailor hormone regimens to allow for some changes and not others. Patients should be given the option to stop hormone therapy whenever they feel the medication is no longer affirming or desired. Some patients may wish to start on lower­than­usual doses and slowly increase their dosage over time. Giving the option for slowly experiencing the effects of hormones may provide relief from dysphoria, decreased anxiety, and autonomy over the process. A safe but flexible approach to dosing should be presented during the informed consent process for all patients when initiating hormone therapy. FOLLOW­UP AND MONITORING The important aspects of monitoring include gender affirmation and safety of GAHT. Despite premedication assessment and expectation setting, a person will not know whether the effects of GAHT will feel affirming to their gender until they start GAHT. It is important to follow up with patients to assess their experience and satisfaction with treatment. Additionally, a person’s goals, gender, safety profile, and support can change over time, which may require individualized adjustments in medication or supportive referrals. Follow­up office visits are recommended regularly within the first year and semiregularly thereafter to ensure that GAHT is meeting their needs and expectations. Follow­up visits also provide an opportunity to reassess behavioral health, social supports, and stability to provide holistic care for general health and well­being. Another aspect of follow­up care may include laboratory monitoring to determine if hormone levels are within expected or therapeutic safe ranges. It may also be important to monitor underlying medical conditions, organ systems, or other aspects of the body that may be affected by GAHT and pose a potential health risk to the patient. As with other aspects of gender­affirming care, these recommendations can be individualized to a patient’s specific risks and ability to access care (such as insurance coverage or distance from the clinic). A patient­centered, harm­reduction approach is encouraged. Requiring regular laboratory testing in order to continue on GAHT can pose unnecessary risk and harm to certain patients who require lower barriers to care to remain engaged. Medical professionals should thoughtfully assess risks versus benefits of the lab studies ordered before recommending them to patients. Suggestions for follow­up laboratory testing are presented in Tables 7­4 and 7­5. SUMMARY GAHT is one aspect of gender affirmation. It is sought out by TGD individuals to reduce gender dysphoria. GAHT is known to be generally safe, effective, and lifesaving for many TGD individuals. A flexible, patient­centered approach to initiation and maintenance of care is strongly encouraged. GAHT has been shown to decrease depression, anxiety, and suicidality, while improving overall health outcomes, making accessibility to gender­ affirming medical care important in the overall well­being of TGD individuals. Providing low­barrier access to GAHT through the informed consent process promotes engagement of the patient with the health care professional to discuss expectations, potential risks, and all available options for treatment—both medical and nonmedical. Clinicians should know about medication options and their associated risks, benefits, and limitations in order to best educate and guide patients in joint decision­making that best meets their goals. Creating an environment that empowers patients to discuss individual needs as they develop over time is an important aspect of guiding care and providing management as it may relate to physical changes, adverse side effects, family planning, or safety over months to years. Follow­up monitoring to assess for affirmation and reduction in dysphoria, as well as social and medical safety, are also important aspects of care. Regular check­ins within the first years can provide support during a dynamic time in an individual’s physical, emotional, and social life. Laboratory monitoring may also be recommended depending on individual risks, medication, and access to care. CASE STUDY 1: CH CH is a 65­year­old, self­identified Caribbean­American trans woman who presents to Dr. York’s office for the first time seeking estrogen and Downloaded 2024­5­23 2:0 P Your IP is 138.92.199.188 antiandrogen hormone therapy. As her new primary care physician, Dr. York welcomes her to the practice, “I’m so happy that you came in.Page Please share Chapter 7: Gender­Affirming Hormone Therapy for Adults, Julie Thompson 11 / 20 with me how you have experienced your gender over time and how you came to the decision to ©2024 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility medically affirm your gender at this point in your life.” CH responds that she has known she is a woman most of her life, but never had the language to define these thoughts, nor did she have any role models to show her it was a possibility. She married a woman when she was in her early 20s and had two children with this partner. She reports that  Regular check­ins within the first years can provide support during a dynamic time in an individual’s physical, emotional, and social life. Laboratory monitoring may also be recommended depending on individual risks, medication, and access to care. Canisius University Access Provided by: CASE STUDY 1: CH CH is a 65­year­old, self­identified Caribbean­American trans woman who presents to Dr. York’s office for the first time seeking estrogen and antiandrogen hormone therapy. As her new primary care physician, Dr. York welcomes her to the practice, “I’m so happy that you came in. Please share with me how you have experienced your gender over time and how you came to the decision to medically affirm your gender at this point in your life.” CH responds that she has known she is a woman most of her life, but never had the language to define these thoughts, nor did she have any role models to show her it was a possibility. She married a woman when she was in her early 20s and had two children with this partner. She reports that her life has been fulfilling, but she has always suffered from depression, which she associates with her gender dysphoria. In her 30s, she attempted suicide and was admitted to the hospital for a week because she felt hopeless about never being able to socially or physically affirm her female identity. However, due to fear of rejection at the time, she told her family and medical professionals that her depression was caused by extreme work stress. She goes on to say that her wife of 40 years passed away 2 years ago, and since then, she has been researching hormone therapy options and becoming more interested in pursuing gender­affirming care. She has bought “female clothes” and wears them at home but has not yet felt safe wearing them in public. She is close to her children and active in her church, and is very concerned about what gender affirmation will mean in terms of her relationship with her family and community, but feels she can no longer wait to affirm her female gender identity. When she broached the topic briefly with her children, they were shocked, marginally supportive, and said they needed time to process the news. Dr. York reviews CH’s medical history. She has hypertension and diabetes, for which she is taking lisinopril 20 mg daily, amlodipine 10 mg, metformin 1000 mg ER, and Lantus 60 U daily. Both conditions are moderately well­controlled: current blood pressure is 130/80 and hemoglobin A1c is 7.5%. Her goals today are clear: she would like to affirm her female identity with estradiol and decrease her testosterone. She is also interested in connecting with the TGD community for peer support, as she is worried about rejection from her current family and friends. Discussion Questions 1. Dr. York asks CH what brings her in to affirm her gender at the age of 65. How can understanding an individual’s gender narrative and gender history help you as their health care professional? 2. What identities—besides her trans identity—may have impacted CH’s choices to start hormone therapy, and how may these intersecting identities continue to impact her sense of self and community acceptance? 3. CH discloses a history of chronic depression and a suicide attempt. How might this history, and the context in which it occurred, influence Dr. York’s assessment of CH’s behavioral health stability and appropriateness to start on GAHT, if at all? If the suicide attempt were more recent, how might a harm reduction approach to care be applied? 4. What aspects of CH’s medical history might impact Dr. York’s discussion of feminizing hormone therapy? Might Dr. York consider a certain type of estradiol or dosing considerations? 5. What laboratory tests might Dr. York want to monitor for CH based on her medical history and risks? How often should they be monitored? 6. CH is 65 years old, and a cisgender woman of this age would likely be postmenopausal with very low estrogen levels. Would you consider not starting CH on estrogen for this reason or starting on a very low dose of estradiol? What could be the physical and emotional benefits vs. the risks of not offering her estrogen? How do you think CH would feel or respond to Dr. York if estradiol were not offered? CASE STUDY 2: XB XB is a 19­year­old self­identified Latinx, nonbinary individual who was assigned female sex at birth and has been in care with physician assistant (PA) Ruiz­Marquez since they were 11 years old. XB has been using they/them pronouns since age 15, feels very comfortable talking to their PA about their gender, and has had good support from their friends and school. Both PA Ruiz­Marquez and XB speak Spanish as their first language, but now mostly speak English in their daily lives and speak English with each other. XB scheduled an appointment with PA Ruiz­Marquez to discuss starting on gender­affirming testosterone therapy to further affirm their nonbinary identity. They are able to clearly describe aspects of themself they do not identify with and that cause them dysphoria—menses, their chest (breasts), and voice. However, they are equally clear that they have no interest in growing a beard, losing their hair, or having big muscles; none of those things would feel affirming. XB is asking about options to affirm their identity. Downloaded 2024­5­23 2:0 P Your IP is 138.92.199.188 When ChapterPA7: Ruiz­Marquez asks about Gender­Affirming socialTherapy Hormone and familyfor support, XB acknowledges Adults, Julie Thompson that their friends continue to be very supportive, but they have Pagebeen 12 / 20 struggling more and more with their family. XB is quite close to their parents and siblings, ©2024 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility as well as their large extended family. Initially, XB was forgiving with their family when they did not use their affirmed name and pronouns, but they now feel increasingly frustrated and irritated by their lack of understanding. XB speaks Spanish at home with family and has modified their Spanish to make it less gendered but has received negative feedback  Canisius XB scheduled an appointment with PA Ruiz­Marquez to discuss starting on gender­affirming testosterone therapy to further affirm their University nonbinary Access Provided by: identity. They are able to clearly describe aspects of themself they do not identify with and that cause them dysphoria—menses, their chest (breasts), and voice. However, they are equally clear that they have no interest in growing a beard, losing their hair, or having big muscles; none of those things would feel affirming. XB is asking about options to affirm their identity. When PA Ruiz­Marquez asks about social and family support, XB acknowledges that their friends continue to be very supportive, but they have been struggling more and more with their family. XB is quite close to their parents and siblings, as well as their large extended family. Initially, XB was forgiving with their family when they did not use their affirmed name and pronouns, but they now feel increasingly frustrated and irritated by their lack of understanding. XB speaks Spanish at home with family and has modified their Spanish to make it less gendered but has received negative feedback from their parents that XB is not respecting the Spanish language and culture. XB asks PA Ruiz­Marquez for suggestions and support. Discussion Questions 1. XB is requesting support to further affirm their nonbinary identity with testosterone. Besides testosterone, what other medical or nonmedical options are available that might affirm XB’s identity and meet their goals? 2. Would XB be a good candidate for testosterone? If so, what recommendations for testosterone might PA Ruiz­Marquez discuss with XB in regards to formulations and dosing? In what ways might the idea of “microdosing” meet or not meet XB’s goals? If Dr. Ruiz­Marquez were going to prescribe testosterone for XB, what aspects of informed consent might be key in setting expectations? 3. How might a shared language or culture positively or negatively impact the formation of a productive relationship between XB and PA Ruiz­ Marquez? XB feels very comfortable with PA Ruiz­Marquez, but can you envision a situation where a shared culture, identity, or religion might make it harder to disclose identity? 4. What supportive resources can you think of for XB? Are there any resources to support gender identity, gender­affirming language, or nongendered language in non­English speaking, nonwestern cultures that you can think of? How can we work to create these? CASE STUDY 3: DG DG is a 31­year­old self­identified white transgender male who has been engaged in care with nurse practitioner (NP) Hwang for the past 8 years. DG has a history significant for cerebral palsy (CP), and he also sees a neurologist, physiatrist, and physical therapist at a nearby medical facility. DG is on oxcarbazepine for his CP and muscle contractions. He has never been on testosterone therapy but had gender­affirming chest reconstruction 3 years ago. DG is quite healthy and is very active in adaptive sports (sled hockey, skiing, wheelchair basketball, rock climbing, etc.), which is where he gets his social supports and connections, as well as self­esteem and empowerment. DG was referred to NP Hwang by his neurologist after he asked his neurology team what the impacts of testosterone therapy might be on his CP if he were to start gender­affirming hormones. DG comes into NP Hwang’s office today looking for some answers to this question. DG reports to NP Hwang that he has been quite dysphoric due to being often misgendered, and very much wants to start on testosterone. However, he is worried about any negative impact testosterone might have on his CP and whether it could compromise his activity level and engagement in sports. Since there are multiple causes of cerebral palsy, a paucity of information about sex­linked or hormonal influences on CP, and no current research on how exogenous testosterone might impact CP (in either cisgender or transgender individuals), answers to these questions are difficult. NP Hwang can discuss the known effects of testosterone on bone and muscle in individuals without CP but it is unclear if these effects will be the same in those with CP and how testosterone might specifically affect DG’s function. Discussion Questions 1. As a medical professional, how do you provide informed consent in the setting of unknowns? How does this make you feel as a medical professional? As a patient, how would you feel hearing that “the expert” does not have the answers? 2. What are some of the changes that are expected when starting testosterone therapy that might be relevant to DG? 3. What might be some of the benefits of starting testosterone therapy? What might be the risks? Can you speculate how these benefits and risks might impact DG both physically and emotionally? 4. If NP Hwang and DG decided together that the benefits of testosterone likely outweighed the risks, what would be the best way to monitor DG’s response to therapy? How might you engage DG’s medical specialists in this process? Downloaded Table 7­1 2024­5­23 2:0 P Your IP is 138.92.199.188 Chapter 7: Gender­Affirming Hormone Therapy for Adults, Julie Thompson Expected Effects of Testosterone T h e r a p y Page 13 / 20 ©2024 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility Effect Onset (months) Maximum (years) 3. What might be some of the benefits of starting testosterone therapy? What might be the risks? Can you speculate how these benefits and risks Canisius University might impact DG both physically and emotionally? Access Provided by: 4. If NP Hwang and DG decided together that the benefits of testosterone likely outweighed the risks, what would be the best way to monitor DG’s response to therapy? How might you engage DG’s medical specialists in this process? Table 7­1 Expected Effects of Testosterone T h e r a p y Effect Onset (months) Maximum (years) Acne and skin oiliness 1–6 1–2 Fat redistribution 1–6 2–5 Cessation of menses 2–6 Clitoral/phallus enlargement 3–6 1–2 Atrophy of frontal canal/vagina 3–6 1–2 Deepening of voice 3–12 1–2 Increased sex drive Variable Emotional changes Variable Facial/body hair growth 6–12 4–5 Scalp hair loss Variable Variable Increased muscle mass and strength 6–12 2–5 Coarser skin/increased sweating 3–12 Weight gain/fluid retention Variable Tendon injury Variable; may be more likely with heavyweight training exercise Adapted with permission from Hembree WC, Cohen­Kettenis PT, Gooren L, et al: Endocrine Treatment of Gender­Dysphoric/Gender­Incongruent Persons: An Endocrine Society Clinical Practice Guideline, J Clin Endocrinol Metab 2017 Nov 1;102(11):3869­3903. Table 7­2 Expected Effects of Estrogen and Antiandrogen Therapy Effect Onset (months) Maximum (years) Decreased libido 1–3 0.25–0.5 Decreased spontaneous erections 3–6 Decreased testicular volume 3–6 2–3 Decreased sperm production Variable Variable Breast growth/breast tenderness 3–6 2–3 Downloaded 2024­5­23 2:0 P Your IP is 138.92.199.188 Chapter 7: Gender­Affirming Redistribution of body fat Hormone Therapy for Adults, Julie Thompson 6–12 2–3 Page 14 / 20 ©2024 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility Decreased muscle mass 3–6 1–2  Tendon injury Variable; may be more likely with heavyweight training exercise Canisius University Access Provided by: Adapted with permission from Hembree WC, Cohen­Kettenis PT, Gooren L, et al: Endocrine Treatment of Gender­Dysphoric/Gender­Incongruent Persons: An Endocrine Society Clinical Practice Guideline, J Clin Endocrinol Metab 2017 Nov 1;102(11):3869­3903. Table 7­2 Expected Effects of Estrogen and Antiandrogen Therapy Effect Onset (months) Maximum (years) Decreased libido 1–3 0.25–0.5 Decreased spontaneous erections 3–6 Decreased testicular volume 3–6 2–3 Decreased sperm production Variable Variable Breast growth/breast tenderness 3–6 2–3 Redistribution of body fat 6–12 2–3 Decreased muscle mass 3–6 1–2 Softening of skin 3–6 2–3 Decreased or slower growth of facial and body hair 6–12 >3 Adapted with permission from Hembree WC, Cohen­Kettenis PT, Gooren L, et al: Endocrine Treatment of Gender­Dysphoric/Gender­Incongruent Persons: An Endocrine Society Clinical Practice Guideline, J Clin Endocrinol Metab 2017 Nov 1;102(11):3869­3903. Table 7­3 Components of the Medical History Component Description Gender History of experienced gender awareness and the development, exploration, acceptance/rejection, identification, and persistence of narrative that gender Any symptoms of gender dysphoria Goals for nonmedical affirmation of gender, GAHT, or other gender­affirming medical care Medical Personal history of coronary artery or cerebrovascular disease, arterial or venous thromboembolism, hypertension, diabetes, history hormone­sensitive cancer, polycythemia, pituitary adenoma, liver disease, HIV infection, and other sexually transmitted infections Current specialists for any underlying medical issues Use of current or past prescribed and unprescribed hormone use, as well as any history of surgical procedures, including body modifications or injectable silicone use Behavioral History of major depression or bipolar disorder, psychosis, suicidality, impulse control disorder, disordered eating patterns, and health substance use and abuse history Current behavioral health care professionals and any past or present psychiatric medications Psychiatric hospitalizations Past or present sexual, physical, or emotional abuse or trauma (although it may not be necessary or possible to explore this fully in the initial assessment—see Chapter 11, “Basic Principles of Trauma­Informed Care”) Current or previous suicidality or self­injurious behavior Downloaded 2024­5­23 2:0 P Your IP is 138.92.199.188 Chapter 7: Gender­Affirming Hormone Therapy for Adults, Julie Thompson Page 15 / 20 ©2024 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility Family Family history of any cancer, cardiovascular disease, diabetes, or blood clotting disorders history  Decreased or slower growth of facial and body hair 6–12 >3 Canisius University Access Provided by: Adapted with permission from Hembree WC, Cohen­Kettenis PT, Gooren L, et al: Endocrine Treatment of Gender­Dysphoric/Gender­Incongruent Persons: An Endocrine Society Clinical Practice Guideline, J Clin Endocrinol Metab 2017 Nov 1;102(11):3869­3903. Table 7­3 Components of the Medical History Component Description Gender History of experienced gender awareness and the development, exploration, acceptance/rejection, identification, and persistence of narrative that gender Any symptoms of gender dysphoria Goals for nonmedical affirmation of gender, GAHT, or other gender­affirming medical care Medical Personal history of coronary artery or cerebrovascular disease, arterial or venous thromboembolism, hypertension, diabetes, history hormone­sensitive cancer, polycythemia, pituitary adenoma, liver disease, HIV infection, and other sexually transmitted infections Current specialists for any underlying medical issues Use of current or past prescribed and unprescribed hormone use, as well as any history of surgical procedures, including body modifications or injectable silicone use Behavioral History of major depression or bipolar disorder, psychosis, suicidality, impulse control disorder, disordered eating patterns, and health substance use and abuse history Current behavioral health care professionals and any past or present psychiatric medications Psychiatric hospitalizations Past or present sexual, physical, or emotional abuse or trauma (although it may not be necessary or possible to explore this fully in the initial assessment—see Chapter 11, “Basic Principles of Trauma­Informed Care”) Current or previous suicidality or self­injurious behavior Family Family history of any cancer, cardiovascular disease, diabetes, or blood clotting disorders history Social history Biological family, chosen family, friend support, rejection, acceptance Cultural influences that may affect access to care or acceptance by community—religion, ethnicity, age, race, socioeconomic status, etc. Supports at work or school Community involvement, TGD peer support Sexual history, sexual orientation, safety Table 7­4 Laboratory Monitoring for Individuals on Testosterone T h e r a p y Laboratory test Baseline 3 6 12 Yearly As Additional comments months months months needed Total X X X X X testosterone Estradiol X Hematocrit X X X X X Downloaded 2024­5­23 2:0 P Your IP is 138.92.199.188 Lipids Chapter 7: Gender­Affirming Hormone Therapy for Adults, Julie Thompson X Only as recommended by current USPSTF Page 16 / 20 ©2024 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility guidelines Glucose or A1c X Only as recommended by current USPSTF  Supports at work or school Community involvement, TGD peer support Canisius University Sexual history, sexual orientation, safety Access Provided by: Table 7­4 Laboratory Monitoring for Individuals on Testosterone T h e r a p y Laboratory test Baseline 3 6 12 Yearly As Additional comments months months months needed Total X X X X X testosterone Estradiol X Hematocrit X X X X X Lipids X Only as recommended by current USPSTF guidelines Glucose or A1c X Only as recommended by current USPSTF guidelines USPSTF, United States Preventive Services Task Force. Table 7­5 Laboratory Monitoring for Individuals on Estradiol and Antiandrogen Therapy Laboratory Baseline 3 6 12 Yearly As Additional comments test months months months needed Estradiol X X X X X Total X X X X X Monitoring no longer necessary following gonadectomy testosterone BUN, Cr, X X X X X X Only necessary at baseline and monitoring if taking Potassium spironolactone Lipids X Only as recommended by current USPSTF guidelines Glucose or X Only as recommended by current USPSTF guidelines A1c Prolactin X Only if symptoms of prolactinemia or on medications known to cause prolactinemia (i.e., antipsychotics) BUN, blood urea nitrogen; Cr, creatinine; USPSTF, United States Preventive Services Task Force. REFERENCES 1. Nguyen HB, Chavez AM, Lipner E, et al. Gender­affirming hormone use in transgender individuals: impact on behavioral health and cognition. Curr Downloaded 2024­5­23 2:0 P Your IP is 138.92.199.188 Psychiatry Chapter 7: Rep. 2018;20(12):110. Gender­Affirming [PubMed: Hormone 30306351] Therapy for Adults, Julie Thompson Page 17 / 20 ©2024 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility 2. Dhejne C, Van Vlerken R, Heylens G, Arcelus J. Mental health and gender dysphoria: a review of the literature. Int Rev Psychiatry. 2016;28(1):44–57.  BUN, blood urea nitrogen; Cr, creatinine; USPSTF, United States Preventive Services Task Force. Canisius University Access Provided by: REFERENCES 1. Nguyen HB, Chavez AM, Lipner E, et al. Gender­affirming hormone use in transgender individuals: impact on behavioral health and cognition. Curr Psychiatry Rep. 2018;20(12):110. [PubMed: 30306351] 2. Dhejne C, Van Vlerken R, Heylens G, Arcelus J. Mental health and gender dysphoria: a review of the literature. Int Rev Psychiatry. 2016;28(1):44–57. [PubMed: 26835611] 3. Witcomb GL, Bouman WP, Claes L, Brewin N, Crawford J, Arcelus J. Levels of depression in transgender people and its predictors: Results of a large matched control study with transgender people accessing clinical services. J Affect Disord. 2018;235:308–315. [PubMed: 29665513] 4. Defreyne J, Motmans J, T’Sjoen G. Healthcare costs and quality of life outcomes following gender affirming surgery in trans men: a review. Expert Rev Pharmacoecon Outcomes Res. 2017;17(6):543–556. [PubMed: 28972413] 5. James SE, Herman JL, Rankin S, Keisling M, Mottet L, Anafi M. The Report of the 2015 U.S. Transgender Survey. Washington, DC: National Center for Transgender Equality; 2016. 6. Coleman E, Bockting W, Botzer M, et al. Standards of care for the health of transsexual, transgender, and gender­nonconforming people, Version 7. Int J Transgenderism. 2011;13(4):165–232. 7. Cocanour CS. Informed consent: it’s more than a signature on a piece of paper. Am J Surg. 2017;214(6):993–997. [PubMed: 28974311] 8. Cavanaugh T, Hopwood R, Lambert C. Informed consent in the medical care of transgender and gender­nonconforming patients. AMA J Ethics. 2016;18(11):1147–1155. [PubMed: 27883307] 9. Tomson A. Gender­affirming care in the context of medical ethics: gatekeeping v. informed consent. Afr J Bioethics Law. 2018;11(1):24–28. 10. White Hughto JM, Reisner SL. A systematic review of the effects of hormone therapy on psychological functioning and quality of life in transgender individuals. Transgender Health. 2016;1(1):21–31. [PubMed: 27595141] 11. Hawk M, Coulter RW, Egan JE, et al. Harm reduction principles for healthcare settings. Harm Reduct J. 2017;14(1):70. [PubMed: 29065896] 12. Aitken S. The primary health care of transgender adults. Sex Health. 2017;14(5):477–483. [PubMed: 28578758] 13. Defreyne J, T’Sjoen G. Transmasculine hormone therapy. Endocrinol Metab Clin North Am. 2019;48(2):357–375. [PubMed: 31027545] 14. T’Sjoen G, Arcelus J, Gooren L, Klink DT, Tangpricha V. Endocrinology of transgender medicine. Endocr Rev. 2019;40(1):97–117. [PubMed: 30307546] 15. Irwig M. Testosterone therapy for transgender men. Lancet Diabetes Endocrinol. 2017;5(4)301–311. [PubMed: 27084565] 16. de Blok CJM, Dreijerink KMA, den Heijer M. Cancer risk in transgender people. Endocrinol Metab Clin. 2019;48(2):441–452. 17. Unger CA. Hormone therapy for transgender patients. Transl Androl Urol. 2016;5(6):877–884. [PubMed: 28078219] 18. Getahun D, Nash R, Flanders WD, et al. Cross­sex hormones and acute cardiovascular events in transgender persons: a cohort study. Ann Intern Med. 2018;169(4):205–213. Downloaded 2024­5­23 2:0[PubMed: 29987313] P Your IP is 138.92.199.188 Chapter 7: Gender­Affirming Hormone Therapy for Adults, Julie Thompson Page 18 / 20 ©2024 19. NotaMcGraw Hill. All NM, Wiepjes CM,Rights Reserved. de Blok Terms CJM, Gooren of Use LJG, Privacy Kreukels BPC,Policy Notice den Heier Accessibility M. Occurrence of acute cardiovascular events in transgender individuals receiving hormone therapy. Circulation. 2019;139(11):1461–1462. [PubMed: 30776252] 16. de Blok CJM, Dreijerink KMA, den Heijer M. Cancer risk in transgender people. Endocrinol Metab Clin. 2019;48(2):441–452. Canisius University 17. Unger CA. Hormone therapy for transgender patients. Transl Androl Urol. 2016;5(6):877–884. [PubMed: 28078219] Access Provided by: 18. Getahun D, Nash R, Flanders WD, et al. Cross­sex hormones and acute cardiovascular events in transgender persons: a cohort study. Ann Intern Med. 2018;169(4):205–213. [PubMed: 29987313] 19. Nota NM, Wiepjes CM, de Blok CJM, Gooren LJG, Kreukels BPC, den Heier M. Occurrence of acute cardiovascular events in transgender individuals receiving hormone therapy. Circulation. 2019;139(11):1461–1462. [PubMed: 30776252] 20. de Blok CJM, Wiepjes CM, Nota NM, et al. Breast cancer risk in transgender people receiving hormone treatment: nationwide cohort study in the Netherlands. BMJ. 2019;365:l1652. [PubMed: 31088823] 21. Gooren LJ, van Trotsenburg MAA, Giltay EJ, van Diest PJ. Breast cancer development in transsexual subjects receiving cross­sex hormone treatment. Sex Med. 2013;10(12):3129–3134. 22. Van Caenegem E, Taes Y, Wierckx K, et al. Low bone mass is prevalent in male­to­female transsexual persons before the start of cross­sex hormonal therapy and gonadectomy. Bone. 2013;54(1):92–97. [PubMed: 23369987] 23. Wiepjes CM, Vlot MC, de Blok CJM, Nota NM, de Jongh RT, den Heijer M. Bone geometry and trabecular bone score in transgender people before and after short­ and long­term hormonal treatment. Bone. 2019;127:280–286. [PubMed: 31271934] 24. Wiepjes CM, den Heijer M, T’Sjoen GG. Bone health in adult trans persons: an update of the literature. Curr Opin Endocrinol Diabetes Obes. 2019;26(6):296–300. [PubMed: 31573999] 25. Light AD, Obedin­Maliver J, Sevelius JM, Kerns JL. Transgender men who experienced pregnancy after female­to­male gender transitioning. Obstet Gynecol. 2014;124(6):1120–1127. [PubMed: 25415163] 26. Leung A, Sakkas D, Pang S, Thornton K, Resetkova N. Assisted reproductive technology outcomes in female­to­male transgender patients compared with cisgender patients: a new frontier in reproductive medicine. Fertil Steril. 2019;112(5):858–865. [PubMed: 31594633] 27. De Roo C, Tilleman K, T’Sjoen G, De Sutter P. Fertility options in transgender people. Int Rev Psychiatry. 2016;28(1):112–119. [PubMed: 26835612] 28. Radix A. Hormone therapy for transgender adults. Urol Clin North Am. 2019;46(4):467–473. [PubMed: 31582021] 29. Wilson Y, White A, Jefferson A, Danis M. Intersectionality in clinical medicine: the need for a conceptual framework. Am J Bioeth. 2019;19(2):8–19. [PubMed: 30784384] 30. Krempasky C, Harris M, Abern L, Grimstad F. Contraception across the transmasculine spectrum. Am J Obstet Gynecol. 2020;222(2):134–143. [PubMed: 31394072] 31. Asscheman H, Giltay EJ, Megens JAJ, Pim de Ronde W, van Trotsenburg MAA, Gooren LJG. A long­term follow­up study of mortality in transsexuals receiving treatment with cross­sex hormones. Eur J Endocrinol. 2011;164(4):635–642. [PubMed: 21266549] 32. Tangpricha V, den Heijer M. Oestrogen and anti­androgen therapy for transgender women. Lancet Diabetes Endocrinol. 2017;5(4):291–300. [PubMed: 27916515] 33. Olson J, Schrager SM, Clark LF, Dunlap SL, Belzer M. Subcutaneous testosterone: an effective delivery mechanism for masculinizing young transgender men. LGBT Health. 2014;1(3):165–167. [PubMed: 26789709] 34. Canonico M, Oger E, Plu­Bureau G, et al. Hormone therapy and venous thromboembolism among postmenopausal women: Impact of the route of Downloaded 2024­5­23 2:0 P Your IP is 138.92.199.188 estrogen7:administration Chapter and progestogens: Gender­Affirming The ESTHER Hormone Therapy for Adults, JulieCirculation Study. Thompson. 2007;115(7):840–845. [PubMed: 17309934] Page 19 / 20 ©2024 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility 35. Straczek C, Oger E, Yon de Jonage­Canonico MB, et al. Prothrombotic mutations, hormone therapy, and venous thromboembolism among postmenopausal women: Impact of the route of estrogen administration. Circulation. 2005;112(22):3495–3500. [PubMed: 16301339] [PubMed: 27916515] Canisius University 33. Olson J, Schrager SM, Clark LF, Dunlap SL, Belzer M. Subcutaneous testosterone: an effective delivery mechanism for masculinizing youngby: Access Provided transgender men. LGBT Health. 2014;1(3):165–167. [PubMed: 26789709] 34. Canonico M, Oger E, Plu­Bureau G, et al. Hormone therapy and venous thromboembolism among postmenopausal women: Impact of the route of estrogen administration and progestogens: The ESTHER Study. Circulation. 2007;115(7):840–845. [PubMed: 17309934] 35. Straczek C, Oger E, Yon de Jonage­Canonico MB, et al. Prothrombotic mutations, hormone therapy, and venous thromboembolism among postmenopausal women: Impact of the route of estrogen administration. Circulation. 2005;112(22):3495–3500. [PubMed: 16301339] 36. Shufelt CL, Merz CNB, Prentice RL, et al. Hormone therapy dose, formulation, route of delivery, and risk of cardiovascular events in women: Findings from the WHI Observational Study. Menopause. 2014;21(3):260–266. [PubMed: 24045672] 37. Sinclair R, Patel M, Dawson TL, et al. Hair loss in women: medical and cosmetic approaches to increase scalp hair fullness: approaches to increase scalp hair fullness. Br J Dermatol. 2011;165:12–18. [PubMed: 22171680] 38. Liang JJ, Jolly D, Chan KJ, Safer JD. Testosterone levels achieved by medically treated transgender women in a United States endocrinology clinic cohort. Endocr Pract. 2018;24(2):135–142. [PubMed: 29144822] 39. Prior JC, Vigna YM, Watson D. Spironolactone with physiological female steroids for presurgical therapy of male­to­female transsexualism. Arch Sex Behav. 1989;18(1):49–57. [PubMed: 2540730] 40. Leaning MC, Feustel PJ, Joseph J. Hormonal treatment of transgender women with oral estradiol. Transgender Health. 2018;3(1):74–81. [PubMed: 29756046] 41. Verman A. Spironolactone, a controversial drug used in hormone replacement therapy, is not right for all trans women. Slate Magazine. 2019. https://slate.com/technology/2019/06/spironolactone­hormone­trans­women­side­effects.html. Accessed December 19, 2019. 42. Cosgrove B. The case against spironolactone. MTF Trans Hormonal Therapy. 2018. https://moderntranshormones.com/2018/01/01/whats­wrong­ with­spironolactone/. Accessed December 19, 2019. 43. Jain J, Kwan D, Forcier M. Medroxyprogesterone acetate in gender­affirming therapy for transwomen: results from a retrospective study. J Clin Endo Metab. 2019;104(11):5148–5156. 44. Wierckx K, Gooren L, T’Sjoen G. Clinical review: Breast development in trans women receiving cross­sex hormones. J Sex Med. 2014;11(5):1240– 1247. doi: 10.1111/jsm.12487 45. Mueck AO. Postmenopausal hormone replacement therapy and cardiovascular disease: the MEDICAL CARE OF TRANS AND GENDER DIVERSE ADULTS 53 value of transdermal estradiol and micronized progesterone. Climacteric. 2012;15(Suppl 1):11–17. doi: 10.3109/13697137.2012.669624 Downloaded 2024­5­23 2:0 P Your IP is 138.92.199.188 Chapter 7: Gender­Affirming Hormone Therapy for Adults, Julie Thompson Page 20 / 20 ©2024 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility