Version May 2024
INTRODUCTION — The terms transgender and gender incongruence describe a situation where an individual's gender identity differs from other aspects of the person's reproductive biology (typically external sexual anatomy at birth). Health care providers should be familiar with commonly used terms (table 1). Gender identity-affirming care, for those who desire, can include hormone therapy and surgeries, as well as other procedures, such as hair removal or speech therapy [1,2].
This topic will use the term transgender in the broadest sense to include any person with incongruence between gender identity and sex recorded at birth (typically based on visualization of external sexual anatomy at birth). The evaluation and management of transgender women are discussed here. The evaluation and management of transgender men, the primary care of the transgender adult, gender diversity in children and adolescents, and gender-affirming surgery are reviewed separately. (See "Transgender men: Evaluation and management" and "Primary care of transgender individuals" and "Gender development and clinical presentation of gender diversity in children and adolescents" and "Management of transgender and gender-diverse children and adolescents" and "Gender-affirming surgery: Male to female".)
EPIDEMIOLOGY
●Prevalence – Available data suggest that 0.6 percent of the adult population is transgender [3-5]. The prevalence of transgender individuals depends upon the definition. For example, in studies that include only individuals who received hormone therapy, gender-affirming surgery, or had diagnostic codes documenting being transgender, the reported prevalence was 7 to 9 per 100,000 people [6]. However, studies that include transgender status based upon self-report indicate a prevalence of approximately 871 per 100,000 people [6].
In survey-based studies, the self-reported transgender identity was up to 0.5 percent of adults and 2.7 percent in adolescents [7]. One study estimated that there are approximately 25 million transgender individuals worldwide [8]. The number of people seeking gender-affirming care has been increasing, thought to be due to the greater safety transgender people feel coming forward. However, the number seeking treatment is still far below the number anticipated based on anonymous self-report surveys.
●Evidence for biologic basis – Although the mechanisms remain unclear, there is some evidence for a biologic basis of gender identity [9]. Evidence for a biologic basis for gender identity primarily includes:
•Data on gender identity in intersex individuals (also known as differences of sex development [DSD]).
•Data from twins showing greater transgender concordance among identical twins relative to fraternal twins [10].
•Neuroanatomical differences associated with gender identity [11].
•Possible influence of prenatal androgen exposure [12].
Because sample sizes of most studies on this subject are small, further research is required to assign specific biologic mechanisms for gender identity [9].
INITIAL PRESENTATION — Typically, transgender adults report gender incongruence throughout their lives, starting well before puberty.
●Age – Most transgender individuals present in adulthood or late adolescence. Transgender individuals now tend to present at a younger age than in the past, in parallel to greater exposure in public media, societal acceptance, and access to care [13].
●Initial provider – While some transgender individuals present to mental health providers for diagnosis, it is now common for transgender individuals to see their primary care providers for initial guidance. Other transgender individuals present directly to endocrinologists for hormone prescriptions.
●Coexisting mental health issues – Some transgender individuals have coexisting mood disorders [14]. If these are present, they may improve with gender-affirming hormone therapy [15-17].
DIAGNOSIS
The diagnosis of gender incongruence should be made by qualified health care providers who are familiar with the diagnostic criteria [18,19] and have the necessary experience assessing whether there are mental health concerns that could confound the diagnosis and require treatment before considering hormone therapy (table 1).
Gender incongruence — The current criterion for gender incongruence is persistent incongruence between gender identity and sex recorded at birth, typically from visualization of external sexual anatomy at that time.
The diagnosis of gender incongruence must be made before considering gender-affirming hormone and surgical therapy [18]. Such diagnosis should include screening for co-existing mental health concerns. (See 'Pretreatment assessment' below.)
In addition, it is essential to identify any medical diagnoses that may require treatment before considering hormone therapy [18,19]. (See 'Pretreatment assessment' below.)
Presently, most cases of transgender identity are still diagnosed in adulthood, but increasingly, transgender children and adolescents present for diagnosis and treatment. The clinical presentation of gender diversity in children is reviewed separately. (See "Gender development and clinical presentation of gender diversity in children and adolescents", section on 'Clinical presentation'.)
Gender dysphoria — Patients also may be diagnosed with gender dysphoria, which is defined as the discomfort arising in some individuals from the incongruence between their gender identities and their sex recorded at birth. Gender dysphoria is currently the diagnostic code in the World Health Organization's International Classification of Diseases-10th Revision (ICD-10) for being transgender, but it is a mental health code. Of note, the term gender dysphoria will be removed from the 11th Revision (ICD-11), and the code will become "gender incongruence." Mental health codes in transgender individuals will be the same as for other individuals.
The diagnosis of gender dysphoria is generally done by a mental health professional; however, other health care professionals who have the appropriate experience and training can also diagnose gender dysphoria. Mental health providers typically use the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) to make a diagnosis [20]. Core components of the DSM-5 diagnosis of gender dysphoria include longstanding discomfort with the incongruence between gender identity and external sexual anatomy at birth along with interference with social, school, or other areas of function [20].
HORMONAL THERAPY
Pretreatment assessment
Guidelines/Standards of care — Several large medical professional organizations have issued guidelines to assist providers in the evaluation and care of transgender individuals (the World Professional Association for Transgender Health [WPATH] [7], the Endocrine Society [18] (table 1), and the American College of Obstetricians and Gynecologists [ACOG] [21]).
Criteria for starting hormonal therapy — The criteria for starting hormone therapy include [7]:
●Persistent, well-documented gender dysphoria/gender incongruence
●Capacity to make a well-informed decision
●Mental health issues, if present, must be addressed sufficiently to move treatment forward
Address underlying medical issues — In addition to these established criteria, clinicians should address any medical conditions or risk factors that could be impacted by hormone therapy, most importantly, cardiovascular risk factors. Several relative contraindications for estrogen require additional evaluation and treatment prior to the initiation of hormones, including a history of breast cancer, venous thromboembolism (VTE), cardiovascular disease, cerebrovascular disease, and severe liver dysfunction. Hyperprolactinemia should be evaluated before starting estradiol therapy. (See 'Adverse events' below.)
Patient counseling — The clinician should discuss a number of issues prior to initiating hormonal therapy, including patient treatment goals, expectations, risks and benefits of therapy, and the potential impact on future fertility.
●Goals – The usual aim of gender-affirming hormone therapy is to induce physical changes to match gender identity [22]. The treatment goal is to maintain hormone levels in the female physiological range. Administration of estrogens alone will suppress gonadotropin output and, therefore, androgen production, but addition of a second agent that suppresses androgen secretion or action may permit lower estrogen dosing and thus potentially reduce the risk of VTE. (See 'Adverse events' below.)
●Care team – Optimally, a transgender patient seeking medical treatment should have access to providers with expertise in transgender-appropriate primary care, gender-affirming hormone therapy, and mental health support.
●Expectations – Priorities for many transgender women include elimination of facial hair growth, induction of breast formation, a change in voice, and a more female fat/muscle distribution. To accomplish this, a reduction of the biological effects of androgens to female levels is required. Contacts with other transgender individuals who are already undergoing treatment may be helpful in shaping an individual's expectations of what can be achieved and what problems, personally and socially, may arise during treatment. A supportive network of family/caregivers and friends is often important.
The physical changes that occur with hormone therapy progress at different rates. Some changes occur within months (softening of skin) while others take years (breast growth) (table 2). (See 'Feminizing effects' below.)
●Risks and benefits of treatment – The patient should be fully informed about the risks and benefits of hormonal or surgical therapy [23,24]. (See 'Clinical outcomes' below.)
●Future fertility – Transgender women who undergo gender identity-affirming therapy may lose reproductive potential. Thus, before starting any treatment, patients should be encouraged to first consider fertility issues [19] (see 'Fertility considerations' below). However, gender-affirming hormone therapy does not reliably suppress spermatogenesis (ie, infertility or subfertility is not uniformly present and not permanent). Therefore, in transgender women who have vaginal intercourse with cisgender women, contraceptive options should be discussed [25-29].
Androgen suppression — Spironolactone, gonadotropin-releasing hormone (GnRH) agonists, and cyproterone acetate (CPA) (in Europe) have been used as therapies for androgen suppression or inhibition. After gender-affirming genital surgery that includes orchiectomy, antiandrogen therapy may be discontinued [30,31].
●Spironolactone – Spironolactone, a mineralocorticoid receptor antagonist, is the most widely used drug in the United States for transgender women. It is a competitive inhibitor of the androgen receptor as well as an inhibitor of testosterone biosynthesis (by inhibiting 17-hydroxylase and 17,20-lyase) [32-36].
The recommended dose of spironolactone is 100 to 300 mg/day (table 3) [37].
●GnRH agonists – GnRH agonists are an ideal therapy given their ability to suppress gonadotropin and testosterone secretion [18,38]. Historically, they were second-line therapy because of their high cost. However, they are now used routinely for transgender women in some countries, including the UK, but somewhat less so in the United States because of insurance coverage challenges. Dosing of these drugs is found in the table (table 3).
●CPA – CPA is both a progestin (which suppresses gonadotropins) and an androgen receptor antagonist that is available in most countries but not the United States. Because CPA has been associated with a worse lipid profile, small prolactin elevations, and rare meningiomas, it has become less popular [39,40].
If CPA is used, doses should be limited to ≤10 mg/day to avoid the adverse effects [18]. In addition, 10 mg of CPA in combination with estradiol is as effective as higher CPA doses for suppressing serum testosterone concentrations to <2 nmol/L (<58 ng/dL) [41].
Estrogen therapy — The usual approach includes estrogen therapy to help suppress endogenous androgen secretion and to replace it with estrogen. There is a wide range of estrogens from which to choose (table 3). However, 17-beta-estradiol is the preferred estrogen.
Transdermal estrogen has been associated with a lower risk of venous thromboembolism (VTE) and stroke than oral estrogens in postmenopausal women. However, oral estradiol, which is considerably less expensive than transdermal estradiol, is most often used in transgender women, as they tend to have a low baseline risk for VTE.
We suggest 17-beta-estradiol over conjugated estrogens so that serum E2 levels can be monitored.
Transgender women with testis intact may require relatively high doses of estrogens to suppress testosterone into the female range, even with the addition of a GnRH agonist or an antiandrogen agent.
Typical estradiol regimens include (table 3):
●Transdermally, 0.025 to 0.2 mg/24 hours. The patch changed once or twice a week, depending on the product.
●Orally, 2 to 6 mg/day [18,42].
●In Europe, oral 17-beta-estradiol valerate 2 to 4 mg/day is also used.
●Parenteral estrogens (estradiol valerate or cypionate) are sometimes used (table 3).
We suggest against the use of oral ethinyl estradiol (EE), a potent estrogen used in most combined estrogen-progestin oral contraceptives. It was previously used for transgender women in doses of 50 to 100 mcg/day, but was associated with an excess risk of venous thrombosis and an increased risk of cardiovascular death, particularly in patients over 40 years [32,43-46]. (See 'Adverse events' below.)
Estrogen therapy is administered continuously to avoid symptoms of sex hormone deficiency and to prevent bone loss and osteoporosis [47-49]. The appropriate doses of estrogen are described above and in the table (table 3).
Several relative contraindications for estrogen require additional evaluation and treatment prior to the initiation of hormones, including a history of breast cancer, VTE, cardiovascular disease, cerebrovascular disease, and severe liver dysfunction. Hyperprolactinemia should be treated before starting estradiol therapy. (See 'Adverse events' below.)
Agents not routinely used
●Progestogens – While progestogens, such as medroxyprogesterone acetate (MPA), are sometimes used to suppress gonadotropins and, therefore, testosterone secretion, we do not suggest them as part of standard hormonal care for transgender women. MPA has been associated with excess cardiovascular and breast cancer risk in older postmenopausal women taking conjugated estrogen. (See "Menopausal hormone therapy: Benefits and risks", section on 'Women's Health Initiative (WHI)'.)
The harms associated with CPA in transgender women are noted above. (See 'Androgen suppression' above.)
Some other progestogens are associated with an increased VTE risk when combined with estrogens [50]. A systematic review of progestin use in transgender women found little benefit and increased harm, including lower HDL cholesterol and increased risk of thrombosis [40].
●Finasteride and dutasteride – Finasteride inhibits 5-alpha-reductase 2 activity and dutasteride inhibits 5-alpha-reductase 1 and 2 activity, therefore inhibiting conversion of testosterone to the more potent dihydrotestosterone (DHT). They have been used in the management of benign prostatic hyperplasia, prostate cancer, hair loss in men and women, and, occasionally, for hirsutism in women. There are no available data for their use in transgender individuals, where it would be predicted to have little utility if the testosterone levels are low and there is no substrate to generate DHT. (See "Male pattern hair loss (androgenetic alopecia in males): Management", section on 'Oral finasteride' and "Management of hirsutism in premenopausal women", section on 'Antiandrogens'.)
●Flutamide and nilutamide – We suggest against the use of nonsteroidal antiandrogens such as flutamide and nilutamide. They increase gonadotropin secretion, causing increased secretion of testosterone and estradiol (only the latter would be desirable). More importantly, flutamide has been associated with hepatotoxicity. (See "Management of hirsutism in premenopausal women", section on 'Antiandrogens'.)
Monitoring
●Frequency – Clinical monitoring of transgender women taking hormone therapy should occur with each dose titration, typically every three months during the first year. When stable, typically after the first year, monitoring should be once or twice yearly (table 4). In addition to clinical assessment that the patient is comfortable with the regimen, monitoring should include the following:
●Biochemical testing
•Serum total testosterone concentrations to determine when the level is within the female range if the patient desires a conventional regimen. Optimally, testosterone should be measured using mass spectrometry assay [51].
•For patients using spironolactone, we measure a serum potassium concentration after the first month of treatment and after dose titrations. More frequent serum potassium measurements are not necessary, given the low prevalence of hyperkalemia in transgender women with normal kidney function taking spironolactone (table 4) [52,53].
•E2 concentrations should be monitored to avoid supraphysiologic levels (eg, maintain levels <200 pg/mL [734 pmol/L]) (table 4).
•Some guidelines suggest monitoring serum prolactin levels because rare cases of elevated prolactin have been described in transgender women who have received gender-affirming hormone therapy [18]. However, only cyproterone acetate-containing regimens have been associated with prolactin elevations [54]. In the only studies of transgender women using spironolactone in addition to estrogen, no similar impact on prolactin has been observed [55,56]. And in cisgender females, estrogen does not increase serum prolactin, nor does it cause prolactinomas. We suggest measuring a baseline prolactin level before starting gender-affirming hormone treatment in order to treat pre-existing hyperprolactinemia.
●Cancer screening
•In the absence of transgender-specific data, standard breast screening guidelines developed for women should be followed. (See "Primary care of transgender individuals", section on 'Breast cancer'.)
•All individuals with prostate tissue require monitoring for prostate carcinoma. In the absence of transgender-specific data, standard prostate screening guidelines developed for cisgender men should be followed [18], even though prostate cancer might be rare in transgender women who have undergone genital surgery that includes gonadectomy. (See "Primary care of transgender individuals", section on 'Prostate cancer'.)
●Bone health – For transgender women at low risk, the Endocrine Society suggests screening for osteoporosis conducted at age 60 years or earlier in those who are not compliant with hormone therapy [18]. (See "Primary care of transgender individuals".)
CLINICAL OUTCOMES
Feminizing effects — Although a goal of therapy is to reduce the hormonally induced male secondary sex characteristics (if puberty is not delayed with gonadotropin-releasing hormone [GnRH] agonists), complete elimination is not possible. In transgender women, effects of androgens on the skeleton, such as greater height, size and shape of hands, feet, jaws, and pelvis, and voice (laryngeal prominence), cannot be reversed.
However, there are many changes that do occur (table 2). The changes during the first three to six months include a possible decrease in sexual desire and decreased rates of growth of facial and body hair. There will also be some initial growth of breast tissue, a decrease in oiliness of the skin, and early redistribution of fat mass [18]. Hematocrit/hemoglobin levels fall as might be expected with lower levels of testosterone [57].
The main clinical outcomes include (table 2):
●Sexual hair – Adult male beard growth is very resistant to inhibition by combined hormonal intervention and, especially in individuals with European ancestry, additional measures such as laser hair removal or electrolysis are usually necessary. Eflornithine 12.9% cream can slow facial growth, but its use is somewhat limited by costs and continuous twice daily application that is required for the effect to be sustained. (See "Management of hirsutism in premenopausal women", section on 'Role of direct hair removal methods'.)
●Breast development – Breast formation starts almost immediately after initiation of estrogen administration and is typically maximal at two years [32,58-60]. Some report nipple tenderness and discomfort during breast growth. Androgens have an inhibitory effect on breast formation, and therefore, estrogens will be most effective when testosterone has been lowered to the female range.
●Skin – Decreased testosterone leads to a decreased activity of the sebaceous glands and may result in dry skin or brittle nails [61].
●Body composition – Following a decrease in testosterone, there is an increase in subcutaneous fat and a decrease in lean body mass [62]. Body weight usually increases in parallel with an increase in body mass index (BMI) [63].
●Testes – Atrophy of the testes (if not surgically removed) occurs over many years. Lacking gonadotropic stimulation, the testes become atrophic and may occasionally enter the inguinal canal, which may cause discomfort.
●Prostate – Atrophy of the prostate also occurs over many years.
●Voice – Antiandrogens and estrogens have no effect on the properties of the voice, so transgender women may choose to consult a specialized phoniatric center for speech therapy. Pitch and resonance are the usual focus of therapy because the combination of these two voice characteristics are thought to account for the majority of how a speaker's gender is perceived [64]. Speech therapy may lead to more feminine speech [65]. Laryngeal surgery is reported by some to change the pitch of the voice but reduces its range.
●Sexual function – Feminizing hormone therapy may reduce sexual desire, reduce erectile function, and decrease ejaculation among transgender women [66]. Some transgender women choose to reduce hormone doses to balance the degree of feminization with the level of sexual function, while others report no need for dose adjustments. Following genital surgery, sexual function (sexual desire, arousal, pain with sex, and orgasm) is variable for transgender women and depends on preoperative sexual function, the type of surgery performed, and hormonal status [67].
Psychosocial outcomes — Transgender treatment that includes hormonal therapy results in significant improvement in quality-of-life and psychosocial outcomes, as illustrated in a meta-analysis of 28 studies that enrolled 1833 transgender individuals (1093 transgender women, 801 transgender men) who underwent gender-affirming treatment that included hormones [15]. Evidence from the pooled analysis suggested improvements in gender dysphoria symptoms, psychological functioning, sexual function, and overall quality of life. Improvements in quality of life and a decrease in depression and anxiety were reported in a meta-analysis of 20 studies [68].
Bone health — The International Society for Clinical Densitometry (ISCD) recommends using T-scores based on the adjusted female reference database to diagnose osteoporosis for transgender women greater than age 50 [69]. Z-scores can be used for younger individuals using the reference database that matches their gender identity. (See "Primary care of transgender individuals".)
Adverse events
Cardiovascular — The increased risk of cardiovascular events reported in early studies of transgender women receiving gender-affirming hormone therapy was likely in part related to the use of the potent oral estrogen, ethinyl estradiol [46,70,71].
Observational studies suggest that the use of estrogen by transgender women may confer an increased risk for cardiovascular disease (CVD) [72-76], perhaps due to a deleterious effect on CVD risk factors [77,78]. Persistent gender minority stress has been proposed as one possible factor for the potentially increased cardiovascular risk in transgender women [79]. (See "Primary care of transgender individuals", section on 'Cardiovascular disease' and "Overview of established risk factors for cardiovascular disease".)
Some epidemiological studies have suggested that transgender women have a higher risk of myocardial infarction (MI) and ischemic strokes, compared with cisgender women. However, in a meta-analysis of 29 studies including over 3200 transgender women receiving hormone therapy, increases in serum triglycerides were observed (with oral estrogens), but very few MI or strokes were seen [75]. Stroke occurred in 8 of 859 patients (3 percent) and myocardial infarction in 14 of 1073 (1 percent). Some of these events occurred in centers where high doses of oral ethinyl estradiol (100 mcg/day) were originally used [43].
Until further data are available, risk factors for CVD should be reviewed in transgender individuals treated with hormones [37,74]. (See "Primary care of transgender individuals", section on 'Cardiovascular disease' and "Overview of established risk factors for cardiovascular disease".)
Venous thromboembolism
●Studies have demonstrated an increased risk of venous thromboembolism (VTE) in transgender individuals receiving gender-affirming hormone therapy, particularly in those taking ethinyl estradiol [80]. In one cohort, no excess risk was seen in transgender women taking estrogen preparations other than ethinyl estradiol [46]. Based upon these observations, current guidelines recommend against the use of ethinyl estradiol [18].
●In the meta-analysis of 29 studies described above [75], 56 of 1767 transgender women experienced VTE (3 percent).
●In a second meta-analysis of 18 studies including over 11,000 transgender women undergoing gender affirming hormone therapy, the overall rate of VTE was 2 percent [81]. No events were seen in those under age 37.5 years, while the VTE rate in those over age 37.5 years was 3 percent.
●In an electronic medical record-based cohort study that included 2842 transgender women matched to approximately 48,000 cisgender men and 48,000 cisgender women, the transgender women had a higher rate of VTE (5.5/1000 years) than both control groups [82]. Most transgender women were receiving oral estradiol; the average maximum daily dose was 4 mg (range 1 to 10 mg) and was the same for those who did or did not have a VTE.
The difference seemed more pronounced with increased follow-up, with two- and eight-year absolute risk differences of 4.1 and 16.7 per 1000 persons relative to cisgender men and 3.4 and 13.7 per 1000 persons relative to cisgender women. This pattern is different from that seen in postmenopausal women taking hormone therapy, where VTE risk is highest in the first year of use and then declines. This suggests that long-term monitoring is important in this population. (See "Menopausal hormone therapy and cardiovascular risk", section on 'Venous thromboembolism'.)
●Gender-affirming estrogen therapy is typically discontinued in the perioperative period to minimize the risk of VTE. However, a retrospective study from a single center reported that VTE rates were similar in patients who discontinued estrogen compared with those who continued estrogen through the perioperative period [83]. This issue is reviewed in more detail separately. (See "Gender-affirming surgery: Male to female", section on 'Perioperative management of systemic estrogen therapy'.)
●The incidence of thrombophilias appears to be the same in the transgender population as the general population. Therefore, routine pretreatment screening for thrombophilias is not suggested.
Other
●Triglycerides – A small increased risk of elevated triglycerides has been reported during estrogen treatment. Very high levels of triglycerides (>2000 mg/dL [22.59 mmol/L]) would place patients at risk for acute pancreatitis. A meta-analysis of 16 studies concluded that cross-sex hormone therapies slightly increase serum triglycerides [75]. Oral estrogens should be avoided in those with known familial hypertriglyceridemia [84,85].
●Mortality – The increased mortality rates in transgender women observed in early reports may be related to morbidity due to failure to treat rather than from the treatment itself. For example, in a report of 966 transgender women and 365 transgender men, the mortality rate was 51 percent higher in the transgender individuals compared with the general population, mainly due to drug abuse, human immunodeficiency virus (HIV), cardiovascular disease, and suicide [46]. Users of oral ethinyl estradiol, an estrogen that is no longer used for transgender women, had a threefold excess risk of cardiovascular death.
Current estimates of mortality rates in one study of transgender persons was approximately 9.3 percent over a 10-year follow-up period. The causes of death were similar to those in the United States population over the same study period with the exception of suicide, which was higher in the transgender individuals compared with the general population [86]. An update of one cohort found increased mortality rates in transgender women but not transgender men, compared with the expected mortality rates among cisgender men and women [87,88]. They found increased death rates among transgender women in cardiovascular diseases, infections, cancer, and non-natural causes (including suicide) compared with cisgender men and women.
FERTILITY CONSIDERATIONS — Transgender individuals who are considering gender-affirming hormone therapy or surgery should be encouraged to consider fertility issues [89,90]. Sperm cryopreservation (ideally before initiating hormone therapy) is available for transgender women [91]. Unfortunately, only a small percentage of patients are taking advantage of sperm cryopreservation. In one report of 99 transgender women, 75 individuals considered banking sperm, but only 9 actually did [92,93]. (See "Effects of cytotoxic agents on gonadal function in adult men", section on 'Semen cryopreservation'.)
GENDER-AFFIRMING SURGERY — Individuals can and do live successfully in the gender role that aligns with their gender identity without gender-affirming surgery. The steps that are required before initiating surgical treatment are reviewed above. The approach to gender-affirming surgery in these patients is reviewed in detail separately. (See "Gender-affirming surgery: Male to female".)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Transgender health".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topic (see "Patient education: Being transgender (The Basics)")
SUMMARY AND RECOMMENDATIONS
●Definitions – Transgender is an umbrella term that is used to describe individuals with gender diversity; it includes individuals whose gender identity is different from their sex recorded at birth. Such individuals may define themselves as transmasculine, transfeminine, or nonbinary (the last term meaning they have gender identity attributes that are both male and female) (table 1). (See 'Introduction' above.)
●Diagnosis – Transgender individuals should have their gender incongruence confirmed by medical professionals with appropriate experience. It is necessary to ascertain that there is persistent gender incongruence and that the person is able to understand the risks and benefits of intervention. (See 'Initial presentation' above.)
●Hormone therapy – Before initiating transgender hormonal or surgical treatment, the clinician should counsel the patient about risks and benefits of the hormonal or surgical therapy, including impact on fertility, as well as realistic expectations about outcomes. (See 'Patient counseling' above.)
For estrogen therapy in transgender women, we suggest either transdermal or oral 17-beta-estradiol (Grade 2C). We suggest against the use of ethinyl estradiol because of an increased risk of venous thromboembolism (VTE) (see 'Estrogen therapy' above). In addition, we add a gonadotropin-releasing hormone (GnRH) agonist for androgen suppression, spironolactone, or low doses of CPA to inhibit androgen action (table 3).
Transgender women receiving hormone therapy should be monitored to avoid supraphysiologic serum estradiol (E2) concentrations (eg, maintain E2 levels <200 pg/mL [734 pmol/L]) and to verify that serum testosterone levels reach the physiologic female range (table 4). Serum potassium should be checked when titrating spironolactone. (See 'Monitoring' above.)
●Adverse effects – For transgender women, the most important risk associated with estrogen therapy is VTE, seen primarily with ethinyl estradiol. (See 'Venous thromboembolism' above.)
●Screening guidelines – We agree with the Endocrine Society guidelines that transgender individuals should follow the screening guidelines for all tissues present, independent of gender identity. For example, prostate cancer screening should be done in individuals with a prostate. (See 'Monitoring' above.)
●Surgery – A detailed review of gender-affirming surgery is found separately. (See "Gender-affirming surgery: Male to female".)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Louis JG Gooren, MD, who contributed to earlier versions of this topic review.
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