Version May 2024
INTRODUCTION — The terms transgender and gender incongruence describe a situation where an individual's gender identity differs from 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 affirming surgeries as well as other procedures such as hair removal or speech therapy [1-7].
This topic will use the term transgender in the broadest sense to include any person with incongruence between gender identity and external sexual anatomy at birth. The evaluation and management of transgender men are discussed here. The evaluation and management of transgender women, the primary care of the transgender adult, and gender diversity in children and adolescents are reviewed separately. (See "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".)
STANDARDS OF CARE — Several large medical professional organizations have issued guidelines to assist providers in the care of transgender individuals (the World Professional Association for Transgender Health [WPATH] [8], the Endocrine Society [9], the American College of Obstetricians and Gynecologists [ACOG] [10]).
The Endocrine Society has released updated guidelines for the treatment of gender dysphoria/gender incongruence [9]. The new guidelines replace the term "transsexual" with "gender dysphoria" or "gender incongruence" and specify detailed professional qualifications for clinicians who diagnose, assess, or treat individuals with gender dysphoria/gender incongruence. Specifically, they now suggest that decisions regarding social transition for prepubertal youth be made in conjunction with a mental health or similarly experienced professional. They continue to recommend the management and monitoring of transgender adolescents and adults by a multidisciplinary team, as well as counseling patients about the time course of hormone-induced physical changes and options for fertility preservation. We agree with the updated guidelines (table 2).
OVERVIEW — The following considerations are similar for transgender men and women and are discussed in detail in the topic on transgender women.
●Epidemiology (see "Transgender women: Evaluation and management", section on 'Epidemiology')
●Pathophysiology (see "Transgender women: Evaluation and management")
●Initial presentation (see "Transgender women: Evaluation and management")
●Initial assessment (see "Transgender women: Evaluation and management")
●Counseling before treatment (see "Transgender women: Evaluation and management")
EVALUATION AND DIAGNOSIS
Diagnostic criteria — The current criteria for gender incongruence include:
●Persistent incongruence between gender identity and external sexual anatomy at birth
●The absence of a confounding mental disorder or other abnormality
The diagnosis of gender incongruence must be made before considering transgender hormone and surgical therapy [11]. Such diagnosis should include screening for confounding mental health concerns.
In addition, it is essential to identify any medical and/or psychiatric diagnoses that may require treatment before considering hormone therapy [11,12].
Presently, most cases of transgender identity are diagnosed in adulthood, but increasingly, children and adolescents with gender dysphoria 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".)
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 external sexual anatomy at birth.
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 [13]. 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 [13].
HORMONAL THERAPY
Transgender men (female-to-male, FTM)
Goals — The usual aim of transgender hormone therapy is to induce physical changes to match gender identity [14]. The treatment goal is to maintain hormone levels in the normal physiological range for the target gender. Some individuals may identify as nonbinary (eg, having both masculine and feminine identity attributes). While hypogonadism carries risk to bone health and should be addressed, both male and female hormone patterns, along with the entire continuum in between, can be safe.
Historically, some transgender individuals self-medicated with hormones for a variety of reasons, including fear of rejection by health care providers, delays in initiation of hormone therapy, and the cost of undergoing treatment. Therefore, there should be careful assessment for self-medication, both past and current [15].
In transgender men, the typical goal is to stop menses and induce virilization, including a male pattern of sexual and facial hair, change in voice, and male physical contours. The principal hormonal treatment is a testosterone preparation.
Criteria for starting — Criteria for starting hormone therapy include [12]:
●Persistent, well-documented gender dysphoria/gender incongruence
●Capacity to make a well-informed decision
●Relevant medical or mental health issues are well controlled
Testosterone therapy — There are many available testosterone preparations and routes of administration including injectables, gels, and buccal tablets. We suggest either testosterone esters (administered intramuscularly or subcutaneously) or testosterone gels, depending upon patient preference. However, higher testosterone levels are more easily achieved with parenteral therapy (table 2).
It is common to use 50 to 100 mg of testosterone enanthate or testosterone cypionate weekly or 200 mg every two weeks. Route of administration can be intramuscular or subcutaneous with similar effects. Although the subcutaneous route is not approved in the United States by the US Food and Drug Administration (FDA), it appears to be effective and well tolerated [16-18]. In one report of 22 patients who had tried both the intramuscular and subcutaneous route, all preferred subcutaneous administration [18].
With parenteral testosterone therapy, serum testosterone is typically measured midway between injections. However, some clinicians measure serum testosterone 24 hours after injection and again just before the subsequent injection. Some clinicians start with lower doses of testosterone because transgender men are often smaller than average men in size. The goal remains to achieve normal male levels and that can be done as quickly as practical.
Testosterone gel (1% or 1.6%, 2.5 to 10 g/day) may also be used [11], but virilization might be slower if lower serum testosterone concentrations are achieved than with testosterone injection. Some clinicians switch to gels once initial virilization is complete. This may help to avoid supraphysiologic testosterone concentrations [19]. (See "Testosterone treatment of male hypogonadism", section on 'Is the testosterone dose therapeutic?'.)
Masculinizing effects — There are a variety of consequences of hormonal therapy in transgender men (table 3). Testosterone causes male-pattern hair growth and an increase in lean body mass, muscle mass, and fat mass. It also causes growth in midline structures like the larynx and the clitoris (which may be associated with an increase in sexual desire).
●Hair – The development of sexual hair follows the pattern observed in pubertal boys: first the upper lip, then chin, then cheeks, etc [20,21]. The degree of hair growth might be predicted from the pattern in male members of the same family. The same applies to the occurrence of androgenetic alopecia, "male-pattern baldness."
●Voice – Deepening of the voice may occur due to oropharyngeal growth and may be irreversible [22,23].
●Body composition – Androgen administration leads to a reduction in subcutaneous fat but increases in abdominal fat [24]. The increase in lean body mass is on average 4 kg, and the increase in body weight may be greater [25].
●Acne – Acne occurs in approximately 40 percent, similar to that observed in hypogonadal men starting androgen treatment past the age of normal puberty [20,21].
●Clitoral enlargement – Clitoral enlargement occurs in all, but the degree varies.
●Sexual desire – Most subjects will note an increase in sexual desire [26-28].
●Breasts – Androgen administration may cause a decrease in glandular tissue [29].
●Guidelines have suggested hysterectomy to avoid cancer risk from endometrial exposure to androgen [11]. However, there is no evidence for an excess risk of endometrial cancer in transgender men receiving androgen therapy. In one trial of 35 transgender men receiving testosterone undecanoate 1000 mg every 12 weeks for one year, mean endometrial thickness (on pelvic ultrasound) decreased from 9.9 to 5.7 mm [26]. In a second study, histologic analysis found inactive, atrophic endometrium in transgender men taking long-term testosterone therapy, similar to that seen in postmenopausal biological women not taking estrogen therapy [30].
●The relatively lower height and the broader hip configuration of transgender men compared with nontransgender men does not change with testosterone treatment.
Routine monitoring — We agree with the monitoring schedule recommended by the Endocrine Society: Evaluate the patient every three months in the first year corresponding to dose adjustment and then one to two times per year thereafter (table 4).
Serum testosterone concentrations should be maintained in the physiologic range for men; endocrine monitoring should include serum testosterone, with goals of maintaining serum concentrations approximately 400 to 800 ng/dL (13.9 to 27.7 nmol/L). For patients on testosterone injections, trough levels should be towards the lower end of this range, while peak levels should not exceed 1000 ng/dL (34.7 nmol/L). Individuals taking testosterone gels should have similar targets, but the serum testosterone levels achieved tend to be at the lower end of the normal range. Serum estradiol is monitored during the first six months of testosterone treatment or until there has been no uterine bleeding for six months. Estradiol levels should be <50 pg/mL (184 pmol/L) (table 4).
In addition to monitoring weight and blood pressure, lab testing should include a hematocrit because erythrocytosis is a common consequence of testosterone administration, reported more with testosterone ester injections. Details of biochemical testing, bone mineral density (BMD) testing, and need for mammograms are outlined in the table (table 4). (See 'Adverse events' below.)
Cancer screening is reviewed in detail separately. Briefly, transgender men who have undergone mastectomy do not require mammograms [31], but breast self-exam may still be important for appropriate surveillance. However, if mastectomy is delayed or not performed, mammography should be performed as for females in general. In addition, pap smears should be performed in transgender men who have cervical tissue present (table 5). (See "Primary care of transgender individuals", section on 'Screening/preventive care'.)
Adverse events — Androgen therapy is safe for most patients [30,32]. However, there are some potential adverse events.
Persistent bleeding — Menses usually stop within a few months of starting testosterone [33]. However, in some individuals, bleeding may continue. Our approach is to increase the testosterone dose modestly. Another approach is to add an oral progestin such as medroxyprogesterone acetate (MPA; 5 to 10 mg daily continuously) or treatment with a gonadotropin-releasing hormone (GnRH) agonist to stop the menstrual bleeding [11].
Metabolic — The most commonly observed consequence of androgen therapy is erythrocytosis. We agree with the Endocrine Society and suggest that men receiving androgen therapy be monitored to keep the hematocrit less than 50 percent (table 4). Lipid changes may necessitate intervention [32].
Heart disease — As described above, the effects of androgens on transgender men on biochemical risk markers are somewhat mixed [34]. A meta-analysis of 16 studies concluded that cross-sex hormone therapies increase serum triglycerides in both transgender women and transgender men [35]. However, data about patient-important outcomes such as atherosclerosis were limited and inconclusive. In spite of limited data, transgender persons treated with hormones should be evaluated for cardiovascular risk factors [11]. (See "Primary care of transgender individuals", section on 'Cardiovascular disease' and "Overview of established risk factors for cardiovascular disease".)
Fertility considerations — Transgender individuals who take hormone therapy may limit fertility potential unless hormones are stopped. Individuals who undergo transgender genital surgery that includes loss of gonads lose their reproductive potential altogether. Thus, before starting any treatment, patients should be encouraged to consider fertility issues.
Transgender men may consider cryopreservation of oocytes or embryos [36,37]. While these options may provide preservation of fertility, the associated costs are high, particularly for cryopreservation of oocytes or embryos, which requires ovarian stimulation and oocyte retrieval in addition to storage fees. (See "Fertility and reproductive hormone preservation: Overview of care prior to gonadotoxic therapy or surgery", section on 'Fertility preservation' and "In vitro fertilization: Overview of clinical issues and questions".)
GENDER CONFIRMATION SURGERY — Gender confirmation surgery (also referred to as gender-affirming surgery) is often the last (and most considered) step in the treatment process. Individuals can and do live successfully in their preferred gender role without genital surgery.
The criteria for initiating genital surgical treatment include the same criteria for hormone therapy, but an additional criterion is added due to its increased invasiveness [1] (see 'Criteria for starting' above):
One year of continuous hormone therapy and living in the desired gender role is expected, unless it has been determined the hormone therapy is not medically indicated. This criterion is not required for surgeries like chest reconstruction or other nongenital surgeries.
Additional details for surgical procedures are available in the World Professional Association for Transgender Health (WPATH) Standards of Care [1]. (See 'Standards of care' above.)
Prior to surgery, the clinician should continue to counsel the patient to acknowledge the limitations of what gender confirmation surgery can achieve. In addition, the patient should continue to work closely with the supporting medical and mental health providers as appropriate.
The most commonly desired gender confirmation surgery for transgender men is chest reconstruction surgery (breast reduction [38]). Note that surgeons experienced with this surgery for men should be sought out (similar to men with gynecomastia in general).
For some transgender men, oophorectomy, hysterectomy, and/or vaginectomy may be considered after one to two years of androgen therapy, although practice patterns vary [11].
Genital reconstruction procedures are best performed in the few centers with specialized expertise. The surgeries can be less popular because of their cost and relatively high morbidity. One option is creation of a neophallus [11,39]. In other cases, a metaidoioplasty may be performed [39,40]. With this technique, the urethra is lengthened using an anterior vaginal wall flap to reach the tip of the phallic glans, and the clitoris is partially released and stretched by resection of the ventral chordae. From the labia majora, a scrotum can be constructed in which testicular prostheses can be implanted. This surgical intervention allows the patient to urinate standing. Alternatively, free flaps removed from arms or legs can be used to construct a neophallus.
Sexual function after genital reconstruction surgery — Little attention has been given to this subject, and research has been based on self-reports. As expected for those transgender men with a neophallus, there is a correlation between sexual function and the quality of the neophallus [41]. While not all transgender persons are orgasmic after a neophallus is created, many report sexual satisfaction [27,42-44]. Transgender men receiving androgens generally report an increase in sexual interest [45]. Systematic investigation is needed to gain more insight [28].
Regrets after gender confirmation surgery — Given the irreversibility of gender confirmation surgery and, to a lesser degree, of cross-sex hormone administration, it would be desirable to have insight into factors that predict success or failure. Although regrets are rare, they do occur. Regrets are seen more often in those with difficulty in transitioning their appearance or limited social skills [42,46].
PSYCHOSOCIAL OUTCOMES OF TREATMENT — Transgender treatment that includes hormonal therapy results in significant improvement in quality-of-life and psychosocial outcomes [47]. This was illustrated in a meta-analysis of 28 studies that enrolled 1833 transgender individuals (1093 transgender women, 801 transgender men) who underwent transgender treatment that included hormones [42]. In the pooled analysis, the percentage of patients reporting improvements in symptoms included:
●Gender dysphoria – 80 percent
●Psychological symptoms – 78 percent
●Quality of life – 80 percent
●Sexual function – 72 percent
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
●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. (See 'Introduction' above.)
●Transgender individuals should have their gender incongruence diagnosed 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 'Evaluation and diagnosis' above.)
●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 'Overview' above.)
●For transgender men (female-to-male [FTM]), we suggest either testosterone esters (administered intramuscularly or subcutaneously) or testosterone gels, depending upon patient preference (table 2) (Grade 2C). However, higher testosterone levels are more easily achieved with parenteral therapy. (See 'Testosterone therapy' above.)
●Transgender men who have undergone mastectomy do not require mammograms but may benefit from continued chest self-exam. However, if mastectomy is delayed or not performed, mammography should be performed as for females in general. In addition, pap smears should be performed in transgender men who have cervical tissue present (table 5). (See 'Routine monitoring' above.)
●We suggest that transgender men receiving testosterone therapy be monitored for erythrocytosis and dyslipidemia, two potential consequences of androgen therapy (table 4). (See 'Metabolic' above.)
●Although they are not as popular as chest reconstruction surgeries, gender confirmation (or affirmation) genital and gonad-removing surgeries can be considered after living one year in the desired gender role and after one year of continuous hormone therapy (unless there a medical contraindication to hormone therapy). This criterion is specific to genital and gonad removing surgeries but not to other procedures such as chest reconstruction surgeries. Details of surgery are described above. (See 'Gender confirmation surgery' above.)
ACKNOWLEDGMENT — The editorial staff at UpToDate would like to acknowledge Louis JG Gooren, MD, who contributed to earlier versions of this topic review.
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