Approach
The aim of treatment is to improve the quality of life to the maximum attainable degree by means of the safe and sustainable relief of gender incongruence/dysphoria. Options for gender-affirming care include hormone therapies and surgeries. Adjunctive options include hair removal, speech and language therapy and supportive counselling. Management is highly individualised, and that there is no ‘one size fits all’ approach. Transgender people may choose to undergo all, some, or none of the above interventions to support their gender affirmation.
Meta-analysis evidence demonstrates that, for the majority of transgender people, gender-affirming treatment (including hormonal therapy) results in significant improvements in quality of life and psychosocial functioning.[41][42][43]
Several large professional medical bodies have published guidance on care of transgender people, including gender-affirming care; this includes US guidance from the Endocrine Society and American College of Obstetricians and Gynecologists (ACOG), and international guidance from the World Professional Association for Transgender Health (WPATH).[4][31][44]
An overarching general principle is that reversible steps are successfully negotiated before irreversible steps are contemplated.[4] A multidisciplinary approach to management is strongly recommended; relevant disciplines include (but are not limited to) endocrinology, surgery, voice and communication, primary care, reproductive health, sexual health, and mental health.[4] All transgender people seeking gender-affirming medical treatment should be given information on options for fertility preservation prior to treatment with hormones or surgery.[31]
It is important to note that transgender people as a group experience relatively poorer access to health services compared to other patient groups. Barriers include bias and stigma by healthcare professionals as well as lack of knowledge around best practices, including safety and efficacy of treatments.[45][46] An open, non-judgemental and inclusive approach is important and may help to encourage people to be forthcoming with their concerns, and less likely to obtain hormones from unlicensed sources.[44] As with any patient group, effective patient-clinician collaboration and shared decision making can facilitate development of therapeutic alliance.
When caring for transgender people use their patient-identified name and gender-neutral terminology until pronoun preferences are made clear. The most straightforward way to determine pronouns is simply to ask, ‘What are your preferred pronouns?’ Using the wrong pronoun can cause transgender people to feel invalidated or disrespected, particularly if it occurs repeatedly. If you make a mistake, apologise and carry on, aiming to get it right thereafter.[47]
Healthcare workers should also be aware of the lack of standardisation in recording gender identity and that there may be insufficient options in electronic health record platforms.
Outside of specific transgender-related care, transgender people have similar health care needs to the general population. However, depending on their history of gender-affirming care (e.g., hormone therapy), some specific primary and preventive care considerations may be required. When treating people who take gender-affirming hormones, it is important to remember these may affect laboratory test results (e.g., liver function tests, prostate specific antigen [PSA]) and modify disease-specific risk factors or increase the risk of in-hospital complications (e.g., venous thromboembolism).[48]
Social transition
Social transition is the process of adopting a new or evolving gender role or gender presentation in everyday life. Whether social transition should necessarily precede hormone treatment is a matter of some debate. Usually, clinicians maintain that hormone treatment should generally not be started unless the patient has already changed gender role.[31] This may include legally changing registration to that of the preferred sex and changing the person’s name on all documents, as well as making friends, family, and other contacts aware of this change and asking them to treat the person as the chosen sex. Based on clinical experience, advantages of this approach are that it can allow both patient and clinician to appreciate the degree to which the change in gender expression and role can be practically applied. Regrets following gender-affirming treatment are rare, but do occur; regret is more likely to occur in those who experience difficulties with social transition.[41][49] Furthermore, changes of social gender role to a non-binary role may be harder to accomplish than people anticipate, and after experiencing an initial period of social transition to a non-binary role, some people may prefer to modify their social transition in favour of developing a more distinct, social gender role.
Less commonly, hormone treatment is used for patients who do not wish to make a social gender role transition, or who are unable to do so.[4] Some patient groups maintain that hormone treatment should precede a change of gender role. Clinical experience suggests that potential disadvantages of this approach are that it involves a prolonged period of treatment with hormones, with associated potential for adverse effects, that may result in the person being unhappy with the degree of bodily change (which may be permanent), and indefinitely postponing any change of role.
Patients with autogynephilia may seek hormone treatment without any change of gender role and may put forward this argument (explicitly or covertly) to achieve that aim. Their autogynephilia may subsequently dissipate, leaving them with unwanted feminisation.
There is universal agreement that a period of social transition of at least 6 months to 1 year (including at least 1 year of consistent hormone treatment, unless unsuitable or contraindicated) should precede any genital surgery.[4][31] Longer periods may be needed if there are any problems living in the new gender role, to allow time for these problems to be addressed. Patients should not undergo surgical treatment until they are thriving (not merely surviving) in their new gender role.
Note that legal transition should not be dependent on use of medication or surgery, and varies according to local (i.e., national or state) laws; clinicians and patients should consult their relevant local legal guidance.[44]
Fertility and contraception
Pre-treatment discussion of the consequence of medical and surgical treatment on fertility is essential, including a discussion of fertility preservation options, including sperm banking, oocyte preservation, embryo preservation and (less commonly) ovarian or testicular tissue cryopreservation.[31][44] All patients should be counselled on barrier methods of contraception for prevention of sexually transmitted infections. Gender-affirming hormone therapy is not effective contraception; transgender people with retained gonads should be counselled about the possibility of pregnancy if they are having sexual activity that involves sperm and oocytes. Testosterone therapy is contraindicated during pregnancy, but transgender men may safely achieve pregnancy after cessation of testosterone.[44]
Gender-affirming hormone treatment
Hormone therapy for transgender people is given with the aim of achieving one or more of the following goals:[4][31]
Reduce endogenous hormone levels (with a resultant reduction in secondary sex characteristics of the person’s birth-assigned sex).
Replace these endogenous hormones with those of the reassigned sex following principles of hormone replacement for hypogonadal patients.
Provide hormone replacement therapy (HRT) to prevent the effects of hypogonadism following surgical treatment.
Individualised treatment is required based on the patient’s goals, any medical contraindications, and the side effect profile of the medications used. According to the WPATH, criteria for starting hormone therapy include:[4]
Gender incongruence is marked and sustained.
The individual meets diagnostic criteria for gender incongruence prior to gender-affirming hormone treatment in regions where a diagnosis is necessary to access health care.
The individual demonstrates capacity to consent for the specific gender-affirming hormone treatment.
Other possible causes of apparent gender incongruence have been identified and excluded.
Mental health and physical conditions that could negatively impact the outcome of treatment have been assessed, with risks and benefits discussed.
The individual understands the effect of gender-affirming hormone treatment on reproduction and they have explored reproductive option.
Transgender care is an interdisciplinary field, and so coordination of care and referral for hormone treatment within a patient’s overall care team is recommended.
Hormone treatment varies with the birth sex of the patient.
Clinicians should stress the importance of smoking cessation, as smoking increases the thromboembolic risk from oestrogen treatment and polycythaemia with testosterone treatment (see Smoking cessation).
Feminising treatment for transgender women
The term ‘transgender woman’ is used to mean a person who was assigned male at birth, but who identifies as a woman or trans woman.
A thorough discussion of the risks versus benefits of treatment is essential prior to treatment initiation, and guides shared decision-making.
Gender-affirming hormone treatment aims to elicit in a birth-assigned male patient the secondary sexual changes seen in birth-assigned females at puberty. These changes will be superimposed on whatever male pubertal changes have already occurred and will not reverse them. Effects of treatment may include breast growth, increased body fat percentage, decreased libido, decreased testicular size and decreased erectile function.[44] There is no effect on vocal quality.[44] Facial and bodily hair growth is slowed only slightly and never stopped. For information on expected timing of feminising effects of oestrogen (see Patient discussions).
According to the Endocrine Society in the US, risks associated with oestrogen therapy in transgender women include:[31]
Very high risk of adverse outcomes
Thromboembolic disease
Moderate risk of adverse outcomes
Macroprolactinoma
Breast cancer
Coronary artery disease
Cerebrovascular disease
Cholelithiasis
Hypertriglyceridaemia
ACOG advises that there are no absolute contraindications to feminising therapy in transgender women.[44] However, clinicians should evaluate for (and potentially treat) a number of conditions at baseline, given that relative risks may be increased with hormone treatment; these include hormone sensitive cancer, coronary artery disease, cerebrovascular disease, hyperprolactinaemia, hypertriglyceridaemia, and cholelithiasis.[4]
WPATH advises that people seeking feminising treatment who have a history of thromboembolic events (e.g., deep vein thrombosis or pulmonary embolism) should undergo evaluation and treatment prior to the initiation of hormone therapy.[4] For those with non-modifiable risk factors which may increase the risk of thromboembolic disease, for example, a known history of thrombophilia, a past history of thrombosis, or a strong family history of thromboembolism, WPATH advise that offering an anticoagulant in addition to treatment with transdermal oestrogen may decrease the risk of thromboembolism, although data to guide treatment decisions are extremely limited.[4]
Oestrogen, with or without an agent to suppress androgen, is used as feminising treatment in transgender women. However, there are no randomised controlled trials to assess the safety and efficacy of this treatment.[50] A wide variety of different formulations and preparations are available, and local formularies vary considerably. In practice, both oral and transdermal oestrogens are commonly used. In theory, transdermal oestrogen may be associated with a lower risk of venous thromboembolism (VTE) and stroke (based on knowledge of the ‘first pass effect’ and from extrapolation of data derived from post-menopausal women receiving HRT).[51] Any absolute risk will be dependent on the individual’s baseline risk for VTE. In clinical practice, oral oestrogen is commonly used in transgender women who have a low baseline risk for VTE. For those aged 45 years or over, or with other risk factors for VTE, transdermal preparations are usually preferred.[44]
Currently available data do not provide clear guidance on dose titration; instead this should generally be based on patient goals.[44] As with any medication, use of the lowest dose possible to achieve the desired results is recommended.[44] Based on clinical experience, one approach is to start treatment with a low/moderate dose and build over time. Ultimately the goal is to reach a dose that produces a serum oestradiol in the normal female pre-menopausal range.[44] Clinical experience suggests that high-dose treatment from the outset may be associated with early duct fusion and the eventual formation of small, hard, conical breasts that cannot be made larger or more naturally textured with any subsequent hormonal manipulation.
Usually, adjunctive therapy is required to achieve testosterone levels in the normal female range (androgen suppression), particularly in younger people(<40 years).[31] Androgen suppression using a gonadotrophin-releasing hormone (GnRH) agonist is preferred where available, given favourable safety and efficacy data.[31][52] This treatment carries fewer adverse effects than when used for prostate cancer and is usually well tolerated, with bone density being protected by the parallel sex steroid therapy. Disadvantages of GnRH agonists are the requirement for parenteral administration and a relatively greater cost, which sometimes prevents placement on available formularies. GnRH agonists are used routinely in some countries, including the UK, but in other parts of the world, including the US, their use is limited due to cost and insurance coverage difficulties.
Alternative options for androgen suppression where GnRH agonists are not available include spironolactone, cyproterone, and 5-alpha reductase inhibitors.[4][31] Spironolactone is commonly used in the US.[44] Cyproterone is available in most countries, but not the US; overall, its use is decreasing due to its association with a number of adverse effects, including hyperlipidaemia and raised prolactin levels.[53]
Progesterone is not indicated, as there is insufficient evidence that the benefits outweigh the risk; although there are anecdotal reports of its use for breast development, there is currently insufficient evidence as to the efficacy of this, and it is known to raise the risk of breast cancer and has been associated with depression.[4]
It typically takes 2 or more years for patients to achieve maximal feminising results from hormones. If there was gonadal suppression with a GnRH agonist, the same dose will be needed after any genital surgery, although in later life doses might need to be lowered to achieve the same hormone levels as hepatic sex steroid metabolism can decrease with age. For patients who go on to have orchidectomy, hormone therapy with oestrogen is usually continued lifelong, unless contraindications develop.[4]
For recommended blood test monitoring regimens for patients newly started and established on hormone therapy (see Monitoring).
Masculinising treatment for transgender men
The term ‘transgender man’ is used to mean a person who was assigned female at birth, but who identifies as a man or trans man.
A thorough discussion of the risks versus benefits of treatment is essential prior to treatment initiation, and guides shared decision-making.
Gender-affirming hormone treatment aims to elicit in a birth-assigned female patient the secondary sexual changes seen in birth-assigned males at puberty. These changes will be superimposed on whatever female pubertal changes have already occurred and will not reverse them. Goals of treatment may include development of facial hair, deepening of the voice, and increasing body hair and muscle mass. Other effects of treatment may include fat redistribution, hairline recession, changes in body odour, reduced libido, cessation of menses, vaginal atrophy and increased clitoral size.[44] Vaginal atrophy may increase susceptibility to small amounts of vaginal tearing during penetrative sexual intercourse (similar to in post-menopausal women), and so prescription of a topical lubricant/oestrogen may be required.[44] For information on expected timing of masculinising effects of testosterone (see Patient discussions).
According to the US Endocrine Society, risks associated with testosterone therapy in transgender men include:[31]
Very high risk of adverse outcomes
Polycythaemia (haematocrit > 50%)
Moderate risk of adverse outcomes
Severe liver dysfunction (transaminases > threefold upper limit of normal)
Coronary artery disease
Cerebrovascular disease
Hypertension
Breast or uterine cancer
According to the ACOG, the only absolute contraindications to masculinising treatment with testosterone are current pregnancy, unstable coronary artery disease and polycythaemia (haematocrit greater than 55%).[44] WPATH note that relative contraindications to masculinising treatment with testosterone include severe hypertension and sleep apnoea, since both may be exacerbated by testosterone administration.[4]
Preparations, doses, and licensing restrictions for testosterone vary according to country of practice. A variety of preparations and routes of administration are available, including injectables, gels, patches, and buccal tablets.
The aim of therapy is to achieve serum testosterone levels in the normal physiological range for young males at all times.[44]
Data from studies reported in the literature between 1980 and 2010 suggest that treatment of female-to-male transgender people with supra-physiological doses of testosterone is associated with minimal adverse effects and no increase in mortality, breast cancer, vascular disease, or other major health problems.[54] However clinicians can achieve a good clinical response and minimise the risk of adverse effects by avoiding supraphysiological levels of testosterone.
Androgens are administered in doses sufficient to induce menopause, usually once monthly but, more rarely, as often as once every 2 weeks. Once menopause is achieved, it is often possible to decrease the frequency without menstrual periods returning.
Gonadotrophin suppression is not usually needed in transgender men, as androgens alone suppress ovarian function very well. All patients should be offered the opportunity for gamete storage before hormone treatment, as is the case for any medically mandated treatment that removes natural fertility.[4]
It typically takes 2 or more years for patients to achieve maximal masculinising/feminising results from hormones. If there was gonadal suppression with a GnRH agonist, the same dose will be needed after any genital surgery; although, in later life doses might need to be lowered to achieve the same hormone levels, as hepatic sex steroid metabolism can decrease with age.
For patients who go on to have gonadectomy, hormone therapy with oestrogen or testosterone is usually continued lifelong, unless contraindications develop.[4]
For recommended blood test monitoring regimens for patients newly started and established on hormone therapy, (see Monitoring).
Gender-affirming surgery
Some transgender people live successfully in their preferred gender role without surgery, but for others, genital surgery is the final (and most considered) step in the treatment process.[4]
According to the WPATH, criteria for genital surgery include:[4]
Gender incongruence is marked and sustained.
Meets diagnostic criteria for gender incongruence prior to gender-affirming surgical intervention in regions where a diagnosis is necessary to access health care.
Demonstrates capacity to consent for the specific gender-affirming surgical intervention.
Understands the effect of gender-affirming surgical intervention on reproduction and they have explored reproductive options.
Other possible causes of apparent gender incongruence have been identified and excluded.
Mental health and physical conditions that could negatively impact the outcome of gender-affirming surgical intervention have been assessed, with risks and benefits have been discussed.
Stable on their gender affirming hormonal treatment regime (which may include at least 6 months of hormone treatment or a longer period if required to achieve the desired surgical result, unless hormone therapy is either not desired or is medically contraindicated).*
*This was graded as a suggested criterion. Note that there is an absence of consensus as to whether or not hormone treatment should always precede certain surgical procedures, and if so, for what duration. WPATH notes that gender-affirming hormone treatment leads to anatomical, physiological and psychological changes. The onset of anatomical changes (clitoral growth, vaginal atrophy) may begin early after initiation of treatment, with peak effects expected at 1-2 years. Depending on the surgical result required, a period of hormone treatment may be necessary prior to surgery for anatomical reasons, for example, to cause clitoral viralisation prior to phalloplasty, or may be desired, for example, to cause breast growth and skin expansion prior to breast augmentation. Hormone treatment prior to surgery may also be preferred for psychological reasons.[4] For patients not taking hormone treatment, an individualised approach is required, ideally with multidisciplinary input, and it is important that surgeons carefully review the impact that a lack of prior hormone therapy may have on any proposed surgery. Furthermore, many clinics prefer that the patient has experienced 1-2 years in the desired gender role prior to surgery.[32]
Counselling to discuss expectations and limitations of surgery is essential, including likely effects on sexual function. Requirements on clinical authorisation of gender-affirmation procedures differ according to location of practice, and clinicians should consult local guidance; for example, in some locations (e.g., the US), agreement between a mental health professional and a physician overseeing hormone therapy is required for authorisation and medical clearance prior to surgery.[31] Genital surgeries should be performed within centres with specialist expertise wherever possible.
Ongoing mental health and psychosocial support may be required before and after surgery, as appropriate. Lifelong urological follow-up is encouraged for transgender men who have undergone metoidioplasty/phalloplasty.[4] Long-term follow-up by the primary surgeon/gynaecologist/primary care physician is encouraged for transgender women who have undergone vaginoplasty.[4]
The percentage of people who regret their gender-affirming surgical intervention is low (estimated to be between 0.3% and 3.8%).[4] Regret may be temporary or permanent; in this scenario multidisciplinary input is recommended in order to explore this further, with possible outcomes being medical and/or surgical treatment to continue the transition, or revision surgery to return anatomy to the sex assigned at birth.[4]
Transgender women: feminising treatments and surgeries
Hair removal
This can be done with electrolysis or laser treatment. All other methods are non-permanent.
Speech and language therapy
Transgender women wishing to achieve increased congruence between their voice and experienced gender may benefit from referral to a speech and language therapist/pathologist with specific training and experience in this field.[44]
Aesthetic procedures
Options are varied, and include liposuction, lipofilling, gluteal augmentation, and hair reconstruction.[44]
Head and neck surgery
Thyroid cartilage reduction surgery is sometimes needed in tall, thin, patients whose thyroid cartilage is unacceptably prominent. It is usually an unproblematic procedure. It can be combined with a cricothyroid approximation.
Cricothyroid approximation can be done alone or combined with a thyroid cartilage reduction. It alters vocal quality to a more feminine pitch. It should only be attempted when speech therapy has failed, and usually requires follow-up speech therapy.[44]
Craniofacial surgery is a complex and sometimes very radical surgery that is sometimes helpful but should only be contemplated when treatment with hormones has been fully utilised and when simpler cosmesis has failed.
Augmentation mammoplasty
Although not a formal prerequisite, it is desirable that patients receive feminising hormone treatment (for a minimum of 12 months) prior to surgery.[32] Based on clinical experience, a minimum of 2 years is preferable. This is because it can be aesthetically problematic if natural breast development under oestrogen stimulation follows an augmentation mammoplasty.
Genital surgery
Patients should be stable on their gender affirming hormonal treatment regime (which may include at least 6 months of hormone treatment or a longer period if required to achieve the desired surgical result, unless hormone therapy is either not desired or is medically contraindicated).
Furthermore, many clinics prefer that the patient has experienced 1-2 years in the desired gender role. The patient must, over that period of time, have shown improved psychological, social, and, probably, occupational function.[32]
Genital surgery typically involves penectomy and orchidectomy. The surgery uses the existing genitals to fashion a vulva, neoclitoris and hood, labia, and (often) neovagina.[44]
Pre-operative genital hair removal is sometimes needed, particularly in patients who have been circumcised. Clinical experience suggests that the cosmetic results can be very good.
Transgender men: masculinising treatments and surgeries
Aesthetic procedures
Options are varied, and include liposuction, lipofilling, and pectoral implants.[44]
Bilateral mastectomy (‘top surgery’)
There is no consensus about when patients should undergo bilateral mastectomy.[31] Although hormone therapy is not a formal prerequisite to bilateral mastectomy, nearly all practitioners take the view that bilateral mastectomy should come after a change of gender role and treatment with androgens. Some patient groups argue that it should precede both. Body weight and shape can change considerably when patients are treated with androgens, and it may be that an initially good post-surgical appearance alters negatively with subsequent androgen treatment. Difficulties may arise when a patient initially asserts that a non-binary role is desired, and requests bilateral mastectomy and chest reconstruction without preceding treatment with testosterone. There may then be a subsequent evolution to a more clearly male role and corresponding need for testosterone treatment, which may have a negative impact on the patient’s post-surgical appearance.
Hysterectomy and bilateral oophorectomy
Previously, total hysterectomy and oophorectomy were recommended for transgender men taking testosterone therapy, but WPATH now recommends against routine oophorectomy or hysterectomy solely for the purpose of preventing ovarian or uterine cancer for transgender people undergoing testosterone treatment and who have an otherwise average risk of malignancy.[4][31] Gender-affirming hormones have not been shown to affect cancer risk, but the quality of evidence is low and longer-term studies are needed.[55]
The route of hysterectomy is dependent on clinical findings, surgical, and patient preference.[44]
Approaches include laparoscopic, transvaginal, and transabdominal. An advantage of the laparoscopic approach is that it avoids leaving a large abdominal scar. Vaginal access may be difficult if patients are nulliparous and have often not experienced penetrative intercourse. A transabdominal approach may utilise any incision other than a Pfannenstiel incision, as this incision is pathognomonic of gynaecological surgery and the resulting scar may look unusual in a male.
Phalloplasty
This complex, often multi-stage procedure is typically considered only when the patient has received continuous hormone treatment, unless contraindicated, for 1 year at the very minimum.[32] Furthermore, many clinics prefer that the patient has experienced 1-2 years in the desired gender role. The patient must, over that period of time, have shown improved psychological, social, and, probably, occupational function.
Donor sites for phalloplasty can include the forearm, abdominal skin, or tissue from elsewhere on the body. The complexity, duration, and expense of the procedure are such that only a minority of patients choose to undergo this surgery. Clinical experience suggests that the cosmetic and functional results are fairly good, but the result in even the best centres is clearly distinguishable from a native penis.
Primary care: special considerations
The primary health care needs of transgender people are similar to those of any other patient.[4] However for people receiving gender-affirming care, some additional considerations may be required. Depending on service arrangements, primary care practitioners may be involved in the prescription of gender-affirming hormone therapy, preferably in conjunction with a specialist secondary-care based team, and with access to an endocrinologist if necessary.[32] Physical assessment and ongoing monitoring of heamatological, endocrinological and biochemical parameters are essential, and ideally should be carried out under shared/collaborative care arrangements with secondary care (see Monitoring).
Note that in some (less common) clinical circumstances, a non-specialist, for example, primary care clinician may consider prescribing a ‘bridging prescription’ of hormonal treatment to cover the patient’s care until they are able to access specialist services, as part of a harm reduction approach. This provides the opportunity to undertake blood tests and health checks to screen for contraindications to treatment. The suitability of this approach depends on the training and experience of the individual clinician, as well as on local guidelines and policy, and should only typically be considered when:[56]
The patient is already self-prescribing, or seems highly likely to self-prescribe, with hormones obtained from an unregulated source (online or otherwise on the black market).
The bridging prescription is intended to mitigate a risk of self-harm or suicide.
The clinician has sought the advice of a gender specialist and prescribes the lowest acceptable dose in the circumstances.
It is important to note that in some parts of the world, speciality services for transgender people are limited or wholly unavailable, highlighting a need for all health providers to undergo training in the safe provision of gender-affirming care.[4]
With respect to preventive health care, evidence on the long-term impact of gender-affirming hormone treatment is currently lacking. Cancer screening should commence, in general, according to local guidance, although there are a few specific issues to consider for people on hormonal therapy and/or those who have received surgery (e.g., with respect to breast, cervical, and prostate cancer screening, and osteoporosis screening) (see Monitoring).[4]
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