Approach

The aim of treatment is to improve the quality of life to the maximum attainable degree by means of safe and sustainable relief of gender dysphoria. An overarching principle is that reversible steps should have been successfully negotiated before irreversible steps are contemplated.[1] Further, significant or irreversible steps should be approved by two suitably qualified and experienced gender identity specialists (often, but not necessarily, mental health professionals) before they are undertaken. Subspecialty consultation is required. No medical treatment should ever be undertaken without appropriately qualified psychological support.[1]

Quality of diagnosis

As the diagnosis is the gateway to potentially drastic and irreversible treatment, it is appropriate for comorbidities to be identified, differential diagnoses excluded, and a proper diagnosis to be made by a suitably qualified gender dysphoria specialist working in the context of a multidisciplinary team in a gender identity clinic.

Patients should have been biochemically screened for other possible diagnoses, such as Klinefelter syndrome, polycystic ovary syndrome, congenital adrenal hyperplasia, or a partial androgen insensitivity syndrome. Such screening ensures that the patient is fit to be treated with cross-sex hormone treatment, when this is indicated; a partial androgen insensitivity syndrome also indicates a need for genetic counseling for the patient's family.

Practical, real world experience

The process of fully adopting a new or evolving gender role or gender presentation in everyday life is known as the ‘real world’ or ‘real life’ experience.[26] Many clinicians maintain that hormone treatment should generally not be started unless the patient has already changed gender role.[26] This includes legally changing registration to that of the preferred sex and changing name on all documents. All other people should be made aware of this change and asked to treat the patient as the chosen sex, even if they know that this was not always the case. The degree to which the change in gender expression and role can be practically applied then becomes apparent to clinician and patient alike. Changes of social gender role to a real life, nonbinary role may be harder to accomplish than patients anticipate, and after practical experience, can be modified into a more direct change to another, more distinct, social gender role.

Some patient groups maintain that hormone treatment should precede a change of gender role. However, this approach involves a prolonged period of potentially dangerous treatment with hormones that may result in the patient being forever unhappy with the degree of bodily change and indefinitely postponing any change of role.

Patients with autogynephilia 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 feminization.

There is universal agreement that a period of practical experience of at least 1 year (including at least 1 year of consistent hormone treatment, unless unsuitable or contraindicated) should precede any genital surgery.[1][26] Longer periods would 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.

Cross-sex hormone treatment

Hormone therapy involves giving exogenous hormones in order to:[1][26]

  • Reduce endogenous hormone levels (with a resultant reduction in secondary sex characteristics of the person’s biological sex)

  • Replace these endogenous hormones with those of the reassigned sex following principles of hormone replacement for hypogonadal patients.

Individualized treatment is required based on the patient’s goals, any medical contraindications, and the side effect profile of the medications used. Hormone therapy may lead to irreversible physical changes, and so informed consent is essential, including a full discussion of the risks and benefits, and effects on reproductive capacity.[1] Screening for and addressing acute and chronic mental health concerns is a key part of this process.

Hormone treatment varies with the birth sex of the patient. Most practitioners take the view that hormone treatment should come after a change of gender role.[26] Rarely, hormone treatment is used for patients who do not wish to make a social gender role transition or undergo surgery, or who are unable to do so.[1]

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. The World Professional Association for Transgender Health guidelines advise that health professionals who recommend hormone therapy share the ethical and legal responsibility for that decision with the physician who provides the service.[1]

Criteria for hormone therapy include the following:[1]

  • Persistent, well-documented gender dysphoria

  • Capacity to make a fully informed decision and to consent for treatment

  • Relevant medical or mental health problems are well controlled.

Hormone treatment in born males

  • Estrogen, with or without gonadotropin suppression with a gonadotropin-releasing hormone (GnRH) agonist, is used in born males. While androgen blockers such as spironolactone, cyproterone, and 5-alpha reductase inhibitors are noted by some guidelines to be the most frequently used gonadotropin suppression agents,[1] the author of this topic does not recommend them because their frequent use is reflective not of superiority but rather of local or national formulary availability or economic affordability. The ideal agent is one that inhibits all testicular function with minimal or zero side effects, something which can be achieved with a GnRH agonist. Disadvantages of GnRH agonists are the requirement for parenteral administration and a relatively greater cost, which sometimes prevents placement on available formularies.

  • Risks associated with estrogen therapy in born males include:[26]

    • Very high risk of adverse outcomes

      • Thromboembolic disease

    • Moderate risk of adverse outcomes

      • Macroprolactinoma

      • Breast cancer

      • Coronary artery disease

      • Cerebrovascular disease

      • Cholelithiasis

      • Hypertriglyceridemia.

  • Contraindications to feminizing treatment with estrogen include:[1]

    • Previous venous thrombotic events related to an underlying hypercoagulable state

    • History of estrogen-sensitive cancer

    • End-stage chronic liver disease.

Hormone treatment in born females

  • Gonadotropin suppression is not usually needed in born females, as androgens alone suppress ovarian function very well.

  • Risks associated with testosterone therapy in born females include:[26]

    • Very high risk of adverse outcomes

      • Polycythemia (hematocrit > 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.

  • Contraindications to masculinizing treatment with testosterone include:[1]

    • Pregnancy

    • Unstable coronary artery disease

    • Untreated polycythemia with a hematocrit of 55% or higher.

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.[1]

It typically takes 2 or more years for patients to achieve maximal masculinizing/feminizing 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 estrogen or testosterone is usually continued lifelong, unless contraindications develop.[1]

Criteria for genital surgery and removal of gonads

Some patients with gender dysphoria are able to 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.[1] As with hormone treatment, the mental health professional who recommends genital surgery shares the ethical and legal responsibility for that decision with the clinician who performs the surgery. The criteria for starting genital surgery are the same as for starting hormone therapy, with one additional criterion (due to its increased invasiveness):[1]

  • One year of continuous hormone therapy and living in the desired gender role (unless hormone therapy is not medically indicated).

Endocrine Society clinical practice guidelines recommend that genital surgery and removal of gonads should be considered only if the physician overseeing hormone treatment and the mental health professional overseeing the patient’s gender dysphoria both agree that surgery is medically necessary and beneficial for the patient overall, and the clinician overseeing hormone treatment has medically cleared the patient for surgery.[26]

Born males: adjunctive surgeries and treatment

Hair removal

  • This can be done with electrolysis or laser treatment.[1] All other methods are non-permanent. Laser treatment works only with dark-colored hair and light-colored skin.

Head and neck surgery

  • Thyroid cartilage reduction surgery is sometimes needed in tall, thin, born-male 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.

  • 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 utilized and when simpler cosmesis has failed.

Augmentation mammoplasty

  • Although not a formal prerequisite, it is recommended that patients receive feminizing hormone treatment (for a minimum of 12 months) prior to surgery.[1] In the author’s experience, a minimum of 2 years is preferable. This is because it can be aesthetically problematic if natural breast development under estrogen stimulation follows an augmentation mammoplasty.[26]

Genital surgery

  • This procedure is indicated only when the patient has experienced a minimum of 1 year of continuous hormone therapy and living in the desired gender role (unless hormone therapy is not medically indicated).[1] Many clinics would want 2 years.The patient must over that period of time have shown improved psychological, social, and, probably, occupational function.

  • The surgery uses the existing genitals to fashion a vulva, neoclitoris and hood, labia, and (often) neovagina. Preoperative genital hair removal is sometimes needed, particularly in patients who have been circumcised. The cosmetic results can be very good.

Born females: adjunctive surgeries and treatment

Bilateral mastectomy

  • There is no consensus about when born-female patients should undergo bilateral mastectomy.[26] Although hormone therapy is not a formal prerequisite to bilateral mastectomy,[1] 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 postsurgical 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 postsurgical appearance.

Hysterectomy and bilateral oophorectomy

  • Consideration of hysterectomy and bilateral oophorectomy is recommended within 2 years of the start of androgen treatment to obviate the risk of gynecologic malignancy.[26]

  • For patients who have not had previous abdominal surgery, the laparoscopic technique for hysterectomy and bilateral oophorectomy is recommended to avoid a lower abdominal scar.[1]

  • Other approaches are transvaginal and transabdominal. Vaginal access may be difficult as most patients are nulliparous and have often not experienced penetrative intercourse.[1] A transabdominal approach may utilize any incision other than a Pfanenstiel incision, as this incision is pathognomic of gynecologic surgery and the resulting scar looks odd in a male.

Phalloplasty

  • This complex, often multistage procedure is indicated only when the patient has lived in a male role receiving continuous hormone treatment, unless contraindicated, for 1 year at the very minimum[1] (many clinics would want 2 years). 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. The cosmetic and functional results are fairly good, but the result in even the best centers is clearly distinguishable from a native penis.

Craniofacial surgery

  • This complex and sometimes very radical surgery is sometimes helpful but should only be contemplated when treatment with hormones has been fully utilized and when simpler cosmesis has failed.[26]

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