World Professional Association for Transgender Health advises that medical treatment should only occur after a thorough psychosocial assessment has been undertaken by a clinician experienced in the field. Informed consent must be obtained from the patient.2 Standard treatment in adults is based on a gender-affirming hormone. This is testosterone for female to male transition and estrogen, supplemented by an anti-androgen, for male to female transition.
Treatment of transwomen (male to female) produces variable changes including:
- breast growth
- softening of the skin
- reduction and fining of body hair
- change in body fat distribution
- reduced muscle mass and strength in the upper body
- emotional change
- decline in libido
- decreased spontaneous erections
- testicular shrinkage and cessation of spermatogenesis.
The effects of testosterone on transmen (female to male) are:
- deepening of the voice
- increased muscle mass and strength (particularly upper body)
- change in body fat distribution
- increased hair growth (body and face)
- increase in skin oiliness and body odour
- atrophy of breasts, vulval and vaginal tissues
- clitoral enlargement
- cessation of menstruation.
In both genders, changes begin to appear in the first few months of treatment and usually reach a maximum after three to five years. Starting treatment after puberty will reverse or regress many primary and secondary sexual characteristics, but obviously some will persist to the extent that reassignment surgery might also be sought by some individuals.
Transwomen
Estrogens in combination with an anti-androgen are the standard first-choice gender-affirming hormone treatments for transwomen.
Estrogen
Estradiol is preferred, as it most closely resembles the hormone produced by the ovaries. It is prescribed in a similar way to hormone replacement therapy for postmenopausal women, but with slightly higher doses. The dose of estradiol valerate tablets starts at 2–4 mg daily, increasing up to 8 mg. Tablets can be given in divided doses if nausea occurs at higher doses.
Patches or implants are preferred for transwomen over 40 years of age (although they can be used in younger people) to minimise the risk of venous thromboembolism. Treatment with patches starts with 100 microgram/24 hours titrated up to 400 micrograms. Implants of 50 and 100 mg are available from compounding pharmacies. Generally, 100 mg is inserted for most transwomen, but a supplementary 50 mg implant can be added for patients with a high body mass index. The duration of drug delivery with implants is on average 6–12 months. Estrogen concentrations should be monitored and a new implant inserted when they fall below physiological levels. Tachyphylaxis can develop with long-term implant use.
Ethinylestradiol and conjugated equine estrogens are generally avoided. They have an increased risk of venous thromboembolism and measurement of their blood concentrations is inaccurate.
Anti-androgens
Anti-androgens suppress the production and effect of endogenous androgens and so reduce masculine characteristics. In combination with estrogen they reduce the estrogen dose required to achieve feminising effects. The most commonly used anti-androgens are cyproterone and spironolactone.
Cyproterone is a synthetic progestogen with a potent anti-androgenic effect. The usual starting dose is 25–50 mg daily (but it can be started at 12.5 mg) and can then be increased to 100 mg daily. Rare cases of fulminant hepatotoxicity have been reported with cyproterone use for treatment of metastatic prostate cancer.
Spironolactone is a potassium-sparing diuretic which in higher doses directly inhibits testosterone production and blocks androgen receptors. The usual starting dose is 100 mg daily in one or two doses up to a maximum of 400 mg daily. Blood pressure and potassium concentrations need to be monitored. Possible adverse effects include polyuria, polydipsia and postural hypotension, particularly at higher doses. Hyperkalaemia is also possible, particularly in patients with impaired kidney function or taking potassium-retaining drugs such as ACE inhibitors.
Progesterone
Progesterone is used by some clinicians in addition to estrogens and anti-androgens. Anecdotal reports suggest that progesterone may improve breast development, but there are no well-designed studies of its use in transwomen. Potential adverse effects include depression, weight gain and an increase in lipids.
Transmen
Testosterone is used for masculinising effects for transmen. Menstruation typically ceases in the first 3–6 months of treatment. In cases where this is delayed or distress arises from menstruation, progesterone can be used.
Testosterone
Testosterone is available in a range of formulations, but injected testosterone is the standard first choice. Tablets are unsuitable for gender affirmation as they are unlikely to achieve physiological concentrations or supress menstruation.
Intramuscular injections
Testosterone enantate was, until recently, commonly used, however it is currently unavailable. It is given by intramuscular injection every 2–3 weeks. Suitable patients can be taught to self-inject. The starting dose is 125 mg titrated up to 250 mg with the aim of reaching male physiological concentrations. There can be cyclical effects of aggression or an expansive mood at the start of the cycle and fatigue and irritability at the end.
Injections of testosterone undecanoate 1000 mg every 10–12 weeks produce similar cyclical effects but with less frequency. This formulation carries a risk of pulmonary microembolism, making it unsuitable for self-injection.
Gels and creams
Testosterone gels and creams are less commonly used, for reasons of practicality. Patients cannot bathe or swim for six hours following application and must avoid contaminating women and children by direct contact. However, for patients who wish to avoid injections or are bothered by their cyclical effects, topical testosterone is a good choice. The standard daily dose is one 50 mg/5 g sachet or 4 actuations of the pump (12.5 mg per actuation) rubbed into the skin of the upper body. Titrate up to 100 mg (2 sachets or 8 actuations). A testosterone cream is also available, with similar dosing. It comes with an applicator which has 0.5 mL gradations.
Patches
Although there is evidence that testosterone patches may eventually achieve similar masculinising effects as injectable formulations, they take a significantly longer time to reach physiological concentrations. For this reason, injectables or topical gels are preferred.