The use of cross-sex hormones (estrogens in male-bodied people and androgens in female-bodied people) to balance gender (induce or maintain the physical and psychological characteristics of the sex that matches the patient's gender identity [see section Transgender Terminology]) is increasing around the world. Cross-sex hormone administration is currently an off-label use of both estrogens and androgens; however, over 50 years of clinical experience have shown that this practice is effective in treating gender dysphoria. (See Hembree, et al (2009) and Gooren, et al (2008) in References.) It is important that the ability to understand and monitor this treatment becomes a part of primary care practice. This protocol is intended to aid in that process.
Not all transgender patients will want to take cross-sex hormones, but if a transgender patient does need to express a gender different from their assigned birth sex on a consistent basis, cross-sex hormones are the most common body modification that transgender patients can access for self-actualization, bringing the endocrine and psychological systems into balance.
An individual may already be receiving cross-sex hormones when they become the physician's patient. Review the current regimen in combination with a thorough assessment of the patient's general health to determine whether to recommend changes in dosage or preparation.
Most medical problems that arise in the transgender patient are not secondary to cross-sex hormone use.
Discuss fertility issues with all patients considering hormone therapy. (See section Fertility Issues)
Note: Testosterone is not a contraceptive substance; transmen having unprotected sex with fertile non-trans males are at risk for pregnancy if they have not had a hysterectomy.
If prescribing cross-sex hormones for a patient who has not used them before, assess for pre-existing conditions, to aid in determining which preparation and dosage to prescribe (see recommendations below). It is the clinician's responsibility to monitor the effects of hormones. (See section Assessing Readiness for Hormones)
Hormonal therapy for transwomen may include anti-androgen therapy as well as estrogen therapy. Non-oral estrogens, including sublingual, transdermal, and injectable hormones are preferable. These have the advantage of avoiding first pass through liver metabolism. (Grade B)
- Dosing: Sublingual (dissolve oral formulation under the tongue) 1-4mg estradiol/day (single or divided dose), 100-200mcg transdermal estradiol/day, 10-20mg estradiol valerate IM every 1-2 weeks (injections continue for no more than 2 years, then change to lower dosage). (Grade C)
- Over 35/smokers: Oral estrogens confer an increased risk of thromboembolic disease. (Grade B)
- After gonadectomy: Lower doses are recommended: 50-100mcg transdermal, 1-2mg sublingual estradiol, 1-2 sprays/day Evamist®. Titrate to effect, considering patient tolerance. (Grade C)
- Progesterone: The risks and benefits of progesterone are not well-characterized. Some providers have found it to have positive effects on the nipple areola and libido. Mood effects may be positive or negative. Different progesterone regimens include daily 5 to 10mg medroxyprogesterone orally, 100-200mg prometrium at bedtime of oral or compounded micronized progesterone, or Depo-Provera 150mg IM every 3 months, for 2-3 years. There is a risk of significant weight gain and depression in some individuals.
As per other studies using oral progesterone in post-menopausal women (e.g., the Women's Health Initiative [WHI] study), the use of medroxyprogesterone orally may increase the risk of coronary vascular disease whereas IM injections (i.e., Depo-Provera) may minimize this additional risk. (Grade B and C)
- Anti-androgens: Initial dose of spironolactone is 100mg daily in a single or divided dose, with titration up by 50mg weekly to a typical dose of 200mg daily (with occasional patients -- especially larger or younger -- requiring as much as 400mg daily. Dose may be divided bid or may be taken all at once in the A.M. (all at once in A.M. is advised against due to diuretic effects interrupting sleep). Check potassium. Progesterone may have some anti-androgenic activity, and may be an alternative if spironolactone is contraindicated.
If patients have significant hair loss issues, finasteride may be added as an adjunct (even initially). Generally 1 - 5mg daily. If patients pay out of pocket, they may buy the 5mg tabs and divide them in half or quarters.
Other meds sometimes prescribed for transwomen
- Eutectic mixture of local anaesthetic (EMLA) and analgesics for hair removal. If no allergy: ibuprofen 400-600mg +/- hydrocodone 5-10mg 1 hour before treatments.
- Viagra® (or related drugs) for patients with significant sexual dysfunction.
Hormone therapy for transmen consists of the androgen testosterone, which is available in several forms: intramuscular, transdermal patch or gel, or subcutaneous implant. (Grade B)
Testosterone therapy is not withheld for hyperlipidemia.
Adult transmen are initiated on depo-testosterone 50-200mg IM every 2 weeks; most adults can start at 200mg. Doses are titrated to effect. Usual dose is 200mg q 2 weeks, but dosage may be split, e.g., 100mg q week. If patients have side effects attributable to peak or trough levels, doses are changed to q 7-10 days depending on patient's preference (weighing the adverse effects against the increased frequency of injections.) Some patients do well on lower doses, and weekly injections, especially those with history of trauma (avoiding excessive peaks and troughs, which may set off emotional reactions). Rarely, doses as high as 250mg q 2 weeks are needed, but usually only if trough levels remain in the low normal range on 200mg q 2 weeks. Excessive testosterone can convert to estrogen and impeded desired effects. (Grade C)
Patients should be taught to self-inject. A family member or friend may be taught to perform the injection for the patient. Patients who develop polycythemia may respond well to transdermal gel preparations.
Allergy Alert: Testosterone cypionate is suspended in cottonseed oil. Testosterone enanthate is suspended in sesame oil; Sustanon® (available in Europe) is suspended in peanut oil. Some patients experience skin reactions to the adhesive in Androderm® (transdermal patch). Compounding pharmacies may be able to provide testosterone cypionate in sesame oil.
Use of transdermal preparations (e.g., Androderm® or Androgel® 1%/Testim®) may be recommended if slower progress is desired, or for ongoing maintenance after desired virilization has been accomplished with intramuscular injection.
Rarely, use a progestin to stop periods if patient only wants a low dose of testosterone, or is having difficulty stopping menses.
Note: Testosterone is not a contraceptive substance; transmen having unprotected sex with fertile males are at risk for pregnancy.
Other meds sometimes prescribed for transmen
- For male-pattern baldness (MPB): finasteride or minoxidil. Caution patients that finasteride will likely slow or decrease secondary hair growth, and may slow or decrease clitoromegaly.
- For patients with concerns about too heavy secondary hair growth (e.g., male relatives are excessively hirsute): finasteride, dutasteride.
- For patients with too significantly increased sexual interest: low dose SSRIs.
- For patients who desire greater clitoromegaly: topical testosterone on clitoris (must be subtracted from total dose and patients must be warned that this may hasten Male Pattern Baldness).
Children/youth (both transgender boys and transgender girls) can be evaluated for GnRH blockers or histrelin implant, but depending on resources, insurance and family desires, cross-sex hormones may be chosen in place of GnRH blockers or histrelin implant for youth 12-13 and up. Individualized treatment is required to meet the physiological and emotional needs of this population. (Grade A)
See section Youth: Special Considerations.