Introduction
Transgender medicine is a developing field of medicine that spans multiple subspecialties. Transgender individuals are defined as those whose gender identity differs from the assigned sex recorded for them at birth based on external sexual characteristics. Gender identity includes an innate biologic component in humans, rather than a reversible trait developed from societal constructs.
This chapter will provide an overview of the different modalities of medical therapy available for transgender individuals. Medicines, mostly in the form of sex hormones, are able to effectively modulate the various endocrine pathways of the human body responsible for sex characteristics considered traditionally male and female. With appropriate supervision, it is now feasible for both transgender men and women who are interested in modifying their physical characteristics to have their body appearance better align with their gender identity.
The Biologic Nature of Gender Identity
The hypothesis that gender identity is of a biologic origin is supported by multiple studies. Research that validates this includes observational studies of genetically male individuals born with congenital abnormalities who were assigned and raised either as males or females, with a proportion undergoing surgical feminization. Individuals who were raised as males were found to have more comfort with their gender identities than those raised as females, findings that went against the long-held belief that gender identity was established through societal or parental influences.
Neuroanatomically, certain regions of the brain in transgender individuals appear more in-line with their gender identity. In a post-mortem analysis of six transgender women (male to female, MTF) and one transgender man (female to male, FTM), the size of the bed nucleus of the stria terminalis of the hypothalamus was similar to the expected size of typical females and males, respectively. This was the case, independent of exposure to sex hormone treatment or sexual orientation. A neuroimaging study with magnetic resonance imaging (MRI) scans of living transgender individuals showed transgender women prior to beginning hormone therapy with larger, “feminized” regional gray matter within the right putamen, whereas therapy-naïve transgender males had “masculinized” gray matter of the right putamen. In another study, positron emission tomography (PET) scans of individuals’ hypothalamus during exposure to 4,16-androstadiene3-one, a compound that reportedly provokes hypothalamus responses in a sexual dimorphic manner, showed that treatment-naïve transgender females had hypothalamus activity responses similar to nontransgender female controls.
Typical Hormone Regimens for Transgender Men
Testosterone replacement is the mainstay therapy for transgender men desiring a more masculine appearance. The treatment regimen very much resembles therapies for males with hypogonadism, with the goal of therapy to achieve testosterone levels within the normal male physiological range (300 to 1000 ng/dL). Patients typically will notice signs of male sexual maturation (increased facial and body hair, muscle mass, acne, and libido), as well as amenorrhea within the first several months after initiating testosterone therapy. Other changes, such as male pattern hair loss, voice deepening, redistribution of fat away from the waist and hips, and clitoromegaly, are also usually seen within the first year of therapy.
Hormone regimens for transgender men are listed in Table 5.1 . Testosterone can be administered via several routes: through daily transdermal patches (2.5 to 7.5 mg/day) and gels (2.5 to 10 g/day); weekly via subcutaneous or intramuscular injections of testosterone enanthate or testosterone cypionate (50 to 200 mg/week or 100 to 200 mg/2 weeks); quarterly via testosterone undecanoate (1000 mg/12 weeks); and orally with oral testosterone undecanoate (160 to 240 mg/day). a
a Oral formulations currently not available in the United States.
Regimens may be initiated at half the estimated effective dose and then titrated quickly to achieve physiological testosterone levels. Although transgender men often use lower doses than required for other men in general, due to being smaller, it is also safe to start regimens at the full effective dose.| Transdermal |
| Patch 2.5–7.5 mg/day |
| Gel 1% 2.5–10 g/day |
| Subcutaneous/intramuscular |
| Testosterone enanthate, cypionate |
| 50–200 mg/week |
| 100–200 mg/2 weeks |
| Testosterone undecanoate |
| 1000 mg/12 weeks |
| Oral |
| Testosterone undecanoate |
| 160–240 mg/day |
Typical Hormone Regimen for Transgender Women
Hormone regimens for transgender women are listed in Table 5.2 . Due to their ease of administration and wide availability, oral formulations of conjugated estrogens (2.5 to 7.5 mg) and 17-beta estradiol (2 to 8 mg) are the typical first line estrogens used. Estrogens may also be administered topically or intramuscularly. However, the regimen for transgender women desiring to achieve female sex characteristics is more complicated, as supplementing exogenous estrogen alone is not usually sufficient in decreasing endogenous testosterone levels to female levels (30 to 100 ng/dL) to achieve feminization.
| Estrogen therapy |
| Transdermal |
| 17-beta estradiol 0.1–0.4 mg 1 or 2 times/week |
| Oral |
| Conjugated estrogens 2.5–7.5 mg/day |
| 17-beta estradiol 2–8 mg/day |
| Intramuscular |
| Estradiol valerate 5–30 mg/2 weeks |
| Antiandrogen therapy |
| Spironolactone (PO) 100–400 mg/day |
| Leuprolide (IM) 3.75–7.5 mg/month |
| Histrelin acetate (SC implant) 50 mg/12 months |
| Goserelin acetate (SC implant) 3.6 mg/month |
| Cyproterone acetate (PO) 50–100 mg/day |
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