Hormone Therapy for Male to Female Gender Affirming Care

Introduction to Feminizing Hormone Therapy

The standard hormone regimen for starting male to female gender affirming care consists of estradiol as the cornerstone medication, typically combined with an anti-androgen such as spironolactone to suppress testosterone production 1, 2, 3

Estradiol is the primary medication for feminizing hormone therapy and is available in multiple formulations, including oral tablets 3, transdermal patches 1, and injectable formulations (estradiol valerate or cypionate) 1, 2
Anti-androgens are typically added to enable lower doses of estrogen while achieving adequate testosterone suppression, with common options including spironolactone 1, cyproterone acetate 3, GnRH agonists (puberty blockers) 1, bicalutamide 3, and finasteride 1, 2

Target hormone levels should be: testosterone <50 ng/dL 2, and estradiol in the cisgender female reference range 1
Monitoring schedule includes baseline assessment before starting therapy, checking hormone levels at 3 months after initiating therapy 3, monitoring every 3-6 months during the first year 2, and annual monitoring once stable 2, 3

Feminizing hormone therapy induces several physical changes, including breast development 1, decreased muscle mass (3.0-5.5% reduction in lean body mass) 1, softening of skin 3, decreased body and facial hair growth 1, decreased libido 2, reduced erectile function 2, and decreased hemoglobin levels to female reference range 1, 2

Feminizing hormone therapy carries several risks that require monitoring, including increased risk of venous thromboembolism 1, increased risk of ischemic stroke and myocardial infarction 1, weight gain 3, and potential compromised bone structure 1, 2, 3

Fertility preservation counseling must be provided before starting hormone therapy, as treatments may affect fertility 2, 3
Some transgender women may use chest binding or genital tucking to minimize gender dysphoria, which can cause physical complications, including restrictive lung defects 4 and risks associated with genital tucking 5
For transgender individuals with pre-existing cardiovascular conditions, more frequent monitoring may be necessary 3
Laboratory values should generally be interpreted based on affirmed gender for individuals on hormone therapy for more than 1 year 2, 3

Complete baseline assessment (labs, medical history, mental health evaluation) before initiating therapy 2, 3
Provide fertility preservation counseling 2, 3
Start with estradiol (typically 2-6 mg daily oral, 0.1-0.4 mg/day transdermal, or 5-20 mg IM every 1-2 weeks) 1 and anti-androgen (typically spironolactone 100-300 mg daily) 1
Check hormone levels at 3 months and adjust dosing as needed 2, 3
Monitor for side effects and continue regular follow-up 1, 2, 3

Failing to provide comprehensive baseline assessment before initiating therapy 2, 3
Not monitoring hormone levels regularly, especially during the first year 2, 3
Overlooking cardiovascular risk factors that may be exacerbated by hormone therapy 1, 3
Neglecting mental health support during transition 3
Using ethinyl estradiol, which carries higher thrombotic risk than other estrogen formulations 1

Feminizing hormone therapy suppresses testosterone to female‑range levels (<50 ng/dL) and adds estradiol, which directly affects genital tissue, leading to decreased testicular size and reduced erectile function【6】.
Anti‑androgen therapy causes testicular atrophy as a documented effect【7】.
The combined hormonal effects result in decreased libido and erectile capacity, contributing to structural changes in penile tissue【7】【6】.

Clinical observations indicate that penile shrinkage occurs in transgender women receiving feminizing hormone therapy and is likely permanent while therapy continues long‑term【7】.

Hormone‑induced structural changes in genital tissue (e.g., penile shortening) are considered irreversible even after cessation of therapy, similar to irreversible changes such as voice deepening in masculinizing regimens【7】.
Assuming all hormonal effects are reversible is inaccurate; structural genital alterations may persist despite hormone discontinuation【7】.

Patients should be informed before initiating therapy that genital changes—including potential penile shrinkage—may occur, especially when future gender‑affirming surgery (vaginoplasty) relies on penile tissue【7】【6】.
Discussing the possibility of preserving erectile function or genital size is important for individuals who prioritize these outcomes【6】.
Failure to address surgical implications can affect tissue availability and surgical outcomes in later vaginoplasty procedures【7】.

Reduced erectile function typically begins within the first few months of feminizing hormone therapy【7】【6】.
Testicular atrophy is an expected and routinely documented effect of therapy【7】.
Anatomical and functional changes generally progress over a period of 12–36 months as hormone levels stabilize within the female range【6】.