Risks and Complications of Gender-Affirming Hormone Therapy and Surgery
Gender-affirming hormone therapy and surgery carry specific, well-documented risks that require careful monitoring, with feminizing hormone therapy posing the most significant cardiovascular and thrombotic risks, while masculinizing therapy primarily affects hematologic and metabolic parameters.
Feminizing Hormone Therapy (Estrogen-Based) Risks
Cardiovascular and Thrombotic Complications
The most serious risks associated with feminizing hormone therapy involve the cardiovascular system. Trans women on estrogen therapy face consistently elevated risk of venous thromboembolism (VTE) compared to both cisgender men and women 1. This increased VTE risk persists despite modifications in estradiol dosing and preparations over time, and remains elevated compared to cisgender women using oral contraceptives or hormone replacement therapy 1.
Trans women also demonstrate elevated risk of ischemic stroke and myocardial infarction relative to cisgender women 1. Population-based cohort studies consistently show this elevated cardiovascular risk pattern 1.
Other Adverse Effects
Additional risks of feminizing hormone therapy include 1:
- Weight gain
- Compromised bone structure
- Infertility (often irreversible)
- Cardiovascular disease risk elevation relative to both cisgender women and men
Anti-Androgen Specific Risks
The anti-androgens used in feminizing therapy carry distinct complications 1:
Spironolactone:
- Acute kidney injury
- Hyperkalaemia
- Hypovolaemia
- Deranged liver function
- Thrombocytopaenia
Bicalutamide:
- Displaces warfarin from binding sites, increasing anticoagulant activity
- Prolonged QT interval
- Risk of interstitial lung disease with long-term use
- Increases serum midazolam concentration significantly
Cyproterone acetate:
- Anaemia
- Can cause fulminant hepatic failure
- Adrenal suppression
Masculinizing Hormone Therapy (Testosterone) Risks
Hematologic and Cardiovascular Effects
Testosterone therapy increases hemoglobin to male reference range within 3 months, leading to polycythaemia and erythrocytosis with theoretical increased blood viscosity 1. This creates potential thrombotic risk, though evidence on actual thrombosis risk in trans men remains conflicting 1.
Cardiovascular Risk Profile
Data for trans men show mixed results: some studies suggest no elevated cardiovascular risk 1, while others indicate elevated risk of myocardial infarction 1.
Additional Adverse Effects
Testosterone therapy carries these documented risks 1:
- Increased risk of obstructive sleep apnoea
- Increased risk of hypertension
- Increased risk of high body weight
- Reduced HDL cholesterol
- Androgenic alopecia
- Acne
- Gynaecological effects including pelvic pain and genital dryness
Perioperative Considerations
Critical Decision Point: Hormone Continuation vs. Discontinuation
The physical and mental health benefits of hormone therapy may outweigh the risk of thrombosis, and discontinuation carries significant psychological consequences including exacerbation of dysphoria, depression, and anxiety 1.
Testosterone therapy should generally be continued perioperatively 1. For estrogen therapy, there is minimal data to support or refute routine discontinuation before surgery, even for vaginoplasty 1. The decision requires individualized discussion of benefits and risks combined with thromboprophylaxis strategies 1.
Perioperative Medication Interactions
Estrogen-specific concerns 1:
- Bound by sugammadex, reducing serum concentration
- Topical estradiol patches require avoiding localized heat from warming devices
- Long-term reduction in serum albumin increases free drug of highly protein-bound medications (e.g., bupivacaine)
- Possible increased risk of postoperative nausea and vomiting
- Potentially reduced plasma cholinesterases, resulting in prolonged block from suxamethonium
Testosterone-specific concerns 1:
- Erythrocytosis and theoretical increased blood viscosity
Surgical Complications
Gender-affirming surgeries carry procedure-specific complications that may require emergency management 2. Both transfeminine and transmasculine genital procedures have unique complication profiles requiring specialized knowledge for diagnosis and management.
Critical Gaps in Evidence
Evidence on perioperative cardiovascular risk factors when taking hormonal therapies remains inconclusive 1. Most published studies are retrospective or cross-sectional, introducing potential confounding bias 3. There is a paucity of well-designed prospective studies examining how hormone therapy affects various health outcomes 3.
Key Clinical Pitfalls to Avoid
Do not routinely discontinue hormone therapy perioperatively without careful risk-benefit discussion, as this can cause severe psychological harm 1
Do not underestimate VTE risk in trans women on estrogen—this risk is consistently elevated and requires appropriate thromboprophylaxis 1
Monitor for polycythaemia in trans men on testosterone, as hemoglobin rises to male reference range within 3 months 1
Be aware of anti-androgen specific risks, particularly cyproterone acetate's potential for fulminant hepatic failure 1
Recognize that some effects are irreversible (voice changes, hair growth patterns) even if hormone therapy is ceased 1