Long-Term Risks
This page covers the potential long-term health risks of feminising HRT. These risks are generally low with appropriate monitoring but should be understood by anyone considering or currently on HRT.
Venous Thromboembolism (VTE)
VTE — blood clots in veins — is the most well-known risk of estrogen therapy.
| Risk Factor | Impact |
|---|---|
| Route of administration | Oral: highest risk; Transdermal: lowest risk (no first-pass) |
| Age | Risk increases with age, especially >40 |
| Smoking | Significantly amplifies VTE risk |
| Obesity (BMI > 30) | Increases baseline VTE risk |
| Personal/family history of clots | Major risk factor |
| Inherited clotting disorders | Factor V Leiden, prothrombin mutation, etc. |
| Duration | Risk highest in first year, persists long-term |
VTE Risk by Route
| Route | Relative Risk | Notes |
|---|---|---|
| No HRT | 1.0× (baseline) | |
| Oral estradiol | 2–4× baseline | Dose-dependent |
| Transdermal estradiol | ~1.0× (same as baseline) | Preferred for risk reduction |
| Injectable estradiol | ~1.0–1.5× | Limited data; likely similar to transdermal |
Mitigating VTE risk
- Use transdermal or injectable estradiol, especially if >40 or with risk factors
- Do not smoke
- Maintain healthy weight
- Know your family history of clotting disorders
Cardiovascular Effects
| Effect | Details |
|---|---|
| Blood pressure | Estrogen may raise systolic BP in some; monitor regularly |
| Triglycerides | Oral estrogen raises triglycerides; transdermal has minimal effect |
| HDL/LDL | Estrogen generally improves lipid profile (raises HDL, lowers LDL) |
| Heart attack risk | Studies show low to no increased risk in trans women under 50 |
| Stroke risk | Small increased risk, primarily linked to VTE (clots travelling to brain) |
Cardiovascular Risk Reduction
- Use transdermal estradiol if you have cardiovascular risk factors
- Monitor blood pressure at least quarterly
- Get annual lipid panel
- Exercise regularly — 150 min/week moderate activity
- Maintain healthy diet
Breast Cancer
| Population | Risk |
|---|---|
| Cisgender men | Baseline (lowest) |
| Trans women on HRT | ~47× higher than cis men |
| Cisgender women | ~3× higher than trans women on HRT |
The 2019 Dutch cohort study (n = 2,260) found the absolute risk remains low — about 4 cases per 1,000 trans women over 10 years. The increased risk appears after 5+ years of estrogen exposure.
Breast cancer screening
Guidelines for breast cancer screening in trans women vary — WPATH SOC8 and various national bodies do not have fully harmonised recommendations. Generally:
- Routine self-exams
- Clinical breast exams by a provider
- A common guideline is mammography if age > 50 and on HRT for > 5 years
- Some guidelines recommend starting mammography at 50 regardless of HRT duration
- Discuss with your provider which screening schedule is right for you
Prolactin Elevation
| Cause | Notes |
|---|---|
| CPA | CPA significantly raises prolactin in many trans women |
| High-dose estrogen | Less common; can stimulate prolactin |
| Prolactinoma | A benign pituitary tumour; very rare |
Monitoring
- Baseline prolactin before starting CPA
- Repeat at 1 year, then every 1–2 years
- If prolactin is elevated, consider switching anti-androgen
Symptoms of high prolactin: galactorrhea (lactation), headaches, vision changes, low libido.
Gallbladder Disease
Estrogen increases cholesterol saturation in bile, promoting gallstone formation. A large study found significantly increased risk of gallbladder disease in trans women on GAHT.
Liver Effects
| Medication | Risk |
|---|---|
| Oral estrogen | Can elevate liver enzymes (ALT/AST); usually mild |
| CPA | Can elevate liver enzymes; usually mild |
| Bicalutamide | Rare hepatotoxicity risk; monitor LFTs |
| Spironolactone | Low liver risk |
Type 2 Diabetes
Some studies suggest estrogen therapy may improve insulin sensitivity, potentially reducing diabetes risk. However, weight gain from CPA or progesterone could offset this benefit.
Bone Health
Estrogen is protective of bone health. Trans women on adequate estrogen have normal to above-normal bone density. The risk only arises if both estrogen and testosterone are low simultaneously.
Mortality
The 2019 Dutch study found no increase in all-cause mortality in trans women on HRT compared to the general population. Overall, the benefits of HRT for quality of life and mental health far outweigh the small medical risks for most people.
References
de Blok CJM, et al. (2019). Breast cancer risk in transgender people receiving hormone treatment: nationwide cohort study in the Netherlands. BMJ. https://www.bmj.com/content/365/bmj.l1652
Nota NM, et al. (2019). Occurrence of acute cardiovascular events in transgender individuals receiving hormone therapy. Circulation. https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.118.038584
Connelly PJ, et al. (2021). Managing the risk of venous thromboembolism in transgender adults undergoing hormone therapy. PMC. https://pmc.ncbi.nlm.nih.gov/articles/PMC6628137/
Collin L, et al. (2024). Gallbladder disease in transgender individuals. International Journal of Transgender Health.
Irwig MS. (2020). Cardiovascular health in transgender people. JCEM. https://academic.oup.com/jcem/article/105/3/e894/5658514