Adjusting Doses
Principles of Dose Adjustment
- Change one thing at a time — never adjust estrogen and anti-androgen simultaneously
- Wait 4–8 weeks between changes — it takes time for levels to stabilise
- Always test before adjusting — base decisions on blood tests, not guesses
- Change by small increments — 1 mg of E2 or 12.5–25 mg of spiro at a time
- Track symptoms — levels aren't the only thing that matters; how you feel matters too
When to Adjust Estrogen
| Situation | Action |
|---|---|
| E2 < 100 pg/mL (trough) and T > 50 ng/dL | Increase E2 dose |
| E2 100–200 pg/mL, T < 50 ng/dL, no issues | Maintain current dose |
| E2 > 300 pg/mL (trough) | Consider reducing dose — no added benefit, may increase risks |
| E2 < 100 pg/mL but T < 50 ng/dL | Potentially increase E2 for feminisation; T is already suppressed |
| E2 > 200 pg/mL but T > 50 ng/dL | Increase AA or switch AA before increasing E2 further |
| SHBG > 150 nmol/L | E2 dose may be too high; reducing E2 may improve free T suppression |
When to Adjust Anti-Androgen
| Situation | Action |
|---|---|
| T > 50 ng/dL (on current AA) | Increase AA dose (if below max) or switch AA |
| T < 50 ng/dL with side effects | Consider reducing AA or switching to lower-side-effect AA |
| T < 30 ng/dL (very suppressed) | Can try reducing AA dose or transitioning to monotherapy |
| Side effects intolerable | Switch to a different AA class |
Sample Adjustment Scenarios
Scenario 1: E2 Too Low, T Not Suppressed
Current: Estradiol 2 mg oral/day, Spiro 50 mg/day Levels: E2 = 45 pg/mL, T = 150 ng/dL
Plan:
- Increase estradiol to 4 mg/day (2 mg twice daily) or switch to sublingual
- Re-test in 6–8 weeks
- If still insufficient, increase spiro to 100 mg/day
Scenario 2: E2 OK, T Still High
Current: Estradiol 4 mg/day, Spiro 100 mg/day Levels: E2 = 120 pg/mL, T = 80 ng/dL
Plan:
- Increase spiro to 150 mg/day, or switch to CPA 12.5 mg/day or bicalutamide 50 mg/day
- Re-test in 6–8 weeks
Scenario 3: E2 High, T Suppressed on Low AA
Current: EV 6 mg every 5 days Levels: E2 = 350 pg/mL (trough), T = 15 ng/dL
Plan:
- Consider reducing EV to 4 mg every 5 days
- T is already well-suppressed — no AA needed if this is monotherapy
- Monitor SHBG — if >150 nmol/L, definitely reduce E2 dose
- Recent evidence shows doses above 4-5 mg weekly often produce supraphysiologic levels without added T suppression benefit
Scenario 4: Everything in Range, But Poor Results
Current: E2 = 150 pg/mL, T = 20 ng/dL, but minimal feminisation after 12+ months
Plan:
- Check SHBG — if very high, E2 may need to be lowered
- Check DHT (dihydrotestosterone) — some people convert T to DHT even with low T
- Consider adding progesterone (if not already)
- Consider switching E2 route (e.g., oral to injectable)
- Consider that genetics and time play a bigger role than levels
Common Pitfalls
| Mistake | Why It's Wrong |
|---|---|
| Adjusting every 2 weeks | Levels need 4–8 weeks to stabilise |
| Increasing E2 when T is the problem | T suppression needs AA adjustment, not more E2 (usually) |
| Increasing both E2 and AA at once | You won't know which change caused the result |
| Chasing "optimal" levels obsessively | Being in range is good enough; more is not better |
| Not testing at trough | Results are meaningless without consistent timing |
Advanced: The SHBG Problem
SHBG (sex hormone-binding globulin) binds to free sex hormones, making them inactive. High SHBG can reduce free estradiol and free testosterone even when total levels look good.
| SHBG Level | Interpretation |
|---|---|
| 40–120 nmol/L | Normal range for trans women on HRT |
| 120–150 nmol/L | Moderate elevation — monitor |
| > 150 nmol/L | Significantly elevated — may reduce free hormone activity |
High SHBG is often caused by high oral estrogen doses. Switching to transdermal or injectable E2 can lower SHBG and free up more active hormone.
References
UCSF Transgender Care. Feminising hormone therapy — dose adjustments. https://transcare.ucsf.edu/guidelines
Hembree WC, et al. (2017). Endocrine Treatment of Gender-Dysphoric/Gender-Incongruent Persons: An Endocrine Society Clinical Practice Guideline. JCEM, 102(11):3869–3903. https://academic.oup.com/jcem/article/102/11/3869/4157558
Coleman E, et al. (2022). Standards of Care for the Health of Transgender and Gender Diverse People, Version 8. International Journal of Transgender Health, 23(S1). https://www.tandfonline.com/doi/full/10.1080/26895269.2022.2100644