HRT Pellet Dosing: Clinical Approach
HRT pellets are not addressed in current evidence-based guidelines, which instead recommend transdermal patches (50-100 μg/24 hours) or oral estradiol (1-2 mg daily) as first-line estrogen delivery methods for hormone replacement therapy. 1, 2, 3
Why Pellets Are Not Guideline-Recommended
The available high-quality guidelines from Blood Reviews (2021) and Praxis Medical Insights (2025) provide detailed dosing protocols for patches, oral formulations, and gels, but make no mention of pellet therapy. 1, 2, 3 This absence is notable given these are comprehensive HRT guidelines covering multiple delivery methods.
Evidence-Based Alternatives to Pellets
Transdermal Patches (First-Line)
- Standard adult dose: 50 μg/24 hours, applied twice weekly (every 3-4 days) 2, 3
- Titrate to 100 μg/24 hours if feminization is inadequate and levels are subtherapeutic 2
- Maintenance dose range: 100-200 μg/day for post-pubertal patients 1
- Sequential combined patches available: 50 μg estradiol for 2 weeks, then 50 μg estradiol + 10 μg levonorgestrel for 2 weeks 1, 3
- Continuous combined option: 50 μg estradiol + 7 μg levonorgestrel daily without interruption 1, 3
Oral Estradiol (Second-Line)
- Adult dose: 1-2 mg daily of 17β-estradiol 1
- Combined formulations available with progestins (dydrogesterone, MPA) 1
- Reserved for patients who cannot tolerate or refuse transdermal administration 1
Vaginal Gel
- Dose range: 0.5-1 mg daily 1
- Alternative to patches when transdermal administration is contraindicated 1
Critical Dosing Principles
Dose should be adjusted according to each woman's tolerance and feeling of wellbeing, not fixed by pellet insertion intervals. 1 This is a fundamental limitation of pellet therapy—the inability to rapidly adjust dosing based on clinical response or adverse effects.
Required Progestin Supplementation
- For women with intact uterus, progestin MUST be added for endometrial protection 1, 3
- First choice: Micronized progesterone (MP) 200 mg daily for 12-14 days every 28 days 1, 3
- Alternatives: MPA 10 mg daily for 12-14 days per month, or dydrogesterone 10 mg for 12-14 days per month 1
- Continuous regimens require minimum: 1 mg norethisterone, 2.5 mg MPA, or 5 mg dydrogesterone daily 1, 3
- Avoid progestins with anti-androgenic effects in patients with low testosterone or sexual dysfunction 1, 3
Safety Considerations Favoring Adjustable Dosing
Trans women face 2-4 fold increased cardiovascular mortality and elevated VTE risk, making lower initial dosing with ability to titrate essential. 2 Pellets cannot provide this flexibility.
- VTE risk increases with age in trans women 2
- Never use ethinyl estradiol—significantly higher thrombotic risk than bioidentical 17β-estradiol 2
- Monitor for VTE signs (leg swelling, chest pain, dyspnea) particularly in first 1-2 years 2
- Screen cardiovascular risk factors: blood pressure, lipids, smoking status 2
Common Pitfalls to Avoid
- Do not use pellets when guideline-recommended formulations (patches, oral, gel) are available and appropriate 1, 2, 3
- Do not prescribe estrogen without progestin in women with intact uterus—endometrial cancer risk 1, 3
- Do not start with high doses (>50 μg daily equivalent)—no additional benefit, increased harm 3, 4
- Do not continue therapy without ability to rapidly adjust dose based on clinical response 1
Monitoring Parameters
- Assess secondary sexual characteristics and symptoms at each visit 1
- Ultrasonographic evaluation of uterine volume and morphology may guide dose escalation 1
- Demonstrate proper endometrial thickness before prescribing progestin 1
- Continue HRT until average age of spontaneous menopause (45-55 years), then reassess 1
The evidence strongly supports using transdermal patches or oral formulations with flexible dosing over pellets, which lack the ability to titrate based on clinical response and have no supporting data in major guidelines. 1, 2, 3