What is the recommended dosage and administration of Hormone Replacement Therapy (HRT) pellets, specifically estradiol and testosterone, in females?

Recommended Dosage and Administration of HRT Pellets in Females

For females requiring hormone replacement therapy, transdermal estradiol patches are the first-line recommendation at doses of 50-100 μg/day, with oral administration as a second choice at 1-2 mg daily, while testosterone therapy should be limited to 24 months with evaluation after 3-6 months. 1

Estradiol Administration

Transdermal Estradiol (First Choice)

• Recommended adult dose: 50-100 μg/day via patches that are changed twice weekly or weekly depending on the specific product 1
• Patches provide steady hormone delivery while avoiding first-pass liver metabolism 1
• Transdermal administration shows better profiles for bone mass accrual and cardiovascular risk compared to oral formulations 1, 2
• For women with intact uterus, progestin must be added to prevent endometrial hyperplasia 3

Oral Estradiol (Second Choice)

• Recommended adult dose: 1-2 mg daily of 17β-estradiol 1
• Consider oral administration when transdermal is contraindicated (e.g., skin disorders) or refused by patient 1
• Combined oral formulations containing 1-2 mg of 17β-estradiol with progestin are available in both sequential and continuous regimens 1

Intramuscular Estradiol

• For injectable estradiol, the usual dosage range is 1-5 mg every 3-4 weeks 3
• For female hypogonadism specifically, 1.5-2 mg injected monthly is recommended 3

Progestin Requirements

For Women with Intact Uterus

• Progestin must be added to estrogen therapy to reduce endometrial cancer risk 3
• Sequential regimens (for cyclic withdrawal bleeding):
  • 200 mg oral/vaginal micronized progesterone for 12-14 days every 28 days, or
  • 10 mg medroxyprogesterone acetate for 12-14 days monthly, or
  • 10 mg dydrogesterone for 12-14 days monthly 1
• Continuous regimens (to avoid withdrawal bleeding):
  • Minimum 1 mg oral norethisterone, or
  • 2.5 mg oral medroxyprogesterone acetate, or
  • 5 mg oral dydrogesterone daily 1
• Micronized progesterone is preferred due to lower cardiovascular and venous thromboembolism risk 1

Testosterone Therapy

• Testosterone therapy for females with diminished libido is supported by limited data 1
• If initiated, treatment effect should be evaluated after 3-6 months 1
• Therapy should be limited to 24 months due to unclear long-term health effects 1
• For testosterone pellets, the release rate is approximately 1.3 mg per 200 mg implant per day 4
• Avoid progestins with anti-androgenic effects in women with hypoandrogenism to prevent worsening sexual dysfunction 1

Administration Considerations

Duration of Therapy

• HRT should be continued until the average age of spontaneous menopause (45-55 years) 1
• After menopause age, continuation decisions should be based on individual risks, family history, and symptom severity 1
• Lower post-menopausal doses have more favorable risk-benefit profiles 1

Monitoring

• Evaluate treatment effect based on symptom relief and patient's feeling of wellbeing 1
• No routine monitoring tests are required but may be prompted by specific symptoms or concerns 1
• Annual clinical review is recommended, with particular attention to compliance 1

Special Considerations and Contraindications

• HRT is generally contraindicated in breast cancer survivors 1
• For women with endometriosis who required oophorectomy, combined estrogen/progestogen therapy can effectively treat vasomotor symptoms 1
• Migraine should not be considered a contraindication to HRT use 1
• Women who underwent total body irradiation or survived Hodgkin lymphoma have increased breast cancer risk and require strict follow-up 1
• For women with increased thromboembolic risk, transdermal estradiol is safer than oral administration 2

Practical Approach to HRT Selection

1. Assess need for contraception (if needed, consider 17β-estradiol-based combined oral contraceptives) 1
2. Determine if withdrawal bleeding is acceptable to the patient 1
3. Choose administration route (transdermal preferred, oral as second choice) 1
4. Select appropriate progestin if uterus is intact 1, 3
5. Adjust dose based on symptom control and tolerability 1