Optimal Bio-identical Hormone Replacement Therapy Protocol
The optimal bio-identical hormone replacement therapy protocol consists of transdermal 17β-estradiol (50-100 μg/day) combined with oral micronized progesterone (100-200 mg/day for 12-14 days per month in women with intact uterus). 1, 2
Estrogen Component
Transdermal 17β-estradiol is the preferred estrogen formulation as it:
- Mimics physiological serum estradiol concentrations 1
- Avoids hepatic first-pass effect 1, 3
- Minimizes impact on hemostatic factors 1, 3
- Provides more beneficial effects on lipid profiles, inflammation markers, and blood pressure 1, 2
- Reduces risk of venous thromboembolism compared to oral formulations 3, 4
Recommended dosage: 50-100 μg of transdermal 17β-estradiol daily 1, 5
17β-estradiol is preferred over ethinylestradiol or conjugated equine estrogens due to its more favorable safety profile 1, 4
Progestogen Component (for women with intact uterus)
Micronized natural progesterone is the recommended progestogen because it:
Recommended dosage: 100-200 mg/day of oral micronized progesterone during 12-14 days of the month 1, 5
Alternative progestogens include dydrogesterone, which has less negative effects on lipid metabolism and fewer androgenic effects 1
Administration Regimen
Sequential/cyclic regimen is generally recommended as it:
Continuous combined regimen can be considered when the woman prefers to avoid withdrawal bleeding 2
Duration of Therapy
HRT should be continued at least until the average age of natural menopause (50-51 years) 1
Regular annual clinical reviews are recommended to assess compliance 1, 2
Discontinuing HRT prematurely can increase risks of osteoporosis, cardiovascular disease, and urogenital atrophy 1
Monitoring
Annual clinical review focusing on compliance is recommended 1, 2
No routine monitoring tests are required but may be prompted by specific symptoms 1, 2
Cardiovascular risk assessment (at least blood pressure, weight, and smoking status) should be performed annually 1
Important Considerations and Pitfalls to Avoid
Using ethinylestradiol-containing contraceptives instead of 17β-estradiol for HRT is not recommended due to higher thrombotic risk 1, 3
Failing to add progestogen in women with an intact uterus increases risk of endometrial hyperplasia and cancer 1, 5
Using inadequate doses that don't achieve physiological estrogen levels may not provide adequate protection against long-term health consequences 1
Custom-compounded bioidentical hormones lack well-controlled studies examining route of administration, pharmacokinetics, and safety compared to FDA-approved bioidentical hormone products 6, 7
Saliva testing to determine hormone dosing is not supported by scientific evidence 6, 7
Special Considerations
For women with hypertension, transdermal estradiol is strongly preferred due to its more favorable cardiovascular risk profile 1, 2
For women with a history of migraine, HRT is not contraindicated, but dose/route adjustments may be needed if migraines worsen 2
For women with a history of endometriosis who required oophorectomy, combined estrogen/progestogen therapy can be effective for vasomotor symptoms and may reduce risk of disease reactivation 8, 2
For women with BRCA1/2 mutations without personal history of breast cancer, HRT is a treatment option after prophylactic bilateral salpingo-oophorectomy 8, 2
HRT is generally contraindicated in breast cancer survivors 8, 2