What are the differences between oral and topical hormone replacement therapy (HRT)?

Differences Between Oral and Topical Hormone Replacement Therapy (HRT)

Transdermal (topical) HRT is preferred over oral HRT due to its better safety profile, more physiological hormone delivery, and reduced risk of cardiovascular and thrombotic complications. 1

Route of Administration Comparison

Transdermal HRT (First Choice)

• Administered via patches releasing 50-100 μg of 17β-estradiol daily (changed twice weekly or weekly depending on brand) or via vaginal gel (0.5-1 mg daily) 1
• Mimics physiological serum estradiol concentrations better than oral formulations 1
• Avoids hepatic first-pass effect, minimizing impact on hemostatic factor synthesis 1
• Provides more beneficial effects on circulating lipids, markers of inflammation, and blood pressure 1
• More effective in achieving bone mineral density peak and reducing bone resorption markers compared to oral ethinylestradiol formulations 1
• Preferred in women with hypertension 1
• Recommended in patients with diabetes or hypertriglyceridemia due to different metabolism that bypasses hepatic first-pass effect 2

Oral HRT (Second Choice)

• Administered as 1-2 mg of oral 17β-estradiol daily or 0.625-1.25 mg of conjugated equine estrogens daily 1
• Associated with increased risk of venous thromboembolism compared to transdermal formulations 1
• Undergoes hepatic first-pass metabolism, leading to greater effects on clotting factors and liver proteins 1, 2
• Should be considered when transdermal administration is contraindicated (e.g., diffuse cutaneous disorders like chronic skin GvHD) or refused by the patient 1

Clinical Considerations

Safety Profile

• Transdermal estrogen does not increase venous thromboembolism (VTE) risk in healthy women, unlike oral HRT which increases VTE risk approximately 2-fold 1
• Oral HRT in patients with prothrombotic mutations increases VTE risk 25-fold compared to mutation-free women not receiving HRT 1
• Natural micronized progesterone (when progestin is needed) has a more favorable cardiovascular risk profile than synthetic progestogens 1

Efficacy for Specific Symptoms

• Both routes effectively treat vasomotor symptoms (hot flashes, night sweats) 3, 4
• Both routes prevent urogenital atrophy, though local vaginal preparations may be preferred for isolated vaginal symptoms 3, 5
• Both routes are effective for bone protection, with maximal bone-sparing doses being 2 mg oral estradiol, 50 μg transdermal estradiol, or 0.625 mg conjugated equine estrogens 2

Special Populations

• Transdermal route is preferred in women with:
  • Hypertension 1
  • Diabetes or hypertriglyceridemia 2
  • Risk factors for thrombosis 1
  • Migraine headaches 1, 4
  • Nausea with oral formulations 4

Practical Considerations

• Transdermal patches may cause skin irritation in some patients 1
• Oral formulations may be more convenient for some patients but can cause more nausea and gastrointestinal side effects 4
• Combined estrogen-progestin patches (for women with intact uterus) may improve treatment compliance 1
• Hormone doses should be adjusted according to each woman's tolerance and feeling of wellbeing 1

Contraindications

• HRT (both oral and topical) is strongly discouraged in patients with metastatic breast cancer 1
• HRT is contraindicated in women with antiphospholipid syndrome or positive antiphospholipid antibodies 1
• Topical vaginal estrogens should be used with caution in breast cancer patients on aromatase inhibitors 1