What is the best regimen to start a woman on hormone replacement therapy (HRT)?

Best Regimen for Starting Hormone Replacement Therapy (HRT) in Women

The best regimen to start a woman on HRT is transdermal 17β-estradiol (50-100 μg/day) combined with oral micronized progesterone (200 mg/day for 12-14 days per month) for women with an intact uterus. 1

Estrogen Component Selection

• Transdermal 17β-estradiol is preferred over oral formulations as it:

  • Mimics physiological serum estradiol concentrations 1
  • Provides better safety profile by avoiding hepatic first-pass effect 1
  • Minimizes impact on hemostatic factors, reducing thrombotic risk 1
  • Has more beneficial effects on lipid profiles, inflammation markers, and blood pressure 1, 2
  • Is more effective for bone mineral density preservation 1
  • Is particularly recommended for women with hypertension 1

• The recommended starting dose for transdermal estradiol is 50-100 μg/day, with adjustments based on symptom control 1, 3

• Oral 17β-estradiol (1-2 mg/day) should be considered as a second choice when transdermal administration is contraindicated or not tolerated 1

• 17β-estradiol is preferred over ethinylestradiol or conjugated equine estrogens for all routes of administration 1

Progestogen Component (for women with intact uterus)

• Micronized natural progesterone (200 mg/day for 12-14 days per month) is the first-choice progestogen due to: 1

  • More favorable cardiovascular risk profile compared to synthetic progestogens 1
  • Neutral or beneficial effects on blood pressure 1
  • Better safety profile regarding thrombotic risk 1

• Alternative progestogens if micronized progesterone is not tolerated: 1

  • Medroxyprogesterone acetate (MPA) 10 mg/day for 12-14 days per month
  • Dydrogesterone 10 mg/day for 12-14 days per month

• Women should be informed that while micronized progesterone has advantages, the strongest evidence for endometrial protection is for oral cyclical combined treatment 1

Administration Regimens

• For most women, a sequential regimen is recommended: 1

  • Continuous estrogen administration
  • Progestogen added for 12-14 days every 28 days
  • Results in regular withdrawal bleeding

• Continuous combined regimens (both estrogen and progestogen daily without interruption) can be considered when: 1, 4

  • The woman prefers to avoid withdrawal bleeding
  • At least 12 months have passed since the last menstrual period

Special Considerations

• Start with the lowest effective dose and increase as needed based on symptom control 3, 5, 4

• For women without a uterus, progestogen is not required 3

• For women with specific conditions:

  • Hypertension: Transdermal estradiol is strongly preferred 1
  • Migraine: HRT is not contraindicated, but dose/route adjustments may be needed if migraines worsen 1
  • Endometriosis history: Combined estrogen/progestogen therapy is recommended 1
  • History of VTE or coagulation disorders: Transdermal route is preferred 6
  • BRCA1/2 mutations without breast cancer: HRT is a treatment option 1
  • Breast cancer survivors: HRT is generally contraindicated 1

• Annual clinical review is recommended once therapy is established, with particular attention to compliance 1

• No routine monitoring tests are required but may be prompted by specific symptoms or concerns 1

• Patient preference for route and method of administration should be considered when prescribing, as should contraceptive needs 1

Common Pitfalls to Avoid

• Using ethinylestradiol or conjugated equine estrogens as first-line therapy instead of 17β-estradiol 1

• Starting with doses that are too high, which can lead to side effects like breast tenderness and irregular bleeding 5, 4

• Failing to provide progestogen protection for women with an intact uterus 1

• Not considering route-specific benefits (e.g., transdermal for reduced thrombotic risk) 1, 2

• Inadequate follow-up to assess symptom control and compliance 1