What is the best hormone replacement regimen for a woman with vulvar atrophy and an intact uterus?

Best Hormone Replacement Regimen for Women with Vulvar Atrophy and Intact Uterus

For women with vulvar atrophy and an intact uterus, the best hormone replacement regimen is a combination of transdermal 17β-estradiol (50-100 μg daily) with either oral or vaginal micronized progesterone (200 mg for 12-14 days per month in sequential regimens or continuous if bleeding is to be avoided). 1

Initial Treatment Approach

Step 1: Non-Hormonal Options

• Try vaginal moisturizers and lubricants first for mild symptoms 1
• Moisturizers should be applied 3-5 times per week to the vagina, vaginal opening, and external vulvar folds 1
• These provide temporary relief but do not address the underlying atrophy 2

Step 2: Low-Dose Vaginal Estrogen (for those who don't respond to non-hormonal options)

• Low-dose vaginal estrogen can be used for those who don't respond to moisturizers or have more severe symptoms at presentation 1
• Must be combined with progestogen in women with an intact uterus to prevent endometrial hyperplasia 3

Step 3: Systemic Hormone Replacement Therapy

Estrogen Component:

• First choice: Transdermal 17β-estradiol (50-100 μg daily) 1

  • Advantages:
    • Mimics physiological serum estradiol concentrations 1
    • Better safety profile than oral formulations 1
    • Avoids hepatic first-pass effect 1
    • Minimizes impact on hemostatic factors 1
    • More beneficial effects on lipids, inflammation markers, and blood pressure 1
    • More effective for bone mineral density 1

• Second choice: Oral 17β-estradiol (1-2 mg daily) 1

  • Consider when transdermal administration is contraindicated or refused 1

Progestogen Component (mandatory with intact uterus):

• First choice: Micronized progesterone (MP) (200 mg orally or vaginally) 1

  • Advantages:
    • Lower cardiovascular risk compared to synthetic progestogens 1
    • Neutral or beneficial effect on blood pressure 1
    • Better safety profile for thrombotic risk 1
    • Endorsed by European Society for Human Reproduction and Embryology 1

• Second choices: 1

  • Medroxyprogesterone acetate (MPA) (10 mg for 12-14 days per month in sequential regimens or 2.5 mg daily in continuous regimens)
  • Dydrogesterone (10 mg for 12-14 days per month in sequential regimens or 5 mg daily in continuous regimens)
  • Norethisterone (1 mg daily in continuous regimens)

Administration Regimens

Sequential Combined Regimen

• Estrogen administered continuously
• Progestogen administered cyclically for 12-14 days every 28 days 1
• Advantages: Allows earlier recognition of pregnancy if ovulation occurs 1
• Results in monthly withdrawal bleeding 1

Continuous Combined Regimen

• Both estrogen and progestogen administered daily without interruption 1
• Advantages: Prevents withdrawal bleeding 1
• Better option for women who prefer to avoid monthly bleeding 1

Special Considerations

Women with History of Breast Cancer

• Systemic hormone therapy is contraindicated in women with hormone-sensitive cancers 1
• For women with hormone-positive breast cancer who are symptomatic and not responding to conservative measures, low-dose vaginal estrogen can be considered after thorough discussion of risks and benefits 1
• Vaginal dehydroepiandrosterone may be offered to women with breast cancer on aromatase inhibitors who haven't responded to other treatments 1

Monitoring and Duration

• Women using HRT should have annual clinical reviews, with particular attention to compliance 1
• HRT should be continued until the average age of natural menopause (approximately 51 years) 1
• Beyond age 51, HRT should be intermittently evaluated for long-term use 1
• The lowest effective dose should be used for the shortest duration consistent with treatment goals 3

Common Pitfalls and Caveats

• Failure to add progestogen in women with intact uterus increases risk of endometrial hyperplasia and cancer 1, 3
• Using synthetic progestogens like MPA may negatively impact cardiovascular risk through effects on lipid profiles and carbohydrate metabolism 1
• Estrogen-only therapy is appropriate only for women who have had a hysterectomy 1
• Natural progesterone and dydrogesterone are associated with lower risk of breast cancer compared to other progestins 4
• Sequential regimens may lead to lower breast cancer risk elevation compared to continuous regimens 4