What progestin therapy is recommended for women with an intact uterus undergoing estrogen therapy for vaginal atrophy and dyspareunia?

Progestin Therapy for Women with Intact Uterus on Estrogen Therapy

For women with an intact uterus undergoing estrogen therapy for vaginal atrophy and dyspareunia, oral micronized progesterone 200 mg daily for 12 days per 28-day cycle is the recommended progestin therapy to prevent endometrial hyperplasia.

Rationale for Progestin Use

When prescribing estrogen therapy for women with an intact uterus, progestin supplementation is essential to prevent endometrial hyperplasia and cancer:

• Unopposed estrogen significantly increases endometrial hyperplasia risk (64% with unopposed estrogen vs. 6% with combined therapy) 1
• Women with an intact uterus must receive progestogen with estrogen therapy to reduce endometrial hyperplasia risk 2, 3
• The American College of Obstetricians and Gynecologists recommends adding progestogen to prevent endometrial hyperplasia and cancer 2

Recommended Progestin Options

First-line recommendation:

• Micronized progesterone 200 mg orally daily for 12 days per 28-day cycle 1
  • FDA-approved regimen specifically for endometrial protection
  • Less negative impact on lipid metabolism compared to synthetic progestins 2

Alternative options:

• Medroxyprogesterone acetate (MPA):
  • 2.5-10 mg daily in continuous regimen
  • 5-10 mg for 12-14 days per month in sequential regimen 2
• Dydrogesterone (has less negative effect on lipid metabolism) 2

Administration Regimens

Two main approaches are available:

1. Sequential regimen (preferred for initial therapy):

   • Estrogen daily with progestin added for 12-14 days per 28-day cycle
   • Results in regular withdrawal bleeding
   • Example: Conjugated estrogens 0.625 mg daily + micronized progesterone 200 mg for 12 days per cycle 1

2. Continuous combined regimen:

   • Both estrogen and progestin taken daily without interruption
   • Aims to prevent withdrawal bleeding
   • Lower risk of endometrial hyperplasia than sequential therapy 4
   • Example: Low-dose estrogen with minimum 1 mg norethisterone acetate or 1.5 mg medroxyprogesterone acetate daily 3

Important Considerations

• Vaginal vs. systemic estrogen: For women using low-dose vaginal estrogen primarily for vaginal atrophy, progestins may not be required if estrogen cream is used only 1-2 times weekly for maintenance after symptoms resolve 5

• Monitoring: Regular follow-up every 3-6 months initially, with annual gynecological assessment 2

• Contraindications to hormone therapy include:

  • History of breast cancer
  • Active or recent venous thromboembolism
  • Active liver disease
  • Uncontrolled hypertension
  • Current smoking, especially if >35 years 2

Alternative Approaches for Women Who Cannot Use Hormonal Therapy

For women with contraindications to hormone therapy:

• Vaginal moisturizers for ongoing relief
• Vaginal lubricants for intercourse-related dryness 5
• Lidocaine for persistent introital pain and dyspareunia 6
• Cognitive behavioral therapy and pelvic floor exercises 6

Pitfalls to Avoid

• Never use unopposed estrogen in women with an intact uterus due to significantly increased risk of endometrial hyperplasia and cancer 3, 4
• Avoid micronized progesterone in continuous combined regimens, as it may not provide adequate endometrial protection compared to synthetic progestins 4
• Don't assume low-dose vaginal estrogen is always safe without progestin - deep vaginal application or use beyond 6 months may require progestin supplementation 7
• Be aware that some progestins like depot medroxyprogesterone acetate can actually cause vaginal atrophy in some women due to hypo-estrogenic effects 8