Can progesterone be taken every day without a break?

Progesterone Administration Schedule for Women with Intact Uterus

For women with an intact uterus, progesterone should NOT be taken continuously every day without a break, as this can increase the risk of endometrial hyperplasia and potentially endometrial cancer. 1, 2, 3

Appropriate Progesterone Administration Patterns

For Postmenopausal Hormone Therapy

• Sequential regimen (preferred for endometrial protection):

  • Micronized progesterone 200 mg/day for 12-14 days per month 4
  • This regimen provides effective endometrial protection for up to 5 years
  • Results in regular, predictable withdrawal bleeding

• Continuous combined regimen:

  • While continuous combined estrogen-progestogen therapy generally provides better endometrial protection than sequential therapy 3
  • Recent evidence suggests micronized progesterone specifically may not be as effective when used continuously 2
  • The 2016 systematic review found that micronized progesterone notably increased endometrial cancer risk even when administered continuously 2

Alternative Administration Routes

• Vaginal micronized progesterone:

  • May provide endometrial protection if applied sequentially for at least 10 days/month
  • Recommended dosage: 4% (45 mg/day) or 100 mg every other day
  • Safe for up to 3-5 years (though this is considered off-label use) 4

• Transdermal micronized progesterone:

  • Does NOT provide adequate endometrial protection 4

Clinical Considerations and Risks

Endometrial Protection Requirements

• Unopposed estrogen significantly increases the risk of endometrial hyperplasia and carcinoma 3
• This risk increases with duration of treatment, with odds ratios ranging from 5.4 at 6 months to 15.0 at 36 months 3
• In the PEPI trial, 62% of women taking moderate-dose unopposed estrogen developed hyperplasia by 36 months 3

Comparison of Progesterone Types

• Micronized progesterone may have advantages over synthetic progestogens:
  • Does not increase cell proliferation in breast tissue compared to synthetic progestogens like medroxyprogesterone acetate 5
  • May be the optimal choice for women requiring combined hormone therapy 5
  • Has fewer metabolic and vascular side effects than synthetic progestins 6

Common Pitfalls to Avoid

1. Continuous administration without breaks: This pattern increases endometrial cancer risk 2
2. Long-cycle sequential therapy: Administering progesterone every three months rather than monthly increases hyperplasia risk 3
3. Inadequate duration: Progesterone should be given for at least 10-14 days per month for endometrial protection 6
4. Relying on transdermal progesterone: This route does not provide adequate endometrial protection 4

Bleeding Patterns and Adherence

• During the first year of therapy, irregular bleeding and spotting is more common with continuous combined therapy
• In the second year, bleeding and spotting becomes more common with sequential regimens 3
• Continuous therapy may be more protective against endometrial hyperplasia over long-term use 3

The American College of Obstetricians and Gynecologists clearly states that for women with an intact uterus, progesterone must be added to estrogen therapy to prevent endometrial hyperplasia, with recommended options including micronized progesterone (100-200 mg/day for 12-14 days of the month) 1.