When should a patient take progesterone (a hormone) for 12 days a month, taken nightly?

Progesterone Administration: 12 Days a Month vs. Nightly

Progesterone should be administered for 12-14 days per month when used in a sequential regimen with estrogen therapy, particularly in patients with premature ovarian insufficiency (POI) or those requiring endometrial protection. 1

Sequential vs. Continuous Regimens

Sequential Regimen (12-14 days per month)

• Recommended for patients who accept or prefer withdrawal bleeding 1
• Typically involves:
  • Transdermal 17β-estradiol administered continuously for 28 days
  • Oral/vaginal progesterone administered for 12-14 days every 28-day cycle 1
• Standard adult doses in sequential regimens:
  • 200 mg of oral or vaginal micronized progesterone (MP) for 12-14 days every 28 days, OR
  • 10 mg of medroxyprogesterone acetate (MPA) for 12-14 days per month, OR
  • 10 mg of dydrogesterone for 12-14 days per month 1
• Allows for earlier recognition of pregnancy, as women with POI may spontaneously ovulate 1

Continuous Regimen (Daily/Nightly)

• Recommended for patients who prefer to avoid withdrawal bleeding 1
• Involves continuous administration of both estrogen and progesterone without interruption 1
• Standard adult doses in continuous regimens:
  • Minimum of 1 mg of oral norethisterone, OR
  • 2.5 mg of oral MPA, OR
  • 5 mg of oral dydrogesterone daily 1

FDA-Approved Indications and Dosing

• Prevention of Endometrial Hyperplasia: 200 mg orally at bedtime for 12 days sequentially per 28-day cycle in postmenopausal women receiving daily conjugated estrogens 2
• Treatment of Secondary Amenorrhea: 400 mg orally at bedtime for 10 days 2

Clinical Considerations for Progesterone Administration

Route of Administration

• Oral micronized progesterone is recommended to be taken at bedtime due to potential side effects of drowsiness and dizziness 2
• Vaginal administration provides direct vagina-to-uterus transport with preferential uterine uptake, allowing for lower systemic doses 3, 4

Progesterone Type Selection

• Micronized progesterone (MP) is the first choice among progestins due to:
  • Lower risk of cardiovascular disease and venous thromboembolism when taken cyclically 1
  • Better safety profile regarding metabolic effects, breast cancer risk, and thromboembolism risk 5
  • Fewer psychological side effects compared to synthetic progestins 3, 6
• Second choices include MPA, dydrogesterone, or norethisterone 1

Common Pitfalls and Caveats

• Progesterone is >90% metabolized during first hepatic pass when taken orally, limiting efficacy of once-daily administration 3
• Metabolites can cause dizziness and drowsiness, which is why bedtime administration is recommended 2, 3
• Progestins with anti-androgenic effects should be avoided in patients with POI who may already suffer from diminished libido or impaired sexual function 1
• Standing position with a glass of water is recommended for patients who have difficulty swallowing progesterone capsules 2

Decision Algorithm for Progesterone Administration

1. Determine clinical indication:

   • Endometrial protection with HRT: 12-14 days per month (sequential) 1, 2
   • Secondary amenorrhea: 10 days (cyclic) 2
   • Continuous endometrial protection without withdrawal bleeding: Daily/nightly 1

2. Consider patient preferences:

   • If withdrawal bleeding is acceptable: Sequential regimen (12-14 days/month) 1
   • If withdrawal bleeding is not desired: Continuous regimen (daily/nightly) 1

3. Select appropriate formulation:

   • First choice: Micronized progesterone 1
   • Alternative options: MPA, dydrogesterone, norethisterone 1

4. Administer at appropriate time:

   • All oral progesterone formulations should be taken at bedtime to minimize side effects 2