What is the proper protocol for prescribing continuous progesterone (Progesterone)

Continuous Progesterone Prescription Protocol

For continuous progesterone therapy, the recommended protocol is 200 mg of micronized progesterone administered daily without interruption when combined with estrogen therapy to prevent endometrial hyperplasia. 1

Dosing Options Based on Clinical Context

For Postmenopausal Women with a Uterus (Endometrial Protection)

• First-line approach: 200 mg oral micronized progesterone daily at bedtime for continuous regimens 2
• Alternative options if oral route not tolerated:
  • Vaginal micronized progesterone 200 mg daily 1
  • Transdermal combined patches containing estrogen and progestin (e.g., patches releasing 50 μg of 17βE and 7 μg of levonorgestrel daily) 1

For Women with Premature Ovarian Insufficiency

• Continuous combined regimen (to avoid withdrawal bleeding):
  • Combined patches containing 17βE and progestin administered continuously 1
  • Oral tablets containing 1-2 mg of 17βE and 5 mg of dydrogesterone (or 2 mg of dienogest) administered continuously 1

Administration Considerations

• Timing: Administer progesterone at bedtime to minimize side effects of drowsiness and dizziness 2, 3
• Position: Take with a glass of water while standing if swallowing difficulties occur 2
• Duration: For postmenopausal women, continue until the average age of spontaneous menopause (45-55 years) 1

Safety Considerations and Monitoring

Endometrial Protection

• Continuous progesterone (200 mg daily) with estrogen significantly reduces the risk of endometrial hyperplasia compared to estrogen alone (6% vs 64% over 36 months) 2
• Regular monitoring for abnormal bleeding is essential 2

Mood Effects

• Continuous progesterone may contribute to depressive symptoms in some women 4
• Consider cyclical administration (12-14 days every 28 days) if mood symptoms develop 4
• Micronized progesterone has fewer mood effects than synthetic progestins 3, 5

Cardiovascular Risk

• Micronized progesterone is associated with lower cardiovascular risk compared to synthetic progestins 1
• Transdermal estrogen administration with progesterone has a better cardiovascular profile than oral administration 1, 4

Common Pitfalls to Avoid

1. Drowsiness: Progesterone can cause significant drowsiness - always advise patients to take it at bedtime 2, 3
2. Allergic reactions: Progesterone capsules contain peanut oil - contraindicated in patients with peanut allergies 2
3. Anti-androgenic progestins: Avoid progestins with anti-androgenic effects in women with diminished libido or sexual function 1, 4
4. Inadequate endometrial protection: Never use estrogen alone in women with an intact uterus 2
5. Continuous vs. cyclical confusion: Continuous regimens (daily without breaks) are different from cyclical regimens (12-14 days per month) - be clear which you're prescribing 1

Special Populations

Women with History of Cancer

• Cancer survivors have higher cardiovascular risk and may benefit from transdermal administration 1
• Women who underwent TBI or survived Hodgkin lymphoma have increased breast cancer risk - annual imaging from age 25 is recommended 1

Women Requiring Contraception

• If contraception is needed, consider 17βE-based combined oral contraceptives rather than continuous progesterone alone 1

Micronized progesterone is the preferred progestogen due to its natural structure, better metabolic profile, and fewer side effects compared to synthetic progestins 1, 3, 6. The bioavailability of oral micronized progesterone is similar to other natural steroids, with clear dose-ranging effects and established long-term endometrial protection 3.