When should I begin micronized progesterone after starting Oestrogel (estradiol gel) if I have an intact uterus?

When to Start Micronized Progesterone After Initiating Oestrogel

If you have an intact uterus, you must start micronized progesterone immediately—on the same day you begin Oestrogel—to prevent endometrial cancer. Delaying progesterone even briefly exposes the endometrium to unopposed estrogen, which increases endometrial cancer risk 10- to 30-fold after 5 years of use. 1

Critical Timing Principle

Progesterone must accompany estrogen from day one in any woman with a uterus. 1 The evidence is unequivocal:

• Unopposed estrogen raises endometrial cancer risk with a relative risk of 2.3 (95% CI 2.1–2.5) after just one year, escalating to 9.5-fold after 10 years 1
• Adding progesterone reduces this cancer risk by approximately 90% 2, 1
• The FDA explicitly mandates that progestin must be initiated concurrently when estrogen is prescribed to a woman with an intact uterus 1

Recommended Progesterone Regimen

Micronized progesterone 200 mg orally at bedtime for 12–14 days every 28-day cycle is the evidence-based first-line regimen. 2, 1, 3 This dosing:

• Provides complete endometrial protection by fully inhibiting mitoses 4
• Offers superior breast safety compared to synthetic progestins (medroxyprogesterone acetate) 2, 1
• Induces amenorrhea in 91–93% of women by 6 months, improving compliance 4
• Causes only mild, transient drowsiness—minimized by bedtime dosing 5

Alternative Regimens

If you prefer to avoid withdrawal bleeding entirely:

• Continuous daily micronized progesterone 100 mg at bedtime (taken every day without interruption) provides robust endometrial protection and eliminates monthly bleeding 1, 4
• This lower continuous dose is as effective as the higher sequential dose because daily exposure prevents any estrogen-driven proliferation 4

If micronized progesterone is unavailable or not tolerated:

• Medroxyprogesterone acetate 10 mg daily for 12–14 days per month is an acceptable alternative, though it carries slightly higher breast cancer and metabolic risks 2, 1

Why 12–14 Days Is Non-Negotiable

Progesterone must be given for at least 12 days per cycle in sequential regimens. 2, 1, 6 Shorter durations fail:

• Regimens using progesterone for fewer than 10 days per cycle carry a 1.8-fold increased endometrial cancer risk 7
• The natural luteal phase lasts 12–14 days; replicating this duration ensures complete secretory transformation of the endometrium 1
• All studies demonstrating endometrial safety used 12–14 day exposure 3, 6, 5

Common Pitfall to Avoid

Never start Oestrogel alone with a plan to "add progesterone later." 1 Even a few weeks of unopposed estrogen begins endometrial proliferation. The correct sequence is:

1. Day 1: Start Oestrogel (transdermal estradiol 50 μg patch twice weekly or gel 1–2 mg daily) 2, 1
2. Day 1: Start micronized progesterone 200 mg at bedtime for days 1–14 of each 28-day cycle 1, 3
3. Days 15–28: Continue Oestrogel alone; withdrawal bleeding typically occurs during this hormone-free interval 3
4. Day 29: Restart the cycle

Monitoring and Follow-Up

• 3-month review: Assess bleeding pattern, symptom control, and adherence 7
• Annual review: Confirm ongoing necessity, check blood pressure, and screen for contraindications 1
• Endometrial assessment (ultrasound or biopsy) is indicated only if: significant bleeding persists beyond 6 months despite adequate progesterone exposure 7

Special Consideration: Post-Hysterectomy

If you have had a hysterectomy, you do not need progesterone at all. 1 Estrogen-alone therapy (Oestrogel without progesterone) is appropriate and actually reduces breast cancer risk (RR 0.80) compared to combined therapy. 1