What is a typical regimen for a postmenopausal woman with an intact uterus requiring hormonal therapy with Clairo (estradiol) 0.025 patch and a progestogen schedule?

Estradiol 0.025 Patch with Progestogen Regimen

For a postmenopausal woman with an intact uterus using a 0.025 mg (25 mcg) estradiol patch, add oral micronized progesterone 200 mg daily for 12-14 days every 28 days to provide adequate endometrial protection. 1, 2

Estrogen Component

• Apply the estradiol 0.025 mg patch continuously without interruption, changing it according to the manufacturer's instructions (typically twice weekly or weekly depending on brand) 2
• The 25 mcg dose is lower than the standard 50-100 mcg doses typically recommended in guidelines, but the same progestogen protection principles apply 2

Progestogen Component: First-Line Recommendation

Prescribe oral micronized progesterone 200 mg daily for 12-14 days every 28 days (days 15-28 of each cycle). 1, 2

• Micronized progesterone is the preferred progestogen due to its superior cardiovascular safety profile, lowest thrombotic risk, and neutral effects on blood pressure compared to synthetic progestogens 2, 3, 4
• The 12-14 day duration is critical—never use less than 12 days, as shorter durations provide inadequate endometrial protection 2, 5
• This can be administered orally or vaginally with equivalent endometrial protection 1

Alternative Progestogen Options

If micronized progesterone is unavailable or not tolerated:

• Second choice: Medroxyprogesterone acetate (MPA) 10 mg daily for 12-14 days every 28 days 2, 3
• Preferred alternative: Norethisterone acetate 1 mg daily for 12-14 days monthly offers better cardiovascular and metabolic outcomes than MPA while maintaining endometrial protection 3
• Third choice: Dydrogesterone 10 mg daily for 12-14 days monthly 6, 3

Expected Bleeding Pattern

• Withdrawal bleeding typically occurs during or shortly after the progestogen phase (around days 15-28) 2
• This bleeding pattern is normal and expected with sequential dosing 1
• If breakthrough bleeding occurs outside the expected withdrawal period, increase the progestogen duration to 14 days or consider switching to continuous combined therapy 2

Critical Monitoring Requirements

Perform a baseline transvaginal ultrasound before starting progestogen therapy to confirm appropriate endometrial thickness. 1

• Reassess at 3 months to evaluate bleeding pattern and symptom control 2
• Conduct annual clinical review focusing on compliance and bleeding patterns 2
• If undiagnosed persistent or abnormal vaginal bleeding occurs, undertake endometrial sampling to rule out malignancy 5

Important Caveats

• The 25 mcg estradiol dose is lower than standard doses, but still requires progestogen protection for at least 12-14 days monthly 1, 2, 5
• Women with cardiovascular risk factors should preferentially receive micronized progesterone rather than synthetic progestogens like MPA 2
• Avoid progestogens with anti-androgenic effects in women with low libido or sexual dysfunction 6
• Continue therapy with the lowest effective dose for the shortest duration consistent with treatment goals 5
• Attempts to discontinue or taper should be made at 3-6 month intervals 5

Alternative Delivery System

If systemic progestogen side effects are problematic, consider the levonorgestrel intrauterine system, which provides reliable endometrial protection with fewer systemic effects 3, 2