Prescribing HRT for a Postmenopausal Woman with a Uterus

Step 1 - Confirm Indications

• Bothersome vasomotor symptoms (hot flushes, night sweats)
• Genitourinary syndrome of menopause (vaginal dryness, dyspareunia, recurrent UTI)
• Prevention of osteoporosis (where other agents are unsuitable)
• Premature ovarian insufficiency (POI) - until average age of menopause (~51 years)

Step 2 - Confirm the Patient is Truly Postmenopausal

Step 3 - Choose the Route of Estrogen

Transdermal (First-line preferred)

• Patches (e.g., Evorel 25-100 mcg, Oestradot 25-100 mcg) - changed twice weekly, applied to abdomen/buttocks
• Gel (e.g., Oestrogel 0.06%, 1-3 pumps daily; Sandrena 0.5-1.5 mg/day sachets) - applied to thighs/arms, allow to dry
• Spray (e.g., Lenzetto 1.53 mg/dose, 1-3 squirts daily)

• Avoids first-pass hepatic metabolism
• Does not increase VTE risk (unlike oral estrogen)
• Does not increase stroke risk
• Is preferred in women with hypertriglyceridaemia, migraines, or VTE risk factors

Oral (Second-line or patient preference)

• Estradiol 1-2 mg daily (e.g., Elleste Solo, Zumenon)
• Associated with slightly higher VTE and stroke risk compared to transdermal

Step 4 - Choose the Progestogen

1. Micronised Progesterone (Utrogestan) - Preferred / First-line

• Structurally identical to endogenous progesterone
• Better cardiovascular and breast safety profile vs. synthetic progestogens
• Fewer side effects
• Doses:
  • Continuous combined: 100 mg orally at night, daily
  • Sequential: 200 mg orally at night for 12-14 days per month
• Note: oral bioavailability is variable; vaginal progesterone gel is NOT licensed for endometrial protection

2. Dydrogesterone (available in combined preparations, e.g., Femoston)

• Good safety profile, neutral lipid effect
• Continuous: 5 mg/day
• Sequential: 10 mg/day for 14 days/month
• Contraindicated in meningioma history

3. Norethisterone (NETA)

• Available in combined patches (Evorel Sequi, Evorel Conti) and tablets
• Continuous minimum: 0.5 mg/day

4. Medroxyprogesterone acetate (MPA)

• Continuous minimum: 2.5 mg/day
• Higher breast cancer risk signal with long-term use; less preferred

Levonorgestrel-IUS (Mirena)

• Can be used as the progestogen component (off-label for HRT endometrial protection in UK but widely used)
• Provides local endometrial protection with minimal systemic absorption
• Useful for women who cannot tolerate systemic progestogens
• Replace every 5 years

Step 5 - Choose a Regimen (Summary Table)

• Femoston Conti (estradiol + dydrogesterone) - oral
• Evorel Conti patches (estradiol + NETA) - transdermal
• Bijuve (estradiol + progesterone oral capsule, continuous)

Step 6 - Contraindications to Check Before Prescribing

• Undiagnosed vaginal/uterine bleeding
• Estrogen-sensitive cancers (breast, endometrial)
• Active or recent VTE (DVT/PE)
• Active liver disease with abnormal LFTs
• Uncontrolled hypertension
• Pregnancy

• Personal or first-degree family history of VTE - prefer transdermal estrogen
• Cardiovascular disease - individualize
• Migraines with aura - prefer transdermal

Step 7 - Practical Prescribing Points

1. Start low, titrate up based on symptom response - not serum hormone levels (routine monitoring of levels is not recommended)
2. Warn about initial bleeding: breakthrough bleeding is common in the first 3-6 months on continuous combined HRT
3. If bleeding persists beyond 6 months, or is heavy/unexpected, investigate with pelvic USS and/or endometrial biopsy to exclude hyperplasia or carcinoma
4. Review at 3 months after initiation, then annually
5. At each annual review: reassess symptoms, risks, and benefits; continue as long as benefits outweigh risks
6. There is no mandatory maximum duration - individualise based on ongoing risk-benefit assessment
7. If estrogen dose is increased, increase progestogen proportionately to maintain endometrial protection

Step 8 - Monitoring

Special Considerations

• TSEC (Tissue-Selective Estrogen Complex): Conjugated equine estrogens + bazedoxifene (Duavive) - an alternative for women intolerant of progestogens; provides endometrial protection without a classic progestogen
• Progestogen intolerance: Reduce dose/duration (e.g., micronised progesterone 100 mg for 7-10 days/month) but mandatory endometrial surveillance with USS ± biopsy is then required
• Women post-endometrial ablation: Can use continuous combined HRT but endometrium may persist in patches - still recommend progestogen; some use estrogen-only with careful surveillance
• Local (topical) estrogen for genitourinary symptoms only (vaginal creams, pessaries, rings) does not require progestogen addition at licensed doses

Quick Reference Card

Postmenopausal + intact uterus
→ COMBINED HRT (estrogen + progestogen)
→ CONTINUOUS regimen (both daily)

1st line:
  Estrogen:    Transdermal estradiol (patch 50 mcg or gel 1-2 pumps)
  Progestogen: Micronised progesterone 100 mg nightly

Review at 3 months, then annually
Investigate any unscheduled bleeding >6 months