3. Menopause Hormone Therapy (MHT/HRT): Principles and Prescribing
Pedagogy: This lesson uses prescribing-decision simulation — walking through real consultation scenarios to build confidence in initiating, dose-titrating, and route-selecting HRT in primary care.
Learning Objectives
- Conduct a pre-treatment assessment before initiating MHT
- Select appropriate starting doses and formulations based on patient risk factors
- Manage common side effects: breast tenderness, bloating, mood changes
- Choose the correct route based on BMI, VTE risk, migraine, and individual preference
Key Facts
Pre-Treatment Assessment
Before starting HRT, conduct a structured multi-domain assessment (precision menopause approach). Key elements: symptom assessment (MRS/Greene); blood pressure; BMI and waist circumference; personal/family history of breast cancer, VTE, CVD; migraine (aura status); liver disease; current medications (1,2).
Starting Doses and Titration
| Preparation | Starting Dose | Standard Dose | Titration |
|---|---|---|---|
| Oestrogel | 1 pump (0.75mg) | 2 pumps (1.5mg) | Increase by 1 pump every 4-6 weeks |
| Sandrena gel | 0.5mg | 1mg | Increase to 1mg, then 1.5mg if needed |
| Patch | 25 mcg | 50 mcg | Step up to 50mcg, then 75mcg |
| Oral oestradiol | 1mg | 2mg | Increase to 2mg if needed |
Start LOW, titrate to symptom control. Review at 3 months. Full benefit may take 3-6 months. Progestogen dose must match oestrogen dose (2).
Route Selection by Risk Factor
| Risk Factor | Preferred Route | Rationale |
|---|---|---|
| BMI >30 | Transdermal | No VTE increase (unlike oral) |
| VTE history/risk | Transdermal | Avoids first-pass hepatic activation of clotting factors |
| Migraine with aura | Transdermal | Stable oestrogen levels; oral causes fluctuations |
| Hypertension | Transdermal | No adverse BP effect (oral may raise BP) |
| Liver disease / gallbladder | Transdermal | Bypasses first-pass hepatic metabolism |
| No specific risk factors | Either (patient choice) | Both oral and transdermal are effective |
Managing Common Side Effects
Breast tenderness: Common in first 3 months; usually resolves. Reduce oestrogen dose temporarily if severe, then re-titrate. Bloating/nausea: More common with oral; consider switching to transdermal. Mood changes: May indicate progestogen sensitivity; consider switching progestogen type or using the LNG-IUS (1).
Clinical Pearl Transdermal oestrogen is preferred whenever there is ANY risk factor for VTE, obesity, migraine with aura, or hypertension. When in doubt, go transdermal — it is never wrong.
Clinical Pearl Start low and titrate upwards every 4-6 weeks. Full symptom benefit may take 3-6 months. Do NOT judge HRT failure at less than 3 months on an adequate dose.
Case-Based Examples
Case 1: 50-year-old with BMI 34 and family history of DVT requesting HRT
Presentation: A 50-year-old with severe VMS (10/day), BMI 34, and her sister had a DVT aged 45. No personal VTE history. BP 142/88.
Question: Design an HRT regimen for this patient.
Model Answer: Multiple risk factors mandate transdermal route: BMI >30, family history of VTE, borderline hypertension. Start: transdermal oestradiol gel 1 pump daily (low dose). Progestogen: micronised progesterone 200mg for 14 days/month (sequential — she is likely perimenopausal). Address BP: lifestyle advice, consider antihypertensive; monitor at HRT review. Review at 3 months: if VMS persist, increase to 2 pumps. Annual review: BP, weight, symptoms, bleeding pattern. If/when postmenopausal: switch to continuous combined.
Case 2: Switching from oral to transdermal HRT due to side effects
Presentation: A 52-year-old on oral oestradiol 2mg + Utrogestan 100mg continuous for 1 year reports persistent bloating and a 3kg weight gain. VMS are well controlled.
Question: How would you manage the switch?
Model Answer: Bloating and weight gain can be related to first-pass hepatic effects of oral oestrogen. Switch to transdermal oestradiol: 2mg oral roughly equivalent to 50mcg patch or 2 pumps Oestrogel. Continue Utrogestan 100mg continuous (progestogen unchanged). Review at 3 months for side effect resolution and symptom control. If bloating persists, consider the progestogen as the cause — trial of dydrogesterone or LNG-IUS as alternative.
Self-Assessment Questions
PLAB/MLA Route selection for VTE risk
A woman with BMI 36 and previous DVT requests HRT. Which route is most appropriate?
A. Oral conjugated equine oestrogens
B. Transdermal oestradiol
C. HRT is absolutely contraindicated
D. Oral oestradiol with aspirin cover
Answer: B. Transdermal oestradiol does not increase VTE risk (no first-pass metabolism). Oral oestrogen would be contraindicated. Previous DVT is a relative contraindication for oral but not for transdermal HRT.
MRCGP Dose titration and timeline for benefit
A patient started on Oestrogel 1 pump 6 weeks ago reports only mild improvement in VMS. She wants to stop HRT as 'it isn't working.' What is your advice?
A. Agree — HRT has failed, try CBT instead
B. Increase to 2 pumps, ensure adequate progestogen, and review at 3 months — full benefit may take 3-6 months
C. Switch to oral oestrogen for faster absorption
D. Add fezolinetant immediately
Answer: B. Start low, titrate up. 6 weeks on a low dose is too early to judge. Increase to standard dose (2 pumps), ensure matched progestogen, and review at 3 months. Full benefit may take 3-6 months.
Professor Oral vs transdermal: the evidence base for safety differences
Evaluate the quality of evidence for VTE risk differences between oral and transdermal oestrogen in HRT.
A. Multiple RCTs demonstrate no VTE risk with transdermal
B. The evidence is predominantly observational (case-control studies, notably ESTHER) with no RCTs specifically designed to compare VTE risk by route
C. The WHI directly compared oral and transdermal
D. There is no evidence for any difference
Answer: B. No RCT has been powered to compare VTE risk by route. The ESTHER case-control study provided the key signal (OR ~4 for oral; no increase for transdermal). The NICE guideline acknowledges this evidence as observational but includes it in recommendations. This is an example of clinical practice appropriately informed by consistent observational evidence in the absence of RCTs — a pragmatic approach given the ethical and logistical challenges of conducting such a trial.
Take-Away Messages
- Conduct a structured pre-treatment assessment before starting HRT: symptoms, BP, BMI, personal/family history
- Start low, titrate to symptom control every 4-6 weeks; full benefit may take 3-6 months
- Transdermal route preferred for: BMI >30, VTE risk, migraine with aura, hypertension, liver/gallbladder disease
- Progestogen dose must be proportionate to oestrogen dose — this is an endometrial cancer safety issue
- Common side effects (breast tenderness, bloating) usually resolve within 3 months; switch route or progestogen type if persistent