3. Menopause Hormone Therapy (MHT/HRT): Principles and Prescribing
Pedagogy: This lesson uses contraindication mapping and referral-threshold identification — building the decision framework for when primary care can manage and when specialist input is essential.
Learning Objectives
- List absolute and relative contraindications to systemic MHT
- Describe prescribing considerations for women with breast cancer history, VTE, CVD, migraine with aura, endometriosis, and fibroids
- Identify referral criteria for secondary care menopause services
- Apply the ESE framework for complex prescribing decisions
Key Facts
Absolute Contraindications
Known or suspected breast/endometrial cancer; oestrogen-dependent neoplasia; undiagnosed vaginal bleeding; untreated endometrial hyperplasia; active VTE or arterial thromboembolic disease; active liver disease; porphyria (1,2).
Relative Contraindications and Special Considerations
| Condition | Considerations | Management |
|---|---|---|
| Breast cancer history | Generally contraindicated; specialist/oncology involvement essential | Non-hormonal options: fezolinetant, elinzanetant, CBT. Low-dose vaginal oestrogen may be considered for GSM with oncology agreement |
| VTE history | Oral oestrogen contraindicated; transdermal safe | Transdermal oestradiol + micronised progesterone (VTE-neutral) |
| CVD / QRISK3 >=10% | BMS cautions against initiating in uncontrolled CVD risk | Optimise risk factors first; low-dose transdermal with non-androgenic progestogen may be considered |
| Migraine with aura | Oral oestrogen may exacerbate; stroke risk concern | Transdermal (stable oestrogen levels); avoid oral |
| Endometriosis | Symptoms may recur; continuous combined preferred | Continuous combined regimen to avoid cyclical stimulation; specialist referral if symptoms recur |
| Fibroids | May enlarge on HRT | Monitor; transdermal route preferred; refer if symptomatic enlargement |
Referral Criteria for Secondary Care
Refer to a healthcare professional with expertise in menopause: persistent side effects; poor symptom control; complex medical history; past history of hormone-dependent cancer; bleeding problems on HRT (BMS 2026) (1).
Clinical Pearl Breast cancer history is the most common reason for specialist referral. Non-hormonal options are expanding: fezolinetant (NICE TA1143) and elinzanetant now provide evidence-based alternatives. CBT is also NICE-recommended.
Clinical Pearl Previous VTE does NOT mean HRT is impossible — it means ORAL oestrogen is contraindicated. Transdermal oestradiol with micronised progesterone is safe and appropriate in many cases.
Case-Based Examples
Case 1: 53-year-old breast cancer survivor with severe VMS
Presentation: A 53-year-old with ER-positive breast cancer (treated 3 years ago, now on tamoxifen) has severe VMS (15/day), insomnia, and significant impact on work. She is desperate for help.
Question: What treatment options can you offer?
Model Answer: Systemic HRT is contraindicated (ER-positive breast cancer). Options: (1) Fezolinetant 45mg OD (NICE TA1143 — for moderate-to-severe VMS when HRT unsuitable); (2) Menopause-specific CBT (NICE NG23); (3) Avoid paroxetine with tamoxifen (CYP2D6 inhibition); venlafaxine or escitalopram are alternatives if SSRI/SNRI needed; (4) For GSM: discuss low-dose vaginal oestrogen with oncologist — most guidelines consider it safe, but involvement of oncologist is necessary, especially on aromatase inhibitors; (5) Lifestyle: exercise, weight management, cooling strategies. Refer to menopause specialist if symptoms remain uncontrolled.
Case 2: 48-year-old with previous DVT requesting HRT
Presentation: A 48-year-old with a history of DVT during pregnancy (provoked, 10 years ago, completed anticoagulation) presents with moderate VMS and vaginal dryness.
Question: Can you prescribe HRT and if so, what formulation?
Model Answer: Provoked DVT in pregnancy 10 years ago is a relative, not absolute, contraindication. Transdermal oestradiol does NOT increase VTE risk (avoids first-pass hepatic activation of clotting factors). Prescribe: transdermal oestradiol gel or patch (start low, titrate) + micronised progesterone (VTE-neutral, unlike synthetic progestins). Add vaginal oestrogen for GSM (negligible systemic absorption). Discuss with haematology if additional thrombophilia factors are suspected. Document the shared decision and rationale clearly.
Self-Assessment Questions
PLAB/MLA Absolute contraindication to systemic HRT
Which is an ABSOLUTE contraindication to systemic HRT?
A. Family history of breast cancer
B. Previous DVT during pregnancy
C. Known oestrogen receptor-positive breast cancer
D. BMI >35
Answer: C. Known/suspected breast cancer or oestrogen-dependent neoplasia is an absolute contraindication. Previous DVT and obesity are relative contraindications (transdermal HRT can be used).
MRCGP HRT after VTE: what is safe?
A patient with previous DVT asks if HRT is completely ruled out. What is your answer?
A. Yes — all HRT is absolutely contraindicated
B. Oral HRT is contraindicated but transdermal oestradiol with micronised progesterone can be safely prescribed
C. She needs lifelong anticoagulation to take HRT
D. Only vaginal oestrogen is ever permissible
Answer: B. Transdermal oestradiol has no VTE risk increase. Micronised progesterone is VTE-neutral. Oral oestrogen is contraindicated. This is a common misconception that denies symptomatic women effective treatment.
Professor Managing menopausal symptoms in a breast cancer patient on aromatase inhibitors
A postmenopausal woman on an aromatase inhibitor (letrozole) for ER-positive breast cancer develops severe GSM. Discuss the evidence and controversy around vaginal oestrogen use in this context.
A. Vaginal oestrogen is absolutely safe in all breast cancer patients
B. Low-dose vaginal oestrogen results in minimal systemic absorption and most guidelines consider it safe; however, aromatase inhibitors are designed to suppress residual oestrogen, creating a pharmacological conflict that requires oncology input
C. Vaginal oestrogen is completely contraindicated with aromatase inhibitors
D. There is no controversy — guidelines are unanimous
Answer: B. Low-dose vaginal oestrogen (e.g. Vagifem 10mcg, estriol creams) results in minimal systemic absorption and most international guidelines (IMS, NAMS) consider it safe even in breast cancer survivors. However, a pharmacological paradox exists with aromatase inhibitors: these drugs aim to suppress all oestrogen production, and even small systemic absorption may theoretically counteract their mechanism. Some studies have shown transient rises in serum oestradiol with vaginal oestrogen initiation. This is why oncology involvement is essential — it is a shared decision based on symptom severity, cancer stage, and individual risk tolerance.
Take-Away Messages
- Absolute contraindications: known breast/endometrial cancer, active VTE, undiagnosed vaginal bleeding, active liver disease
- Previous VTE: oral HRT contraindicated, but transdermal oestradiol + micronised progesterone is safe
- Breast cancer survivors: non-hormonal options include fezolinetant, elinzanetant, CBT; specialist referral essential
- Migraine with aura: use transdermal route only (stable oestrogen levels)
- Refer to menopause specialist: persistent symptoms, complex history, hormone-dependent cancer, bleeding problems on HRT