Hormone Replacement Therapy (HRT)
NICE CKS Menopause – Hormone replacement therapy (HRT). Last revised: Nov 2024.
NICE BNF Treatment Summaries Sex hormones.
Prescription Information
Contraindications and Cautions
Contraindications
- Breast cancer (current / past / suspected)
- Oestrogen-dependent cancer (known / suspected)
- Due to risk of endometrial cancer
- Undiagnosed vaginal bleeding
- Untreated endometrial hyperplasia
- Due to risk of thromboembolism
- Active or recent arterial thromboembolism (e.g. angina, MI)
- Previous idiopathic or current DVT / PE (unless already on anticoagulant)
- Known thrombophilia disorder
- Pregnancy
- Active liver disease with abnormal LFTs
Cautions
- Porphyria cutanea tarda
- Diabetes mellitus (increased risk of heart disease)
- Factors predisposing to venous thromboembolism
- History of endometrial hyperplasia
- Migraine and migraine-like headaches
- Increased risk of breast cancer
Choosing and Administration of HRT
There are a few aspects to consider while choosing HRT
Route of Administration
There are 2 main routes: oral or transdermal (gel / patch / spray)
Indications for transdermal HRT (over oral HRT):
- History / increased risk of venous thromboembolism (DVT / PE)
- Presence of cardiovascular risk factors (e.g. obesity, uncontrolled hypertension, hypertriglyceridemia)
- Concomitant hepatic enzyme-inducing drug treatment
- Factors associated with inappropriate oral HRT
- Troublesome adverse effects with oral treatment
- GI disorder that may affect the absorption of oral treatment
- Lactose sensitivity (most oral preparations contain lactose)
- History of migraine / gallbladder disease
Components of HRT
Choice depends on whether the patient has a uterus:
- Intact uterus → combined oestrogen and progestogen HRT
- Without a uterus (e.g. hysterectomy) → oestrogen-only HRT
Oestrogen-only HRT should NOT be given to women with a uterus. It increases the risk of endometrial cancer significantly (due to unopposed oestrogen).
Choice of Regimen
The choice of HRT regimen depends mainly on menopausal status:
| Menopausal status | Preferred regimen | Administration |
|---|---|---|
| Peri-menopausal (last menstrual period <12 months) | Monthly cyclical (sequential) HRT | Oestrogen is given daily, and progestogen is given at the end of the cycle for 12–14 days
|
| Post-menopausal (amenorrhoea for 12 months) | Continuous HRT | Both oestrogen AND progestogen are taken daily
|
Women who are >45 y/o and are taking cyclical HRT should be offered a change to continuous combined HRT, after 5 years of use or by 54 y/o (whichever comes first).
This is because by this time of point, the patient is likely postmenopausal, continuous HRT would offer better endometrial protection and withdrawal bleed-free for the patient
Choice of Hormone
| Choice of oestrogen |
|
| Choice of progestogen |
|
Tibolone monotherapy is an option for post-menopausal continuous HRT
- Tibolone combines both oestrogenic and progestogenic activity (and weak androgenic activity)
- NB it can only be given continuously (thus only appropriate for post-menopausal women)
- The extra androgenic activity is beneficial for those with impaired libido and sexual function
- Complication profile, compared to standard combined continuous HRT
- Slightly higher endometrial cancer risk (duration use-dependent)
- Slightly higher stroke risk (age-dependent)
Patient Counselling
Benefits
Important benefits of HRT include:
- Relief of vasomotor symptoms
- Improvement in genitourinary symptoms
- Improve sleep quality and mood
- Bone protection (reduce risk of fragility fracture)
Adverse Effects
3 main categories of adverse effects associated with HRT:
| Category | Description |
|---|---|
| Oestrogen-related |
|
| Progesterone-related |
|
| Vaginal bleeding problems | When unscheduled vagina bleeding is normal / acceptable:
Expected vaginal bleeding patterns after the first 3 months:
|
Complications
Notable and important complications associated with HRT:
| Complication | Notes |
|---|---|
| ↑ Breast cancer risk | By the addition of progesterone |
| ↑ Endometrial cancer risk | By unopposed oestrogen (therefore it is important to add progesterone in those with a uterus) |
| ↑ DVT / PE risk | From oestrogen’s pro-coagulant effect
**Risk could be almost eliminated by using transdermal preparation |
| ↑ Stroke risk | |
| ↑ Ischaemic heart disease risk | Note that if HRT started <10 years post-menopausal, it may be protective, but late initiation (≥ 10 years post-menopausal) increases risk of ischaemic heart disease |
Management of Unscheduled Bleeding on HRT
Remember the “normal”:
- Unscheduled vaginal bleeding is a common adverse effect of HRT within the first 3 months initiation (and is acceptable up to first 6 months if there are no risk factors for endometrial cancer).
- Unscheduled vaginal bleeding is also acceptable if happened within the first 3 months of changing HRT dose / preparation
- Expected vaginal bleeding patterns after the first 3 months:
- Monthly cyclical regimen → regular withdrawal bleeding (towards the end of the progesterone phase)
- Continuous regimen → complete amenorrhoea after 6 months
Summarised and simplified guideline:
- If there is abnormal unscheduled bleeding (after first 3-6 months of treatment initiation or change in HRT) → urgent TVUS to measure endometrial thickness
- TVUS interpretation
- Thickened endometrium needs urgent suspected cancer pathway referral
- Definition of thickened is >4mm in continuous HRT and >7mm in cyclical HRT
If TVUS is normal (i.e. not thickened) → adjust HRT to reduce unscheduled bleeding episodes
- Assess adherence and understanding of how to use the prescribed preparation
- LNG-IUD reduces episodes of unscheduled bleeding
- Consider offering oral preparations (if there are no risk factors for thrombosis)
Full Management (NICE CKS)
NICE CKS states to assess for risk factors of endometrial cancer to guide management:
| Major risk factors | Minor risk factors |
|
|
Subsequent action:
- Refer, using an urgent suspected cancer pathway for endometrial cancer if there are 1 major risk factor or 3 minor risk factors irrespective of bleeding type or interval since starting or changing HRT preparations
- Refer for urgent TVUS if
- There is any heavy or prolonged bleeding or two minor cancer risk factors are identified, irrespective of interval since starting or changing HRT or,
- The first presentation with bleeding occurs more than six months after starting HRT or more than 3 months after a change in dose or preparation.