Hormone Replacement Therapy (HRT)
Hormone replacement therapy (HRT) is used to replace declining sex hormones, mainly oestrogen, with or without progestogen. It is primarily used to treat menopausal symptoms and is also routinely recommended in premature ovarian insufficiency unless contraindicated.
This updated UKMLA guide to hormone replacement therapy (HRT) is based on NICE NG23 and NICE CKS, which covers contraindications, types, selection, benefits, risks, adverse effects, and management of unscheduled bleeding.
Indications
The key indications for HRT are:
- Menopause – 1st line to manage vasomotor symptoms (see the Menopause article)
- Premature ovarian insufficiency – recommended in ALL patients unless contraindicated (see the Premature Ovarian Insufficiency article)
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
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. post-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 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 |
|
| Progestogen-related |
|
| Vaginal bleeding | Unscheduled vaginal bleeding is a normal and common adverse effect, if it happens within the following time frames:
Expected vaginal bleeding patterns after the first 3 months:
|
Complications
Key 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
Such risk could be almost eliminated by using a 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
Unscheduled vaginal bleeding is a common side effect of HRT, when it occurs during the following timeframes:
- During the first 6 months of initiating HRT
- During the first 3 months of changing HRT (dose or preparation)
Expected vaginal bleeding patterns after the above timeframes:
- Monthly cyclical regimen → regular withdrawal bleeding (towards the end of the progesterone phase)
- Continuous regimen → complete amenorrhoea
If unscheduled vaginal bleeding occurs beyond the above-mentioned timeframes (i.e. >6 months of initiating HRT and >3 months of changing HRT) → advise patients to seek medical review promptly
Summarised and simplified guideline for abnormal bleeding:
- Perform urgent TVUSTrans-vaginal ultrasound to measure endometrial thickness
- TVUSTrans-vaginal ultrasound interpretation
- Thickened endometrium needs urgent suspected cancer pathway referral
- Definition of thickened is >4mm in continuous HRT and >7mm in cyclical HRT
If TVUSTrans-vaginal ultrasound 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)
References
NICE CKS Menopause: Hormone replacement therapy (HRT)
NICE BNF Treatment summaries Sex hormones