Hormone Replacement Therapy (HRT)
Summary
Hormone Replacement Therapy (HRT), also called Menopausal Hormone Therapy (MHT), is the administration of systemic Oestrogen (with or without Progestogen) to replace declining ovarian hormones in peri-menopausal and post-menopausal women. It is the most effective treatment for vasomotor symptoms (Hot flushes, Night sweats) and Genitourinary Syndrome of Menopause (GSM). It also provides bone protection (reduces osteoporosis and fracture risk). The key prescribing principle is: Oestrogen for all, add Progestogen ONLY if the Uterus is present (to protect against endometrial hyperplasia/cancer). Route (Oral vs Transdermal) matters for VTE risk. [1,2]
Clinical Pearls
"Progestogen for Protection (of the Uterus)": If a woman has a Uterus, give Combined HRT (Oestrogen + Progestogen). If she has had a Hysterectomy, give Oestrogen Only.
Transdermal is Safer: Transdermal oestrogen (patches, gels) bypasses the liver, has NO increased VTE risk, and is preferred for obese women, smokers, and those with VTE risk factors.
"Start Low, Go Slow, But Aim High (Enough)": Begin with a low dose and titrate up to achieve symptom control. Many women are undertreated.
Contraception is Still Needed: Women are considered potentially fertile for 2 years after last period (if under 50) or 1 year (if over 50). HRT is not contraceptive (except the Mirena IUS as the progestogen component).
Indications for HRT
- Vasomotor Symptoms: Hot flushes, Night sweats.
- Genitourinary Syndrome of Menopause (GSM): Vaginal dryness, Dyspareunia, Urinary urgency/frequency/recurrent UTIs. (Can use Local Vaginal Oestrogen).
- Premature Ovarian Insufficiency (POI): Women with menopause less than 40 years. HRT strongly recommended until at least age 51 to replace normal hormones and protect bones/heart.
- Osteoporosis Prevention: HRT is an option for bone protection.
Timing
- "Window of Opportunity": Benefits are greatest and risks lowest when HRT is started less than 60 years old or within 10 years of menopause.
Menopause Physiology
- Ovarian Follicle Depletion: Ovaries run out of oocytes.
- Oestrogen Decline: Oestrogen levels fall dramatically.
- Loss of Negative Feedback: LH and FSH rise (FSH >30 IU/L is diagnostic).
- Symptoms: Vasomotor instability (hot flushes), Urogenital atrophy, Bone loss, Mood changes.
How HRT Works
- Oestrogen: Replaces the deficient hormone. Controls vasomotor symptoms, reverses urogenital atrophy, maintains bone density.
- Progestogen: Opposes the proliferative effect of oestrogen on the endometrium, preventing hyperplasia and cancer.
| Absolute Contraindications | Relative Cautions (Needs Assessment) |
|---|---|
| Active/Recent Breast Cancer | Strong Family History Breast Cancer |
| Active/Recent Coronary Heart Disease / Stroke | Previous VTE (Consider Transdermal) |
| Undiagnosed Vaginal Bleeding | Obesity, Smoking (Consider Transdermal) |
| Active Liver Disease | Migraine with Aura |
| Pregnancy | Gallbladder Disease |
| Active VTE/PE | Endometriosis (May need progestogen even if no uterus) |
Symptoms
- Vasomotor: Hot flushes, Night sweats, Palpitations.
- Urogenital (GSM): Vaginal dryness, Itching, Dyspareunia, Urinary symptoms.
- Psychological: Low mood, Anxiety, Irritability, Brain fog, Poor concentration.
- Sleep Disturbance: Often secondary to night sweats.
- Musculoskeletal: Joint aches.
Diagnosis of Menopause
- Clinical (in women >45): Typical symptoms in a woman with cycle changes. No blood test needed.
- FSH Testing: Only useful if diagnostic uncertainty (e.g., young woman, post-hysterectomy). FSH >30 IU/L suggests menopause.
Clinical Assessment
- History: Symptoms, Last Menstrual Period, Contraception needs, Medical history, VTE history, Family history (Breast Cancer).
- Examination: BMI, Blood Pressure.
- Breast Screening: Ensure up to date with NHS mammography (every 3 years from age 50).
Investigations (Not Routinely Required)
- Blood tests are not routinely needed to start HRT in women >45 with typical symptoms.
- Consider FSH if young (less than 45) or uncertain diagnosis.
- Baseline Mammogram if not up to date.
- Consider DEXA scan if osteoporosis is the indication.
Management Algorithm
MENOPAUSAL SYMPTOMS
↓
DISCUSS BENEFITS vs RISKS
(Individualised)
↓
UTERUS PRESENT?
┌──────────────┴──────────────┐
YES NO
↓ ↓
COMBINED HRT OESTROGEN-ONLY HRT
(Oestrogen + Progestogen)
↓ ↓
STILL HAVING PERIODS? ROUTE?
┌────┴────┐ Transdermal preferred if:
YES NO - VTE history/risk
↓ ↓ - Obesity, Smoker
SEQUENTIAL CONTINUOUS ↓
(Cyclical) Combined OESTROGEN
(Monthly (No bleed) (Patch/Gel)
bleed)
↓
PROGESTOGEN OPTIONS:
- Oral (e.g. Norethisterone, Medroxyprogesterone)
- Mirena IUS (Provides progestogen + contraception)
- Patch (e.g. Evorel)
↓
START LOW, TITRATE UP
REVIEW AT 3 MONTHS
HRT Regimens
1. Oestrogen Component
| Route | Examples | Notes |
|---|---|---|
| Oral | Estradiol (Elleste Solo), Conjugated Equine Oestrogen (Premarin) | First-pass liver metabolism. Increases VTE risk. |
| Transdermal Patch | Estradot, Evorel | No first-pass. No VTE risk increase. Preferred for high-risk women. |
| Transdermal Gel | Oestrogel, Sandrena | No VTE risk. Easy to titrate. |
| Vaginal (Local only) | Vagifem (pessary), Ovestin (cream), Estring | For GSM symptoms only. Minimal systemic absorption. Safe even with Breast Cancer history. |
2. Progestogen Component (If Uterus Present)
| Type | Regimen | Notes |
|---|---|---|
| Sequential (Cyclical) | Daily Oestrogen + Progestogen for last 12-14 days of 28-day cycle. | Causes predictable monthly withdrawal bleed. For Perimenopausal women (still having some cycles). |
| Continuous Combined | Daily Oestrogen + Daily Progestogen. | No bleed. For Postmenopausal women (>12 months since LMP). |
| Mirena IUS (Levonorgestrel IUS) | Provides progestogen locally to uterus. | Also provides contraception. Progestogen component for 4 years when used with Oestrogen HRT. |
3. Combined Preparations
- Oral: Kliovance (Continuous), Femoston (Sequential or Continuous versions).
- Transdermal Patch: Evorel Conti (Continuous), Evorel Sequi (Sequential).
Additional Therapies
- Vaginal Oestrogen (Local): Can be used ALONGSIDE systemic HRT for persistent GSM symptoms. Can be used ALONE if GSM is the only issue.
- Testosterone: Unlicensed in UK. Can be added for low libido (Hypoactive Sexual Desire Disorder). Specialist initiation.
Benefits of HRT
| Benefit | Notes |
|---|---|
| Vasomotor symptom relief | Most effective treatment. 80-90% relief. |
| GSM symptom relief | Reverses vaginal atrophy. |
| Bone Protection | Prevents osteoporosis and fractures. |
| Cardiovascular Protection (if started early) | Some evidence for reduced CHD if started less than 60yo and within 10 years of menopause (not approved indication). |
| Reduced Colorectal Cancer Risk | Small benefit. |
| Improved Quality of Life | Sleep, Mood, Cognition all improved. |
Risks of HRT
| Risk | Magnitude | Notes |
|---|---|---|
| Breast Cancer (Combined HRT) | Small increased risk (~5 extra cases per 1000 women over 5 years). Similar to obesity/alcohol risk. Risk returns to baseline within ~5 years of stopping. | Oestrogen-only HRT has little/no increased risk if less than 5 years use. |
| VTE (Oral HRT only) | ~2-fold increase (but baseline risk is low). | Transdermal HRT has NO increased VTE risk. Prescribe transdermal if VTE risk factors present. |
| Stroke (Oral HRT only) | Small increased risk. | Transdermal is safer. |
| Endometrial Cancer | Risk if Oestrogen Only given to woman WITH Uterus. | Prevented by adding Progestogen. Not a risk with Combined HRT. |
| Ovarian Cancer | Very small increased risk. | ~1 extra case per 1000 women over 5 years. |
- Symptom Relief: Majority of women experience significant improvement in menopausal symptoms within weeks to months.
- Duration of Treatment: No arbitrary time limit. Review annually. Continue as long as benefits outweigh risks. Many women use HRT for 5-10+ years.
- Stopping HRT: Can stop abruptly or gradually. Symptoms may return.
Key Guidelines
| Guideline | Organisation | Key Recommendations |
|---|---|---|
| NICE NG23 | NICE | HRT is first-line for vasomotor symptoms. Transdermal preferred if VTE risk. No increased VTE risk with transdermal. No arbitrary limits on duration. |
| BMS Consensus Statement | British Menopause Society | Benefits outweigh risks for most symptomatic women under 60. Progestogen via Mirena IUS is acceptable. |
Landmark Evidence
1. Women's Health Initiative (WHI)
- Initial results (2002) overstated risks. Led to a significant decline in HRT use.
- Reanalysis: For women less than 60yo, benefits outweigh risks. Timing hypothesis confirmed.
2. NICE NG23 (2015)
- Clarified risks are small. Endorsed transdermal as safe for VTE. Improved HRT prescribing.
What is HRT?
HRT replaces the hormones (mainly Oestrogen) that your ovaries stop making during menopause. It is the most effective treatment for hot flushes, night sweats, and vaginal dryness.
Is it safe?
For most women under 60, the benefits outweigh the risks. The risks (like breast cancer and blood clots) are small and depend on the type and how you take it. Patches and gels are safer than tablets for blood clots.
Do I need to add Progesterone?
Only if you still have your womb. Progesterone protects the lining of your womb from becoming too thick. If you've had a hysterectomy, you only need Oestrogen.
How long can I take it?
There is no fixed time limit. You should review it with your doctor every year. Many women take HRT for many years.
What if I can't take HRT?
There are non-hormonal options for hot flushes (e.g., SSRIs, Gabapentin) and vaginal dryness (e.g., moisturisers). These are less effective but can help.
Primary Sources
- NICE Guideline NG23. Menopause: diagnosis and management. 2015 (Updated 2019).
- British Menopause Society. Tools for Clinicians. bms.org.uk.
- Stuenkel CA, et al. Treatment of Symptoms of the Menopause: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2015.
Common Exam Questions
- Prescribing: "Woman with Uterus needs HRT. What must you add?"
- Answer: Progestogen (to prevent endometrial cancer).
- Safety: "Patient has history of DVT. Can she have HRT?"
- Answer: Yes, but give Transdermal (no VTE risk increase).
- Contraindication: "Active Breast Cancer. Can she have HRT?"
- Answer: No. Absolute Contraindication.
- Regimen: "Woman 1 year post-menopause, no periods. Cyclical or Continuous?"
- Answer: Continuous (no bleed regimen).
Viva Points
- Mirena IUS as Progestogen: Explain that the Mirena IUS can act as the progestogen component of HRT, providing endometrial protection AND contraception.
- WHI Controversy: Be able to discuss why initial WHI results overstated risk (older population, older HRT) and how reanalysis supports the "Timing Hypothesis".
Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.