Educational draft · awaiting clinical reviewThe full textbook explains uncertainty but does not replace live national or local guidance, specialist advice, or current prescribing information.
Hormone-replacement therapy choices and contraindications
Obstetrics and gynaecology · UK scope · Sources checked 27 Aug 2026 · Clinical review pending
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Stop and assess a possible serious complication
New chest pain, breathlessness, unilateral leg swelling, focal neurology, jaundice, major blood-pressure rise, new migraine-type headache or pregnancy during systemic HRT may represent a contraindication or acute adverse event.
Action: Stop the relevant systemic product, assess observations and the suspected thrombotic, arterial, hepatic or pregnancy complication urgently, and do not simply switch formulation before the diagnosis is clear.
Purpose and principles
Select systemic HRT by uterine status, menopausal stage, route and risk while applying product contraindications, proportional endometrial protection, licensed doses and balanced absolute-risk communication.
Begin with treatment goals and anatomy. Systemic HRT is offered for troublesome vasomotor and related menopausal symptoms after shared discussion. A person with a uterus requires adequate progestogen to oppose systemic oestrogen; someone who has had a total hysterectomy is usually offered oestrogen alone. Subtotal hysterectomy may leave endometrium, and extensive endometriosis can remain hormone responsive after hysterectomy, so specialist advice may favour continued progestogen. HRT is not contraception, and ovulation remains possible during perimenopause.
Choose regimen according to bleeding biology. Sequential HRT supplies oestrogen continuously and progestogen for part of each 28-day cycle, producing an expected withdrawal bleed; it suits people still cycling or close to the final menstrual period. Continuous combined HRT supplies both every day and aims for amenorrhoea after an initial settling period; introducing it too early can cause irregular bleeding. Current BMS advice is to offer a switch from sequential to continuous combined HRT after five years of sequential use beyond age 45 or by age 54, whichever occurs first.
Practice
Two practice questions
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Question 1 of 2
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Obstetrics and gynaecologyOriginal SBA
Protecting an intact uterus
A 51-year-old with troublesome hot flushes wants systemic HRT. She has an intact uterus, no contraindication and periods stopped fourteen months ago. Which hormonal structure is generally appropriate?
Sources and review status6 sources · checked 27 Aug 2026 · clinical review pending+
Sources
Sources and review status
National guidance is shown before implementation-dependent detail. Typical adult dose examples remain subject to patient factors, contraindications and the live BNF or specialist protocol. Source check completed 27 Aug 2026; clinical approval remains outstanding.
Route changes risk and convenience. Oral oestrogen undergoes first-pass hepatic metabolism and increases VTE risk; transdermal estradiol avoids this first pass and is preferred when thrombosis risk is raised, including BMI over 30 kg/m². NICE also describes stroke risk as unlikely to increase with transdermal oestrogen, whereas oral-oestrogen risk rises with dose, duration and older age at initiation. Patches provide fixed delivery but can irritate skin; gels and sprays allow titration but depend on correct application and drying. Oral regimens may give more predictable bleeding but are unsuitable for some thrombotic or metabolic profiles.
Dose is product specific. The August 2026 BMS practical table groups patches delivering 25 to 37.5 micrograms per 24 hours as low dose, 40 to 75 as medium and 100 as high; oral estradiol 0.5 mg is low, 1 to 2 mg medium and 3 mg high, with 3 mg outside licence; Oestrogel one pump is low, two to three medium and four high. These bands guide proportional progestogen, not automatic escalation. Check the exact SmPC: for example, Evorel is changed twice weekly and commonly starts at 50 micrograms per 24 hours, while Oestrogel is usually started at two pumps, 1.5 mg estradiol, once daily.
Separate licence contraindications from conditions needing expert balance. Current systemic-oestrogen labels list known, past or suspected breast cancer; known or suspected oestrogen-dependent malignancy; unexplained genital bleeding; untreated endometrial hyperplasia; previous or current DVT or pulmonary embolism; known thrombophilia; active or recent angina, myocardial infarction or other arterial thromboembolism; acute liver disease or past liver disease before normalisation; porphyria; pregnancy and hypersensitivity. Fibroids, endometriosis, migraine, controlled hypertension, diabetes, gallstones, epilepsy, asthma and lupus are not an automatic universal ban, but require product-aware review and monitoring.
Discuss risk with absolute numbers and uncertainty. In the 2024 NICE aid, among 1,000 people followed from age 50 to 69, about 59 who never use HRT develop breast cancer. The estimate is 79 after five years of combined HRT and 92 after ten years; with oestrogen-only HRT it is 69 after five years and 71 after ten. Combined risk increases with duration, is lower with sequential than continuous combined treatment, falls after stopping but persists for at least ten years, and evidence is insufficient to claim micronised progesterone eliminates it. These population estimates must be integrated with individual baseline risk.
Other outcomes require equal precision. From age 50 to 54, NICE estimates endometrial cancer in 4 per 1,000 non-users, 1 per 1,000 continuous-combined users, 8 per 1,000 sequential-combined users and 11 per 1,000 people with a uterus using unopposed oestrogen. Ovarian cancer rises only very slightly, from about 1 to 2 per 1,000 over five years. HRT reduces fragility fractures while taken; coronary heart disease and cardiovascular mortality do not increase in people without previous disease, and overall life expectancy is unlikely to change. Starting combined HRT at 65 or over might increase dementia risk, so HRT should not be started to prevent dementia.
Before prescribing, document symptom burden, uterine and menstrual status, pregnancy and contraception, breast and gynaecological history, VTE and arterial history, migraine, liver disease, medicines, smoking, BMI and blood pressure. Ensure screening is current without delaying necessary symptom care solely for routine mammography. Enzyme inducers can reduce hormone exposure and provoke bleeding; systemic oestrogen can lower lamotrigine concentrations, risking loss of seizure control. Avoid compounded products whose purity, dose and safety are unregulated. Review at three months, then annually, and rediscuss continuation rather than imposing an arbitrary stopping age.
Key points
Offer combined oestrogen-progestogen HRT to someone with a uterus and oestrogen-only HRT after total hysterectomy; residual endometriosis or uncertain residual endometrium needs specialist individualisation.
Use a sequential combined regimen while periods continue or early in the transition, and a continuous combined regimen after menopause when a bleed-free regimen is appropriate.
Start with a licensed low or standard dose, review after three months and titrate to the lowest dose that controls the agreed symptoms; high or off-label dosing is exceptional.
Prefer transdermal oestrogen when VTE risk is increased, including BMI above 30 kg/m², because NICE reports no increased VTE risk with transdermal HRT but an increase with oral HRT.
Systemic product labels contraindicate use with known, past or suspected breast cancer, oestrogen-dependent cancer, unexplained bleeding, untreated hyperplasia, current or previous VTE, thrombophilia, active or recent arterial thromboembolism, active liver disease and porphyria.
A previous coronary event or stroke requires specialist discussion: NICE supports individualised consideration, while active or recent arterial disease remains a product-label contraindication.
HRT does not provide contraception, and transdermal delivery does not remove the need for progestogen when a uterus is present.
Indications, selection and cautions
Sequential candidate
Ongoing menstrual activity or early perimenopause favours cyclic progestogen and an anticipated withdrawal bleed rather than immediate continuous-combined treatment.
Continuous-combined candidate
Established postmenopause and a preference for amenorrhoea support daily combined therapy after counselling that early spotting can occur.
Transdermal advantage
Raised VTE risk, BMI above 30, migraine or concern about first-pass hepatic effects often shifts the balance toward a patch or gel.
Specialist-risk context
Previous breast cancer, coronary disease, stroke, complex thrombophilia, significant liver disease or uncertain uterine anatomy requires condition-specific expertise before systemic treatment.
Possible over-treatment
Breast tenderness, bloating, headache, persistent bleeding or new adverse effects after escalation prompts review of dose, route and progestogen rather than further automatic increase.
Red flags requiring action
Sudden breathlessness, pleuritic pain, haemoptysis or unilateral painful leg swelling requires urgent venous-thromboembolism assessment and interruption of systemic HRT.
New facial or limb weakness, speech disturbance, severe acute headache or retinal symptoms requires an emergency stroke pathway.
Jaundice, dark urine, pale stools or marked right-upper-quadrant symptoms suggests liver injury and requires treatment interruption and liver assessment.
Assessment before treatment
01Pre-treatment history, BMI and blood pressureFirst step
Why
Identify systemic-HRT contraindications, route modifiers and a baseline for monitoring.
Interpretation and limitations
A raised but non-emergency blood pressure is managed before or alongside an individual decision; active thrombotic, malignant or hepatic contraindications prevent routine prescribing.
02Pregnancy assessment when relevant
Why
Exclude pregnancy before exposing a potentially fertile person to a non-contraceptive hormone regimen.
Interpretation and limitations
A negative test addresses the current episode only; ongoing contraception remains necessary until established stopping criteria are met.
03Bleeding and uterine-status assessment
Why
Determine whether progestogen is required and whether abnormal bleeding needs investigation before treatment.
Interpretation and limitations
An intact or possibly residual endometrium needs protection, while unexplained postmenopausal bleeding takes priority over HRT initiation.
04Targeted thrombosis or specialist assessment
Why
Clarify treatment safety when personal or strong family VTE history, thrombophilia, stroke or coronary disease is present.
Interpretation and limitations
The result informs route or avoidance; a transdermal route lowers VTE impact but does not make active thromboembolic disease safe for routine prescribing.
Treatment approach
01DesignChoose the hormonal architectureFirst stepSystemic HRT is desired after benefits, risks and alternatives have been discussed.+
1Confirm uterine status, menstrual stage, contraception, symptom priorities and whether previous endometriosis alters the usual oestrogen-only approach after hysterectomy.
2Select sequential combined, continuous combined or oestrogen-only treatment and ensure progestogen exposure is proportional to the oestrogen dose.
3Choose oral or transdermal delivery from VTE, stroke, migraine, liver, metabolic, adherence and preference considerations.
02SafetyReconcile history with the product labelA formulation and dose are being considered for prescription.+
Provides oestrogen replacement without oral first-pass metabolism for vasomotor and other systemic menopausal symptoms.
Evorel estradiol transdermal patch
Apply a patch delivering 50 micrograms of estradiol per 24 hours and replace it twice weekly; adjust within the licensed 25 to 100 microgram range.
Add adequate progestogen when a uterus is present, rotate application sites below the waist, check the exact product schedule and reassess before using the maximum dose.
Allows transdermal oestrogen titration when a gel is preferred to a patch or oral regimen.
Oestrogel estradiol gel
Apply two metered pumps, containing 1.5 mg estradiol in total, to clean dry skin once daily; the licensed maximum is four pumps daily.
Allow it to dry, prevent transfer to others, keep away from breasts and genital skin, and provide dose-proportional progestogen for anyone with a uterus.
Provides a licensed continuous-sequential transdermal regimen with cyclic norethisterone for a person who retains a uterus.
Evorel Sequi
Use an Evorel 50 patch twice weekly for days 1 to 14, then an Evorel Conti patch twice weekly for days 15 to 28 without a treatment gap.
Expect a withdrawal bleed, use the patches in the correct order, assess contraindications to both hormones and investigate bleeding outside the expected settling pattern.
Complications, monitoring and follow-up
At the three-month review, document symptom response, side effects, adherence, application technique, bleeding and whether the current dose remains the lowest effective option.
Measure blood pressure and review weight, smoking, mobility, VTE and cardiovascular history as clinically indicated rather than repeating reproductive-hormone concentrations.
Ask about breast symptoms and support age- and risk-appropriate screening; refer a new mass or nipple change without attributing it to expected tenderness.
Review progestogen dose whenever systemic oestrogen is increased and verify the age, regimen and insertion date of any 52 mg levonorgestrel IUD used for protection.
At least annually, rediscuss current benefits, route-specific and cancer risks, alternatives, contraception and the person's preference to continue, reduce or stop.
Special situations
Route is a risk intervention
Choosing transdermal rather than oral oestrogen changes hepatic coagulation effects and can be more important than choosing between two brands.
The uterus sets one rule
Any functioning endometrium exposed to systemic oestrogen needs protection, regardless of whether delivery is oral, through skin or marketed as body-identical.
Sequential is not risk free
Cyclic progestogen produces lower breast-cancer risk than continuous combined HRT but remains higher risk than no HRT and may slightly increase endometrial risk.
Numbers need a denominator
Absolute risk estimates describe a population over a specified period; they should modify, not replace, the person's baseline risks and priorities.
No arbitrary finish line
Continuation depends on current symptom benefit, age, route and evolving health rather than an automatic birthday or fixed number of treatment years.
Common pitfalls
01
Prescribing oestrogen alone to someone with an intact uterus because the preparation is transdermal or described as body-identical.
02
Treating previous VTE as solved simply by choosing a patch, without recognising systemic-product contraindications and seeking appropriate expertise.
03
Starting continuous combined HRT during active perimenopausal cycling and then misclassifying the resulting irregular bleeding as treatment failure.
04
Quoting relative cancer risk without duration, baseline risk or the major difference between combined and oestrogen-only treatment.
05
Escalating beyond licensed doses before checking adherence, application, absorption, diagnosis and adequacy of progestogen.
06
Assuming HRT prevents pregnancy or using FSH during combined hormonal contraception to decide that contraception is no longer required.
Review efficacy, adverse effects, bleeding, blood pressure and evolving risk at three months then annually; there is no universal maximum duration when benefits continue to outweigh risks.
Undiagnosed genital bleeding or known untreated endometrial hyperplasia must be investigated before systemic oestrogen is started.
A new breast mass, nipple change or diagnosis of breast cancer needs prompt breast assessment; systemic HRT is stopped when breast cancer is diagnosed.
05Medication interaction review
Why
Identify enzyme induction, lamotrigine interaction and other medicine-specific constraints before choosing formulation.
Interpretation and limitations
Reduced hormone exposure may cause symptom return or bleeding, while falling lamotrigine concentrations can compromise seizure control and require specialist monitoring.
2
Identify interacting medicines, particularly hepatic enzyme inducers and lamotrigine, and arrange specialist input when a condition makes the balance uncertain.
3Record baseline blood pressure and BMI, provide thrombosis and bleeding safety-netting and explain that systemic HRT is not contraceptive.
03OptimiseAdjust by benefit and harmThe person returns after starting or changing HRT.+
1At three months, review the specific target symptoms, adherence, side effects, bleeding pattern, blood pressure and application technique.
2Change one variable at a time—dose, route, oestrogen or progestogen—using a licensed range where possible and maintaining endometrial protection.
3Continue annual individual review without a fixed stopping date, but stop and investigate a new contraindication or serious adverse-event signal promptly.