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← Obstetrics and gynaecology indexChapter sections
Purpose and principlesIndications, selection and cautionsAssessment before treatmentTreatment approachRegimens, contraindications and interactionsComplications, monitoring and follow-upSpecial situationsCommon pitfallsQuestionsSources
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Educational draft · awaiting clinical reviewThe full textbook explains uncertainty but does not replace live national or local guidance, specialist advice, or current prescribing information.

Non-hormonal symptom treatment

Obstetrics and gynaecology · UK scope · Sources checked 27 Aug 2026 · Clinical review pending

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Recognise toxicity or a mental-health emergency

Jaundice, dark urine, severe abdominal pain or marked fatigue during fezolinetant may indicate liver injury; a new seizure during elinzanetant, suicidal intent, mania, serotonin toxicity, collapse, profound bradycardia or severe hypotension also needs urgent assessment.

Action: Stop the suspected medicine where its safety instructions require this, assess observations and the relevant organ or mental-health emergency urgently, and arrange same-day testing or emergency referral rather than attributing the presentation to menopause.

Purpose and principles

Select evidence-based non-hormonal treatment for vasomotor, sleep and mood symptoms when HRT is unsuitable or not preferred, including the March 2026 NICE fezolinetant pathway and safe medicine monitoring.

Non-hormonal management starts by defining the target symptom and why systemic HRT is unsuitable or unwanted. Vasomotor symptoms, insomnia, depression, anxiety, genitourinary symptoms and sexual pain do not share one treatment. Menopause-specific cognitive behavioural therapy teaches paced breathing, cognitive reframing, behavioural sleep strategies and reduction of avoidance or symptom vigilance; NICE supports it for vasomotor symptoms, sleep disturbance associated with flushes and subthreshold depressive symptoms. Practical measures such as layered clothing, a cool sleeping environment, reducing personally recognised alcohol or caffeine triggers, regular activity and smoking cessation may improve wellbeing, but should not be presented as a guaranteed cure.

Practice

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Obstetrics and gynaecologyOriginal SBA

Fezolinetant safety before starting

A 52-year-old has moderate to severe hot flushes and HRT is unsuitable. Her ALT is 2.3 times the upper limit of normal before treatment. What is the best next step?

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Sources and review status8 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.

  • NICE NG23 menopause recommendations updated April 2026
  • NICE TA1143 fezolinetant recommendation
  • Veoza 45 mg SmPC
  • Lynkuet 60 mg SmPC updated August 2026
  • NICE elinzanetant menopause appraisal awaiting development
  • NICE elinzanetant breast-cancer endocrine-therapy appraisal awaiting development
  • BMS non-hormonal treatments consensus statement
  • Clonidine 25 microgram tablets SmPC

Editorial contact: Doctor’s Passport editorial team. Source-check date is separate from clinical approval. Report a content problem · Content changes

Authoring stateComplete draftClinical stateAwaiting review
The 2026 prescribing change is fezolinetant, a non-hormonal neurokinin-3 receptor antagonist. NICE TA1143 recommends it for moderate to severe vasomotor symptoms associated with menopause when HRT is unsuitable. This is narrower than simply preferring a tablet without discussion. Confirm that flushes are menopausal, review pregnancy possibility, liver and kidney function, and reconcile medicines for CYP1A2 inhibitors. It does not treat vaginal atrophy, prevent osteoporosis or provide contraception. The SmPC does not recommend it during active oncological treatment for breast or another oestrogen-dependent malignancy, or alongside systemic oestrogen HRT, and gives no initiation dose for people over 65 because safety and efficacy are not established. Benefit and tolerability should be reassessed rather than continued automatically.

SSRIs, SNRIs, gabapentin and clonidine have evidence for reducing flush frequency or severity, but NICE advises against routinely using an SSRI, SNRI or clonidine as first-line treatment for vasomotor symptoms alone. They may be considered selectively when licensed or guideline-recommended options do not fit, with transparent discussion of off-label status where relevant. Coexisting depression is treated as depression: assess severity, bipolar history, self-harm risk and interactions, then follow the mental-health guideline rather than choosing an antidepressant solely because it may also reduce flushing. Avoid complementary preparations with uncertain composition or interactions, particularly St John's wort with tamoxifen or other medicines.

Elinzanetant is a newly licensed combined neurokinin-1 and neurokinin-3 antagonist for moderate to severe vasomotor symptoms associated with menopause or caused by breast-cancer adjuvant endocrine therapy. As of 31 August 2026, NICE appraisals for both indications remain awaiting development. Its regimen is 120 mg at bedtime, reduced to 60 mg with a moderate CYP3A4 inhibitor. Strong CYP3A4 inhibitors, severe hepatic impairment and pregnancy are contraindications; Child-Pugh B and eGFR below 30 mL/min/1.73 m² are not recommended. Check baseline liver tests, seizure history, effective contraception and sedating effects, and do not combine it with systemic oestrogen HRT because that combination has not been studied.

Key points

  • Offer menopause-specific CBT for vasomotor symptoms, either alongside HRT or when HRT is contraindicated or declined.
  • NICE TA1143 recommends fezolinetant for moderate to severe menopausal vasomotor symptoms when HRT is unsuitable.
  • Fezolinetant is 45 mg once daily; liver tests and CYP1A2 interactions are central to safe prescribing.
  • Do not routinely offer an SSRI, SNRI or clonidine as first-line treatment for vasomotor symptoms alone.
  • An antidepressant may still be appropriate for a diagnosed depressive or anxiety disorder, selected under the relevant guideline.
  • Gabapentin can reduce flushes but sedation, falls, renal dose adjustment, dependence and withdrawal limit its use.
  • Clonidine has modest benefit and can cause dry mouth, constipation, sedation, hypotension and bradycardia; taper rather than stop abruptly.
  • As of 31 August 2026, elinzanetant is UK-licensed but its two NICE appraisals remain awaiting development; check commissioning and the current SmPC rather than treating licensing as a national recommendation.

Indications, selection and cautions

Vasomotor burden

Quantify flushes and sweats by frequency, severity, sleep interruption and effects on work, driving, relationships and quality of life.

Sleep phenotype

Separate waking caused by sweating from sleep apnoea, restless legs, depression, substance use, pain and primary insomnia because treatment differs.

Reason HRT is unsuitable

A true contraindication, temporary diagnostic uncertainty, unacceptable risk, adverse effect or informed preference creates a different non-hormonal discussion.

Psychological comorbidity

Depression, anxiety, mania, trauma, self-harm and problematic alcohol use can coexist with menopause and require their own assessment.

Cancer-treatment interaction

Breast-cancer endocrine therapy matters because some antidepressants inhibit CYP2D6 and can reduce conversion of tamoxifen to its active metabolite.

Atypical flushing

Fever, diarrhoea, wheeze, weight loss, tremor, persistent tachycardia or a medicine relationship directs investigation toward an alternative cause.

Red flags requiring action

  • Jaundice, dark urine, pale stools, right-upper-quadrant pain or unexplained marked fatigue while taking fezolinetant
  • ALT or AST above five times the upper limit of normal, or at least three times the limit with bilirubin above twice the limit or liver symptoms
  • Suicidal thoughts, severe depression, mania, psychosis or inability to maintain personal safety
  • Fever, agitation, clonus and autonomic instability after a serotonergic medicine change
  • Syncope, severe postural hypotension, new bradycardia or conduction symptoms during clonidine
  • A new seizure, collapse or altered consciousness while taking elinzanetant requires urgent neurological and medicine assessment
  • New focal neurological deficit, chest pain, breathlessness, pelvic mass symptoms or unexplained weight loss that should not be labelled as menopause

Assessment before treatment

  1. 01
    Symptom and treatment recordFirst step
    Why
    Establish a baseline frequency and functional burden and identify triggers or previous responses.
    Interpretation and limitations
    A brief diary supports a specific treatment goal and distinguishes a meaningful response from natural fluctuation or recall bias.
  2. 02
    Medicine and interaction reconciliation
    Why
    Identify CYP1A2 inhibitors, serotonergic combinations, tamoxifen, sedatives, antihypertensives and complementary products.
    Interpretation and limitations
    Moderate or strong CYP1A2 inhibition contraindicates fezolinetant; other interactions may favour CBT or a different pharmacological option.
  3. 03
    Baseline ALT, AST and bilirubin
    Why
    Check suitability before fezolinetant and provide a comparison if symptoms of liver injury develop.
    Interpretation and limitations
    Do not start if ALT or AST is at least twice the upper limit of normal or total bilirubin is at least twice the limit; investigate the abnormality.
  4. 04
    Renal and hepatic assessment
    Why
    Select and dose medicines safely, particularly fezolinetant, elinzanetant and gabapentin.
    Interpretation and limitations
    Fezolinetant is not recommended at eGFR below 30 mL/min/1.73 m² or in Child-Pugh B or C chronic hepatic impairment. Elinzanetant is not recommended below eGFR 30 or in Child-Pugh B and is contraindicated in Child-Pugh C; gabapentin requires renal adjustment.
  5. 05
    Targeted alternative-cause testing
    Why
    Investigate atypical symptoms rather than ordering a routine panel for every menopausal flush.
    Interpretation and limitations
    TSH, blood count, glucose, inflammatory, infection or malignancy assessment is driven by the history and examination; normal FSH does not validate a non-hormonal prescription.

Treatment approach

01First non-hormonal choiceUse CBT and define the targetFirst stepVasomotor symptoms are troublesome and HRT is contraindicated, unsuitable or declined.+
  1. 1AlternativeConfirm a menopausal pattern, identify alternative diagnoses and agree whether flush frequency, sleep or distress is the primary outcome.
  2. 2Offer menopause-specific CBT and practical symptom strategies, addressing access, language, disability and digital-exclusion needs.
  3. 3Review after an agreed course using baseline symptom and function measures; add or switch treatment if benefit is insufficient.
022026 NICE medicine pathwayPrescribe fezolinetant safelyModerate to severe menopausal vasomotor symptoms persist and HRT is unsuitable.+
  1. 1Check pregnancy possibility, liver and kidney status and all prescription, over-the-counter and herbal CYP1A2 interactions before prescribing.
  2. 2Start 45 mg orally once daily and arrange monthly liver tests for the first three months, with explicit symptoms and thresholds for stopping.
  3. 3Review symptom benefit, diarrhoea, insomnia and liver results; stop for specified liver injury, pregnancy, unacceptable harm or absent worthwhile benefit.
03Individualised alternativeMatch other medicines to comorbidityPreferredAlternativeCBT and the preferred licensed pathway do not meet need or another condition creates a therapeutic reason for a different medicine.+
  1. 1Treat diagnosed depression or anxiety under its own guideline; consider tamoxifen, blood pressure, renal function, falls, dependence and withdrawal risks.
  2. 2Agree that any off-label vasomotor trial has one target, a cautious titration and a defined review date rather than stacking several sedating medicines.
  3. 3Continue only if benefit is meaningful; taper venlafaxine, gabapentin or clonidine gradually according to exposure and product advice to avoid withdrawal.

Regimens, contraindications and interactions

NICE-recommended non-hormonal option for moderate to severe menopausal vasomotor symptoms when HRT is unsuitable.

Fezolinetant (Veoza)

Take 45 mg orally once daily at about the same time, with or without food; swallow the tablet whole.

Contraindicated with moderate or strong CYP1A2 inhibitors and in known or suspected pregnancy. Do not initiate with ALT, AST or bilirubin at least twice the upper limit; avoid eGFR below 30 and Child-Pugh B or C, and follow monthly liver testing for three months. The SmPC does not recommend use during active oncological treatment for breast or another oestrogen-dependent malignancy, with systemic oestrogen HRT, or initiation above age 65.

May reduce vasomotor symptoms and can treat a coexisting depressive or anxiety disorder when chosen under the appropriate guideline.

Venlafaxine modified release (off-label for vasomotor symptoms)

A specialist menopause regimen may start at 37.5 mg orally once daily and increase according to response and tolerability, commonly to 75 mg daily and no higher than 150 mg daily for this purpose.

Check blood pressure, bipolarity, suicide and overdose risk, serotonin interactions and tamoxifen context; nausea and sexual dysfunction occur, and abrupt cessation causes withdrawal.

Can reduce flushes and may be useful when night-time symptoms dominate and other options are unsuitable.

Gabapentin (off-label for vasomotor symptoms)

A commonly used regimen starts at 300 mg orally at night or once daily, then titrates gradually if needed toward 300 mg three times daily with renal adjustment.

Dizziness, somnolence, oedema, falls, respiratory depression with opioids, dependence and withdrawal are important; do not stop abruptly after regular use and reduce the dose in renal impairment.

A licensed but generally less effective option for menopausal flushing when better tolerated choices are unsuitable.

Clonidine

Start 50 micrograms orally twice daily; if there is no remission after two weeks, the current product SmPC permits 75 micrograms twice daily.

Not routine first-line therapy. Check blood pressure, pulse, conduction disease, renal function, constipation and sedatives; taper over two to four days rather than stopping suddenly because rebound hypertension and autonomic symptoms can occur.

Newly licensed non-hormonal NK1/NK3 antagonist for moderate to severe vasomotor symptoms associated with menopause or breast-cancer adjuvant endocrine therapy.

Elinzanetant (Lynkuet)

The August 2026 SmPC dose is 120 mg orally at bedtime as two 60 mg capsules; use 60 mg nightly with a moderate CYP3A4 inhibitor, returning to 120 mg after three to five inhibitor half-lives once it is stopped.

NICE appraisals are still awaiting development. Strong CYP3A4 inhibitors, severe hepatic impairment and pregnancy are contraindications; Child-Pugh B and eGFR below 30 are not recommended, and no dose recommendation can be made above age 65. Obtain baseline liver tests, use caution with seizure risk and sedation, advise effective contraception, and avoid concomitant systemic oestrogen HRT; local vaginal oestrogen is excluded from that interaction warning. Moderate or strong CYP3A4 inducers can reduce efficacy, and grapefruit juice is not recommended.

Complications, monitoring and follow-up

  • For fezolinetant, obtain liver tests before treatment and monthly during the first three months; test immediately if symptoms suggest liver injury.
  • Stop fezolinetant if transaminases exceed five times the upper limit, or reach at least three times the limit with bilirubin above twice the limit or clinical liver symptoms, and investigate.
  • Review any treatment against a baseline measure of flushes, night waking, function and the patient's priority outcome rather than continuing by default.
  • During serotonergic treatment, review early activation, mood, suicidal thinking, blood pressure, sexual effects, interactions and withdrawal planning.
  • For gabapentin, review alertness, falls, driving, oedema, renal function, co-prescribed opioids or sedatives, dose escalation and evidence of dependence.
  • With clonidine, check sitting and standing blood pressure, pulse, dizziness, constipation, sedation and the safe taper plan.
  • For elinzanetant, check baseline liver function and review benefit, fatigue, dizziness, somnolence, seizure symptoms, pregnancy prevention and CYP3A4 interactions; repeat liver tests when symptoms suggest injury rather than applying the fezolinetant monthly schedule automatically.
  • Revisit whether HRT remains unsuitable and whether GSM, osteoporosis risk or another symptom needs separate treatment at each menopause review.

Special situations

Licence and NICE differ

The licensed population and the NICE-funded population may differ because TA1143 specifically positions fezolinetant when HRT is unsuitable.

No oestrogen replacement

Fezolinetant treats neurokinin-mediated vasomotor symptoms but supplies no oestrogen, so it neither protects bone nor treats vaginal atrophy.

CYP1A2 matters

Smoking induces CYP1A2 whereas fluvoxamine inhibits it, making a complete interaction check safer than reasoning from one familiar example.

CBT is active treatment

Menopause-specific CBT uses symptom-focused cognitive and behavioural components and does not imply that vasomotor symptoms are imaginary.

Tamoxifen interaction

Avoid casual selection of a potent CYP2D6 inhibitor during tamoxifen treatment and coordinate antidepressant choice with oncology or pharmacy.

New licence needs context

Elinzanetant's 2026 licence is genuine, but both NICE appraisals remained awaiting development on 31 August 2026; prescribing must also follow local formulary status and its distinct SmPC safeguards.

Common pitfalls

  1. 01

    Starting fezolinetant without baseline liver tests or an interaction screen.

  2. 02

    Describing fezolinetant as a treatment for GSM or as osteoporosis prevention.

  3. 03

    Using an SSRI, SNRI or clonidine routinely as first-line therapy for flushes alone despite NICE advice.

  4. 04

    Treating depressive illness as merely a menopause symptom and omitting suicide or bipolar assessment.

  5. 05

    Prescribing gabapentin alongside opioids and sedatives without reviewing respiratory, falls and dependence risk.

  6. 06

    Stopping clonidine, venlafaxine or gabapentin abruptly after sustained use.

  7. 07

    Assuming newly licensed elinzanetant is already NICE-recommended, or copying fezolinetant's interaction and liver-monitoring rules onto a drug with different SmPC safeguards.

JurisdictionUnited Kingdom