Key Clinical Summary: Identification & Management of Vasomotor Symptoms (VMS) in Menopause

This is a micro-learning module summary of DrJill Liss's Menopause Education session which you can find here.

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This program was supported by an independent medical education grant from Bayer.

This content is intended for US Healthcare Professionals only.

Introduction

Prevalence & Impact: Up to 80 % of menopausal women experience VMS. Symptoms often persist ~7 years (30 % > 10 years; 10 % beyond age 70).

Why It Matters: Moderate-to-severe VMS impair sleep, cognition, work performance and are increasingly linked to cardiovascular, bone and brain health.

Clinical Imperative: All clinicians who care for mid-life women should be comfortable diagnosing and treating VMS—specialist referral alone is not sufficient.

Recognising & Assessing VMS

Patient History Essentials

Frequency, severity (mild, moderate, severe), day vs night pattern.
Triggers (alcohol, stress, spicy foods, ambient heat).
Sleep disruption, mood/cognitive effects, work or social interference.
Previous therapies tried (including OTC supplements).

Validated Tools

Hot-Flash Related Daily Interference Scale (HFRDIS).
Menopause-specific Quality-of-Life questionnaire (MENQOL).

Red-Flag Exclusions

Thyroid disease, infections, malignancy, medication side-effects.

Pathophysiology – KNDy Neuron Model

Estrogen normally inhibits kisspeptin/neurokinin B/dynorphin (KNDy) neurons in the hypothalamic thermoregulatory centre.
Falling estradiol removes this brake; excess neurokinin B activity at NK3 receptors narrows the thermoneutral zone, initiating flushing, vasodilation and sweating.
Direct NK receptor antagonism aims to act as a mechanism-based non-hormonal strategy.

First-Line Therapy: Menopausal Hormone Therapy (MHT)

Effectiveness: Most rapid and potent VMS relief; ideal for women < 60 y or within 10 y of the final menstrual period.

Absolute Contraindications: Unexplained genital bleeding, estrogen-sensitive cancer, severe acute liver disease, prior VTE/MI/stroke, known thrombophilia.

Important Clarifications: Migraine with aura, controlled hypertension, smoking, diabetes, family history of breast cancer and BRCA status are not absolute barriers.

Evidence-Based Non-Hormonal Pharmacotherapy

SSRIs/SNRIs

Paroxetine is FDA-approved; escitalopram, citalopram, venlafaxine, desvenlafaxine off-label.
Expect ~40-65 % reduction in hot-flash frequency within 4-8 weeks.
Watch for GI effects, dizziness, fatigue, hypertension (SNRIs) and interaction with tamoxifen.

Gabapentinoids

Gabapentin and pregabalin are off label.
Similar efficacy to SSRIs; useful if insomnia or neuropathic pain co-exist.
Sedation and dizziness limit daytime use.

Anticholinergic Agent

Oxybutynin is off label.
May reduce hot-flash frequency up to 70 %
Dry mouth, constipation and cognitive concerns in older adults.

Neurokinin-3 Receptor Antagonist (Fezolinetant)

First-in-class, FDA-approved.
Efficacy comparable to hormone therapy.
Safety: Check LFTs at baseline, monthly × 3, then at 6 & 9 months; hold if ALT/AST > 5× ULN or > 3× ULN with hyperbilirubinemia.
Contraindicated with CYP3A4 inhibitors and consider drug–drug checks (famotidine, systemic estrogen).

Emerging & Pipeline Therapies

Elinzanetant: Dual NK1/NK3 antagonist; phase-3 data show VMS relief with potential sleep improvement and with the possibility that there will be no routine LFT monitoring—although not yet FDA approved.

Estetrol (E4): “Natural” fetal-liver estrogen is under investigation and not FDA licensed; aims for endometrial and VTE safety advantages over estradiol.

Additional NK antagonists and non-neurokinin agents (e.g., MT-8554, Q-122) are in development.

Behavioural & Procedural Adjuncts

Cognitive-behavioural therapy and clinical hypnosis have level-I evidence for VMS reduction and sleep benefit.

Weight loss, paced respiration, yoga and acupuncture provide modest support.

Stellate-ganglion block considered in refractory cases but remains investigational.

Practical Step-Wise Approach

Confirm diagnosis and exclude secondary causes.

Quantify baseline symptom burden with diary or validated scale.

Offer MHT if no contraindications and patient is within age/timing window.

If MHT inappropriate or declined:

Begin with SSRI/SNRI, gabapentin or oxybutynin based on comorbidities and patient preference.
Consider fezolinetant for moderate-to-severe VMS needing rapid, non-hormonal control or after other agents fail.

Layer behavioural strategies for all patients.

Reassess at 8–12 weeks; adjust dose, switch classes, or combine therapies as needed.

Long-term follow-up: Monitor treatment efficacy, adverse effects, bone/cardiovascular health and evolving patient goals.

Core Take-Home Messages

Mechanistic Breakthrough: Blocking NK3 receptors delivers hormone-free relief on par with estrogen.

Contraindications to MHT are fewer than many clinicians assume—use it when appropriate.

Non-hormonal choices now span serotonergic, GABAergic, anticholinergic and neurokinin pathways—tailor to comorbidities and patient preference.

Treat VMS proactively: improved sleep, mood and possibly reduced long-term cardiometabolic risk justify intervention.