Curriculum
Module 05 · 55 min

Non-Hormonal Therapy for Vasomotor Symptoms

For the women who cannot, or will not, take oestrogen — and there are many.

Endocrine & MHTOncology & survivorshipBrain, mood & sleepPrimary care track
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Learning objectives

By the end of this module you will be able to

  • L01Rank non-hormonal options by effect size relative to placebo.
  • L02Avoid paroxetine and fluoxetine in women taking tamoxifen and explain the CYP2D6 mechanism.
  • L03Describe hepatic monitoring requirements for fezolinetant.
  • L04Offer CBT as an evidence-based option with a realistic account of what it changes.
  • L05Respond to requests for black cohosh, evening primrose oil and phytoestrogens using graded evidence.
Scope

Topics covered

01NK3 and NK1/NK3 antagonists: efficacy, hepatic monitoring, cost
02SSRIs and SNRIs: paroxetine, venlafaxine, escitalopram — and the tamoxifen interaction
03Gabapentin, oxybutynin and clonidine
04Cognitive behavioural therapy and clinical hypnosis
05Weight loss, cooling strategies and what lifestyle actually delivers
06Supplements with no supporting evidence, and how to have that conversation
Module narrative

How this plays out in practice

Primary care view· your track

If MHT is contraindicated or declined, offer in order: an NK3 antagonist where accessible, or an SSRI/SNRI (venlafaxine 37.5–75 mg, escitalopram 10–20 mg, paroxetine 7.5–12.5 mg — never with tamoxifen), or gabapentin 300–900 mg at night if night sweats dominate. Offer CBT alongside, not instead. Be candid that most supplements perform no better than placebo, while acknowledging the placebo response is real.

Specialist view

In breast cancer survivors, sequence non-hormonal options against endocrine therapy interactions and the symptom that dominates. Venlafaxine is the default with tamoxifen; gabapentin suits nocturnal-predominant symptoms; oxybutynin has trial support but anticholinergic burden matters in older women and in those with cognitive concerns. Vaginal oestrogen for GSM is a separate risk conversation from systemic therapy and is often acceptable after specialist discussion.

Advanced note

Compare effect sizes honestly: oestrogen reduces moderate-severe VMS frequency by roughly 75%, fezolinetant and elinzanetant by roughly 60–65% versus 40% placebo in phase 3, SSRIs and SNRIs by roughly 50–60% versus 40%. Read the placebo arms first — a trial reporting only within-group change is uninterpretable in this indication.

Expected takeaways

What you should walk away believing

  • →NK3/NK1-NK3 antagonists are the first genuinely mechanism-targeted non-hormonal class, with effect sizes approaching but not matching oestrogen.
  • →Paroxetine and fluoxetine are potent CYP2D6 inhibitors and reduce conversion of tamoxifen to endoxifen — use venlafaxine or citalopram instead.
  • →CBT does not reduce flush frequency much but reliably reduces the bother and interference score — a legitimate outcome.
  • →Placebo response in VMS trials runs at 30–50%, which is why uncontrolled testimonials for supplements are so persuasive and so unreliable.
  • →Fezolinetant requires baseline and periodic liver function monitoring following post-marketing hepatic injury reports.
Myth-buster

What patients — and colleagues — get wrong

The claim

“Phytoestrogens are a natural, safe alternative to HRT.”

Reality

Isoflavone trials are heterogeneous with mostly small or null effects against placebo. Equol-producer status varies by individual gut microbiome, which explains inconsistent responses. 'Natural' also does not mean oestrogen-free: some preparations have measurable oestrogenic activity, which matters in hormone-sensitive cancer.

Graded claims

Evidence grading for this module

A

Fezolinetant reduces moderate-severe VMS frequency and severity vs placebo

Established — RCT / guideline-grade — SKYLIGHT 1 and 2, replicated.

A

Elinzanetant improves VMS and sleep disturbance vs placebo

Established — RCT / guideline-grade — OASIS 1–3.

B

Venlafaxine and escitalopram reduce VMS frequency vs placebo

Supported in defined populations — MsFLASH network trials — modest but consistent.

A

Paroxetine should be avoided in women on tamoxifen

Established — RCT / guideline-grade — CYP2D6 inhibition reduces endoxifen; associated with worse breast cancer outcomes in cohort data.

B

CBT reduces the bother and impact of hot flushes

Supported in defined populations — MENOS trials — impact scores improve more than objective frequency.

E

Black cohosh reduces moderate-severe VMS

Popular, weak or conflicting support — Heterogeneous, largely null vs placebo; hepatotoxicity case reports.

F

Evening primrose oil relieves VMS

Refuted or actively misleading — No convincing controlled evidence.

Evidence summary

Graded claims, key takeaways and sources for this module.

Open printable summary
Clinical vignettes

Apply it in clinic

Severe VMS on an aromatase inhibitor

A 58-year-old, 2 years after ER-positive breast cancer, on anastrozole, has 15 flushes daily and is considering stopping her endocrine therapy.

Priority action?

Self-assessment

Check your recall

Q1

A woman on tamoxifen needs treatment for severe hot flushes. Which agent should be avoided?

Q2

Fezolinetant requires which monitoring?

Q3

Typical placebo response rate in vasomotor symptom trials is approximately:

Flashcards

Retrieval practice

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Glossary

Terms used in this module

Endoxifen
The active metabolite of tamoxifen, generated by CYP2D6 — the reason potent CYP2D6 inhibitors are avoided.
MsFLASH
Menopause Strategies: Finding Lasting Answers for Symptoms and Health — an NIH network of non-hormonal VMS trials.
Equol
A bacterial metabolite of the soy isoflavone daidzein produced only by some individuals' gut flora.
Primary sources

Read the evidence yourself