Design: Clinical practice guideline based on GRADE-assessed systematic reviews
Population: Females in outpatient care seeking treatment for menopausal vasomotor symptoms
Primary outcome: Recommended order of pharmacological treatment
Effect: First line oestrogen ± progestogen (strong, high certainty); second line SNRI (conditional, moderate)

The American College of Physicians' Clinical Guidelines Committee graded systematic reviews of effectiveness, harms, patient values and cost for drugs used to treat menopausal vasomotor symptoms in outpatients, using GRADE.

For women seeking treatment, it strongly recommends starting oestrogen with a progestogen in women with a uterus, or oestrogen alone in women without one, both on high-certainty evidence. For those who cannot take or tolerate hormones, it suggests venlafaxine or desvenlafaxine (moderate certainty). Third line, it suggests escitalopram or paroxetine, gabapentin (both low certainty), or the neurokinin receptor antagonists fezolinetant or elinzanetant (moderate certainty). Every choice is to be made with the woman, weighing harms, other conditions, preferences, cost and access.

The practical shift is in tone as much as content. Hormone therapy is placed first on the strongest evidence, rather than treated as a last resort, while the newer neurokinin antagonists sit behind cheaper drugs. This is one society's guideline; other national guidelines, including those followed in India, may sequence options differently, and contraindications to oestrogen are unchanged.

For a woman seeking treatment for hot flushes without contraindications, offer hormone therapy first.
Women with a uterus need a progestogen with oestrogen; those without one can take oestrogen alone.
Where hormones are unsuitable, try venlafaxine or desvenlafaxine next.
Escitalopram, paroxetine, gabapentin, fezolinetant and elinzanetant are third-line options.
Avoid paroxetine in women taking tamoxifen, because it blocks tamoxifen's activation.

Why it matters

It places hormone therapy at the front of the queue, where many clinicians still treat it as a last resort.

The statistics, in plain English

'High certainty' means further research is very unlikely to change confidence in the effect; 'low certainty' means the true effect may be quite different. A strong recommendation is one most women would want; a conditional one depends more on the individual.