Review compares nonhormonal drugs for hot flashes after breast cancer
Several medicines reduced symptoms compared with placebo, but safety comparisons were too limited to rank the drugs reliably.
High evidenceReviewSome caution advised
Medical disclaimer: This article summarizes research findings and is for informational purposes only. It is not medical advice.
Editorial illustration — not from the study.
Researchers searched medical databases and trial registries through July 2026 for randomized studies of nonhormonal prescription drugs used for breast cancer-related vasomotor symptoms. The analysis compared symptom changes, treatment discontinuation, and adverse events across medicines and placebo.
Escitalopram, two studied strengths of desvenlafaxine, elinzanetant, and venlafaxine showed greater symptom improvement than placebo in the analysis. Elinzanetant had high-certainty evidence, while some other findings were based on fewer data. The review found no statistically significant differences from placebo in discontinuation outcomes, but the researchers cautioned that the safety evidence was too sparse to conclude that the medicines had equivalent tolerability.
What the review covered
The researchers reviewed randomized controlled trials involving adult women with breast cancer or breast cancer survivors who had breast cancer-related vasomotor symptoms, such as hot flashes. Eighteen publications representing 19 study or substudy records and 2,224 randomized or allocated participants were included. The review compared eligible nonhormonal prescription drugs with placebo or with one another. It assessed symptom improvement, the number of participants who responded, treatment discontinuation, discontinuation because of adverse events, any adverse events, and serious adverse events. The researchers used a frequentist random-effects network meta-analysis and a Bayesian analysis as a sensitivity check, and assessed risk of bias and certainty of evidence.
Key conclusions
Five interventions were statistically more effective than placebo for the main continuous symptom outcome: escitalopram, desvenlafaxine 50 mg, desvenlafaxine 100 mg, elinzanetant, and venlafaxine 75 mg. The reported standardized mean differences were -1.08 for escitalopram, -0.87 for desvenlafaxine 50 mg, -0.80 for desvenlafaxine 100 mg, -0.51 for elinzanetant, and -0.42 for venlafaxine 75 mg. In this analysis, more negative values represented greater symptom reduction compared with placebo.
Elinzanetant had high-certainty evidence, while venlafaxine 75 mg and gabapentin 900 mg had moderate-certainty evidence for the outcomes assessed. The review described the evidence for escitalopram and desvenlafaxine as promising but sparse. Sertraline, bupropion, gabapentin 300 mg, and clonidine were ranked lower in the review's comparisons. No statistically significant differences from placebo were found for discontinuation outcomes, but the safety networks were too limited to establish a reliable safety ranking. These results show associations within the included trials and do not establish that any medicine is appropriate for every person.
Where this may apply
These findings may be relevant to adult women with breast cancer or a history of breast cancer who have treatment-related vasomotor symptoms and who resemble participants in the included randomized studies. They do not necessarily apply to people without breast cancer-related symptoms, men, children, or people with substantially different medical circumstances. The review does not establish that any particular medicine will work for an individual or that the medicines have equivalent safety. The findings also may not reflect newer evidence published after the search ended in July 2026.
What this could mean
Breast cancer treatment, particularly endocrine therapy, can be associated with vasomotor symptoms, and this review brings together randomized evidence on several nonhormonal prescription options. It suggests that the medicines do not have identical evidence for symptom relief. At the same time, the limited safety comparisons mean that apparent similarities in discontinuation or adverse-event results should not be treated as proof that the drugs are equally well tolerated.
Limitations & evidence assessment
The review included 2,224 participants, but some individual drug comparisons, including those for escitalopram and desvenlafaxine, were supported by sparse evidence. The safety networks were particularly limited, preventing a dependable comparison of tolerability. Although the researchers reported moderate heterogeneity and no significant global or local inconsistency, differences among the underlying trials and participants may still affect comparisons. The abstract does not provide enough detail about follow-up duration, the characteristics of each study population, or the specific adverse events to assess how consistently the findings apply across settings. As a review of randomized trials, its conclusions are also limited by the quality and coverage of the available trials.
Why this evidence level: Meta-analysis pooling multiple studies sits at the top of common evidence hierarchies.
Evidence levels are editorial estimates derived from study metadata — they are not clinical appraisals.
// Source
Frontiers in Pharmacology · 2026 · DOI: 10.3389/fphar.2026.1952323
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