Evidence mapPaperPMID 41519709Full record

Trial reportThe journal of headache and pain2026

Sildenafil provokes headache but not migraine in men with migraine without aura: a randomized, placebo-controlled crossover trial.

Anas Mohammad, Ditte Bork Iversen, Nete Lundager Klokker Rausgaard, Christina Kruuse, Dagmar Beier, Tore Bjerregaard Stage, Lanfranco Pellesi

Abstract readRandomized Controlled Trial
In one paragraph

Trial report in The journal of headache and pain, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Anas MohammadClinical Pharmacology, Pharmacy and Environmental Medicine, Department of Public Health, University of Southern Denmark, Odense, Denmark.
Ditte Bork IversenClinical Pharmacology, Pharmacy and Environmental Medicine, Department of Public Health, University of Southern Denmark, Odense, Denmark.ORCID https://orcid.org/0000-0002-5519-9091
Nete Lundager Klokker RausgaardClinical Pharmacology, Pharmacy and Environmental Medicine, Department of Public Health, University of Southern Denmark, Odense, Denmark.ORCID https://orcid.org/0000-0003-1662-3547
Christina KruuseDepartment of Brain- and Spinal Cord Injuries, Copenhagen University Hospital - Rigshospitalet, Glostrup, Denmark.ORCID https://orcid.org/0000-0002-4210-0523
Dagmar BeierDepartment of Neurology, Odense University Hospital, Odense, Denmark.ORCID https://orcid.org/0000-0002-3336-157X
Tore Bjerregaard StageClinical Pharmacology, Pharmacy and Environmental Medicine, Department of Public Health, University of Southern Denmark, Odense, Denmark.ORCID https://orcid.org/0000-0002-4698-4389
Lanfranco PellesiClinical Pharmacology, Pharmacy and Environmental Medicine, Department of Public Health, University of Southern Denmark, Odense, Denmark. lpellesi@health.sdu.dk.ORCID https://orcid.org/0000-0003-4137-5039

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundCyclic guanosine monophosphate (cGMP)-mediated mechanisms plays a role in migraine pathophysiology. Sildenafil, a phosphodiesterase type 5 inhibitor, increases intracellular cGMP and can reliably induce migraine attacks in women. However, its migraine-inducing potential in men remains largely unknown.

methodsIn this randomized, double-blind, placebo-controlled crossover trial, 12 men with migraine without aura received sildenafil (100 mg) and placebo in separate sessions ≥ 7 days apart. An open-label parallel cohort of 15 women with migraine received sildenafil (100 mg) under similar experimental conditions. The primary endpoints were (i) the incidence of migraine-like attacks after sildenafil compared with placebo in men, and (ii) the incidence of migraine-like attacks after sildenafil in men and women.

resultsIn men, sildenafil induced headache more frequently than placebo (83% vs. 25%, p = 0.033), whereas the incidence of migraine-like attacks did not differ between sildenafil and placebo (25% vs. 17%, p = 0.500). In women, sildenafil induced headache in all participants and migraine-like attacks in 67%, a significantly higher proportion than in men (67% vs. 25%, p = 0.038). Adverse events were more frequent after sildenafil than placebo, most commonly flushing and nasal congestion.

conclusionsSildenafil provoked headache but not migraine in men with migraine without aura, whereas women showed a markedly greater susceptibility to migraine induction. These findings suggest that cGMP-mediated mechanisms contribute less prominently to migraine generation in men.

Indexed as

HeadacheMigraine without AuraPhosphodiesterase 5 InhibitorsPiperazinesSulfonesAdultCross-Over StudiesDouble-Blind MethodFemaleHumansMaleMiddle AgedPurinesSildenafil CitrateYoung AdultPhosphodiesterase 5 InhibitorsPiperazinesPurinesSildenafil CitrateSulfonescGMPCGRPGenderHeadachePainSex

Identifiers

PMID41519709
PMCPMC12801661

What Socratic holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.